ORCID Profile
0000-0001-7484-4036
Current Organisations
University of Otago Christchurch
,
Canterbury District Health Board
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Publisher: Elsevier BV
Date: 04-2002
DOI: 10.1016/S0735-1097(02)01737-0
Abstract: We sought to assess the relationship of antecedent hypertension to neurohormones, ventricular remodeling and clinical heart failure (HF) after myocardial infarction (MI). Heart failure is a probable contributor to the increased mortality observed after MI in those with antecedent hypertension. Hence, neurohormonal activation, adverse ventricular remodeling and a higher incidence of clinical HF may be expected in this group. However, no previous report has documented serial postinfarction neurohumoral status, serial left ventricular imaging and clinical outcomes over prolonged follow-up in a broad spectrum of patients with and without antecedent hypertension. Inpatient events were documented in 1,093 consecutive patients (436 hypertensive and 657 normotensive) with acute MI. In 68% (282 hypertensive, 465 normotensive) serial neurohormonal s ling and radionuclide ventriculography were performed one to four days and three to five months after infarction. Clinical outcomes were recorded over a mean follow-up of two years. Plasma neurohormones were significantly higher in hypertensives than in normotensives one to four days and three to five months after infarction. From similar initial values, left ventricular volumes increased significantly in hypertensives, compared with normotensives. Left ventricular ejection fraction rose significantly in normotensive but not hypertensive patients. Together with higher inpatient (8.1% vs. 4.4%, p < 0.002) and post-discharge mortality (9.5% vs. 5.5%, p = 0.043), hypertensive patients incurred more inpatient HF (33% vs. 24%, p < 0.001) and more late HF requiring readmission to hospital (12.4% vs. 5.5%, p 64 years of age with neurohormonal activation and early left ventricular dilation. Antecedent hypertension interacts with age, neurohumoral activation and early ventricular remodeling to confer greater risk of HF after MI.
Publisher: BMJ
Date: 19-01-2019
DOI: 10.1136/HEARTJNL-2018-314077
Abstract: Ethnic differences in the prevalence of atrial fibrillation (AF) in heart failure (HF) remain unclear. We compared the prevalence and clinical correlates of AF among different ethnicities in an Asian-Pacific population with HF. Patients with validated HF were prospectively studied across Singapore and New Zealand (NZ). Among 1746 patients with HF (62% Asian, 26% women, mean age 66 (SD 13) years, mean ejection fraction (EF) 37 (SD 16%), 39% had AF. The prevalence of AF was markedly lower in Singapore-Asians than NZ-Europeans (24% vs 63% p .001), even after adjusting for age, clinical and echocardiographic covariates, regardless of EF group (p interaction for EF=0.39). Patients with AF were older, had higher body mass index and were more likely to have a history of hypertension, stroke, peripheral vascular disease, renal disease, chronic respiratory disease and increased alcohol intake, but less likely to have diabetes. Clinical correlates were similar for Asians and NZ-Europeans, except diabetes: Asian diabetic patients with HF had less AF compared with Asian patients without diabetes (OR 0.66, 95% CI 0.50 to 0.88), whereas among NZ-Europeans there was no significant association between diabetes and AF (OR 1.22, 95% CI 0.85 to 1.75) (p interaction for ethnicity=0.01). AF was associated with a higher crude composite outcome of mortality and HF hospitalisations at 2 years (HR 1.19, 95% CI 1.02 to 1.38). There is a strikingly lower prevalence of AF among Asian compared with NZ-European patients with HF. The underlying mechanisms for the lower prevalence of AF among Asians, particularly in the presence of diabetes, deserve further study. ACTRN12610000374066.
Publisher: Oxford University Press (OUP)
Date: 07-2018
DOI: 10.1373/CLINCHEM.2017.285700
Abstract: Increased cardiac troponin I or T detected by high-sensitivity assays (hs-cTnI or hs-cTnT) confers an increased risk of adverse prognosis. We determined whether patients presenting with putatively normal, detectable cTn concentrations [& limit of detection and & upper reference limit (URL)] have increased risk of major adverse cardiovascular events (MACE) or all-cause mortality. A prospective 5-year follow-up of patients recruited in the emergency department with possible acute coronary syndrome (ACS) and cTn concentrations measured with hs-cTnI (Abbott) and hs-cTnT (Roche) assays. Cox regression models were generated with adjustment for covariates in those without MACE on presentation. Hazard ratios (HRs) for hs-cTn were calculated relative to the HRs at the median concentration. Of 1113 patients, 836 were without presentation MACE. Of these, 138 incurred a MACE and 169 died during a median 5.8-year follow-up. HRs for MACE at the URLs were 2.3 (95% CI, 1.7–3.2) for hs-cTnI and 1.8 (95% CI, 1.3–2.4) for hs-cTnT. Corresponding HRs for mortality were 1.7 (95% CI, 1.2–2.2) for hs-cTnI and 2.3 (95 % CI, 1.7–3.1) for hs-cTnT. The HR for MACE increased with increasing hs-cTn concentration similarly for both assays, but the HR for mortality increased at approximately twice the rate for hs-cTnT than hs-cTnI. Patients with hs-cTnI ≥10 ng/L or hs-cTnT ≥16 ng/L had the same percentage of MACE at 5-year follow-up (33%) as patients with presentation MACE. Many patients with ACS ruled out and putatively normal but detectable hs-cTnI concentrations are at similar long-term risk as those with MACE. hs-cTnT concentrations are more strongly associated with 5-year mortality than hs-cTnI.
Publisher: Wiley
Date: 11-12-2017
DOI: 10.1111/ACEM.13343
Abstract: Early discharge of patients with presentations triggering assessment for possible acute coronary syndrome (ACS) is safe when clinical assessment indicates low risk, biomarkers are negative, and electrocardiograms (ECGs) are nonischemic. We hypothesized that the Emergency Department Assessment of Chest Pain Score (EDACS) combined with a single measurement of high-sensitivity cardiac troponin (hs-cTn) could allow early discharge of a clinically meaningful proportion of patients. We pooled data from four patient cohorts from New Zealand and Australia presenting to an emergency department with symptoms suggestive of ACS. The primary outcome was major adverse cardiac events (MACE) within 30 days of presentation. In patients with a nonischemic ECG we evaluated the sensitivity for MACE and percentage low risk of every combination of high-sensitivity cardiac troponin T (hs-cTnT) concentration and high-sensitivity cardiac troponin I (hs-cTnI) concentration with EDACS. We used a standard smoothing technique on the probability density function for hs-cTn and EDACS and applied bootstrapping to determine the optimal threshold combinations, namely, the combination that maximized the percentage low risk with ≥98.5% sensitivity for MACE. From 2,536 patients, 2,258 presented without an ischemic ECG of whom 272 (12.1%) had a MACE within 30 days. The optimal threshold for hs-cTnI was 7 ng/L combined with an EDACS threshold of 16 (36.8% patients low risk). The optimal thresholds for hs-cTnT were 8 ng/L combined with an EDACS threshold of 15 (30.2% patients low risk). Single measurements of both hs-cTnI and hs-cTnT at presentation combined with EDACS to identify over 30% of patients as low risk and therefore eligible for safe early discharge after only one blood draw.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2023
DOI: 10.1161/CIRCHEARTFAILURE.123.010661
Abstract: Selecting high-risk patients with heart failure with potentially modifiable cardiovascular events is a priority. Our objective was to evaluate NT-proBNP (N-terminal pro-B-type natriuretic peptide) changes during a 30-day screening to establish (1) the frequency and direction of changes (2) whether a relationship exists between changes in NT-proBNP and the primary composite outcome of cardiovascular death and heart failure hospitalization and (3) whether changes in NT-proBNP relate to vericiguat’s clinical benefit. VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) randomized 5050 patients with heart failure with reduced ejection fraction and a recent worsening heart failure event. We studied 3821 patients who had NT-proBNP measured during screening and at randomization. Sixteen hundred exhibited a % reduction, 1412 had ≤20% change, and 809 showed a % rise in NT-proBNP levels. As compared with the primary composite outcome of 28.4/100 patient-years (497 events 31.1%) in patients with a % decline in NT-proBNP, those with % during screening had worse outcomes 48.8/100 patient-years (359 events 44.4%) adjusted hazard ratio, 1.61 (95% CI, 1.39–1.85). Those patients with a ≤20% change in NT-proBNP had intermediate outcomes 39.2/100 patient-years (564 events 39.9%) adjusted hazard ratio, 1.33 (95% CI, 1.17–1.51). No relationship existed between NT-proBNP changes during screening and vericiguat’s effect on cardiovascular death and heart failure hospitalization. Substantial differences occurred in the rates of cardiovascular death and heart failure hospitalization, especially in patients with a % change in NT-proBNP levels during screening interval. Sequential NT-proBNP levels add important prognostic information meriting consideration in future heart failure trials. URL: www.clinicaltrials.gov Unique identifier: NCT02861534.
Publisher: Wiley
Date: 28-12-2012
DOI: 10.1111/CHF.12016
Abstract: Many proven heart failure (HF) therapies decrease N-terminal pro B-type natriuretic peptide (NT-proBNP) values over time, yet some patients have an NT-proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT-proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT-proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT-proBNP over time was associated with increased cardiovascular event rates while a decreasing NT-proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P<.001). Importantly, responders showed improved left ventricular remodeling parameters (all P<.001), while nonresponders did not. A risk model for predicting nonresponse had a C statistic of 0.82 (P<.001) and predicted outcomes well. Using data from the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) cohort, the risk score was validated for its ability to predict nonresponse (C statistic 0.73, P<.001). Serial changes in NT-proBNP inform risk for adverse outcome and are associated with prognostically meaningful metrics. Prediction of future NT-proBNP nonresponse to HF therapy is possible.
Publisher: Wiley
Date: 13-09-2016
DOI: 10.1002/EJHF.612
Abstract: This study was conducted to test the diagnostic performance of NT-proBNP for discrimination of acute decompensated heart failure (ADHF) among breathless patients presenting in an Asian compared with a Western centre. Patients with breathlessness were prospectively and contemporaneously recruited in Emergency Departments in Singapore and New Zealand (NZ). The diagnosis of ADHF was adjudicated by two clinician specialists. A total of 606 patients were recruited in Singapore and 500 in NZ. The discriminative power of NT-proBNP for ADHF was superior in Singapore compared with NZ [area under the curve (AUC) 0.926 vs. 0.866 P = 0.012] both overall and among selected subgroups stratified according to age, renal function, body mass index, and presence or absence of AF or diabetes. Previously established cut-off point values of plasma NT-proBNP yielded comparable sensitivity and negative predictive values, but superior specificity and accuracy in Singapore compared with NZ. The difference in test performance was driven by the younger age (median age 56 years vs. 73 years P < 0.001), associated with better renal function (estimated glomerular filtration rate 89 vs. 62 mL/min/1.73 m Considering emerging evidence of a lower average age of presentation with ADHF over most of Asia compared with Western countries, NT-proBNP is likely to be more accurate when applied in Asian centres than in the West.
Publisher: Wiley
Date: 19-12-2012
DOI: 10.1111/CHF.12010
Publisher: BMJ
Date: 13-03-2020
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.AHJ.2007.01.039
Abstract: The objective of this study is to compare the use of transesophageal echocardiography (TEE) vs multidetector computed tomography (MDCT) for detecting pulmonary vein stenosis. Pulmonary vein isolation is increasingly used to treat atrial fibrillation. Pulmonary vein stenosis remains a potential complication of pulmonary vein isolation and ideal methods for detection of stenosis are still to be determined. Thirty-six subjects who underwent pulmonary vein isolation returned for follow-up MDCT and TEE. Percent diameter loss was reported for each pulmonary vein stenosis by MDCT. A 50% narrowing was considered as an indication of a stenosis. Pulsed-wave Doppler using TEE was used to measure peak velocities of all pulmonary veins. Multidetector computed tomography and TEE were performed in all subjects (58 +/- 10 years) at 4 +/- 2 months after pulmonary vein isolation. Atrial fibrillation was present in 14% at time of follow-up. Multidetector computed tomography was able to evaluate all 4 (100%) pulmonary veins in 36 subjects, whereas full interrogation by TEE was possible in 138 (96%) of 144 veins. Pulmonary vein stenosis >50% by MDCT was present in 7 pulmonary veins. Analysis of the receiver operating curve for TEE showed that it had optimum detection of pulmonary vein stenosis at peak velocities approximately 100 cm/s with 86% sensitivity and 95% specificity. Area under the curve for TEE was 0.93. Clinically significant stenosis was observed in 2 subjects and was detected by both TEE and MDCT. Transesophageal echocardiography was able to detect most pulmonary veins with good sensitivity and specificity in comparison to MDCT. Pulmonary veins may be visualized more frequently by MDCT however, TEE provides additional data about the functional significance of a pulmonary vein stenosis.
Publisher: Oxford University Press (OUP)
Date: 13-05-2008
Publisher: Oxford University Press (OUP)
Date: 11-11-2013
Abstract: The natriuretic peptides are important tools to establish diagnosis and prognosis in heart failure (HF). With application of therapies for HF, changes in both B-type natriuretic peptide (BNP) and its amino terminal cleavage fragment (NT-proBNP) parallel the benefits of the HF therapy applied. This dynamic nature of BNP and NT-proBNP relative to therapeutic intervention in HF has led to the concept of using the biomarkers as a 'guide' for intensification of HF care with a goal of not only achieving guideline-directed medical therapy goals accompanied by targeted natriuretic peptide suppression below prognostic thresholds. In studies achieving this combination of therapy optimization and BNP/NT-proBNP suppression, superior outcomes have been observed, and the approach was well tolerated. Natriuretic peptide-guided HF therapy has recently been given a recommendation in US HF guidelines to achieve guideline-directed medical therapy (Class IIa) and possibly improve outcome (Class IIb), while other clinical practice guidelines (including those from the European Society of Cardiology) await results from emerging clinical trial data. We will review lessons learned in the past regarding this novel concept of biomarker guided HF care, and discuss future directions for the approach.
Publisher: Elsevier BV
Date: 07-2006
Publisher: Massachusetts Medical Society
Date: 07-07-2011
Publisher: Elsevier BV
Date: 06-2012
Publisher: Springer Science and Business Media LLC
Date: 13-05-2020
DOI: 10.1038/S41598-020-64795-7
Abstract: C-type Natriuretic Peptide (CNP) and Endothelin-1 (ET-1) have reciprocal roles in maintaining vascular homeostasis and are acutely modulated by statins in human cultured endothelial cells. Whether these actions of statins in vitro are reflected in studies in vivo is unknown. In a prospective study of 66 subjects with or without post- acute coronary syndrome (ACS), plasma concentrations of bioactive CNP and bio-inactive aminoterminal proCNP (NTproCNP), ET-1, B-type Natriuretic Peptide (BNP) and high sensitivity C Reactive Protein (hsCRP) were measured together with lipids before and at intervals of 1, 2 and 7 days after commencing atorvastatin 40 mg/day - and for a further period of 6months in those with ACS. Plasma lipids fell significantly in all subjects but plasma CNP, NTproCNP and ET-1 were unchanged by atorvastatin. In ACS, baseline hsCRP, BNP and CNP but not NTproCNP or ET-1 were significantly raised compared to values in age-matched controls. The ratio of NTproCNP to CNP was significantly lower in ACS throughout the study and was unaffected by statin therapy. We conclude that conventional doses of atorvastatin do not affect plasma CNP products or ET-1. Elevated CNP after cardiac injury likely results from regulated changes in clearance, not enhanced production.
Publisher: Wiley
Date: 25-08-2015
Abstract: Sympatholytic and vasodilator drugs have been of major therapeutic benefit in patients with heart failure (HF). Urocortin-2 (Ucn2) is a small corticotrophin-related peptide distributed throughout the cardiovascular system which inhibits cardiac sympathetic nerve activity (CSNA) and is also a powerful vasodilator. This study analysed the effects of a 60-min infusion of Ucn2 (25 μg) on muscle sympathetic nerve activity (MSNA) recorded from the lower limb in eight healthy men and four men with stable HF. During Ucn2 infusion, mean arterial pressure fell to a nadir of 84 ± 2 compared to 95 ± 2 mmHg during placebo (P = 0.001) and heart rate increased to a maximum of 74 ± 1 compared to 64 ± 1 b.p.m. (P < 0.001). Total peripheral resistance fell by 23 ± 4% compared with an increase of 23 ± 4% (P < 0.001) and cardiac output increased by 22 ± 4 compared to 4 ± 4% (P = 0.001). The MSNA burst frequency increased by 9 ± 2 compared to 1 ± 2 burst/min (P = 0.005) and burst area/min by 133 ± 7 vs 107 ± 7% (P = 0.01). Burst incidence and baroreflex sensitivity were not significantly altered. Qualitatively similar changes were observed in stable HF patients. Ucn2-induced vasodilatation increased MSNA in humans, as opposed to the decrease in CSNA we observed in sheep. Therefore, if Ucn2 has a central inhibitory effect on MSNA, it was over-run by off-loading the cardiovagal baroreflex. Alternatively, CSNA may be less responsive to baroreflex off-loading than MSNA.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.JACC.2012.02.035
Abstract: The purpose of this study was to determine whether a new accelerated diagnostic protocol (ADP) for possible cardiac chest pain could identify low-risk patients suitable for early discharge (with follow-up shortly after discharge). Patients presenting with possible acute coronary syndrome (ACS), who have a low short-term risk of adverse cardiac events may be suitable for early discharge and shorter hospital stays. This prospective observational study tested an ADP that included pre-test probability scoring by the Thrombolysis In Myocardial Infarction (TIMI) score, electrocardiography, and 0 + 2 h values of laboratory troponin I as the sole biomarker. Patients presenting with chest pain due to suspected ACS were included. The primary endpoint was major adverse cardiac event (MACE) within 30 days. Of 1,975 patients, 302 (15.3%) had a MACE. The ADP classified 392 patients (20%) as low risk. One (0.25%) of these patients had a MACE, giving the ADP a sensitivity of 99.7% (95% confidence interval [CI]: 98.1% to 99.9%), negative predictive value of 99.7% (95% CI: 98.6% to 100.0%), specificity of 23.4% (95% CI: 21.4% to 25.4%), and positive predictive value of 19.0% (95% CI: 17.2% to 21.0%). Many ADP negative patients had further investigations (74.1%), and therapeutic (18.3%) or procedural (2.0%) interventions during the initial hospital attendance and/or 30-day follow-up. Using the ADP, a large group of patients was successfully identified as at low short-term risk of a MACE and therefore suitable for rapid discharge from the emergency department with early follow-up. This approach could decrease the observation period required for some patients with chest pain. (An observational study of the diagnostic utility of an accelerated diagnostic protocol using contemporary central laboratory cardiac troponin in the assessment of patients presenting to two Australasian hospitals with chest pain of possible cardiac origin ACTRN12611001069943).
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.AHJ.2008.06.013
Abstract: Polymorphisms of the angiotensin-converting enzyme 2 (ACE2) gene, which is located on the X chromosome, have been associated with hypertension and left ventricular hypertrophy in previous studies. We tested the hypothesis that the rare allele of an ACE2 gene polymorphism was associated with risk factors for and adverse outcome after acute coronary syndrome (ACS) events. Patients (n = 1,042) were recruited after admission for an ACS event and were genotyped for the A1075G polymorphism of the angiotensin-converting enzyme 2 gene. This genetic marker was tested for association with baseline measurements, echocardiographic measurements, and clinical outcome, over a median 2.19 years follow-up. As the ACE2 gene is X-linked, analyses were performed separately for males and females. Patients were predominantly of European ethnicity (90.1%). The A1075 allele was significantly associated with covariate-adjusted mortality in male patients (hazard ratio 1.95, 95% CI 1.10-3.46, P = .047) but not unadjusted (hazard ratio 1.14, 95% CI 0.736-1.76, P = .56). The G1075 (P < .035) allele was more frequent in patients of Maori compared to European ancestry. E/E', an echocardiographic index of left ventricular diastolic function and filling pressure, was higher in males in the A1075 group (G allele group 10.5 [95% CI 10.0-11.0], A allele group 11.4 [95% CI 10.8-12.1], P = .024). A1075 genotype was significantly associated with male survival in the absence of (mortality: A 12.8%, n = 39 G 29.2%, n = 48 P = .037) but not in the presence of beta-blocker treatment (mortality: A 13.5% n = 273 G 8.2% n = 304, P = nonsignificant). The A1075 allele was associated with covariate-adjusted mortality in male patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-10-2020
DOI: 10.1161/CIRCULATIONAHA.119.045158
Abstract: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery. We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, res ling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF. In the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-β binding protein-4, and follistatin-related protein-3, as well. Large-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation.
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.AHJ.2005.12.015
Abstract: The AMPD1 gene C34T polymorphism has previously been associated with prolonged survival in small cohorts of heart failure (HF) and coronary artery disease patients. This study aimed to corroborate the association of the AMPD1 C34T polymorphism with survival in larger myocardial infarction (MI) and HF cohorts. Genotypes were obtained for 935 post-MI (PMI) and 433 patients with established HF, with median follow-up times of 5.4 and 3.1 years, respectively. At admission, cardiac function was assessed by nuclear ventriculography (PMI) and echocardiography (HF) and plasma cardiac neurohormones were assayed. Differences in mortality by AMPD1 genotype did not achieve significance, either for the overall HF (P = .07) or the overall PMI group (P = .28), but AMPD1 genotype predicted mortality in patients of both cohorts with a history of MI (HxMI). In contrast to previous studies, the mutant T allele was associated with poorer outcome. Mortality in HF HxMI patients was significantly different between genotype groups (n = 144, mortality CC 56.5%, CT/TT 77.8%, P = .027), but not in patients without HxMI. In PMI patients, the association of genotype with survival in the HxMI subgroup trended toward significance (n = 147, mortality CC 29.8%, CT/TT 45.5%, P = .093). Multivariate analysis of combined PMI and HF cohorts showed that HxMI patients with CT/TT genotype were at greater risk than all other groups (P < .001). This study suggests that AMPD1 C34T genotype is not a predictor of survival in heart disease patients, except possibly those with HxMI.
Publisher: BMJ
Date: 22-11-2011
DOI: 10.1136/EMERMED-2011-200222
Abstract: To investigate whether a high-sensitivity troponin assay, shown to improve early detection of acute myocardial infarction (AMI), permits accelerated rule-in/rule-out of AMI. Patients who presented to the emergency department within 4 h of the onset of chest pain suggestive of acute coronary syndrome were prospectively recruited from November 2007 to April 2010. Blood s les were taken at 0, 1, 2 and 12-24 h after presentation and were analysed for clinically applied troponin I and for high-sensitivity troponin T (hsTnT). The dynamic change in hsTnT levels between time points was measured. The primary outcome was admission diagnosis of AMI. Of the 385 patients recruited, 82 (21.3%) had AMI. The sensitivity of hsTnT by 2 h was 95.1% (88.7-98.1%), specificity 75.6% (73.8-76.5%), positive predictive value 53.8% (50.2-55.5%) and negative predictive value 98.3% (96.0-99.3%). The sensitivity was not statistically different between peak values at 2 h and 24 h. Adding ECG results reduced the false negative rate to 1.2%. The additional application of ≥20% delta criterion over the 2 h period for 0-2 h s les increased specificity to 92.4% (90.2-94.3%) but reduced sensitivity to 56.1% (48.0-63.2%). hsTnT taken at 0 and 2 h after presentation, together with ECG results, could identify patients suitable for early stress testing with a false negative rate for AMI of 1.2%. Further trials of such an approach are warranted. The specificity of hsTnT for diagnosing AMI could be improved by the use of a delta of ≥20%, but at the cost of major reductions in sensitivity.
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.JCMG.2008.12.006
Abstract: Echocardiography and the B-type natriuretic peptides (BNPs) provide powerful incremental assessment of cardiac function, clinical status, and outcome across the spectrum of cardiac disease. There is strong evidence to support their integrated use in the diagnosis and management of cardiovascular disease. Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) or BNP may guide more effective use of echocardiography in screening for asymptomatic left ventricular dysfunction Doppler echocardiography improves the accuracy of heart failure diagnosis in the setting of intermediate BNP or NT-proBNP levels. Combined assessment of peptides and echocardiography provides more powerful stratification of risk across all stages of heart failure, and integrated use of both tests may identify subjects with valvular disease at greatest risk for progression and guide decision-making for timely intervention.
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S0002-9343(98)00019-9
Abstract: Emotions can reflect how in iduals internalize identities, social roles, and broader power structures, including abortion stigma. Abortion accompaniment, in the form of logistical, informational, and emotional support offered by in iduals and organizations, takes a person-centered, feminist, and rights-based approach. We tested the extent to which abortion accompaniment may decrease negative and increase positive feelings an in idual holds related to their abortion. Using observational longitudinal data collected between January 2017 and mid-2018, we compared negative and positive emotional responses to a personal abortion experience one month and six months following the abortion to emotions immediately prior to the abortion ("baseline"), among women travelling from outside of Mexico City to abortion clinics in Mexico City with and without support of the accompaniment organization, Fondo MARIA. We used doubly robust longitudinal mixed effects models with inverse probability weighting methods. At baseline, accompanied and unaccompanied participants experienced an average of 4.9 and 4.4 negative emotions out of eight respectively (i.e., anguish, nervousness, scared, anxious, sadness, guilt, anger, shame) and 1.7 and 1.9 positive emotions of out 4 respectively (happiness, calmness, decidedness, and relief). From our model results, women accompanied (n = 77) had larger decreases in negative feelings (p < .05) and larger increases in positive feelings (p < .01) toward their abortion compared to those who were not accompanied (n = 119) at six months. These changes led the majority of accompanied respondents to have primarily positive feelings about their abortion by endline. Abortion accompaniment through Fondo MARIA in Mexico City was associated with a larger decrease in negative feelings, particularly those related to stigma, and a larger increase in positive feelings six months after abortion. Accompaniment's focus on person-centered support, self-determination, and autonomy may enable people seeking abortion to view their decision as one that is valid and legitimate, and resist the predominant stigmatizing narratives framing abortion as something that is transgressive.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.IJCARD.2014.12.051
Abstract: To determine the prognostic implications of diastolic filling grades and identify whether age-stratified E/A ratio alone can identify patients at high risk of death post-AMI and HF. We hypothesized that in response to ageing and pathology, a normal E/A (>1) could be considered abnormal in patients post-AMI older than 65years, and that in patients with symptomatic HF, a normal E/A always represents advanced diastolic dysfunction. This is a sub-analysis of the Meta-analysis Research Group in Echocardiography (MeRGE) which combined in idual patient data from 30 prospective studies and demonstrated that restrictive filling was an important and independent predictor of all-cause mortality. This sub-analysis is restricted to those studies in which continuous E/A data were available (20 studies) and includes a total of 3082 AMI and 2321 HF patients. Patients were classified at the time of echocardiography into four filling patterns: normal, abnormal relaxation, pseudonormal, and restrictive filling. Post-AMI patients were ided into four groups on the basis of age and E/A, while patients with HF were classified into three groups, based on only E/A. Mortality across groups was compared using Kaplan-Meier survival analysis and Cox proportional hazards. In multivariable analyses in the AMI patients, age-stratified E/A was an independent predictor of outcome (HR 1.43 (95% CI: 1.31-1.56)), and in the HF cohort, E/A was confirmed as an independent predictor of mortality (HR 1.12 (95% CI 1.09-1.16)) alongside age and ejection fraction. Age-stratified E/A is an independent predictor of mortality after AMI and in HF patients, regardless of left ventricular ejection fraction, age and gender. E/A ratio could be a first step echocardiographic risk stratification, which could precede and indicate the need for more advanced diagnostic and prognostic considerations in high-risk AMI and HF patients.
Publisher: Oxford University Press (OUP)
Date: 02-2018
DOI: 10.1373/CLINCHEM.2017.280354
Abstract: In community studies, plasma B-type natriuretic peptide (BNP) is positively associated with cardiovascular disorders. Those born with very low birth weight (VLBW) have increased risk of metabolic and vascular disorders in later life, but plasma concentrations of natriuretic peptides have not been studied. The objectives here were to evaluate BNP and C-type natriuretic peptide (CNP)—a putative marker of vascular risk—in young adults born with VLBW. In all, 220 VLBW cases and 97 matched controls were studied 28 years after birth during a 2-day period at 1 research center. Aminoterminal (NT) products (NTproBNP, NTproCNP) and a range of conventional vascular risk factors including echocardiographic indices were measured along with genetic polymorphisms known to increase plasma NTproBNP. VLBW in iduals were smaller, had smaller hearts, reduced stroke volume and endothelial function, and higher systolic blood pressure and arterial elastance. Of the many humoral vascular and metabolic risk factors measured, including NTproBNP, only plasma NTproCNP (higher in VLBW in iduals) differed significantly. Across all in iduals, associations of NTproCNP with each of 7 conventional risk factors, as well as with arterial elastance, were positive, whereas associations of NTproBNP with risk were all inverse. In multivariate analysis, the genetic variant rs198358 was independently associated with NTproBNP. In young adults at increased risk of cardiovascular disease, higher NTproCNP likely reflects a compensatory vascular response to vascular stress, whereas the negative link with NTproBNP likely reflects beneficial genetic mutations. The ratio of NTproBNP to NTproCNP may provide a novel index of ideal cardiovascular health.
Publisher: Oxford University Press (OUP)
Date: 2012
DOI: 10.1373/CLINCHEM.2011.165704
Abstract: Plasma B-type cardiac natriuretic peptides reflect cardiac structure and function and have proven roles in assisting in the diagnosis of acute heart failure. They are independent prognostic indicators across the full spectrum of cardiovascular disease. Serial changes in plasma B-type cardiac natriuretic peptides parallel prognosis in chronic heart failure. Beneficial responses to medications and devices used in the treatment of heart failure are associated with decreases in plasma B-type peptide concentrations. This effect has led to the hypothesis that intensified treatment directed at reducing B-peptide concentrations may improve outcomes in heart failure. The efficacy of serial measurements of plasma B-type peptides in guiding titration of therapy for chronic heart failure has been the subject of several randomized controlled trials reported in the peer-reviewed literature since 2000. These reports are summarized in this review. Trial design, characteristics of the heart-failure population studied, duration of follow-up, exact end points recorded, and target peptide concentrations pursued all differ somewhat between trials. In addition, in studies in which benefits were seen, the exact mechanisms mediating the improvements in outcome were unclear. However, an overall consistency is emerging that is supported by 2 metaanalyses. In aggregate the existing trial data suggest that adjustment of treatment in chronic heart failure according to serial B-type peptide measurements, used in conjunction with established clinical methods, is likely to reduce cardiac mortality and hospital admissions with heart failure, at least in patients with systolic heart failure who are younger than 75 years and relatively free of comorbidities.
Publisher: Portland Press Ltd.
Date: 02-2004
DOI: 10.1042/CS20030131
Abstract: Acute myocardial infarction (MI) results in activation of neurohormonal systems and increased plasma concentrations of myocardial enzymes and structural proteins. We hypothesized that plasma levels of N-terminal pro-brain natriuretic peptide (NT-BNP) would respond more vigorously after MI than those of other natriuretic peptides. We also sought to compare this response with that of the established myocardial injury markers troponin T (TnT), myoglobin and creatine kinase MB (CK-MB). We obtained multiple blood s les for measurement of atrial natriuretic peptide (ANP), N-terminal pro-ANP, brain natriuretic peptide (BNP) and NT-BNP along with CK-MB, TnT and myoglobin in 24 patients presenting to the Coronary Care Unit within 6 h of onset of MI. Multiple s les were obtained in the first 24 h, then at 72 h, 1 week, 6 weeks and 12 weeks. NT-BNP increased rapidly to peak at 24 h and exhibited greater (P& .001) absolute increments from baseline compared with BNP and ANP, whereas NT-ANP did not change from baseline. Proportional increments in NT-BNP were also greater than those for the other natriuretic peptides (P& .05). Natriuretic peptide levels reached their peak around 24 h, later than peak TnT, CK-MB and myoglobin (peak between 1–10 h), and NT-BNP and ANP remained elevated on average for 12 weeks. Our present results, with detailed s ling of a cohort of acute MI patients, demonstrate greater absolute and proportional increments in NT-BNP than ANP or BNP with sustained elevation of these peptides at 12 weeks.
Publisher: Oxford University Press (OUP)
Date: 14-05-2015
DOI: 10.1093/QJMED/HCV087
Publisher: Springer Science and Business Media LLC
Date: 14-04-2009
DOI: 10.1038/TPJ.2009.9
Abstract: The aims of this study were to examine the relationships between CYP2D6 genotype and metoprolol dose, S- and R-metoprolol concentrations and clinical effects in patients with systolic heart failure. Data were obtained for 52 subjects, of which 27 had 2 functional alleles (24/27, CYP2D6*1/*1), 22 had 1 functional allele (18/22, CYP2D6*1/*4) and 3 had no functional alleles (CYP2D6*4/*4). Median dose-adjusted concentrations of S-metoprolol (active) were 6.3- and 3.2-fold higher in subjects with zero or one functional allele (P=0.016 and P=0.006), respectively, compared with subjects with two functional alleles. For the R-enantiomer (inactive), these concentrations were 10.7- and 3.7-fold higher (P=0.013 and P=0.003), respectively. Despite clear gene-concentration differences, no relationships between CYP2D6 genotype and dose or clinical effects could be shown. Although the number with no functional alleles was too small (n=3) to show effects, in patients with 1 functional allele other sources of variance are likely to be obscuring differences in clinical effects.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.CARDFAIL.2010.10.001
Abstract: The ratio of peak transmitral pulsed Doppler early velocity to early diastolic tissue Doppler velocity (TDI) of the lateral or septal mitral annulus (E/Ea) is considered a reliable estimation of LV filling pressure. We aim to examine the impact of left ventricular (LV) dimensions on the relationship between lateral and septal E/Ea in the determination of diastolic dysfunction patterns in the setting of chronic systolic heart failure (HF). In 207 patients with chronic systolic HF (LV ejection fraction ≤40%, New York Heart Association Classes I-IV), comprehensive transthoracic echocardiography was performed and long-term outcomes followed up to a median of 40 months. The median lateral and septal Ea (interquartile range) were 7.0 (4.7 to 9.5) cm/s and 4.5 (3.5 to 5.6) cm/s, respectively. The median E/lateral Ea, E/septal Ea, and E/average Ea (interquartile range) were 10.8 (7.1 to 15.1), 16.1 (11.1 to 23.0), and 12.7 (8.8 to 17.7), respectively. In the first 2 tertiles of indexed left ventricular end-diastolic volume (LVEDVi) (<92 mL/m(2) and 92 to 130 mL/m(2)), all 3 E/Ea indices rise with increasing diastolic stage (all P < .001). However, in the highest tertile of indexed LVEDVi (≥130 mL/m(2)), E/average Ea and E/septal Ea (but not E/lateral Ea) increased with increasing diastolic stage, and only E/septal Ea correlated with natriuretic peptide levels (r = 0.38, P = .018) and adverse cardiac events (Hazard ratio 1.91, 95% confidence interval 1.25 to 2.96, P = .003). In the setting of chronic systolic heart failure with extensive cardiac remodeling, septal TDI measurements may be more reliable and clinically relevant than lateral TDI measurements in the assessment of diastolic dysfunction.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.HLC.2015.10.009
Abstract: Radial arterial access (RA) and femoral arterial access (FA) rates for invasive coronary angiography (ICA) vary widely internationally. The European Society of Cardiology (ESC) suggests default RA is feasible. We aim to investigate the variation in RA rates across all New Zealand public hospitals. Patient characteristics, procedural details, and inpatient outcome data were collected in the All New Zealand Acute Coronary Syndrome - Quality Improvement (ANZACS-QI) registry on consecutive patients undergoing ICA over five months. Of the 5894 ICAs 81% were via RA. Hospitals averaged 25 - 176 procedures/month (46.5% - 96.4% via RA). Operators averaged 17 procedures/month. Those performing more than 20 ICAs/month had RA rates between 61% - 99%. Of the 75 operators, 69% met the ESC recommendation. After multivariable adjustment higher operator (RR 1.12, CI 1.09 - 1.30) and hospital (RR 1.21, CI 1.15 - 1.28) volume were independent predictors of RA. Those with prior CABG (RR 0.51, CI 0.45 - 0.57), STEMI <12h (RR 0.91, CI 0.87 - 0.96), and female sex (RR 0.96, CI 0.94 - 0.99) were less likely to receive RA. New Zealand has a high RA rate for ICAs. Rates vary substantially between both operators and centres. Radial arterial was highest amongst the highest volume operators and centres.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2010
DOI: 10.1161/CIRCGENETICS.109.917443
Abstract: Chromosome 9p21.3 (chr9p21.3) recently was identified by several genome-wide association studies as the genomic region most strongly associated with the risk of coronary artery disease. Within the chr9p21.3 locus, the single-nucleotide polymorphism rs1333049 has been demonstrated to be most strongly associated with susceptibility to developing coronary artery disease. However, the effect of rs1333049 on clinical outcomes in patients with established coronary disease has yet to be determined. Coronary Disease Cohort Study (CDCS) (n=1054) and Post-Myocardial Infarction (PMI) (n=816) study participants were genotyped for rs1333049. Clinical history, circulating lipids, neurohormones, cardiac function, and discharge medications were documented. All-cause mortality and cardiovascular hospital readmissions were recorded over a median follow-up period of 4.0 years for the CDCS cohort and 9.1 years for the PMI cohort. The CDCS patients homozygous for the high-risk C allele had an age of onset 2 to 5 years earlier for coronary disease ( P =.005), angina ( P =.025), myocardial infarction ( P =.022), and percutaneous transluminal coronary angioplasty ( P =.009). Patients with the CC genotype also had higher levels of total cholesterol ( P =.033) and triglycerides ( P =.003). The PMI participants with the CC genotype were 3 years younger on admission ( P =.009). Cox proportional hazards analysis adjusting for established predictors of increased risk showed no significant association between rs1333049 genotype and mortality in either the CDCS ( P =.214) or the PMI ( P =.696) cohorts. The chr9p21.3 polymorphism rs1333049 was associated with an earlier age of disease onset in 2 coronary disease cohorts but not with poorer clinical outcome in either cohort.
Publisher: Springer Science and Business Media LLC
Date: 15-08-2018
Publisher: Oxford University Press (OUP)
Date: 29-01-2018
Abstract: Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).
Publisher: Public Library of Science (PLoS)
Date: 02-03-2012
Publisher: Public Library of Science (PLoS)
Date: 11-03-2014
Publisher: BMJ
Date: 2012
Publisher: Elsevier BV
Date: 04-2003
DOI: 10.1016/S0167-0115(03)00021-1
Abstract: Despite its positive inotropic effects and its propensity to stimulate the renin system, adrenomedullin (AM) is hypotensive as a result of dramatic reductions in peripheral resistance. Furthermore, it does not appear to increase aldosterone secretion in spite of often vigorous activation of circulating renin. Hence, we postulate that AM may act as a functional antagonist to angiotensin II both in the vasculature and the adrenal glomerulosa. In the series of studies performed in sheep and human (normal and circulatory disorders) reviewed here, we report significant hemodynamic and hormonal actions of AM. These actions include consistent reduction of arterial pressure associated with rises in cardiac output and hence a dramatic reduction in calculated total peripheral resistance (CTPR). AM also consistently attenuates the pressor effects of angiotensin II (but not norepinephrine). Furthermore, AM consistently increases plasma renin activity (PRA) and induces either a reduction in plasma aldosterone, dissociation between aldosterone/PRA ratio, or attenuation of angiotensin II-induced aldosterone secretion. Thus, these results clearly point to a role for AM in pressure and volume homeostasis acting, at least in part, by interaction with the renin-angiotensin-aldosterone system (RAAS).
Publisher: Elsevier BV
Date: 08-2011
Publisher: Public Library of Science (PLoS)
Date: 02-07-2013
Publisher: Springer Science and Business Media LLC
Date: 12-03-2014
Publisher: Elsevier BV
Date: 11-2001
DOI: 10.1016/S0196-9781(01)00508-3
Abstract: Although the biological effects of adrenomedullin (AM) and PAMP have been reported extensively in animal studies and from in-vitro experiments, relatively little information is available on responses to the hormone administered to man. This review summarizes data from the few studies carried out in man. In healthy volunteers, i.v. infusion of AM reduces arterial pressure, probably at a lower rate of administration than is required to elicit other responses. AM stimulates heart rate, cardiac output, plasma levels of cAMP, prolactin, norepinephrine and renin whilst inhibiting any concomitant response in plasma aldosterone. Little or no increase in urine volume or sodium excretion has been observed. Patients with essential hypertension differ only in showing a greater fall in arterial pressure and in the development of facial flushing and headache. In patients with heart failure or chronic renal failure, i.v. AM has similar effects to those seen in normal subjects but also induces a diuresis and natriuresis, depending on the dose administered. Infusion of AM into the brachial artery results in a dose-related increase in forearm and skin blood flow, more prominent and more dependent on endogenous nitric oxide in healthy volunteers than in patients with cardiac failure. When infused into a dorsal hand vein, AM partially reversed the venoconstrictor action of norepinephrine. Although much more information is required to clarify the role of AM under physiological and pathophysiological circumstances, it is clear that it has prominent hemodynamic and neurohormonal effects, though generally lesser urinary effects when administered short-term in doses sufficient to raise its levels in plasma to those seen in a number of clinical disorders. The only study of PAMP in man showed that its skeletal muscle vasodilator potency, when infused into the brachial artery of healthy volunteers, was less than one hundredth that of AM, and it was without effect on skin blood flow.
Publisher: Elsevier BV
Date: 07-2013
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.JACC.2012.07.047
Abstract: This study sought to examine the ability of left ventricular (LV) global longitudinal strain (GLS) to assess disease severity in patients with chronic systolic heart failure (HF). Left ventricular GLS is a sensitive measure of LV mechanics. Its relationship with standard clinical markers and long-term adverse events in chronic systolic HF is not well established. In 194 chronic systolic HF patients, we performed comprehensive echocardiography with assessment of GLS by velocity vector imaging averaged from apical 4-chamber and 2-chamber views. Death, cardiac transplantation, and HF hospitalization were tracked for 5 years. In our study cohort (age 57 ± 14 years, left ventricular ejection fraction [LVEF] 26 ± 6%, median N-terminal pro-B-type natriuretic peptide [NT-proBNP] 1,158 pg/ml), the mean GLS was -7.1 ± 3.3%. The GLS worsened with increasing New York Heart Association functional class (rank-sum p < 0.0001) and higher NT-proBNP (r = 0.42, p < 0.0001). The GLS correlated with LV cardiac structure (LV mass index: r = 0.35, p < 0.0001 LV end-diastolic volume index: r = 0.43, p < 0.0001) and LVEF (r = -0.66, p < 0.0001). A lower magnitude of GLS was associated with worsening LV diastolic function (E/e' septal: r = 0.33, p < 0.0001), right ventricular (RV) systolic function (RV s': r = -0.30, p < 0.0001), and RV diastolic function (RV e'/a': r = 0.16, p = 0.033). GLS predicted long-term adverse events (hazard ratio: 1.55, 95% confidence interval: 1.21 to 2.00 p < 0.001). Worsening strain (GLS ≥-6.95%) predicted adverse events after adjustment for age, sex, ischemic etiology, E/e' septal, and NT-proBNP (hazard ratio: 2.04, 95% confidence interval: 1.09 to 3.94 p = 0.025) and age, sex, ischemic etiology, and LVEF (hazard ratio: 2.15, 95% confidence interval: 1.19 to 4.02 p = 0.011). In chronic systolic HF, worsening LV GLS is associated with more severe LV diastolic dysfunction and RV systolic and diastolic dysfunction, and provides incremental prognostic value to LVEF.
Publisher: Elsevier BV
Date: 02-2012
Publisher: Public Library of Science (PLoS)
Date: 29-06-2012
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 07-1970
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.JACC.2013.02.078
Abstract: The study objective was to validate a new high-sensitivity troponin I (hs-TnI) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain. Protocols using sensitive troponin assays can accelerate the rule out of acute myocardial infarction in patients with low-risk (suspected) acute coronary syndrome (ACS). This study evaluated 2 prospective cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results, Thrombolysis In Myocardial Infarction (TIMI) risk scores, and electrocardiography. Strategies to identify low-risk patients incorporated TIMI risk scores= 0 or ≤ 1. The primary endpoint was a major adverse cardiac event (MACE) within 30 days. In the primary cohort, 1,635 patients were recruited and had 30-day follow-up. A total of 247 patients (15.1%) had a MACE. The finding of no ischemic electrocardiogram and hs-TnI ≤ 26.2 ng/l with the TIMI = 0 and TIMI ≤ 1 pathways, respectively, classified 19.6% (n = 320) and 41.5% (n = 678) of these patients as low risk 0% (n = 0) and 0.8% (n = 2) had a MACE, respectively. In the secondary cohort, 909 patients were recruited. A total of 156 patients (17.2%) had a MACE. The TIMI = 0 and TIMI ≤ 1 pathways classified 25.3% (n = 230) and 38.6% (n = 351), respectively, of these patients as low risk 0% (n = 0) and 0.8% (n = 1) had a MACE, respectively. Sensitivity, specificity, and negative predictive value for TIMI = 0 in the primary cohort were 100% (95% confidence interval [CI]: 98.5% to 100%), 23.1% (95% CI: 20.9% to 25.3%), and 100% (95% CI: 98.8% to 100%), respectively. Sensitivity, specificity, and negative predictive value for TIMI ≤ 1 in the primary cohort were 99.2 (95% CI: 97.1 to 99.8), 48.7 (95% CI: 46.1 to 51.3), and 99.7 (95% CI: 98.9 to 99.9), respectively. Sensitivity, specificity, and negative value for TIMI ≤ 1 in the secondary cohort were 99.4% (95% CI: 96.5 to 100), 46.5% (95% CI: 42.9 to 50.1), and 99.7% (95% CI: 98.4 to 100), respectively. An early-discharge strategy using an hs-TnI assay and TIMI score ≤ 1 had similar safety as previously reported, with the potential to decrease the observation periods and admissions for approximately 40% of patients with suspected ACS. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study, NCT00470587 A 2 hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker [ADAPT]: a prospective observational validation study, ACTRN12611001069943).
Publisher: Springer Science and Business Media LLC
Date: 28-06-2013
DOI: 10.1038/JHH.2012.24
Abstract: This study examined renin-angiotensin-aldosterone (RAAS) system gene variants for associations with cardiovascular risk factors and outcomes in coronary heart disease. Coronary disease patients (n=1186) were genotyped for 21 single-nucleotide polymorphisms (SNPs) within angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-II type-1 receptor (AGTR1) and aldosterone synthase (CYP11B2). Associations with all-cause mortality and cardiovascular readmissions were assessed over a median of 3.0 years. The AGT M235T 'T' allele was associated with a younger age of clinical coronary disease onset (P=0.006), and the AGT rs2478545 minor allele was associated with lower circulating natriuretic peptides (P=0.0001-P=0.001) and E/E(1) (P=0.018). Minor alleles of AGT SNPs rs1926723 and rs11122576 were associated with more frequent history of renal disease (P0.04) and type-2 diabetes (P0.02), higher body mass index (P0.02) and greater mortality (P0.007). AGT rs11568054 minor allele carriers had more frequent history of renal disease (P=0.04) and higher plasma creatinine (P=0.033). AGT rs6687360 minor allele carriers exhibited worse survival (P=0.02). ACE rs4267385 was associated with older clinical coronary disease onset (P=0.008) and hypertension (P=0.013) onset, increased plasma creatinine (P=0.01), yet greater mortality (P=0.044). Less history of hypertension was observed with the AGTR1 rs12685977 minor allele (P=0.039). Genetic variation within the RAAS was associated with cardiovascular risk factors and accordingly poorer survival.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1111/J.1753-6405.2011.00702.X
Abstract: To report the processes and protocols that were developed in the design and implementation of the Hauora Manawa Project, a cohort study of heart disease in New Zealand and to report the participation at baseline. This study utilised application of a Kaupapa Māori Methodology in gaining tribal and health community engagement, design of the project and random selection of participants from territorial electoral rolls, to obtain three cohorts: rural Māori, urban Māori and urban non-Māori. Logistic regression was used to model response rates. Time invested in gaining tribal and health community engagement assisted in the development and design of clear protocols and processes for the study. Response rates were 57.6%, 48.3% and 57.2%. Co-operation rates (participation among those with whom contact was established) were 74.7%, 66.6% and 71.4%. Use of electoral rolls enables straightforward s ling but results in low response rates because electors have moved. Co-operation rates highlight the acceptability of this research project to the participants they indicate the strength of Kaupapa Māori Methodologies in engaging Māori participants and community. This study provides a model for conducting clinical/biomedical research projects that are compatible with cultural protocols and methodologies, in which the primary aim of the research was Māori health gain.
Publisher: Wiley
Date: 11-2012
Abstract: We examined the prognostic importance of cardiac troponin I (cTnI) in a cohort of patients enrolled in the ASCEND-HF study of nesiritide in acute decompensated heart failure (ADHF). Circulating troponins are a prognostic marker in patients with ADHF. Contemporary assays with greater sensitivity require reassessment of the significance of troponin elevation in HF. Cardiac troponin I was measured in a core laboratory in 808 ADHF patients enrolled in the ASCEND-HF biomarkers substudy using a sensitive assay (VITROS Trop I ES, Ortho Clinical Diagnostics) with a lower limit of detection of 0.012 ng/mL and a 99th percentile upper reference limit (URL) of 0.034 ng/mL. Patients with clinical evidence of acute coronary syndrome or troponin >5× the URL were excluded. Multivariable modelling was used to assess the relationship between log(cTnI) and in-hospital and post-discharge outcomes. Baseline cTnI was undetectable in 22% and elevated above the 99th percentile URL in 50% of subjects. cTnI levels did not differ based on HF aetiology. After multivariable adjustment, higher cTnI was associated with worsened in-hospital outcomes such as length of stay (P = 0.01) and worsening HF during the index hospitalization (P = 0.01), but was not associated with worsened post-discharge outcomes at 30 or 180 days. The relationship between cTnI and outcomes was generally linear and there was no evidence of a threshold effect at any particular level of cTnI. cTnI is elevated above the 99th percentile URL in 50% of ADHF patients and predicts in-hospital outcome, but is not an independent predictor of long-term outcomes.
Publisher: CMA Impact Inc.
Date: 19-08-2018
DOI: 10.1503/CMAJ.180144
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.IJCARD.2019.01.067
Abstract: Non-cardiac chest pain (NCCP) is a common reason for presenting to an emergency department (ED). Many patients re-present with similar symptoms despite reassurance. To investigate the clinical value of a brief cognitive behavioural treatment (CBT) in reducing re-presentations of patients who present with NCCP. A randomised controlled trial (RCT) comparing three or four sessions of NCCP directed CBT with treatment as usual (TAU). The primary outcome measure was reducing health service use measured as re-presentations to the ED and hospitalisations for NCCP over 12 months of follow-up. Secondary outcomes were chest pain, health anxiety, depression, anxiety, quality of life and social functioning. 214 patients received CBT and 210 TAU. There was no difference in ED visits or hospitalisation at three months or 12 months follow-up. Those with prior ED presentations for NCCP were significantly less likely to present with NCCP at three months follow-up but not at 12 months. Health anxiety was less at three months in those who received CBT but this effect was not present at 12 months. No other differences in secondary outcome measures were present. A brief CBT intervention for NCCP failed to reduce representations or improve psychological health over 12 months. We do not recommend such an intervention to unselected patients with NCCP. Patients presenting with prior episodes of NCCP obtain benefit for a three month period. Working with those patients to sustain their improvement might be worthwhile.
Publisher: BMJ
Date: 23-07-2019
DOI: 10.1136/HEARTJNL-2019-315084
Abstract: High-sensitivity cardiac troponin testing is used in the diagnosis of acute coronary syndromes but its role during convalescence is unknown. We investigated the long-term prognostic significance of serial convalescent high-sensitivity cardiac troponin concentrations following acute coronary syndrome. In a prospective multicentre observational cohort study of 2140 patients with acute coronary syndrome, cardiac troponin I concentrations were measured in 1776 patients at 4 and 12 months following the index event. Patients were stratified into three groups according to the troponin concentration at 4 months using the 99th centile (women ng/L, men ng/L) and median concentration of those within the reference range. The primary outcome was cardiovascular death. Troponin concentrations at 4 months were measurable in 99.0% (1759/1776) of patients (67±12 years, 72% male), and were ≤5 ng/L (median) and th centile in 44.8% (795) and 9.3% (166), respectively. There were 202 (11.4%) cardiovascular deaths after a median of 4.8 years. After adjusting for the Global Registry of Acute Coronary Events score, troponin remained an independent predictor of cardiovascular death (HR 1.4, 95% CI 1.3 to 1.5 per doubling) with the highest risk observed in those with increasing concentrations at 12 months. Patients with 4-month troponin concentrations th centile were at increased risk of cardiovascular death compared with those ≤5 ng/L (29.5% (49/166) vs 4.3% (34/795) adjusted HR 4.9, 95% CI 3.8 to 23.7). Convalescent cardiac troponin concentrations predict long-term cardiovascular death following acute coronary syndrome. Recognising this risk by monitoring troponin may improve targeting of therapeutic interventions. ACTRN12605000431628 Results.
Publisher: Informa UK Limited
Date: 21-10-2010
DOI: 10.3109/07853890.2010.526630
Abstract: Whereas the role of the cardiac natriuretic peptides, ANP and BNP, in some aspects of physiology and pathophysiology is clear, their potential in diagnosis, prognosis, and therapeutics in many clinical disorders remains uncertain. We predict that circulating levels of these peptides will find increasing diagnostic utility in patients presenting with dyspnoea, in guiding the complex pharmacotherapy in heart failure, and may likewise be useful in guiding the management of patients on chronic maintenance renal dialysis. We predict also that levels of these peptides will be of practical use as prognostic indicators in 'at-risk' populations (such as those with diabetes, coronary heart disease, hypertension, thalassaemia, etc.) but probably not in the general population. It appears likely that administration of these peptides will find a place in the therapeutics of acute myocardial infarction, but this is less clear for heart failure. We describe the presence of a segment of the signal peptide for BNP within the circulation and discuss its potential clinical utility.
Publisher: Public Library of Science (PLoS)
Date: 10-12-2014
Publisher: Springer Science and Business Media LLC
Date: 07-11-2007
DOI: 10.1007/S11936-007-0038-X
Abstract: Definitive treatment for constrictive pericarditis is surgical pericardiectomy. Because constriction may be transient in a small proportion of patients, particularly those with exudative effusions, the initial treatment for constrictive pericarditis should be conservative, with loop diuretic therapy to manage volume expansion and edema and the use of colchicine, nonsteroidal anti-inflammatory agents, or, if necessary, glucocorticoid therapy for active inflammation. For subjects with persisting evidence of constriction, symptomatic management is advised for those with only minimal symptoms. Surgical pericardiectomy is advised for subjects with New York Heart Association class II or III symptoms and persisting evidence of constriction at echocardiography and cardiac catheterization and with associated pericardial abnormality on CT or MRI. Complete resection of the pericardium and, where possible, the diseased epicardium via a midline sternotomy is the favored approach, although a video-assisted thoracoscopic approach may be suitable in some subjects. Lateral thoracotomy should be used for suppurative pericarditis to avoid sternal infection. Because of higher mortality, increased complication rates, and suboptimal clinical outcomes, pericardiectomy should be avoided in older patients or those with radiation-induced disease, very advanced symptoms, or evidence of myocardial fibrosis.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.IJCARD.2014.09.026
Abstract: The aim of this study is to compare a new improved point of care cardiac troponin assay (new POC-cTnI) with 1. its predecessor (old POC-cTnI) and 2. a high sensitivity assay (hs-cTnI) for the diagnosis of acute myocardial infarction (AMI) and for major adverse cardiac events (MACE) by 30 days. This is a single centre observational study, set in Christchurch Hospital, New Zealand. Patients presenting to the emergency department with non-traumatic chest pain underwent blood s ling at 0 h and 2h post presentation for analysis with the 3 cTnI assays for the outcome of AMI and for analysis using an accelerated diagnostic protocol (ADP-normal 2h troponins, normal electrocardiograms and Thrombolysis In Myocardial Infarction (TIMI) score of 0 or ≤ 1) for 30 day MACE. Of 962 patients, 220 (22.9%) had AMI. Old POC-cTnI was least sensitive at 70.0% (65.4-73.9%) by 2h (p<0.001). New POC-cTnI, sensitivity 93.6% (89.9-96.2%) had similar sensitivity to hs-cTnI, sensitivity 95.0% (91.5-97.3%) (p = 0.508). There were 231 (24.0%) patients with 30 day MACE. When used as part of the ADP, all assays had 100% (98.0-100%) sensitivity using TIMI = 0. Sensitivities of new POC-cTnI ADP, 98.3% (95.4-99.4%), old POC-cTnI, 96.5% (93.2-98.4%) and hs-cTnI, 98.7% (96.0-99.7%) were similar (p = 0.063-0.375) using TIMI ≤ 1. A new POC-cTnI has improved sensitivity for AMI and MACE compared with its predecessor and comparable sensitivity to a high sensitivity assay. Now that sensitivities of the POC assay are improved, the new assay may be a useful alternative to central laboratory assays when rapid turn-around times are not possible.
Publisher: Frontiers Media SA
Date: 15-06-2015
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.CLINBIOCHEM.2015.07.033
Abstract: International guidance recommends that early serial s ling of high sensitivity troponin be used to accurately identify acute myocardial infarction (AMI) in chest pain patients. The background evidence for this approach is limited. We evaluated whether on presentation and 4-hour high-sensitivity troponin I (hs-cTnI) could be used to accurately rule-out AMI. hs-cTnI was measured on presentation and at 4-hours in adult patients attending an emergency department with possible acute coronary syndrome. We determined the sensitivity for AMI for at least one hs-cTnI above the 99th percentile for a healthy population or alone or in combination with new ischemic ECG changes. Both overall and sex-specific 99th percentiles were assessed. Patients with negative tests were designated low-risk. 63 (17.1%) of 368 patients had AMI. The median (interquartile range) time from symptom onset to first blood s ling was 4.8h (2.8-8.6). The sensitivity of the presentation and 4h hs-cTnI using the overall 99th percentile was 92.1% (95% CI 82.4% to 97.4%) and negative predictive value 95.4% (92.3% to 97.4%) with 78.3% low-risk. Applying the sex-specific 99th percentile did not change the sensitivity. The addition of ECG did not change the sensitivity. Hs-cTnI >99th percentile thresholds measured on presentation and at 4-hours was not a safe strategy to rule-out AMI in this clinical setting irrespective of whether sex-specific 99th percentiles were used, or whether hs-cTnI was combined with ECG results.
Publisher: European Respiratory Society (ERS)
Date: 06-2017
Publisher: Elsevier BV
Date: 09-2009
Publisher: Wiley
Date: 30-09-2015
DOI: 10.1002/EJHF.401
Abstract: Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear. To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45% HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45% HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, in idual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41 HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97 interactions P < 0.02). Age (74 ± 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01 increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01 (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02). The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.CARDFAIL.2010.03.011
Abstract: Neurohormonal activation is a pathophysiological hallmark of acute and chronic heart failure (HF). The clinical significance of more recently discovered endogenous vasoactive hormones has not been well-characterized. In 154 subjects with stable, chronic systolic HF (New York Heart Association Class I-IV, left ventricular [LV] ejection fraction <or=40%), we measured plasma levels of urocortin 1 (UCN-1), urotensin II (UT-II), and endothelin-1 (ET-1) and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse clinical events (all-cause mortality, cardiac transplantation or HF hospitalization) were prospectively tracked for a median of 39 months. Plasma levels of UCN-1 and ET-1 (but not UT-II) increased with LV diastolic dysfunction stage, right ventricular systolic dysfunction class, and mitral regurgitation severity (P or=12.1 pM (HR: 2.02, 95% CI: 1.08-3.93, P = .029) and ET-1 >or=2.29 pM (HR: 2.52, 95% CI: 1.24-5.03, P = .011) remained significant independent risk factors for adverse clinical events. Higher levels of plasma levels of UCN-1 and ET-1 but not UT-II were associated with worse LV diastolic performance and poorer long-term clinical outcomes in patients with chronic systolic HF.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.ECHO.2014.02.007
Abstract: Right ventricular (RV) global longitudinal strain (RV strain) is a sensitive measure of RV mechanics. Its relationship with standard clinical markers and long-term events in chronic systolic heart failure is not well established. The aim of this study was to examine the ability of RV strain to provide incremental prognostic value to left ventricular (LV) ejection fraction (LVEF) in patients with chronic systolic heart failure. In 171 patients with chronic systolic heart failure (LVEF ≤ 35%), a retrospective substudy of RV strain was performed using Velocity Vector Imaging to analyze previously recorded, comprehensive echocardiographic images. Death, cardiac transplantation, and heart failure hospitalization were tracked for 5 years. In this study cohort (mean age, 57 ± 14 years mean LVEF, 25 ± 6%), mean RV strain was -11.6 ± 5.4%. More impaired RV strain was associated with increasing New York Heart Association class (rank-sums P < .0001) and greater LV volume (LV end-systolic volume index: r = 0.35, P < .0001). Worse RV strain was associated with reduced LVEF (r = -0.45, P < .0001), worse LV diastolic dysfunction (E/e' septal: r = 0.19, P = .017 left atrial volume index: r = 0.18, P = .031), and standard indices of RV systolic and diastolic dysfunction (RV s': r = -0.43, P < .0001 RV e'/a': r = 0.16, P = .0040 right atrial volume index: r = 0.20, P = .015). RV strain predicted long-term adverse events (hazard ratio, 1.30 95% confidence interval, 1.02-1.70 P = .037). Furthermore, RV strain ≥ -14.8% predicted adverse events after adjustment for age, LVEF, RV s', E/e' septal, and right atrial volume index. In patients with chronic systolic heart failure, worse RV strain provides prognostic value incremental to LV function.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.CARDFAIL.2010.03.010
Abstract: Corin is a serine protease that cleaves pro-atrial and pro-B-type natriuretic peptides into biologically active hormones. The relationship between soluble plasma corin levels, plasma natriuretic peptide levels, myocardial structure and performance, and long-term clinical outcomes in the setting of chronic systolic heart failure has not been described. In 126 patients with chronic systolic heart failure (left ventricular ejection fraction <or=35%, New York Heart Association functional Class I-IV), we measured plasma corin and natriuretic peptide levels and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse clinical events (all-cause mortality, cardiac transplantation, or heart failure hospitalization) were prospectively tracked for a median of 38 months. Plasma corin levels modestly correlated with echocardiographic indices of cardiac structure, including left ventricular mass index (r = 0.30, P = .003) and interventricular septum width (r = 0.22, P = .013). However, plasma corin levels did not correlate with age, arterial pressures, estimated glomerular filtration rate, echocardiographic indices of systolic or diastolic function, or plasma natriuretic peptide levels. In Cox proportional hazards analysis, higher plasma corin levels did not predict reduced risk of adverse clinical events (hazard ratio 0.91 95% confidence interval 0.67-1.24, P = .52), and did not provide incremental prognostic value to natriuretic peptide levels. In our cohort of ambulatory patients with chronic systolic heart failure, soluble plasma corin levels did not provide prognostic utility incremental to that of natriuretic peptides.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.AMJCARD.2007.08.038
Abstract: High-sensitivity C-reactive protein (hs-CRP) is a hepatocyte-derived inflammatory cytokine shown to be increased in the setting of acute heart failure (HF), particularly with increased intracardiac filling pressures. In the chronic HF setting, the relation between hs-CRP and echocardiographic indexes of left ventricular (LV) diastolic performance has not been examined. We measured plasma hs-CRP levels using a particle-enhanced immunonephelometry assay (Dade Behring, Inc., Deerfield, Illinois) in 136 subjects with chronic HF (LV ejection fraction [EF]<or=35%, New York Heart Association functional classes II to IV). We performed echocardiography, including color M-mode and tissue Doppler methods. We prospectively examined subjects' death, cardiac transplantation, and HF hospitalization status over 33+/-17 months. In our study cohort (mean LVEF 26+/-6%, median plasma hs-CRP 3.19 mg/L), plasma hs-CRP levels progressively increased with worsening LV diastolic dysfunction. In particular, plasma hs-CRP levels correlated with mitral E/A wave ratio (Spearman r=0.25, p=0.004), mitral deceleration time (r=-0.28, p=0.002), pulmonary vein systolic wave/diastolic wave ratio (r=-0.32, p<0.001), mitral E wave/color M-mode velocity of propagation ratio (r=0.28, p=0.001), and mitral E wave/tissue Doppler septal E' wave ratio (r=0.28, p=0.001). Plasma hs-CRP levels independently predicted adverse clinical events even after adjustment for LVEF and mitral E wave/tissue Doppler septal E' wave ratio (hazard ratio 2.28, 95% confidence interval 1.18 to 4.39). In conclusion, in patients with chronic systolic HF, expression of circulating CRP was associated with increasing echocardiographic indexes of diastolic dysfunction. High plasma hs-CRP levels portend poor long-term outcomes, particularly in those with severe concomitant systolic and diastolic dysfunctions.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.JCMG.2011.07.004
Abstract: This study sought to determine the accuracy of Doppler echocardiography and tissue Doppler imaging (TDI) measurements in detecting elevated left atrial pressure (LAP) in ambulant subjects with chronic heart failure using directly measured LAP as the reference. Echocardiographic indexes including the ratio of transmitral to annular early diastolic velocities (E/e') may identify raised invasively measured left ventricular filling pressures when tested in cross-sectional studies in some populations. The accuracy of these indexes when measured sequentially remains untested. We determined the accuracy of Doppler echocardiography and TDI measurements in detecting elevated directly measured LAP in ambulant subjects with stable chronic heart failure. Fifteen patients with New York Heart Association functional class II to III heart failure and a permanently implanted direct LAP monitoring device underwent serial echocardiography. Simultaneous resting mean LAP, Doppler mitral inflow, mitral annular TDI, and pulmonary venous inflow velocities were obtained on each occasion. Receiver-operator characteristic curve analysis was used to compare the accuracy of the Doppler variables to detect an elevated device LAP ≥15 and ≥20 mm Hg. The patients (13 men, mean age: 71 years, mean left ventricular ejection fraction: 32 ± 12%) underwent 60 simultaneous echocardiographic studies and LAP measurements with a median of 4 (1 to 7) studies per patient. Mean LAP was 16.9 (range 5 to 39 mm Hg) at echocardiography (n = 60). E/e' had the greatest accuracy for detection of LAP ≥15 mm Hg with an area beneath the receiver-operator characteristic curve >0.9. In comparison, area under the curve for mitral E velocity and mitral E/A were 0.77 and 0.76, respectively (p < 0.008 vs. E/e' medial and average). Single and serial measurements of mitral inflow and mitral annular TDI velocities (E/e') can reliably detect raised directly measured LAP in ambulant subjects with compensated chronic heart failure. (Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients [HOMEOSTASIS] NCT00547729).
Publisher: Wiley
Date: 13-03-2012
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.YJMCC.2011.01.010
Abstract: Polymorphisms within in idual natriuretic peptide genes have been associated with risk factors for cardiovascular disease, but their association with clinical outcomes was previously unknown. This study aimed to investigate the association between genetic variants in key genes of the natriuretic peptide system with cardiovascular outcomes in patients with coronary artery disease. Coronary disease patients (n=1810) were genotyped for polymorphisms within NPPA, NPPB, NPPC, NPR1 and NPR2. Clinical history, natriuretic peptide concentrations, echocardiography, all-cause mortality and cardiovascular hospital readmissions were recorded over a median 2.8 years. Minor alleles of NPPA rs5068, rs5065 and rs198358 were associated with less history of hypertension minor alleles of NPPA rs5068 and rs198358 was also associated with higher circulating natriuretic peptide levels (p=0.003 to p=0.04). Minor alleles of NPPB rs198388, rs198389, and rs632793 were associated with higher circulating BNP and NT-proBNP (p=0.001 to p=0.03), and reduced E/E(1) (p=0.011), or LVESVI (p=0.001) and LVEDVI (p=0.004). Within NPPC, both rs11079028 and rs479651 were associated with higher NT-proBNP and CNP (p=0.01 to p=0.03), and rs479651 was associated with lower LVESVI (p=0.008) and LVEDVI (p=0.018). NPR2 rs10758325 was associated with smaller LVMI (p<0.02). A reduced rate of cardiovascular readmission was observed for minor alleles of NPPA rs5065 (p<0.0001), NPPB rs632793 (p<0.0001), rs198388 (p<0.0001), rs198389 (p<0.0001), and NPR2 rs10758325 (p<0.0001). There were no associations with all-cause mortality. In established cardiovascular disease, natriuretic peptide system polymorphisms were associated with natriuretic peptide levels, hypertension, echocardiographic indices and the incidence of hospital readmission for cardiovascular events.
Publisher: Oxford University Press (OUP)
Date: 06-03-2014
Publisher: Elsevier BV
Date: 02-2015
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/07853890701232057
Abstract: Circulating cardiac natriuretic peptide levels are being used increasingly in a range of clinical circumstances. Since it is evident that drugs used in the treatment of cardiovascular disorders can modulate natriuretic peptide levels, we here review the literature documenting these effects. Diuretics, blockers of the renin-angiotensin system, vasodilator agents, dopamine-like agonists, amiodarone, and perhaps allopurinol and statins suppress natriuretic peptide levels, most obviously in heart failure. Beta-blockers stimulate natriuretic peptide concentrations in hypertensive subjects, whereas in heart failure they have little effect or are stimulatory in the short term and inhibitory with sustained therapy. Digitalis compounds and aspirin tend to increase natriuretic peptide levels, and calcium channel blocking agents have varying effects depending on the in idual drug and duration of administration. The effects of other drugs are less clear. Additional information is needed regarding the effects of medications along with dissection of the role of altered cardiac secretion versus changes in plasma clearance as explanation for drug-induced perturbations in natriuretic peptide concentrations. In the meantime, clinicians need to consider the known effects of medications when interpreting plasma levels of the cardiac natriuretic peptides.
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.JACC.2005.06.085
Abstract: In 1,049 patients with stable ischemic heart disease (IHD), brain natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP) correlated closely (r = 0.09, p < 0.001) and were similarly related to left ventricular ejection fraction (LVEF) (r = -0.50 and -0.46, respectively), age (0.44 and 0.47), and creatinine clearance (-0.51 and -0.51). Receiver-operating characteristic curves for detection of LVEF <30% were similar (area under the curves = 0.83 and 0.80, both p < 0.001), and both peptides had strong negative predictive value (95% and 94%). Both independently predicted all-cause mortality and/or heart failure with closely overlapping event-free survival curves BNP and NTproBNP display strong, near-identical test performance in ruling about severely reduced LVEF and in prediction of all-cause mortality or heart failure in stable IHD. The aim of this work was to test B-type natriuretic peptides for assessment of function and prognosis in stable ischemic heart disease (IHD) and to compare brain natriuretic peptide (BNP) with amino terminal pro-brain natriuretic peptide (NTproBNP), including the relative effects of age and renal function on test performance. Brain natriuretic peptide and NTproBNP are emerging diagnostic and prognostic markers in heart failure and acute coronary syndromes. Their performance in assessing function and prognosis in stable IHD is unknown. Whether one marker is superior and the relative effects of age and renal function on test performance are uncertain. In 1,049 patients with stable IHD, left ventricular ejection fraction (LVEF) was measured by radionuclide scanning and creatinine clearance estimated by the Cockroft-Gault equation. Age, gender, and body mass index were recorded. Twelve-month all-cause mortality or admission with heart failure was prospectively recorded BNP and NTproBNP were measured by radioimmunoassay. Brain natriuretic peptide and NTproBNP correlated closely (r = 0.90, p < 0.001) and had similar relationships to LVEF (r = -0.50 and -0.46, respectively, both p < 0.001), age (0.44 and 0.47, both p < 0.001), and creatinine clearance (-0.51 and -0.51, both p < 0.001). Areas under receiver-operating characteristic curves for detection of LVEF <30% were similar (0.83 and 0.80, both p < 0.001) with strong negative predictive values for both (95% and 94%). Both markers independently predicted the clinical end point with closely overlapping event-free survival curves. In stable IHD, BNP and NTproBNP display strong and near-identical test performance in ruling out severely reduced LVEF and in prediction of all-cause mortality or heart failure despite significant effects of age, gender, and renal function on levels of both markers.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2000
Abstract: Abstract —We examined the effects of the vasodilator peptide adrenomedullin (AM) infused intravenously into subjects with essential hypertension. Eight men 39 to 58 years old with uncomplicated hypertension (147/96±5/3 mm Hg at baseline) were studied in a placebo-controlled, crossover design. Each subject received intravenous AM in a low and a high dose (2.9 and 5.8 pmol · kg −1 · min −1 for 2 hours each) or vehicle-control (Hemaccel) infusion in a random order on day 4 of a controlled metabolic diet (80 mmol/d Na + , 100 mmol/d K + ). Plasma AM reached pathophysiological levels during infusion (18±4 pmol/L in low dose, 34±9 pmol/L in high dose) with a concurrent rise in plasma cAMP (+8.4±1.2 pmol/L, P .05 compared with control). Compared with control, high-dose AM increased peak heart rate (+17.8±2.3 bpm, P .01), lowered systolic (−24.6±0.9 mm Hg P .01) and diastolic (−21.9±1.4 mm Hg P .01) blood pressure, and increased cardiac output (+1.0±0.1 L/min in low dose, +2.9±0.2 L/min in high dose P .01 for both). Despite a rise in plasma renin activity during high dose ( P .05), aldosterone levels did not alter. Plasma norepinephrine levels increased 1295±222 pmol/L ( P .001) and epinephrine increased 74±15 pmol/L ( P .05) with high-dose AM compared with control. AM had no significant effect on urine volume and sodium excretion. In subjects with essential hypertension, the intravenous infusion of AM to achieve pathophysiological levels produced significant falls in arterial pressure, increased heart rate and cardiac output, and stimulated the sympathetic system and renin release without concurrent increase in aldosterone. Urinary parameters were unaltered. Although AM has potent hemodynamic and neurohumoral effects in subjects with essential hypertension, the threshold for urinary actions is set higher.
Publisher: The Endocrine Society
Date: 12-2016
DOI: 10.1210/EN.2016-1448
Publisher: MDPI AG
Date: 31-05-2021
DOI: 10.3390/JMSE9060602
Abstract: Small Island States (SIDS) are among the nations most exposed to climate change (CC) and are characterised by a high degree of vulnerability. Their unique nature means there is a need for more studies focused on the limits to CC adaptation on such fragile nations, particularly regarding their problems and constraints. This paper addressed a perceived need for research into the limitations of adaptation on SIDS, focusing on the many unique restrictions. To this end, the study identified and described the adaptation limits they have by using a review of the literature and an analysis of case studies from a s le of five SIDS in the Caribbean and Pacific regions (Barbados, Trinidad and Tobago, Cook Islands, Fiji, Solomon Islands and Tonga). This research’s findings showed that an adaptable SIDS is characterised by awareness of various values, appreciation and understanding of a ersity of impacts and vulnerabilities, and acceptance of certain losses through change. The implications of this paper are two-fold. It explains why island nations continue to suffer from the impacts of CC and suggest some of the means via which adequate policies may support SIDS in their efforts to cope with the threats associated with a changing climate. This study concluded that, despite the technological and ecological limits (hard limits) affecting natural systems, adaptation to CC is limited by such complex forces and societal factors (soft limits) that more adequate adaptation strategies could overcome.
Publisher: American Medical Association (AMA)
Date: 11-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2006
DOI: 10.1161/01.HYP.0000222893.85662.CD
Abstract: Oxidative stress plays a critical role in the pathogenesis of cardiovascular disease and diabetes. Studies in vascular cells and experimental animals have demonstrated that the angiotensin type-1 receptor (AT1R) contributes to formation of reactive oxygen species by activating nicotinamide-adenine dinucleotide phosphate oxidases, but the relevance of this pathway to human heart disease has not been established. Here we demonstrate that a polymorphism in the AT1R gene (A1166C), linked to increased receptor activity, is associated with elevated levels of oxidative stress markers in heart failure patients but not in healthy controls. Plasma protein carbonyls (PCs), a marker of oxidative protein modification, were 10-fold higher in heart-failure patients compared with controls [geometric means and 95% CIs for patients, 75 (57 to 100) pmol/mg controls, 5 (4 to 7) pmol/mg P .001]. Moreover, levels of PCs were 50-fold higher in patients homozygous for the polymorphism (CC) than in controls and significantly higher than the AA and AC genotype patient groups [CC: 273 (135–550) AC: 59 (35–98) AA: 65 (40–106) pmol/mg P .001]. Levels of myeloperoxidase were also modestly increased in heart-failure patients [51 (46–57) ng/mL] compared with controls [37 (32–44) ng/mL P .001], but were especially elevated in patients with a CC genotype [CC: 72 (58–89) AC: 52 (44–61) AA: 39 (34–46) ng/mL P .001]. The AT1R genotype was demonstrated to be an independent predictor of both PCs and myeloperoxidase levels in heart-failure patients. These findings suggest that oxidative stress in human heart failure is regulated via angiotensin signaling and may involve the nicotinamide dinucleotide oxidase pathway.
Publisher: CMA Joule Inc.
Date: 30-01-2012
DOI: 10.1503/CMAJ.110773
Publisher: Elsevier BV
Date: 02-2010
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.CARDFAIL.2012.01.008
Abstract: Elevated ST2 predicts future heart failure and/or death in patients with pulmonary diseases, heart failure, acute dyspnea, and acute coronary syndromes. This study assesses both diagnostic and prognostic utility of ST2 in patients with chest pain. From November 2007 to April 2010, 995 patients attending the Emergency Department with chest pain were prospectively recruited. Troponin I (TnI), B-type natriuretic peptide (BNP), creatine kinase-myocardial band (CKMB), myoglobin, and ST2 were measured at 0 and 2 hours. The diagnostic utility of ST2 for heart failure and prognostic utility for primary outcome of death and/or heart failure by 18 months was assessed. Elevated ST2 had sensitivity 73.5% (55.8%-86.4%) and specificity 79.6% (79.0%-80.1%) for acute heart failure (n = 34) [compared with BNP sensitivity 88.2% (73.6%-95.3%), specificity 66.2% (65.7%-66.4%)]. Elevated ST2 conveyed risk of 18-month primary outcome (n = 110), with an adjusted hazard ratio (HR) of 1.9 (1.2-3.2), compared with BNP HR 2.8 (1.4-5.7), myoglobin HR 1.9 (1.1-3.3), TnI HR 1.7 (1.0-2.7), and CKMB HR 0.9 (0.5-1.7). When ST2 and BNP were both elevated, risk was greater than if either marker was elevated in isolation (P < .001). ST2 was more specific for acute heart failure than BNP. ST2 is independently predictive of future death and/or heart failure and has incremental utility in combination with BNP.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Wiley
Date: 03-2004
Publisher: Elsevier BV
Date: 03-2005
DOI: 10.1016/J.AMJCARD.2004.10.043
Abstract: We evaluated diastolic function in patients who underwent elective revascularization by standard on-pump coronary artery bypass graft (CABG) surgery versus off-pump CABG. Diastolic function improved in both groups, but indexes of early diastolic filling and myocardial relaxation improved more in patients who underwent on-pump than off-pump CABG.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.CARDFAIL.2019.04.002
Abstract: Amino-terminal pro-B-type natriuretic peptide (NTproBNP) is closely associated with prognosis in acute decompensated heart failure (ADHF). As a result, there has been great interest measuring it during the course of treatment. The prognostic implications in both short-term and follow-up changes in NTproBNP need further clarification. Baseline, 48-72 hour, and 30-day NTproBNP levels were measured in 795 subjects in the ASCEND-HF trial. Multivariable logistic and Cox-proportional hazards models were used to test the association between static, relative, and absolute changes in NTproBNP with outcomes during and after ADHF. The median NTproBNP at baseline was 5773 (2981-11,579) pg/mL at 48-72 hours was 3036 (1191-6479) pg/mL and at 30 days was 2914 (1364-6667) pg/mL. Absolute changes in NTproBNP by 48-72 hours were not associated with 30-day heart failure rehospitalization or mortality (P = .065), relative changes in NTproBNP were nominally associated (P = .046). In contrast, both absolute and relative changes in NTproBNP from baseline to 48-72 hours and to 30 days were closely associated with 180-day mortality (P < .02 for all) with increased discrimination compared to the multivariable models with baseline NTproBNP (P <.05 for models with relative and absolute change at both time points). Although the degree of absolute change in NTproBNP was dependent on baseline levels, both short-term absolute and relative changes in NTproBNP were independently and incrementally associated with long-term clinical outcomes. Changes in NTproBNP levels at 30-days were particularly well associated with long-term clinical outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
Publisher: Wiley
Date: 05-2012
DOI: 10.1111/J.1553-2712.2012.01352.X
Abstract: To assess whether the accelerated diagnostic protocol (ADP) studied in the Asia Pacific Evaluation of Chest Pain Trial (ASPECT) could be optimized to effectively risk stratify patients with symptoms suggestive of acute coronary syndrome (ACS) and allow early discharge of very-low-risk patients. Patients presenting to the emergency department (ED) with chest pain were prospectively enrolled between November 2007 and April 2010. Blood s les were analyzed at 0 and 2 hours postpresentation with a point-of-care multimarker panel (POC-MMP troponin I [TnI], creatine kinase myocardial band [CKMB] isoenzyme fraction, and myoglobin) and a high-sensitivity cardiac troponin T assay (hsTnT). Patients received standard care. The original ADP (Thrombolysis in Myocardial Infarction [TIMI] risk score = 0, no ischemic electrocardiogram [ECG] changes, and the multimarker panel negative) was compared with an ADP using the point of care TnI only, hsTnT only, or TIMI risk score = 0 to 1. Primary outcome was ACS within 30 days. Of the 1,000 patients recruited, 362 (36.2%) had ACS. There were 12.3% identified as low risk by the original ADP with a sensitivity for ACS of 99.2% (95% confidence interval [CI] = 97.5% to 99.8%). The ADP with the point of care TnI only or hsTnT had the same sensitivity, but identified more patients for discharge (15.0% vs. 12.3%). Including patients with a TIMI risk score of 1 identified more patients as low risk (19.7%), but with a lower sensitivity (97.0% vs. 99.2%). An ADP consisting of a TIMI risk score of 0, no new ECG changes, and negative troponin at 0 and 2 hours postpresentation safely identifies patients at low risk of ACS, in whom discharge without further evaluation can be considered.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2018
DOI: 10.1007/S00431-018-3089-Y
Abstract: This study aimed to investigate factors affecting N-terminal pro-B-type natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to predict haemodynamically significant patent ductus arteriosus (HsPDA). Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p < 0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen day 3 NTproBNP value of ≥ 287 pmol/L for the prediction of day 3 HsPDA correctly classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only modest ability to predict severe BPD. Chronological but not gestational age affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence NTproBNP but creatinine level was positively correlated. Day 3 NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in future trial design. What is Known: • NTproBNP is a cardiac hormone used to diagnose and monitor cardiac dysfunction in adults and has been shown to be higher in premature infants with haemodynamically significant ductus arteriosus (HsPDA). What is new: • NTproBNP is highly predictive of ultrasound-defined HsPDA and may be a useful tool for further triage • Early NTproBNP higher in infants who develop severe BPD and with renal impairment but not affected by gestational age, recent exposure to hypoxia or haemoglobin levels while late levels unexpectedly higher in those without BPD or HsPDA.
Publisher: Wiley
Date: 06-12-2019
DOI: 10.1002/EJHF.1660
Abstract: The performance of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in diagnosing acute decompensated heart failure (ADHF) among patients presenting with breathlessness is markedly impaired in the presence of atrial fibrillation (AF). We evaluated the diagnostic performance of mid‐regional pro‐adrenomedullin (MR‐proADM) and cardiac troponin T as possible alternative markers for discrimination of ADHF in this setting. Breathless patients ( n = 1107) were prospectively and contemporaneously recruited in emergency departments in Singapore and New Zealand. The diagnoses of ADHF and presence of AF were adjudicated by two clinician specialists, blinded to MR‐proADM, NT‐proBNP and high‐sensitivity cardiac troponin T (hs‐cTnT) results. MR‐proADM exhibited strong discrimination of ADHF with little change in performance irrespective of the presence of AF (area under the curve 0.83 in non‐AF vs. 0.76 in AF) compared to NT‐proBNP (0.91 vs. 0.71) and hs‐cTnT (0.83 vs. 0.62), respectively. The accuracy of MR‐proADM (73.3%) for diagnosing ADHF among patients with AF was superior to both NT‐proBNP (61.6%) and hs‐cTnT (64.6%). The superior performance of MR‐proADM remained apparent when data from Singapore and New Zealand were analysed separately. In the presence of AF, MR‐proADM showed greater discrimination and accuracy, and less impairment in performance compared to that in non‐AF cases, for the diagnosis of ADHF, compared to the guideline‐endorsed NT‐proBNP.
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.HEALUN.2003.12.006
Abstract: The changes in brain natriuretic peptide (BNP) levels after orthotopic heart transplantation have not been previously described. The use of brain natriuretic peptide levels as a surrogate marker for cellular rejection remains controversial, with conflicting data. We prospectively evaluated the potential utility of BNP levels in the first 6 months after transplantation and sought correlation with histologic grade of rejection and hemodynamic status. Thirty-five patients and 265 biopsy s les were included in the study. BNP levels did not correlate with histologic grade of rejection. They showed good correlation with central venous pressure and pulmonary capillary wedge pressure. BNP levels were elevated after transplant and showed a steep time-dependent decline. BNP levels correlated with echocardiographically derived indices of diastolic dysfunction. BNP levels are not a surrogate marker for rejection in the first 2 months after orthotopic heart transplantation and do not obviate the necessity for endomyocardial biopsy. Whether BNP levels have long-term prognostic significance is unclear and remains the subject of ongoing prospective study.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2007
DOI: 10.1161/01.HYP.0000253061.30170.68
Abstract: Angiotensinogen M235T and T174M polymorphisms have in idually been associated with elevated levels of plasma angiotensinogen, hypertension, and left ventricular hypertrophy. In this study, heart failure patients (n=451) were genotyped for the angiotensinogen M235T and T174M polymorphisms to investigate association with survival (recorded over 4 years of follow-up) and prognostic hormone markers. Patients carrying the 235TT genotype (n=86) were 3 years younger at admission ( P =0.011), and, in those with hypertension, diagnosis was made ≈10 years earlier than other patients. Patients carrying ≥1 174M allele (n=94) were more likely to have a previous history of heart failure ( P =0.044) and increased mortality during follow-up (risk ratio: 1.69, 95% CI: 1.03 to 2.79 P =0.038) compared with 174TT homozygotes (n=355), despite having a higher left ventricular ejection fraction ( P =0.009). “High-risk” genotype combinations (defined a priori as 235TT and/or ≥1 174M allele n=144 32%) were independently predictive of mortality, conferring a 2-fold greater risk of dying during the follow-up period (odds ratio: 2.0 95% CI: 1.3 to 3.0 P =0.001). This study suggested that angiotensinogen gene variants M235T and T174M may provide prognostic information for long-term survival in heart failure patients.
Publisher: Oxford University Press (OUP)
Date: 06-08-2011
Abstract: A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using in idual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation) hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%. Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.
Publisher: Wiley
Date: 18-04-2008
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.JACC.2018.11.060
Abstract: Clinicians need improved tools to better identify nonacute heart failure with preserved ejection fraction (HFpEF). The purpose of this study was to derive and validate circulating microRNA signatures for nonacute heart failure (HF). Discovery and validation cohorts (N = 1,710), comprised 903 HF and 807 non-HF patients from Singapore and New Zealand (NZ). MicroRNA biomarker panel discovery in a Singapore cohort (n = 546) was independently validated in a second Singapore cohort (Validation 1 n = 448) and a NZ cohort (Validation 2 n = 716). In discovery, an 8-microRNA panel identified HF with an area under the curve (AUC) 0.96, specificity 0.88, and accuracy 0.89. Corresponding metrics were 0.88, 0.66, and 0.77 in Validation 1, and 0.87, 0.58, and 0.74 in Validation 2. Combining microRNA panels with N-terminal pro-B-type natriuretic peptide (NT-proBNP) clearly improved specificity and accuracy from AUC 0.96, specificity 0.91, and accuracy 0.90 for NT-proBNP alone to corresponding metrics of 0.99, 0.99, and 0.93 in the discovery and 0.97, 0.96, and 0.93 in Validation 1. The 8-microRNA discovery panel distinguished HFpEF from HF with reduced ejection fraction with AUC 0.81, specificity 0.66, and accuracy 0.72. Corresponding metrics were 0.65, 0.41, and 0.56 in Validation 1 and 0.65, 0.41, and 0.62 in Validation 2. For phenotype categorization, combined markers achieved AUC 0.87, specificity 0.75, and accuracy 0.77 in the discovery with corresponding metrics of 0.74, 0.59, and 0.67 in Validation 1 and 0.72, 0.52, and 0.68 in Validation 2, as compared with NT-proBNP alone of AUC 0.71, specificity 0.46, and accuracy 0.62 in the discovery with corresponding metrics of 0.72, 0.44, and 0.57 in Validation 1 and 0.69, 0.48, and 0.66 in Validation 2. Accordingly, false negative (FN) (81% Singapore and all NZ FN cases were HFpEF) as classified by a guideline-endorsed NT-proBNP ruleout threshold, were correctly reclassified by the 8-microRNA panel in the majority (72% and 88% of FN in Singapore and NZ, respectively) of cases. Multi-microRNA panels in combination with NT-proBNP are highly discriminatory and improved specificity and accuracy in identifying nonacute HF. These findings suggest potential utility in the identification of nonacute HF, where clinical assessment, imaging, and NT-proBNP may not be definitive, especially in HFpEF.
Publisher: Wiley
Date: 08-2006
DOI: 10.1016/J.EJHEART.2006.04.004
Abstract: How best to decide when to introduce drugs and what doses are optimal in in idual patients with chronic heart failure (CHF), is unclear. We will determine whether titration of drug treatment according to plasma NTproBNP is superior regarding clinical outcomes to intensive standardised clinical assessment whether either of the regimens noted above is superior to usual care and whether age alters the relative efficacy of NTproBNP guided treatment. We will randomise 360 patients, stratified by age, to drug treatment directed by plasma NTproBNP, to intensive standardised clinical assessment, or to usual care. The primary outcome is total mortality, and secondary outcomes include death plus hospital admission for any cardiovascular event plus episodes of outpatient decompensated heart failure. Analyses will be conducted at the end of one and two years. 308 patients have been recruited, the majority being in NYHA functional class II, 60.6% being >75 years. The entry plasma NTproBNP level is 238, 50-1250 pmol/l, median and range, approximately 400-11,000 pg/ml. We describe details of a study to test the potential utility of serial measurements of NTproBNP in adjusting the drug treatment of patients with CHF. Projected completion date is 2007.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-01-2021
Abstract: Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR‐19b‐1‐5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio‐cerebrovascular (MACCE) events in patients with ACS. In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR‐19b‐1‐5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow‐up time of 1.01±0.43 years. Low miR‐19b‐1‐5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (‐Log‐miR‐19b‐1‐5p, [unstandardized beta, 44.50 95% CI, 2.20–86.80 P .05]), even after adjusting for age, sex, ethnicity, and prior history of stroke. Lower miR‐19b‐1‐5p expression was independently associated with a higher risk of MACCE (‐Log‐miR‐19b‐1‐5p, [hazard ratio, 1.85 95% CI, 1.23–2.80 P .05]). Furthermore, a significant interaction was noted between the inverse miR‐19b‐1‐5p expression and family history of premature coronary artery disease ( P =0.01) on the risk of MACCE. Lower miR‐19b‐1‐5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR‐19b‐1‐5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.AHJ.2004.05.051
Abstract: We sought to assess the utility of serial BNP measurements in patients with severe heart failure and attempted to correlate values with invasively derived data. In a retrospective study, we analyzed serial BNP levels in patients receiving hemodynamically guided therapy for severe heart failure and sought correlation with invasively derived data. Thirty-nine patients with New York Heart Association Class III-IV, with an ejection fraction of 35% or less, who had a pulmonary artery catheter inserted for hemodynamically tailored heart failure therapy, were identified and serial BNP measurements reviewed. BNP was estimated on admission, at 12 and 36 hours. Normally distributed variables are expressed as mean +/- SD and otherwise as median +/- interquartile range. Mean ejection fraction was 16% +/- 6%. Mean pulmonary artery occlusion pressures (PAOP) fell with therapy and were 25 +/- 7 mmHg, 18 +/- 7 mmHg and 19 +/- 7 mmHg at admission, 12 hours and 36 hours respectively ( P < 0.05). Median BNP levels fell from 1200 +/- 641 to 771 +/- 803 at 12 hours and to 805 +/- 771 at 36 hours (P < .001). There was no correlation between BNP and any hemodynamically derived variable. A change in BNP was not associated with a change in PAOP in any in idual patient. Only 42% remained alive on medical therapy at 30 days. In patients with severe heart failure, BNP levels do not accurately predict serial hemodynamic changes and do not obviate the need for pulmonary artery catheterization.
Publisher: Elsevier BV
Date: 05-2002
DOI: 10.1016/S1043-2760(01)00554-9
Abstract: The pharmacotherapy of heart failure has become complex. Angiotensin-converting enzyme inhibitors (or angiotensin II receptor blockers), beta-blockers, spironolactone, diuretics and digoxin can be prescribed concurrently. Endothelin antagonists and combined inhibitors of converting enzyme and neutral endopeptidase are under investigation. Optimal dosing will become increasingly difficult to judge. Plasma brain natriuretic peptide (BNP) indicates the severity of left ventricular dysfunction. The C-terminal bioactive peptide and N-terminal BNP (N-BNP) circulate at concentrations related to cardiac status. We proposed that plasma levels of N-BNP would provide an index to guide drug treatment in established heart failure. Sixty-nine patients were randomized to treatment adjusted according to clinical criteria or plasma N-BNP. Hormone-guided therapy resulted in fewer clinical end points than did clinical management. This encourages further exploration of hormone guidance of anti-heart failure therapy, which could be extended to patients with preserved ejection fraction, in addition to those with established systolic dysfunction.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 20-08-2019
DOI: 10.1038/S41598-019-48553-Y
Abstract: Natriuretic Peptides (NP) are important in maintaining normal cardiac and metabolic status and have been used to predict cardiovascular events. Whether plasma concentrations of NP products within the normal range reflect cardio-metabolic health is unknown. Plasma NTproANP, NTproBNP and NTproCNP and their bioactive counterparts were measured in a random s le of 348 community dwellers aged 49–51 yr without heart disease and associations sought with established vascular risk factors, echocardiographic indices and a genetic variant previously linked with BNP. Stratified by sex, each of ten vascular risk factors were positively associated with NTproCNP whereas associations with NTproBNP and NTproANP were all negative. In both sexes, higher plasma NTproCNP was associated with higher arterial elastance, lower LV stroke volume and lower LV end diastolic volume. Exactly opposite associations were found with plasma NTproBNP or NTproANP. Sex specific differences were identified: positive association of NTproBNP with LV end systolic volume and the negative association with LV elastance were found only in males. The genetic variant rs198358 was independently associated with NTproBNP but not with NTproANP. In conclusion, higher NTproCNP is likely to be an adaptive response to impaired LV relaxation whereas genetic factors likely contribute to higher NTproBNP and improved cardio-metabolic health at midlife.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2001
Abstract: Abstract —Plasma levels of adrenomedullin are increased in chronic renal failure. The significance of this finding is uncertain, because the biological effects of adrenomedullin in renal impairment are unknown. Therefore, we studied the effects of adrenomedullin infusion in subjects with chronic renal impairment. Eight males with IgA nephropathy and plasma creatinine of 0.19±0.03 mmol/L (mean±SEM) were studied in a vehicle-controlled crossover design. Each subject was studied twice subjects were administered either adrenomedullin at a low dose and then a high dose (2.9 and 5.8 pmol/kg per minute, respectively, for 2 hours each) or a 4-hour vehicle control (Hemaccel), in random order, on day 4 of controlled metabolic diets. Adrenomedullin infusion achieved plasma adrenomedullin concentrations in the pathophysiological range after the low (31.2±5.1 pmol/L) and high (47.4±4.3 pmol/L) dose, and plasma cAMP was increased. Compared with vehicle control, high-dose adrenomedullin increased peak heart rate (+21.7±3.3 bpm, P .01) and cardiac output (+2.9±0.2 L/min, P .01) and lowered both systolic and diastolic blood pressures by mm Hg ( P .05). Plasma renin activity, angiotensin II, and norepinephrine increased by up to 50% above baseline levels ( P .05 for all), whereas aldosterone and epinephrine were unchanged. Urinary volume and sodium excretion increased significantly ( P .05) with low-dose adrenomedullin, whereas creatinine clearance was stable, and proteinuria tended to decrease. In subjects with chronic renal impairment due to IgA nephropathy, adrenomedullin infusion lowered blood pressure, stimulated sympathetic activity and renin release, and caused diuresis and natriuresis. Adrenomedullin may have a role in modulating blood pressure and kidney function in renal disease.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.JACC.2009.02.095
Abstract: The purpose of this study was to compare the effects of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy with those of intensive clinical management and with usual care (UC) on clinical outcomes in chronic symptomatic heart failure. Initial trial results suggest titration of therapy guided by serial plasma B-type natriuretic peptide levels improves outcomes in patients with chronic heart failure, but the concept has not received widespread acceptance. Accordingly, we conducted a longer-term study comparing the effects of NT-proBNP-guided therapy with those of intensive clinical management and with UC of patients with heart failure. Three hundred sixty-four patients admitted to a single hospital with heart failure were randomly allocated 1:1:1 (stratified by age) to therapy guided by NT-proBNP levels or by intensive clinical management, or according to UC. Treatment strategies were applied for 2 years with follow-up to 3 years. One-year mortality was less in both the hormone- (9.1%) and clinically-guided (9.1%) groups compared with UC (18.9% p = 0.03). Three-year mortality was selectively reduced in patients <or=75 years of age receiving hormone-guided treatment (15.5%) compared with their peers receiving either clinically managed treatment (30.9% p = 0.048) or UC (31.3% p = 0.021). Intensive management of chronic heart failure improves 1-year mortality compared with UC. Compared with clinically guided treatment and UC, hormone-guided treatment selectively improves longer-term mortality in patients <or=75 years of age. (NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death [BATTLESCARRED] Australian New Zealand Clinical Trials Registry 12605000735651).
Publisher: Springer Science and Business Media LLC
Date: 31-08-2016
Publisher: Elsevier
Date: 2008
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.HFC.2014.04.006
Abstract: Timely diagnosis, early introduction of appropriate treatment, accurate risk stratification, and optimal titration of therapy are all key to the management of acute and chronic heart failure (HF). Plasma concentrations of the cardiac natriuretic peptides (NPs) are valuable aids in each of these elements of care. However, most data are derived from cohorts with undifferentiated HF or HF with reduced ejection fraction (HFREF), and the performance and best application of NPs in HF with preserved ejection fraction (HFPEF) is less certain. This review outlines the evidence for use of NPs in the evaluation and management of HFPEF.
Publisher: Massachusetts Medical Society
Date: 27-06-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-12-2007
DOI: 10.1161/CIRCULATIONAHA.107.702191
Abstract: Background— We describe the first human experience with a permanently implantable, direct left atrial pressure (LAP) monitoring system in ambulatory patients with chronic heart failure. Methods and Results— Eight patients with established heart failure and at least 1 heart failure hospitalization or unplanned visit for parenteral therapy in the last year underwent device implantation under fluoroscopic guidance. All subjects received aspirin 150 mg and clopidogrel 75 mg daily. Subjects measured LAP twice daily and attended a clinic regularly for data upload and device calibration. Right heart catheterization was performed at the time of device implantation and at 12 weeks. The device was implanted in all subjects with no procedural complications. At the 12-week follow-up, 87% of device LAP measurements were within ±5 mm Hg of simultaneous pulmonary capillary wedge pressure readings over a wide range of pressures (1.6 to 71 mm Hg). Net drift corrected by calibration was −0.2±1.9 mm Hg/mo. During short-term follow-up, there were no device-related complications or systemic emboli. There were no deaths, no unplanned heart failure clinic visits, and no admissions for heart failure. Conclusions— Ambulatory monitoring of direct LAP with a new implantable device was well tolerated, feasible, and accurate at a short-term follow-up. Further follow-up and investigation are warranted to evaluate the clinical utility of LAP monitoring in patients with heart failure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-04-2006
Publisher: Oxford University Press (OUP)
Date: 23-04-2009
Abstract: Aims To determine whether combined renal and cardiac function after acute myocardial infarction (MI) predicts 10 year mortality and heart failure (HF). Methods and results Estimated glomerular filtration rate (eGFR), plasma amino terminal pro-brain natriuretic peptide (NT-proBNP), and radionuclide ventriculography were obtained in 1063 patients with MI between 24-96 h of symptom onset. Mortality and HF were documented over follow-up of 9.3 years. Estimated GFR, NT-proBNP, and left ventricular ejection fraction (LVEF) each independently predicted 10 year mortality. Reduced eGFR (below 60 mL/min/1.73 m(2)) combined with increased NT-proBNP (above 1000 pg/mL) was associated with higher mortality rate compared with preserved eGFR together with lower NT-proBNP (60 vs. 14%, P < 0.001). Similar results for mortality were identified for eGFR combined with LVEF (dichotomized about 50%) (58 vs. 17%, P < 0.001). Corresponding analysis combining eGFR and NT-proBNP to predict HF yielded rates of 34 and 7% for high- and low-risk groups, respectively (P < 0.001). Similar risk stratification for HF was observed when combining eGFR with LVEF (35 vs. 7%, P < 0.001). Conclusion Ten year rates of mortality and HF are 5-10 times higher when lower eGFR is present together with increased NT-proBNP or depressed LVEF.
Publisher: Public Library of Science (PLoS)
Date: 23-05-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-06-2003
DOI: 10.1161/01.CIR.0000070953.76250.B9
Abstract: Background— A recent landmark report has demonstrated that plasma B-type natriuretic peptide (BNP) measured in acute coronary syndromes independently predicts mortality, heart failure, and new myocardial infarction. After acute cardiac injury, left ventricular ejection fraction (LVEF) is also of prognostic significance and plays a major role in determining the therapeutic response. Methods and Results— The present report is the first from a substantial (n=666) cohort of patients with acute myocardial infarction to test the prognostic utility of concurrent measurements of BNP, amino-terminal BNP (N-BNP), norepinephrine, and radionuclide LVEF. The B-type peptides and LVEF were predictors of death, heart failure, and new myocardial infarction (all P .001) independent of patient age, gender, previous myocardial infarction, antecedent hypertension or diabetes, previous heart failure, plasma norepinephrine, creatinine, cholesterol, drug therapy, and coronary revascularization procedures. The combination of N-BNP (or BNP) with LVEF substantially improved risk stratification beyond that provided by either alone. Elevated N-BNP (or BNP) predicted new myocardial infarction only in patients with LVEF %. LVEF % coupled to N-BNP over the group median conferred substantial 3-year risks of death, heart failure, and new myocardial infarction of 37%, 18%, and 26%, respectively. N-BNP and BNP were equivalent prognostic markers for these clinical outcomes. Conclusions— Plasma N-BNP (or BNP) and LVEF are complementary independent predictors of major adverse events on follow-up after myocardial infarction. Combined measurement provides risk stratification substantially better than that provided by either alone.
Publisher: Wiley
Date: 10-2013
Abstract: Since their identification in the circulation, microRNAs have received considerable interest as putative biomarkers of cardiovascular disease. We have investigated the diagnostic utility of microRNAs in differentiating between patients with heart failure (HF) and non-HF-related breathlessness, and between HF with reduced (HF-REF) and preserved (HF-PEF) EF. MicroRNA profiling was performed on plasma from 32 HF and 15 COPD patients, as well as 14 healthy controls. Seventeen microRNAs were selected for validation in 44 HF, 32 COPD, 59 other breathless, and 15 controls. Cases of HF were split evenly between HF-REF and HF-PEF. Diagnostic utility was compared with NT-proBNP and high sensitivity troponin T (hs-troponin T). MiR-103 [area under the curve (AUC) = 0.642, P = 0.007], miR-142-3p (AUC = 0.668, P = 0.002), miR-199a-3p (AUC = 0.668, P = 0.002), miR-23a (AUC = 0.637, P = 0.010), miR-27b (AUC = 0.642, P = 0.008), miR-324-5p (AUC = 0.621, P = 0.023), and miR-342-3p (AUC = 0.644, P = 0.007) were associated with HF diagnosis in regression and receiver operating characteristic (ROC) analyses. In idually, NT-proBNP (AUC = 0.896, P = 9.68 × 10(-14)) and hs-troponin T (AUC = 0.750, P = 2.50 × 10(-6)) exhibited greater sensitivity and specificity. However, combining significantly associated microRNAs with NT-proBNP improved the AUC of NT-proBNP by 4.6% (P = 0.013). Four microRNAs, miR-103, miR-142-3p, miR-30b, and miR-342-3p, were differentially expressed between HF and controls, COPD, and other breathless patients (P = 0.002-0.030). Eight microRNAs that distinguished between HF-REF and HF-PEF in screening (P = 0.017-0.049) were not replicated in the validation. Four microRNAs distinguished between HF and exacerbation of COPD, other causes of dyspnoea, and controls. Seven were associated with HF diagnosis in regression and ROC analysis. Although in idually NT-proBNP was far superior in predicting HF, combining microRNA levels with NT-proBNP may add diagnostic value.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.AHJ.2012.06.025
Abstract: Accelerated diagnostic pathways for risk stratification of patients presenting to the emergency department with potential acute coronary syndromes may identify very-low-risk patients safe for early discharge to outpatient care. Patients presenting with potential acute coronary syndrome to the emergency department were prospectively enrolled between November 2007 and April 2010. Patient characteristics in conjunction with 0- and 2-hour biomarkers and electrocardiograms were analyzed according to a 2-hour thrombolysis in myocardial infarction (TIMI) score and 9 other accelerated diagnostic pathways. The primary outcome was acute coronary syndrome by 30 days. Of 1,000 patients, 362 (36.2%) had a primary outcome. A pathway comprising electrocardiogram, prior ischemic heart disease, 0/2-hour troponin/creatine kinase MB fraction/myoglobin identified the highest proportion (25.0%) as low risk, with 96.1% sensitivity for the primary outcome. A pathway comprising electrocardiogram, history of ischemic heart disease, typical vs atypical symptoms, 0/2-hour troponin was the safest, with 99.7% sensitivity for the primary outcome, but only 9.0% were low risk. A pathway comprising the TIMI score with 0/2-hour troponin and electrocardiograms identified 15.5% as low risk, with a sensitivity of 99.2% for the primary outcome. This compares with standard care in which none were for outpatient care but, 3.3% had a primary outcome postdischarge within 30 days. In this relatively high-risk population, a 2-hour TIMI score safely identified significant numbers of patients suitable for early discharge to outpatient care.
Publisher: Wiley
Date: 2008
DOI: 10.1016/J.EJHEART.2007.10.011
Abstract: The Ile164 variant of the beta2-adrenoceptor has been shown to alter cardiovascular phenotypes and adversely affect survival in heart failure patients. We aimed to replicate this observation by genotyping a cohort of 451 heart failure patients for the Ile164 polymorphism. Patient outcome was recorded over a median follow-up period of 3.09 years, and genotypes were derived by multiplex lification refractory mutation system PCR. Genotypes were obtained for 443 patients, and 3.2% of these (14 patients) were heterozygous for the Ile164 SNP. Demographic data, cardiac function and neurohormonal profiles did not differ between genotype groups. Ile164 genotype did not significantly affect survival in this cohort (Thr164 homozygotes 48.9%, Ile164 heterozygous 42.9%, p=0.66), although multivariate analysis suggested that beta-blocker treatment may negatively impact survival in the heterozygote group. This study suggests that the Ile164 polymorphism of the beta2-adrenoceptor does not have a major impact on outcome in in iduals with heart failure, although it's potential interaction with beta-blockers requires further examination.
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.JCMG.2009.01.012
Abstract: The aim of this study was to determine the relationship between right atrial volume index (RAVI) and right ventricular (RV) systolic and diastolic function, as well as long-term prognosis in patients with chronic systolic heart failure (HF). RV dysfunction is associated with poor prognosis in patients with HF, although echocardiographic assessment of RV systolic and diastolic dysfunction is challenging. The ability to visualize the RA allows a quantitative, highly reproducible assessment of the RA volume that can be indexed to body surface area. The ADEPT (Assessment of Doppler Echocardiography for Prognosis and Therapy) trial enrolled 192 subjects with chronic systolic HF (left ventricular ejection fraction [LVEF] <or=35%). The RA volume was calculated by Simpson's method using single-plane RA area and indexed to body surface area (RAVI). RV systolic function was graded as normal, mild, mild-moderate, moderate, moderately severe, or severe dysfunction. In our study cohort, the mean RAVI was 28 +/- 15 ml/m(2), and increased with worsening RV systolic dysfunction, LVEF, and LV diastolic dysfunction (Spearman's r = 0.61, r = 0.26, and r = 0.51, respectively p < 0.001 for all). RAVI correlated modestly with echocardiographic estimates of RV diastolic dysfunction, including tricuspid early/late velocities ratio (Spearman's r = 0.34, p < 0.0001), hepatic vein systolic/diastolic ratio (Spearman's r = -0.26, p < 0.001) but not tricuspid early/tricuspid annular early velocities ratio (E/Ea) (Spearman's r = 0.12, p = 0.11). Increasing tertiles of RAVI were predictive of death, transplant, and/or HF hospitalization (log-rank p = 0.0002) and remained an independent predictor of adverse clinical events after adjusting for age, B-type natriuretic peptide, LV ejection fraction, RV systolic dysfunction, and tricuspid E/Ea ratio (hazard ratio: 2.00, 95% confidence interval: 1.15 to 3.58, p = 0.013). In patients with chronic systolic HF, RAVI is a determinant of right-sided systolic dysfunction. This quantitative and reproducible echocardiographic marker provides independent risk prediction of long-term adverse clinical events.
Publisher: Wiley
Date: 28-10-2013
DOI: 10.1111/RESP.12152
Abstract: Increasing evidence implicates lymphocytes in pulmonary arterial hypertension (PAH) pathogenesis. Rats deficient in T-lymphocytes show increased propensity to develop PAH but when injected with endothelial progenitor cells are protected from PAH (a mechanism dependent on natural killer (NK) cells). A decreased quantity of circulating cytotoxic CD8+ T-lymphocytes and NK cells are now reported in PAH patients however, the effect of lymphocyte depletion on disease outcome is unknown. This prospective study analysed the lymphocyte profile and plasma brain natriuretic peptide (BNP) levels of patients with idiopathic PAH (IPAH), connective tissue disease-associated PAH (CTD-APAH) and matched healthy controls. Lymphocyte surface markers studied include: CD4+ (helper T-cell marker), CD8+ (cytotoxic T-cell marker), CD56/CD16 (NK cell marker) and CD19+ (mature B-cell marker). Lymphocyte deficiencies and plasma BNP levels were then correlated with clinical outcome. Fourteen patients with PAH (9 IPAH, 5CTD) were recruited. Three patients were deceased at 1-year follow-up all had elevated CD4 : CD8 ratios and deficiencies of NK cells and cytotoxic CD8+ T-lymphocytes at recruitment. Patients with normal lymphocyte profiles at recruitment were all alive a year later, and none were on the active transplant list. As univariate markers, cytotoxic CD8+ T-cell and NK cell counts were linked to short-term survival. Deficiencies in NK cells and cytotoxic CD8+ T-cells may be associated with an increased risk of death in PAH patients. Further research is required in larger numbers of patients and to elucidate the mechanism of these findings.
Publisher: Elsevier BV
Date: 04-2000
DOI: 10.1016/S0140-6736(00)02060-2
Abstract: There is currently no objective practical guide to intensity of drug treatment for in iduals with heart failure. We hypothesised that pharmacotherapy guided by plasma concentrations of the cardiac peptide aminoterminal brain natriuretic peptide (N-BNP) would produce a superior outcome to empirical trial-based therapy dictated by clinical acumen. 69 patients with impaired systolic function (left-ventricular ejection fraction <40%) and symptomatic heart failure (New York Heart Association class II-IV) were randomised to receive treatment guided by either plasma N-BNP concentration (BNP group) or standardised clinical assessment (clinical group). During follow-up (minimum 6-months, median 9.5 months), there were fewer total cardiovascular events (death, hospital admission, or heart failure decompensation) in the BNP group than in the clinical group (19 vs 54, p=0.02). At 6 months, 27% of patients in the BNP group and 53% in the clinical group had experienced a first cardiovascular event (p=0.034). Changes in left-ventricular function, quality of life, renal function, and adverse events were similar in both groups. N-BNP-guided treatment of heart failure reduced total cardiovascular events, and delayed time to first event compared with intensive clinically guided treatment.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.CLINBIOCHEM.2012.11.022
Abstract: The aim of this study was to evaluate a Milliplex NTproBNP immunoassay and to compare its performance with the Roche Elecsys assay and an in house NTproBNP radioimmunoassay (RIA). S les were analyzed for NTproBNP in all 3 assays following the manufacturer's instructions and/or our previously published methodologies. Similar plasma concentrations and assay reproducibility were observed for the Roche assay and in house RIA. However, the Milliplex assay produced much lower concentrations than the other two assays (versus Roche Elecsys bias of -367.9 pg/mL, (LOA -907.6 and 171.8)), and only quantified results for 63 of the 111 s les assessed. Of these 46 s les had acceptable errors of measurement (within s le coefficients of variation <20%) equating to 41% of the total s les measured. The Milliplex assay, in its current form, does not produce results comparable with the Roche Elecsys 2010 assay or our in house RIA, and does not perform well as a quantitative assay. It may provide qualitative results (ie high, medium or low concentration), and serve as a rudimentary screening assay.
Publisher: Wiley
Date: 10-2011
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.IJCARD.2015.02.006
Abstract: We aimed to evaluate the efficacy and safety of using high-sensitivity cardiac troponin T (hs-cTnT) within an accelerated diagnostic protocol (ADP) in patients presenting with symptoms suggestive of acute myocardial infarction (AMI) for rapid rule-out of AMI. In two independent large multicenter studies, levels of hs-cTnT at presentation and at 2 h were combined with the Thrombolysis In Myocardial Infarction (TIMI) risk score and ECG findings. The ADP defined patients with normal levels of hs-cTnT at presentation and 2 h, a TIMI score ≤1, and normal ECG findings as candidates for rapid rule-out of AMI and rapid discharge. Major adverse cardiac events (MACEs) occurring within 30-days were centrally adjudicated by two independent cardiologists. In the derivation cohort, among 1085 consecutive patients 198 patients (18.2%) had a MACE. The ADP classified 374 patients (34.5%) as low-risk. None of these patients had a MACE at 30 days, resulting in a negative predictive value (NPV) of 100% (95% CI, 99.0-100%) and a sensitivity of 100% (95% CI, 98.2%-100%). In the validation cohort, among 1590 consecutive patients 231 patients (14.5%) had a MACE. The ADP classified 641 patients (40.3%) as low-risk. 6 of these patients had a MACE at 30 days, resulting in a NPV of 99.1% (95% CI, 98.0-99.6%) and a sensitivity of 97.4% (95% CI, 94.5-98.8%). The ADP including hs-cTnT allows early identification 35 to 40% of patients to be at extremely low risk of MACE and therefore ideal candidates for outpatient management.
Publisher: Wiley
Date: 31-03-2011
DOI: 10.1111/J.1751-7133.2011.00221.X
Abstract: Various inflammatory biomarkers predict long-term outcomes in patients with acute and chronic heart failure (HF). Their relative contributions when measured in combination have not been evaluated. The authors measured both plasma levels of high-sensitivity C-reactive protein (hsCRP) and myeloperoxidase (MPO) in 136 patients with chronic systolic HF (left ventricular ejection fraction ≤ 40%), and performed echocardiography with prospective follow-up of adverse clinical events (death, cardiac transplant, and HF hospitalizations) over 34 ± 17 months. A lack of significant correlation between log-transformed hsCRP and MPO (Spearman's r = 0.11, P = .185) was observed. Within the lower two hsCRP tertiles (<5.34 mg/L), patients with plasma MPO above median levels demonstrated a 2.9-fold increased risk in adverse clinical events (95% confidence interval [CI], 1.2-8.1 P < .05), whereas within lower plasma MPO levels (<303 pM), increase in hsCRP demonstrated a 1.9-fold increased risk (95% CI, 0.56-6.2 P = not significant). Combined analysis of hsCRP and MPO levels demonstrated a 6-fold increased risk (95% CI, 2.4-16.8 P < .01) when both markers were elevated. Stratifying patients according to hsCRP, MPO, and amino-terminal pro-B-type natriuretic peptide cutoff values provided a stepwise increment of risk prediction of adverse clinical events. Combining hsCRP and MPO measurements provided distinct and complementary prognostic value in a patient cohort of chronic systolic HF.
Publisher: Wiley
Date: 04-2001
Publisher: American Medical Association (AMA)
Date: 2014
DOI: 10.1001/JAMAINTERNMED.2013.11362
Abstract: Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0 electrocardiography and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0% odds ratio, 1.92 95% CI, 1.18-3.13 P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required. anzctr.org.au Identifier: ACTRN12610000766011.
Publisher: The Endocrine Society
Date: 03-2000
DOI: 10.1210/JC.85.3.1016
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.CARDFAIL.2006.06.002
Abstract: Implantable cardiac pressure monitors require assurance of calibration. This study evaluated if airway pressure responses during Valsalva maneuver (VM) can be used for calibrating intracardiac pressure transducers. Thirty-eight heart failure patients performed VMs while cardiac and airway pressures were recorded. Patients were designated as Lower (L) if baseline PCW was <20 mm Hg (n = 17) otherwise, they were categorized as Higher (H) (n = 21). VMs were repeated in 9 H patients after nitroglycerin. Procedural success was 92% and there were no complications. Differences between filling pressure and airway pressure (effective pressure) were eliminated during VM (RA(eff) = -0.9 +/- 1.3, RVED(eff) = 1.2 +/- 1.1, PCW(eff) = 2.1 +/- 2.8, and LVED(eff) = 0.9 +/- 1.6 mm Hg), and filling pressures were highly correlated with airway pressure r = 0.94. On average, group H had higher PCW(eff) and LVED(eff) than L patients by 1.8 and 2.5 mm Hg (P < or = .002), respectively, but after nitrates their responses were identical. The relationships between cardiac filling pressure and airway pressure during the Valsalva maneuver are sufficiently reliable to be considered as a new, noninvasive method for establishing the calibration of cardiac pressure sensors in patients with heart failure.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JCHF.2014.06.014
Abstract: The purpose of this study was to investigate the predictive values of baseline and changes in cystatin C (CysC) and its derived equations for short-term adverse outcomes and the effect of nesiritide therapy on CysC in acute decompensated heart failure (ADHF). Newer renal biomarkers or their derived estimates of renal function have demonstrated long-term prognostic value in chronic heart failure. CysC levels were measured in sequential plasma s les from 811 subjects with ADHF who were enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) biomarker sub-study (randomized to nesiritide therapy vs. placebo), and followed for all-cause death (180 days) and recurrent hospital stay (30 days). Median CysC levels were 1.49 (interquartile range [IQR]: 1.20 to 1.96) mg/l at baseline, 1.56 (IQR: 1.28 to 2.13) mg/l at 48 to 72 h, and 1.58 (IQR: 1.24 to 2.11) mg/l at 30 days. Higher baseline (but not follow-up) CysC levels were associated with increased risk of 30-day adverse events and less improvement in dyspnea after 24 h as well as 180-day mortality, although not incremental to blood urea nitrogen. Worsening renal function (defined as a 0.3 mg/l increase in CysC) occurred in 161 of 701 (23%) patients, but it was not predictive of adverse events. Changes in CysC levels were similar between the nesiritide and placebo groups. Our findings confirmed the prognostic value of baseline CysC levels in the setting of ADHF. However, worsening renal function based on CysC rise was not predictive of adverse events. Nesiritide did not worsen renal function compared with placebo.
Publisher: Elsevier BV
Date: 02-2004
Publisher: Springer Science and Business Media LLC
Date: 05-08-2015
Publisher: Wiley
Date: 24-03-2010
Publisher: Elsevier BV
Date: 04-2013
Publisher: Wiley
Date: 05-2015
DOI: 10.1111/IMJ.12739
Abstract: We aimed to assess differences in patient management, and outcomes, of Australian and New Zealand patients admitted with a suspected or confirmed acute coronary syndrome (ACS). We used comprehensive data from the binational Australia and New Zealand ACS 'SNAPSHOT' audit, acquired on in idual patients admitted between 00.00 h on 14 May 2012 to 24.00 h on 27 May 2012. There were 4387 patient admissions, 3381 (77%) in Australia and 1006 (23%) in New Zealand Australian patients were slightly younger (67 vs 69 years, P = 0.0044). Of the 2356 patients with confirmed ACS, Australian patients were at a lower cardiovascular risk with a lower median Global Registry Acute Coronary Events score (147 vs 154 P = 0.0008), but as likely to receive an invasive coronary angiogram (58% vs 54%, P = 0.082), or revascularisation with percutaneous coronary intervention (32% vs 31%, P = 0.92) or coronary artery bypass graft surgery (7.0% vs 5.6%, P = 0.32). Of the 1937 non-segment elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients, Australian patients had a shorter time to angiography (46 h vs 67 h, P < 0.0001). However, at discharge, Australian NSTEMI/UAP survivors were less likely to receive aspirin (84% vs 89%, P = 0.0079, a second anti-platelet agent (57% vs 63%, P = 0.050) or a beta blocker (67% vs 77%, P = 0.0002). In-hospital death rates were not different (2.7% vs 3.2%, P = 0.55) between Australia and New Zealand. Overall more similarities were seen, than differences, in the management of suspected or confirmed ACS patients between Australia and New Zealand. However, in several management areas, both countries could improve the service delivery to this high-risk patient group.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.JCMG.2015.02.014
Abstract: This study sought to derive age-, sex-, and ethnic-appropriate adult reference values for left atrial (LA) and left ventricular (LV) dimensions and volumes, LV mass, fractional shortening, and ejection fraction (EF) derived from geographically erse population studies. The current recommended reference values for measurements from echocardiography may not be suitable to the erse world population to which they are now applied. Population-based datasets of echocardiographic measurements from 22,404 adults without clinical cardiovascular or renal disease, hypertension, or diabetes were combined in an in idual person data meta-analysis. Quantile regression was used to derive reference values at the 95th percentile (upper reference value [URV]) and fifth percentile (lower reference value [LRV]) of each measurement against age (treated as linear), separately within sex and ethnic groups. The URVs for left ventricular end-diastolic volume (LVEDV), LV end-systolic volume, and LV stroke volume (SV) were highest in Europeans and lowest in South Asians. Important sex and ethnic differences remained after indexation by body surface area or height for these measurements, as well as for the LRV for SV. LVEDV and SV decreased with increasing age for all groups. Importantly, the LRV for EF differed by ethnicity there was a clear apparent difference between Europeans and Asians. The URVs for LV end-diastolic diameter and LV end-systolic diameter were higher for Europeans than those for East Asian, South Asian, and African people, particularly among men. Similarly, the URVs for LA diameter and volume were highest for Europeans. Sex- and/or ethnic-appropriate echocardiographic reference values are indicated for many measurements of LA and LV size, LV mass, and EF. Reference values for LV volumes and mass also differ across the age range.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.AHJ.2005.07.031
Abstract: Brain natriuretic peptide (BNP) levels rise in response to stretch of ventricular myocytes or increases in wall tension, as in congestive heart failure (CHF). Brain natriuretic peptide can be released in bursts, but nonetheless, BNP levels may lag behind clinical changes. We postulated that concomitant measurement of blood volume (BV), BNP, and hemodynamics during treatment of CHF may elucidate interrelationships among changes in these parameters. We studied 10 male patients, aged 60 +/- 8 years, who were admitted for pulmonary catheter-guided treatment of CHF. Hemodynamics, venous BNP, and blood and plasma volumes were measured at baseline before treatment and again on the following morning after 12 to 24 hours of acute treatment for CHF. At baseline, all 10 patients exhibited marked expansion of BV at 29% +/- 19%. At baseline, increased systolic pulmonary artery pressure correlated with BV (r = 0.615) and diastolic pulmonary artery pressure (PAD) with BV (r = 0.609). After treatment, there was an inverse correlation between change (decline) in expanded BV and change (improvement) in mixed venous oxygenation (r = -0.775) and a positive correlation with central venous pressure (CVP) (r = 0.710). Poor correlation was found between BNP and any hemodynamic parameter. Little correlation was found between absolute BNP and BV before or after treatment (r = -0.127 and -0.126, respectively). In this pilot study, changes in BV with treatment correlate better with hemodynamics than do changes in BNP, likely reflecting the lag in BNP response to treatment and its tendency to reflect long-term rather than instantaneous volume status. These preliminary data suggest that BV may be a more accurate guide in optimizing CHF treatment than BNP.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.CLINBIOCHEM.2016.02.015
Abstract: We assessed the ability of B-type natriuretic peptide signal peptide (BNPsp) to assist with the identification of patients with myocardial infarction (MI) and unstable angina pectoris (UAP). We studied 505 patients who presented to hospital within 4h of onset of chest pain suspicious of ACS. Blood s les were drawn at 0, 1, 2 and 24h from presentation and assayed for BNPsp, NT-proBNP, TnI and high sensitivity TnT. The ability of BNPsp and other markers to diagnose acute myocardial infarction (MI) and unstable angina pectoris (UAP) and predict subsequent events within one year was assessed. Statistical analysis was made using ROC AUC in SPSS, v.22. Receiver operator area under the curve (AUC) data for the discrimination of MI was 0.69 for BNPsp and 0.97 for troponin, with BNPsp failing to add to troponin. However, in non-MI patients, BNPsp had discriminative power for UAP (p<0.05), and when combined with presentation values of NT-proBNP, white cell count and potassium into a unique parameter (UARatio), generated an AUC of 0.76 for UAP in patients with normal ECG results (p<0.001). In non-MI patients, the UARatio was significantly predictive of subsequent stroke (AUC=0.70, p<0.05) and heart failure (AUC=0.82, p<0.01) within one year. In patients with chest pain, BNPsp is predictive of MI but is not a useful adjunct to troponin. However, the ability of BNPsp, in conjunction with NT-proBNP and key analytes, to diagnose UAP and other ischemic syndromes merits further investigation.
Publisher: Elsevier BV
Date: 08-2016
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.AMJCARD.2007.11.027
Abstract: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a strong and independent prognostic marker in patients across the spectrum of heart failure (HF) stages, including patients managed in the outpatient setting. Serial measures of NT-proBNP are more valuable than single measures for prognosis, and biologic variation of the marker should allow serial monitoring. Furthermore, given that NT-proBNP levels decrease in response to the addition of therapies with proven benefit for HF (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, spironolactone, exercise therapy, and biventricular pacing), it is logical to expect that targeting therapy to decrease NT-proBNP levels may facilitate more optimal use of proven HF therapies and may reduce adverse clinical outcomes. The optimal strategy for NT-proBNP monitoring with regard to frequency of testing or whether to use standard or in idualized targets is still being determined. Preliminary results are promising for targeting an outpatient NT-proBNP concentration of approximately < or =1,000 ng/L. Current data suggest that when NT-proBNP levels are not at goal or increase from prior measurements, the risk for hazard is increased. Adjustments in treatment and serial clinical follow-up with NT-proBNP retesting should be considered at frequent intervals until biochemical stabilization or achievement of a maximally tolerated medical program.
Publisher: Elsevier BV
Date: 06-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2023
DOI: 10.1161/CIRCHEARTFAILURE.122.009879
Abstract: Sodium restriction is a nonpharmacologic treatment suggested by practice guidelines for the management of patients with heart failure (HF). In this study, we synthesized the data from randomized controlled trials (RCTs) evaluating the effects of sodium restriction on clinical outcomes in patients with HF. In this aggregate data meta-analysis, Cochrane Central, MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase Ovid, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus databases were searched up to April 2, 2022. RCTs were included if they investigated the effects of sodium/salt restriction as compared to no restriction on clinical outcomes in patients with HF. Outcomes of interest included mortality, hospitalization, change in New York Heart Association functional class, and quality of life (QoL). Seventeen RCTs were identified (834 and 871 patients in intervention and control groups, respectively). Sodium restriction did not reduce the risk of all-cause death (odds ratio, 0.95 [95% CI, 0.58–1.58]), hospitalization (odds ratio, 0.84 [95% CI, 0.62–1.13]), or the composite of death/hospitalization (odds ratio, 0.88 [95% CI, 0.63–1.23]). The results were similar in different subgroups, except for the numerically lower risk of death with reduced sodium intake reported in RCTs with dietary sodium at the 2000 to 3000 mg/d range as opposed to mg/d (and in RCTs with versus without fluid restriction as a co-intervention). Among RCTs reporting New York Heart Association change, 2 RCTs (which accounted for two-thirds of the data) showed improvement in New York Heart Association class with sodium restriction. Substantial heterogeneity existed for QoL: 6 RCTs showed improvement of QoL and 4 RCTs showed no improvement of sodium restriction on QoL. In a meta-analysis of RCTs, sodium restriction was not associated with fewer deaths or hospitalizations in patients with HF. Dietary sodium restriction may be associated with improvements in symptoms and QoL.
Publisher: BMJ
Date: 05-2008
Abstract: Natriuretic peptides have actions likely to ameliorate cardiac dysfunction. B-type natriuretic peptide (BNP) is indicated as treatment for decompensated cardiac failure. To determine the utility of BNP in acute myocardial infarction (MI). Double-blind randomised placebo-controlled trial. Tertiary hospital coronary care unit. 28 patients with acute MI with delayed or failed reperfusion and moderate left ventricular dysfunction. Infusion of BNP or placebo for 60 hours after MI. Neurohormonal activation and renal function in response to BNP infusion, secondary end points of echocardiographic measures of left ventricular function and dimension. BNP infusion resulted in a significant rise in BNP (276 pg/l vs 86 pg/l, p = 0.001). NT-proBNP levels were suppressed by BNP infusion (p = 0.002). Atrial natriuretic peptide (ANP) and NT-proANP levels fell with a significant difference in the pattern between BNP infusion and placebo during the first 5 days (p<0.005). C-type natriuretic peptide (CNP) and NT-proCNP levels rose during the infusion with higher levels than placebo at all measurements during the first 3 days (p<0.01). Cyclic guanosine monophosphate (cGMP) was raised during the infusion period showing a peak of 23 pmol/l on day 2 (placebo 8.9 pmol/l, p = 0.002), with a correlation between BNP and cGMP levels (p<0.001). Glomerular filtration rate (GFR) fell with BNP infusion but was not significantly lower than with placebo (71.0 (5.6) vs 75.8 (5.4) ml/min/1.73 m2, p = 0.62). Patients receiving nesiritide exhibited favourable trends in left ventricular remodelling. Nesiritide, given soon after MI, induced increments in plasma cGMP and CNP and decrements in other endogenous cardiac peptides with a neutral effect on renal function and a trend towards favourable ventricular remodelling.
Publisher: Wiley
Date: 16-06-2005
Publisher: Portland Press Ltd.
Date: 19-11-2010
DOI: 10.1042/CS20100388
Abstract: Monitoring of HF (heart failure) with intracardiac pressure, intrathoracic impedance and/or natriuretic peptide levels has been advocated. We aimed to investigate possible differences in the response patterns of each of these monitoring modalities during HF decompensation that may have an impact on the potential for early therapeutic intervention. Six sheep were implanted with a LAP (left atrial pressure) sensor and a CRT-D (cardiac resynchronization therapy defibrillator) capable of monitoring impedance along six lead configuration vectors. An estimate of ALAP (LAP from admittance) was determined by linear regression. HF was induced by rapid ventricular pacing at 180 and 220 bpm (beats/min) for a week each, followed by a third week with daily pacing suspensions for increasing durations (1–5 h). Incremental pacing induced progressively severe HF reflected in increases in LAP (5.9 ± 0.4 to 24.5 ± 1.6 mmHg) and plasma atrial (20 ± 3 to 197 ± 36 pmol/l) and B-type natriuretic peptide (3.7 ± 0.7 to 32.7 ± 5.4 pmol/l) (all P& .001) levels. All impedance vectors decreased in proportion to HF severity (all P& .001), with the LVring (left ventricular)-case vector correlating best with LAP (r2=0.63, P& .001). Natriuretic peptides closely paralleled rapid acute changes in LAP during alterations in pacing (P& .001), whereas impedance changes were delayed relative to LAP. ALAP exhibited good agreement with LAP. In summary, impedance measured with an LV lead correlates significantly with changes in LAP, but exhibits a delayed response to acute alterations. Natriuretic peptides respond rapidly to acute LAP changes. Direct LAP, impedance and natriuretic peptide measurements all show promise as early indicators of worsening HF. ALAP provides an estimate of LAP that may be clinically useful.
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.ANNEMERGMED.2013.01.011
Abstract: This study seeks to examine whether the finding of an abnormal estimated glomerular filtration rate (eGFR) in the emergency department (ED) was associated with acute coronary syndrome in the population of patients presenting for investigation of chest pain. We used prospectively collected data on adult patients presenting with suspected acute coronary syndrome to 2 EDs in Australia and New Zealand. Trained research nurses collected clinical data with a customized case report form. Creatinine measurements were taken on presentation, and the glomerular filtration rate ([GFR] milliliters per minute per 1.73 m(2)) was estimated with the chronic kidney disease epidemiologic collaboration equation. The primary endpoint was acute coronary syndrome within 30 days of presentation, as adjudicated by cardiologists using standardized guidelines. Logistic regression analyses examined the relationship between eGFR and acute coronary syndrome. Acute coronary syndrome was diagnosed in 421 (21%) of the 1,968 patients recruited. Compared with patients with an eGFR greater than 90 mL/minute per 1.73 m(2), patients with an eGFR between 60 and 90 mL/minute per 1.73 m(2) and patients with an eGFR less than 60 mL/minute per 1.73 m(2) were 1.64 (95% confidence interval 1.10 to 2.44) and 1.70 (95% confidence interval 1.01 to 2.77) times more likely to receive a diagnosis of acute coronary syndrome after controlling for age, sex, hypertension, dyslipidemia, family history of cardiac disease, diabetes, patient history of cardiac disease, cardiac troponin level, and ECG findings. There is an independent association between eGFR and acute coronary syndrome risk in patients presenting to the ED with chest pain this association is independent of age, traditional cardiac risk factors, medical history, troponin level, and ECG findings. Reduced eGFR should be considered an acute coronary syndrome risk factor, and clinicians should maintain high clinical suspicion for acute coronary syndrome in patients with abnormal renal function results regardless of whether they have known kidney disease, traditional acute coronary syndrome risk factors, or abnormal diagnostic test results. Risk stratification tools should include reduced eGFR as a high-risk feature.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2021
DOI: 10.1161/CIRCHEARTFAILURE.120.008100
Abstract: Iron deficiency (ID) has a prevalence of ≈40% to 50% among patients in heart failure (HF) with reduced ejection fraction and is associated with worse prognosis. Several trials demonstrated that intravenous ferric carboxymaltose leads to early and sustained improvement in patient-reported outcomes and functional capacity in patients with HF with reduced ejection fraction with ID, yet morbidity and mortality data are limited. The objective of the HEART-FID trial (Ferric Carboxymaltose in Heart Failure With Iron Deficiency) is to assess efficacy and safety of ferric carboxymaltose compared with placebo as treatment for symptomatic HF with reduced ejection fraction with ID. HEART-FID is a multicenter, randomized, double-blind, placebo-controlled trial enrolling ≈3014 patients at ≈300 international centers. Eligible patients are aged ≥18 years in stable chronic HF with New York Heart Association functional class II to IV symptoms, ejection fraction ≤40%, ID (ferritin ng/mL or ferritin 100–300 ng/mL with a transferrin saturation %), and documented HF hospitalization or elevated N-terminal pro-brain natriuretic peptide. Consented patients are assigned to ferric carboxymaltose or placebo at baseline, with repeated visits/assessments every 6 months for additional study drug based on hemoglobin and iron indices for the trial duration. The primary end point is a hierarchical composite of death and HF hospitalization at 12 months and change from baseline to 6 months in the 6-minute walk test distance. The HEART-FID trial will inform clinical practice by clarifying the role of long-term treatment with intravenous ferric carboxymaltose, added to usual care, in ambulatory patients with symptomatic HF with reduced ejection fraction with ID. URL: www.clinicaltrials.gov Unique identifier: NCT03037931.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.AMJCARD.2013.05.007
Abstract: The relation between left atrial (LA) mechanics and left ventricular (LV) diastolic function and adverse cardiovascular events are not well established in chronic systolic heart failure (HF). In 108 patients, we performed comprehensive echocardiography with an assessment of LA global longitudinal strain (LAε) by Velocity Vector Imaging. We also performed complete diastolic examinations including mitral inflow, pulmonary vein flow, and tissue Doppler. Death, cardiac transplantation, and HF hospitalization were tracked for 5 years. In our study cohort (age 57 ± 15 years, LV ejection fraction 25 ± 6%), mean global LA negative (εnegative), positive (εpositive), and total ε (εtotal) were -6.8 ± 4.4%, 7.7 ± 5.7%, and 14.5 ± 8.2%, respectively. All LAε indexes correlated with in idual indexes of LV diastolic dysfunction, including mitral flow early (E) to late diastolic velocity ratio (p <0.05 for all), mitral deceleration time (p <0.01 for all), E to early diastolic velocity of the septal mitral annulus (e') ratio (p <0.05 for all), pulmonary vein flow systolic to diastolic velocity ratio (p <0.001 for all), and maximal LA volume index (p <0.01 for all). All LAε indexes increased across diastolic stage (p <0.001 for all). In multivariate logistic regression analysis, LAεnegative and LAεtotal were associated with the presence of LV diastolic dysfunction grade III even after adjustment for E/e' septal and LA volume index. In Cox proportional hazards analysis, lower magnitude LAεnegative predicted long-term adverse clinical events. In conclusion, more impaired LA mechanics are associated with more severe diastolic dysfunction and predict long-term adverse events in patients with chronic systolic HF.
Publisher: Walter de Gruyter GmbH
Date: 2017
Publisher: Wiley
Date: 10-10-2012
DOI: 10.1111/J.1540-8167.2011.02192.X
Abstract: The KCNE family is a group of small transmembrane channel proteins involved in potassium ion (K(+)) conductance. The X-linked KCNE5 gene encodes a regulator of the K(+) current mediated by the potassium channel KCNQ1. Polymorphisms in KCNE5 have been associated with altered cardiac electrophysiological properties in human studies. We investigated associations of the common rs697829 polymorphism from KCNE5 with baseline characteristics, baseline electrocardiographic (ECG) measurements, and patient survival in a cohort of post-acute coronary syndromes (ACS) patients (the Coronary Disease Cohort Study cohort). DNA s les (n = 1,740) were genotyped for rs697829 using a TaqMan assay. Baseline ECG data revealed corrected QT (QTc) interval was associated with rs697829 in male, but not female, patients, being extended in the G genotype group (A 416 ± 1.71 G 431 ± 4.25 ms, P = 0.002). Covariate-adjusted survival was poorest in G genotype patients in Cox proportional hazard modeling of mortality data of males (P(overall) = 0.020). Male patients with G genotype had a hazard ratio of 1.44 (1.11-2.33) for death when compared to the A genotype male patients (P = 0.048) after adjustment for age, baseline log-transformed N-terminal pro-B-type natriuretic peptide (NTproBNP), β-blocker and insulin treatment, QTc interval, history of myocardial infarction, and physical activity score. This study suggests an association between rs697829, a common single nucleotide polymorphism (SNP) from KCNE5, and ECG measurements and survival in postacute ACS patients. Prolonged subclinical QT interval may be a marker of adverse outcome in this group of patients.
Publisher: Portland Press Ltd.
Date: 07-2001
DOI: 10.1042/CS20010028
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2000
Abstract: Abstract —Omapatrilat is a member of the new drug class of vasopeptidase inhibitors that may offer benefit in the treatment of heart failure (HF) through simultaneous inhibition of angiotensin-converting enzyme and neutral endopeptidase. We examined the effects of omapatrilat in a placebo-controlled crossover study using a pacing model of HF. Seven sheep were paced sequentially at 180 bpm (mild HF) and then 225 bpm (severe HF) for 7 days each. Omapatrilat (0.005 mg/kg) or vehicle was administered by intravenous bolus on days 4 to 7 of each paced period. Omapatrilat lowered mean arterial and left atrial pressure and increased cardiac output acutely and chronically in both mild and severe HF ( P .01 for all). Plasma atrial and brain natriuretic peptide and cGMP levels were stable acutely ( P =NS), while brain natriuretic peptide increased after repeated dosing in severe HF ( P .05). Plasma renin activity rose, whereas angiotensin II and aldosterone levels fell after acute and repeated dosing in both states ( P .01 for all). Omapatrilat increased urinary sodium excretion by day 7 in both mild and severe HF ( P .05). Effective renal plasma flow and glomerular filtration rate increased or were stable after omapatrilat in mild and severe HF after both acute and repeated dosing. Omapatrilat exhibited pronounced acute and sustained beneficial hemodynamic and renal effects in both mild and severe heart failure.
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.JCHF.2013.07.003
Abstract: The purpose of this study is to investigate the effects of urocortin-2 as adjunct therapy in acute decompensated heart failure (ADHF). Urocortin-2 produced favorable integrated effects in experimental heart failure but there are no equivalent human data. We describe the first therapeutic study of urocortin-2 infusion in ADHF. Fifty-three patients with ADHF were randomly assigned to 5 ng/kg/min of urocortin-2 or placebo infusion for 4 h as an adjunct therapy. Changes in vital signs, plasma neurohormonal and renal indices during treatment were compared using repeated-measures analysis of covariance. Ten patients in each arm underwent more detailed invasive hemodynamic evaluation. Urocortin-2 produced greater falls in systolic blood pressure compared to placebo (16 ± 5.8 mm Hg, p < 0.001) with nonsignificant increases in heart rate (5.7 ± 3.8 beats/min, p = 0.07) and increased cardiac output (2.1 ± 0.4 l/min vs. -0.1 ± 0.4 l/min, p < 0.001) associated with a 47% reduction in calculated total peripheral resistance (p = 0.015). Falls in pulmonary artery and pulmonary capillary wedge pressures did not differ significantly between groups. Urocortin-2 reduced urine volume and creatinine clearance during infusion but these returned to above baseline level in the 8 h after infusion. Plasma renin activity rose briefly with urocortin-2 coinciding with reductions in blood pressure (p < 0.001). B-type natriuretic peptide levels fell significantly over 24 h with urocortin-2 (p < 0.01) but not with placebo. Urocortin-2 infusion in ADHF markedly augmented cardiac output without significant reflex tachycardia. Renal indices fell transiently concurrent with urocortin-2-induced reductions in blood pressure. Further investigations are required to uncover the full potential of urocortin-2 in treating ADHF.
Publisher: Future Medicine Ltd
Date: 05-2012
DOI: 10.2217/PME.12.10
Abstract: Aims: The endothelin type A receptor, encoded by EDNRA, mediates the effects of endothelin-1 to promote vasoconstriction, vascular cell growth, adhesion, fibrosis and thrombosis. We investigated the association between EDNRA haplotype and cardiovascular outcomes in patients with coronary artery disease. Methods: Coronary disease patients (n = 1007) were genotyped for the His323His (rs5333) variant and one tag SNP from each of the major EDNRA haplotype blocks (rs6537484, rs1568136, rs5335 and rs10003447). EDNRA haplotype associations with clinical history, natriuretic peptides cardiac function and cardiovascular outcomes were tested over a median 3.8 years. Results: Univariate analysis identified a ‘low-risk’ EDNRA haplotype associated with later age of Type 2 diabetes onset (p = 0.004) smaller BMI (p = 0.021), and reduced mortality (log rank p = 0.001). Cox proportional hazards analysis including established cardiovascular risk factors revealed an independent association between haplotype and mortality (p 0.0001). Conclusion: These data highlight the potential importance of the endothelin system, and in particular EDNRA in coronary disease.
Publisher: Oxford University Press (OUP)
Date: 06-11-2008
Abstract: The aim of this study is to describe the relationship between ventricular mechanical dyssynchrony (VMD) and echocardiographic indices of cardiac remodelling. We evaluated 219 ambulatory patients with chronic systolic heart failure [left ventricular ejection fraction (LVEF) 40 ms and/or inter-VMD > 38 ms). In our study cohort, 59% of patients had evidence of dyssynchrony (including 44% with intra-VMD and 38% with inter-VMD, and 20% with both). Inter-VMD correlated with QRS width (r = 0.48, P < 0.0001) better than intra-VMD (r = 0.24, P < 0.001). Higher inter-VMD was associated with less restrictive filling patterns (rank sums P = 0.012) and larger left ventricular end-diastolic dimension (LVEDD, rank sums P = 0.020), but intra-VMD values were similar across diastolic stages and LVEDD tertiles. In chronic systolic heart failure, evidence of mechanical dyssynchrony is prevalent but the underlying cardiac structure and performance may influence the degree of inter-VMD more so than intra-VMD. Our data suggest that the extent of inter-VMD is directly related to the degree of dilatation of the heart but inversely to diastolic dysfunction.
Publisher: MDPI AG
Date: 08-06-2021
DOI: 10.3390/CARDIOGENETICS11020010
Abstract: Background. Each year, approximately 5000 New Zealanders are admitted to hospital with first-time acute coronary syndrome (ACS). The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) is a prospective longitudinal cohort study embedded within the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry in six hospitals. The objective of MENZACS is to examine the relationship between clinical, genomic, and cardiometabolic markers in relation to presentation and outcomes post-ACS. Methods. Patients with first-time ACS are enrolled and study-specific research data is collected alongside the ANZACS-QI registry. The research blood s les are stored for future genetic/biomarker assays. Dietary information is collected with a food frequency questionnaire and information about physical activity, smoking, and stress is also collected via questionnaire. Detailed family history, ancestry, and ethnicity data are recorded on all participants. Results. During the period between 2015 and 2019, there were 2015 patients enrolled. The mean age was 61 years, with 60% of patients aged years and 21% were female. Ethnicity and cardiovascular (CV) risk factor distribution was similar to ANZACS-QI: 13% Māori, 5% Pacific, 5% Indian, and 74% NZ European. In terms of CV risk factors, 56% were ex-/current smokers, 42% had hypertension, and 19% had diabetes. ACS subtype was ST elevation myocardial infarction (STEMI) in 41%, non-ST elevation myocardial infarction (NSTEM) in 54%, and unstable angina in 5%. Ninety-nine percent of MENZACS participants underwent coronary angiography and 90% had revascularization there were high rates of prescription of secondary prevention medications upon discharge from hospital. Conclusion. MENZACS represents a cohort with optimal contemporary management and will be a significant epidemiological bioresource for the study of environmental and genetic factors contributing to ACS in New Zealand’s multi-ethnic environment. The study will utilise clinical, nutritional, lifestyle, genomic, and biomarker analyses to explore factors influencing the progression of coronary disease and develop risk prediction models for health outcomes.
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.CARDFAIL.2008.01.006
Abstract: The influence of myocardial function on plasma levels of cystatin C (CysC), a sensitive marker of renal function, in chronic systolic heart failure (HF) has not been well established. We prospectively identified 139 subjects with stable, chronic HF (left ventricular ejection fraction < or = 35%) and measured plasma levels of CysC. We prospectively tracked patients' long-term adverse clinical outcomes (death, cardiac transplantation, and HF hospitalizations). Plasma levels of CysC were elevated in 41% of patients with preserved renal function and directly correlated with N-terminal prohormone brain natriuretic peptide (r = 0.57, P < .0001). There was a significant association between CysC and mitral E/septal E' ratio (r = 0.34, P < .001), right ventricular systolic dysfunction severity (r = 0.30, P < .001), and mitral regurgitation severity (r = 0.31, P < .001), but not left ventricular ejection fraction. At the cutoff of 1.23 mg/dL, CysC remains a significant independent risk factor for adverse clinical outcomes (hazard ratio 1.88, 95% confidence interval 1.15-3.09, P = .012) after adjusting for estimated glomerular filtration rate, left ventricular ejection fraction, and E/septal E'. CysC is associated with more advanced left ventricular diastolic dysfunction and right ventricular systolic dysfunction and remains an independent predictor of long-term prognosis in chronic systolic HF after adjusting for myocardial factors.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-03-2010
DOI: 10.1161/CIRCULATIONAHA.108.800490
Abstract: Background— Previous studies suggest that management of ambulatory hemodynamics may improve outcomes in chronic heart failure. We conducted a prospective, observational, first-in-human study of a physician-directed patient self-management system targeting left atrial pressure. Methods and Results— Forty patients with reduced or preserved left ventricular ejection fraction and a history of New York Heart Association class III or IV heart failure and acute decompensation were implanted with an investigational left atrial pressure monitor, and readings were acquired twice daily. For the first 3 months, patients and clinicians were blinded as to these readings, and treatment continued per usual clinical assessment. Thereafter, left atrial pressure and in idualized therapy instructions guided by these pressures were disclosed to the patient. Event-free survival was determined over a median follow-up of 25 months (range 3 to 38 months). Survival without decompensation was 61% at 3 years, and events tended to be less frequent after the first 3 months (hazard ratio 0.16 [95% confidence interval 0.04 to 0.68], P =0.012). Mean daily left atrial pressure fell from 17.6 mm Hg (95% confidence interval 15.8 to 19.4 mm Hg) in the first 3 months to 14.8 mm Hg (95% confidence interval 13.0 to 16.6 mm Hg P =0.003) during pressure-guided therapy. The frequency of elevated readings ( mm Hg) was reduced by 67% ( P .001). There were improvements in New York Heart Association class (−0.7±0.8, P .001) and left ventricular ejection fraction (7±10%, P .001). Doses of angiotensin-converting enzyme/angiotensin-receptor blockers and β-blockers were uptitrated by 37% ( P .001) and 40% ( P .001), respectively, whereas doses of loop diuretics fell by 27% ( P =0.15). Conclusions— Physician-directed patient self-management of left atrial pressure has the potential to improve hemodynamics, symptoms, and outcomes in advanced heart failure. Clinical Trial Registration Information— URL: www.clinicaltrials.gov. Unique identifier: NCT00547729.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.CLINBIOCHEM.2019.05.010
Abstract: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging marker of cardiovascular disease burden. Appropriate assessment of assay performance and reference interval are required to enable interpretation of results to facilitate its clinical application. suPAR was measured using the suPARnostic® ELISA in 155 healthy volunteers. Assay performance was assessed for anticoagulant effect, recovery, interference, linearity and cross-reactivity. The identity of immunoreactive suPAR was confirmed by size-exclusion HPLC. To establish anatomical sites of release and uptake, we measured suPAR in regional s les from subjects undergoing cardiac catheterization. The median concentration of suPAR was 2.1 ng/mL (IQR:1.7-2.3) in health. In comparison with EDTA, suPAR measurements were affected by lithium heparin (>10% change) and increased with serum usage. suPAR reactivity also increased in the presence of haemolysis (10 g/L), but was suppressed with urokinase and lipids (4 g/L). In multiple regression analyses, suPAR associated independently with body weight, NT-proBNP and MR-proADM (P = .03) for healthy in iduals. Regional plasma s ling showed lower suPAR concentrations in the coronary sinus and renal vein compared with concentrations in femoral arterial s les. Immunoreactive circulating suPAR species had M The suPARnostic® assay performs acceptably for a clinical assay but is limited in the presence of high levels of hemolysis, lipids and urokinase. We provide the first evidence for the heart and kidneys as organs of suPAR clearance in humans. Additional investigations are warranted to determine whether there is a need to compare the marker performance of differing circulating forms of suPAR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-02-2006
DOI: 10.1161/CIRCULATIONAHA.105.567727
Abstract: Background— The effect of β-blockade on the cardiac natriuretic peptides is poorly understood but could contribute to their beneficial treatment effect and may be relevant to clinical use of plasma brain natriuretic peptide (BNP)/N-terminal pro brain natriuretic peptide (NTproBNP) measurements in risk stratification and in titration of anti–heart failure therapy. Methods and Results— Sixteen men with mild, stable heart failure (NYHA class II to III left ventricular ejection fraction %) underwent serial blood s ling for plasma natriuretic peptide levels and received infusions of atrial natriuretic peptide (ANP) and BNP before and 6 weeks after the introduction and uptitration of metoprolol or 6 weeks unchanged therapy in a randomized, parallel-group design. Plasma natriuretic peptides (BNP, NTproBNP, ANP, and NTproANP) were increased by metoprolol ( P .01 for all). The natriuretic responses to ANP and BNP infusions were sustained with the introduction of metoprolol despite reduced renal perfusion pressure. The levels of the noninfused natriuretic peptide were increased by both ANP and BNP infusions, and this effect was enhanced by metoprolol. The early plasma half-life (t½α) of BNP was prolonged by metoprolol (5.6±0.45 to 11±1.3 versus 5.7±0.8 to 6.6±1.3 minutes in control subjects P =0.019). Conclusions— Plasma cardiac natriuretic peptide levels increase significantly with the introduction of metoprolol in heart failure as a result of effects on secretion and clearance. Natriuretic responses to NP infusions are sustained with β-blockade despite reduced renal perfusion pressure. Clinicians should be aware that the introduction of metoprolol causes a rise in plasma BNP/NTproBNP that is unrelated to deterioration in clinical status and must be considered when measurements are undertaken for risk stratification or titration of treatment.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.ANNEMERGMED.2016.01.001
Abstract: A 2-hour accelerated diagnostic pathway based on the Thrombolysis in Myocardial Infarction score, ECG, and troponin measures (ADAPT-ADP) increased early discharge of patients with suspected acute myocardial infarction presenting to the emergency department compared with standard care (from 11% to 19.3%). Observational studies suggest that an accelerated diagnostic pathway using the Emergency Department Assessment of Chest Pain Score (EDACS-ADP) may further increase this proportion. This trial tests for the existence and size of any beneficial effect of using the EDACS-ADP in routine clinical care. This was a pragmatic randomized controlled trial of adults with suspected acute myocardial infarction, comparing the ADAPT-ADP and the EDACS-ADP. The primary outcome was the proportion of patients discharged to outpatient care within 6 hours of attendance, without subsequent major adverse cardiac event within 30 days. Five hundred fifty-eight patients were recruited, 279 in each arm. Sixty-six patients (11.8%) had a major adverse cardiac event within 30 days (ADAPT-ADP 29 EDACS-ADP 37) 11.1% more patients (95% confidence interval 2.8% to 19.4%) were identified as low risk in EDACS-ADP (41.6%) than in ADAPT-ADP (30.5%). No low-risk patients had a major adverse cardiac event within 30 days (0.0% [0.0% to 1.9%]). There was no difference in the primary outcome of proportion discharged within 6 hours (EDACS-ADP 32.3% ADAPT-ADP 34.4% difference -2.1% [-10.3% to 6.0%], P=.65). There was no difference in the proportion of patients discharged early despite more patients being classified as low risk by the EDACS-ADP than the ADAPT-ADP. Both accelerated diagnostic pathways are effective strategies for chest pain assessment and resulted in an increased rate of early discharges compared with previously reported rates.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.JACC.2007.02.053
Abstract: The purpose of this study was to explore the relationship between myeloperoxidase (MPO) and cardiac structure, performance, and prognosis. Myeloperoxidase is an inflammatory marker that is elevated in patients with heart failure (HF) and cardiac dysfunction, with mechanistic links to plaque vulnerability and left ventricular (LV) remodeling. We evaluated plasma MPO levels (CardioMPO, PrognostiX, Inc., Cleveland, Ohio) in 140 patients with chronic systolic HF (LV ejection fraction or =3+, and tricuspid regurgitation area > or =1.8 cm2). Plasma MPO levels were predictive of long-term clinical outcomes (risk ratio [95% confidence interval] = 3.35 [1.52 to 8.86]), even after adjustment for age, LV ejection fraction, plasma B-type natriuretic peptide (BNP), creatinine clearance, or diastolic stage. In receiver-operator characteristic curve analyses, addition of MPO to BNP testing augmented the predictive accuracy of future adverse clinical events (area under the curve 0.66 for BNP only [chi-square test = 12.9, p = 0.0003], and 0.70 for BNP plus MPO [chi-square test = 15.87, p = 0.0004]). In chronic systolic HF, elevated plasma MPO levels are associated with an increased likelihood of more advanced HF. Moreover, elevated plasma MPO levels within a HF subject seem to be predictive of increased adverse clinical outcomes.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.IJCARD.2015.04.145
Abstract: High sensitivity assays for cardiac troponin (cTn) have reduced time to diagnosis of myocardial infarction (MI) but at costs to diagnostic specificity. We hypothesised that measurement of an upstream open reading frame peptide (uORF) from the human cTnT gene (TnTuORF) might improve cTn specificity in MI patients. A novel immunoassay to TnTuORF was developed and used to document circulating concentrations in normal healthy volunteers (n=150) assess potential trans-organ secretion in patients undergoing cardiac catheterisation (n=16) characterise temporal TnTuORF concentrations during ST-elevation MI (STEMI, n=4) and assess the potential of TnTuORF to assist the diagnosis and prognosis of MI in patients presenting with chest pain suspicious of ACS (n=502). Plasma immunoreactive TnTuORF was characterised on reverse phase and size exclusion HPLC. In normal volunteers and suspected acute coronary syndrome (ACS) patients, TnTuORF had no relationship with TnI or TnT. Trans-organ venous s ling suggested TnTuORF secretion is not exclusively cardiac based. In STEMI patients, TnTuORF concentrations decreased for up to 12h after onset. In suspected ACS patients, TnTuORF could not diagnose MI (ROC AUC=0.446, P=0.117) but could diagnose cardiac disorders other than MI (AUC=0.79, P<0.001). This is the first evidence for a circulating uORF peptide. TnTuORF does not appear to aid the diagnosis of MI but further studies to assess its potential in cardiovascular disease are required.
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.JACC.2004.06.079
Abstract: This study assessed apparently normal mitral valves from patients with congestive heart failure (CHF) using biochemical and echocardiographic measures of extracellular matrix (ECM) and anatomy. Mitral regurgitation (MR) is frequently found in patients with CHF. This MR is considered purely functional, yet animal studies suggest that altered left ventricular (LV) function leads to increased cellularity and fibrosis of the mitral valve. Therefore, we hypothesized that patients with CHF might have partly organic MR, via dysfunctional valvular remodeling. Mitral valves from transplant recipient hearts of patients with CHF (23 dilated, 14 ischemic) were analyzed for deoxyribonucleic acid (DNA), collagen, glycosaminoglycan (GAG), and water concentrations and compared with autopsy controls. Cardiac dimensions and functional parameters (measured from recent echocardiograms) were compared with biochemical parameters using a repeated measures generalized linear model. The mitral valves in CHF had up to 78% more DNA (p <0.03), 59% more GAGs (p <0.02), and 15% more collagen (p <0.007), but 7% less water (p <0.05) than normal. The absence of anterior leaflet redundancy was associated with these deranged biochemical measures (p <0.03). Associations were found between leaflet thickness and DNA concentration (+, p=0.003), annular diameter and chordal collagen (+, p=0.03), and water concentration and both left atrial diameter (-, p=0.008) and LV collagen concentration (-, p=0.04). Mitral valves in CHF are biochemically different from normal, with ECM changes that are influenced by the altered cardiac dimensions. This remodeling suggests that MR in patients with CHF may not be purely functional, and that these valves are not "normal."
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.AHJ.2014.11.015
Abstract: There is a genetic contribution to the risk of ventricular arrhythmias in survivors of acute coronary syndromes (ACS). We wished to explore the role of 33 candidate single nucleotide polymorphisms (SNPs) in prolonged repolarization and sudden death in patients surviving ACS. A total of 2,139 patients (1680 white ethnicity) surviving an admission for ACS were enrolled in the prospective Coronary Disease Cohort Study. Extensive clinical, echocardiographic, and neurohormonal data were collected for 12 months, and clinical events were recorded for a median of 5 years. Each SNP was assessed for association with sudden cardiac death (SCD)/cardiac arrest (CA) and prolonged repolarization at 3 time-points: index admission, 1 month, and 12 months postdischarge. One hundred six SCD/CA events occurred during follow-up (6.3%). Three SNPs from 3 genes (rs17779747 [KCNJ2], rs876188 [C14orf64], rs3864180 [GPC5]) were significantly associated with SCD/CA in multivariable models (after correction for multiple testing) the minor allele of rs17779747 with a decreased risk (hazard ratio [HR] 0.68 per copy of the minor allele, 95% CI 0.50-0.92, P = .012), and rs876188 and rs386418 with an increased risk (HR 1.52 [95% CI 1.10-2.09, P = .011] and HR 1.34 [95% CI 1.04-1.82, P = .023], respectively). At 12 months postdischarge, rs10494366 and rs12143842 (NOS1AP) were significant predictors of prolonged repolarization (HR 1.32 [95% CI 1.04-1.67, P = .022] and HR 1.30 [95% CI 1.01-1.66, P = .038], respectively), but not at earlier time-points. Three SNPs were associated with SCD/CA. Repolarization time was associated with variation in the NOS1AP gene. This study demonstrates a possible role for SNPs in risk stratification for arrhythmic events after ACS.
Publisher: Elsevier BV
Date: 12-2010
Publisher: Oxford University Press (OUP)
Date: 07-2003
DOI: 10.1373/49.7.1212
Publisher: BMJ
Date: 10-12-2019
DOI: 10.1136/HEARTJNL-2019-315809
Abstract: Following acute coronary syndrome (ACS), patients are managed long-term in the community, yet few tools are available to guide patient-clinician communication about risk management in that setting. We developed a score for predicting cardiovascular disease (CVD) risk among patients managed in the community after ACS. Adults aged 30–79 years with prior ACS were identified from a New Zealand primary care CVD risk management database (PREDICT) with linkage to national mortality, hospitalisation, pharmaceutical dispensing and regional laboratory data. A Cox model incorporating clinically relevant factors was developed to estimate the time to a subsequent fatal or non-fatal CVD event and transformed into a 5-year risk score. External validation was performed in patients (Coronary Disease Cohort Study) assessed 4 months post-ACS. The PREDICT-ACS cohort included 13 703 patients with prior hospitalisation for ACS (median 1.9 years prior), 69% men, 58% European, median age 63 years, who experienced 3142 CVD events in the subsequent 5 years. Median estimated 5 year CVD risk was 24% (IQR 17%–35%). The validation cohort consisted of 2014 patients, 72% men, 92% European, median age 67 years, with 712 CVD events in the subsequent 5 years. Median estimated 5-year risk was 33% (IQR 24%–51%). The risk score was well calibrated in the derivation and validation cohorts, and Harrell’s c-statistic was 0.69 and 0.68, respectively. The PREDICT-ACS risk score uses data routinely available in community care to predict the risk of recurrent clinical events. It was derived and validated in real-world contemporary populations and can inform management decisions with patients living in the community after experiencing an ACS.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.AMJCARD.2005.03.055
Abstract: The prognostic values of tissue Doppler imaging and color M-mode diastolic indexes were studied in 225 patients who had symptomatic systolic heart failure in the ADEPT study. The primary end point of death, transplantation, or hospitalization due to heart failure occurred in 65 patients and was independently predicted by shorter deceleration time, lower ratio of pulmonary vein systolic to diastolic velocity, and increasing levels of the ratios of early transmitral velocity to early annular velocity or velocity of propagation. For the ratio of early transmitral velocity to early annular velocity, this prediction was additive to deceleration time. Newer diastolic indexes provide an independent prediction of clinical outcomes.
Publisher: Oxford University Press (OUP)
Date: 2017
DOI: 10.1373/CLINCHEM.2016.257816
Abstract: C-type natriuretic peptide (CNP) is a paracrine growth factor expressed in the vascular endothelium. Although upregulated in atheromatous arteries, the predictive value of plasma CNP products for outcome in coronary disease is unknown. This study aimed to compare the prognostic value of plasma CNP products with those of other natriuretic peptides in in iduals with coronary artery disease, and investigate their associations with cardiac and renal function. Plasma concentrations of CNP and amino-terminal proCNP (NT-proCNP) were measured at baseline in 2129 in iduals after an index acute coronary syndrome admission and related to cardiac and renal function, other natriuretic peptides [atrial NP (ANP) and B-type NP (BNP)] and prognosis (primary end point, mortality secondary end point, cardiac readmission). Median follow-up was 4 years. At baseline, and in contrast to CNP, ANP, and BNP, plasma NT-proCNP was higher in males and weakly related to cardiac function but strongly correlated to plasma creatinine. All NPs were univariately associated with mortality. Res ling at 4 and 12 months in survivors showed stable concentrations of NT-proCNP whereas all other peptides declined. When studied by diagnosis (myocardial infarction, unstable angina) at index admission using a multivariate model, NT-proBNP predicted mortality and readmission in myocardial infarction. In unstable angina, only NT-proCNP predicted both mortality and cardiac readmission. In contrast to the close association of NT-proBNP with cardiac function, and predictive value for outcome after myocardial infarction, plasma NT-proCNP is highly correlated with renal function and is an independent predictor of mortality and cardiac readmission in in iduals with unstable angina.
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.ATHORACSUR.2005.08.055
Abstract: Because mitral valve dysfunction in adults with Marfan syndrome is poorly characterized, this study compares mitral valve pathophysiology and morphology with that of myxomatous mitral disease, documents types of mitral valve operations, and assesses long-term survival and durability of mitral valve surgery in Marfan patients. From May 1975 to June 2000, 27 adults with Marfan syndrome underwent mitral valve surgery. Their valve pathophysiology and morphology was compared with that of 119 patients with myxomatous mitral disease undergoing surgery from September 1995 to March 1999. Survival and repair durability were assessed at follow-up. Compared with myxomatous disease patients, Marfan patients had less posterior leaflet prolapse (44% versus 70%, p = 0.01), more bileaflet (44% versus 28%, p = 0.09) and anterior leaflet prolapse (11% versus 3%, p = 0.07), and presented earlier for surgery (age 41 +/- 12 years versus 57 +/- 13, p < 0.0001). Marfan patients had longer and thinner leaflets. Mitral valve repair was performed less frequently in Marfan (16 of 27, 59%) than myxomatous disease patients (112 of 119, 94%). There were no hospital deaths at 10 years, survival was 80% and freedom from reoperation 96%, with only 1 reoperation among the 16 repairs. Mitral valve pathophysiology and morphology differ between Marfan and myxomatous mitral valve diseases. Valve repair in Marfan patients is durable and gives acceptable long-term results, even in adults who present with advanced mitral valve pathology. With increasing use of the modified David reimplantation operation and sparing of the aortic valve, mitral valve repair is a greater imperative, particularly since we have not had to reoperate on any Marfan patients with reimplantations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-01-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2011
DOI: 10.1161/CIRCGENETICS.111.960336
Abstract: Genome-wide association studies have identified gene variants associated with coronary artery disease risk however, whether they affect disease progression is largely unknown. This study investigated associations between polymorphisms at 1p13.3 (rs599839), 1q41 (rs17465637), and 3q22.3 (rs9818870) and cardiovascular outcomes in healthy volunteers and in patients with established heart disease. Canterbury Healthy Volunteer study (HV) (n=1649), Coronary Disease Cohort Study (CDCS) (n=1797), and Post-Myocardial Infarction study (PMI) (n=906) participants (New Zealand), were genotyped for rs599839, rs9818870, and rs17465637. Associations between genotype and anthropometric characteristics, neurohormonal analysis, echocardiography, and clinical outcomes over medium-long-term follow-up (median HV, 5.9 years CDCS, 3.7 years PMI, 11.3 years) were tested. At 1p13.3, HV and CDCS participants carrying 1 or more rs599839 G allele had a lower prevalence of dyslipidemia ( P ≤0.005) or lower levels of low-density lipoprotein ( P =0.031) and total ( P =0.004) cholesterol and/or less history of myocardial infarction ( P ≤0.04) compared with AA participants. Moreover, CDCS and PMI AG/GG participants had better cardiac function as indicated by echocardiography ( P ≤0.026), and fewer CDCS AG/GG participants were readmitted for a non-ST-segment elevation MI ( P =0.012) during follow-up. The polymorphism at 1q41 (rs17465637) was associated with better cardiovascular outcomes in the HV ( P =0.028) and PMI ( P =0.008) cohorts, and 3q22.3 (rs9818870) was a predictor of death/admission in the HV cohort ( P =0.045). These data suggest that coronary artery disease genomic risk variants at 1p13.3 and 1q41 are associated with subsequent clinical outcome in heart patients and confirm rs9818870 at 3q22.3 as a predictor of cardiovascular risk in in iduals free of overt heart disease.
Publisher: Elsevier BV
Date: 05-2004
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.CARDFAIL.2014.02.002
Abstract: Inflammation is associated with progression of chronic heart failure (HF). Few data exist on high-sensitivity C-reactive protein (hsCRP) levels and their importance in acute HF. In this biomarker substudy of the ASCEND-HF trial, we measured hsCRP levels at admission (n = 794), 48-72 hours (n = 677), and 30 days (n = 581) and evaluated their association with outcomes. Levels of hsCRP were considerably elevated at admission (median 12.6 mg/L, interquartile range [IQR] 5.23-30.5) and 48-72 hours (median 11.0 mg/L, IQR 4.87-29.9) and declined only at 30 days (median 4.7 mg/L, IQR 1.83-13.1). Admission hsCRP was not associated with dyspnea improvement at 6 hours (74.1%) and 24 hours (86.2%), in-hospital death or worsening HF (n = 37 4.7%), 30-day mortality or HF readmission (death: n = 25 [3.2%] combined death and HF readmission: n = 95 [12.0%]), or 180-day mortality (n = 96 12.1%). Hospital stay (median 5 days, IQR 3-7) was longer among patients with higher admission hsCRP levels (0.57 days per log2-hsCRP in adjusted models 95% confidence interval [CI] 0.33-0.81 P 10% increase over baseline value, had higher 180-day mortality risk compared with those with unchanged or decreased 30-day hsCRP (HR 2.29, 95% CI 1.16-4.52 P = .017). Levels of hsCRP are elevated among patients with acute HF. Increasing levels at 30 days after discharge are associated with higher 180-day mortality.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.IJCARD.2014.07.068
Abstract: The prognostic utility of circulating plasma microRNA in patients with acute coronary syndromes (ACS) has been proposed but not yet demonstrated. We set out to investigate circulating microRNA levels in patients incurring recent ACS and examined associations with neurohormones, cardiac structure and function, and survival over 5 years of follow-up. An initial screen of 375 microRNAs was performed in 35 ACS patients and 16 healthy controls. Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR-103 and miR-208a) were validated in a further cohort of 200 patients at baseline (~ 30 days post-ACS) and at 4 and 12 months post-ACS, and compared with 100 controls. In the validation cohort, significantly higher levels in patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold and 2.3-fold, respectively, adjusted p<0.05). Lower levels of miR-103 were not replicated and miR-208a was undetectable. From baseline to 4 months post-admission, miR-323-3p and miR-652 remained elevated in patients compared to controls (adjusted p<0.01), with no further change in levels between 4 and 12 months whereas miR-27b fell to control levels by 4 months. Baseline levels of miR-652 in the lowest tertile were significantly associated with readmission for heart failure (log-rank p<0.001). In combination with NT-proBNP and LVEF, miR-652 significantly improved risk stratification (p<0.001). Our study identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was markedly elevated in patients for at least a year post-ACS and may be a stable biomarker for ACS.
Publisher: American College of Physicians
Date: 18-04-2017
DOI: 10.7326/M16-2562
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 02-2013
Publisher: JMIR Publications Inc.
Date: 11-01-2023
DOI: 10.2196/37011
Abstract: Heart disease and stroke are major and often unheralded causes of serious morbidity and premature death in middle age. Early detection of those most at risk is an urgent unmet need for instituting preventative measures. In an earlier community study (Canterbury Health, Ageing and Life Course [CHALICE]) of healthy people aged 50 years, contrary to previous reports, low levels of the heart hormone B-type natriuretic peptide (BNP) were associated with reduced measures of heart function and higher markers of vascular risk. A specific gene variant (rs198358) was found to be an independent contributor to higher BNP levels. A closely related vascular hormone (C-type natriuretic peptide [CNP]) showed opposite associations—higher levels were correlated with higher vascular risk and reduced cardiac function. To determine whether these novel findings predict serious heart or vascular disease in later life, this proposal re-examines the same CHALICE participants 15 years later. The primary objective is to determine the predictive value of (1) low plasma concentrations of the circulating cardiac hormones (atrial natriuretic peptide [ANP] and BNP) and (2) high levels of the vascular hormone CNP at age 50 years in detecting impaired cardiac and vascular function 15 years later. Secondary objectives are to determine specific associations of in idual analytes (ANP, BNP, CNP, cyclic guanosine monophosphate [cGMP]) with echo-derived changes in cardiac performance at ages 50 years and 65 years. All of the 348 participants (205/348, 58.9% female 53/348, 15.2% Māori or Pacifica ethnicity) participating in the original CHALICE study—free of history of heart or renal disease at age 50 years and who consented to further study—will be contacted, recruited, and restudied as previously described. Data will include intervening health history, physical examination, heart function (speckle-tracking echocardiography), vascular status (carotid intimal thickness), and genetic status (genome-wide genotyping). Laboratory measures will include fasting blood s ling and routine biochemistry, ANP, BNP, CNP, their downstream effector (cGMP), and their bio-inactive products. Humoral metabolic-cardiovascular risk factors will be measured after an overnight fast. Primary outcomes will be analyzed using multiple linear regression. The study will commence in 2022 and be completed in 2024. Proving our hypothesis—that low BNP and high CNP at any age in healthy people predict premature aging of heart and blood vessels, respectively—opens the way to early detection and improved outcomes for those most at risk. Confirmation of our hypotheses would improve current methods of screening and, in appropriate cases, enable interventions aimed at increasing natriuretic hormones and reducing risk of serious cardiovascular complications using drugs already available. Such advances in detection, and from interventional corrections, have the potential to not only improve health in the community but also reduce the high costs inevitably associated with heart failure. PRR1-10.2196/37011
Publisher: Informa UK Limited
Date: 03-2013
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.CARDFAIL.2013.01.007
Abstract: Heart failure (HF) with preserved ejection fraction (EF) accounts for a substantial proportion of cases of HF, and to date no treatments have clearly improved outcome. There are also little data comparing HF cohorts of differing ethnicity within the Asia-Pacific region. The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study are parallel prospective studies using identical protocols to enroll patients with HF across 6 centers in Singapore and 4 in New Zealand. The objectives are to determine the relative prevalence, characteristics, and outcomes of patients with HF and preserved EF (EF ≥50%) compared with those with HF and reduced EF, and to determine initial data on ethnic differences within and between New Zealand and Singapore. Case subjects (n = 2,500) are patients hospitalized with a primary diagnosis of HF or attending outpatient clinics for management of HF within 6 months of HF decompensation. Control subjects are age- and gender-matched community-based adults without HF from Singapore (n = 1,250) and New Zealand (n = 1,073). All participants undergo detailed clinical assessment, echocardiography, and blood biomarker measurements at baseline, 6 weeks, and 6 months, and are followed over 2 years for death or hospitalization. Substudies include vascular assessment, cardiopulmonary exercise testing, retinal imaging, and cardiac magnetic resonance imaging. The SHOP and PEOPLE studies are the first prospective multicenter studies defining the epidemiology and interethnic differences among patients with HF in the Asia-Oceanic region, and will provide unique insights into the pathophysiology and outcomes for these patients.
Publisher: Elsevier BV
Date: 02-2015
Abstract: Cardiovascular disease (CVD) is the leading cause of mortality in New Zealand with a disproportionate burden of disease in the Māori population. The Hauora Manawa Project investigated the prevalence of cardiovascular risk factors and CVD in randomly selected Māori and non-Māori participants. This paper reports the prevalence of structural changes in the heart. A total of 252 rural Māori, 243 urban Māori and 256 urban non-Māori underwent echocardiography to assess cardiac structure and function. Multivariable logistic regression was used to determine variables associated with heart size. Left ventricular (LV) mass measurements were largest in the rural Māori cohort (183.5,sd 61.4), intermediate in the urban Māori cohort (169.7,sd 57.1) and smallest in the non-Māori cohort (152.6,sd 46.7 p<0.001). Similar patterns were observed for other measurements and indexation had no impact. One-third (32.3%) met the gender-based ASE criteria for LV hypertrophy (LVH) with higher prevalence in both Maori cohorts (highest in the rural cohort). There were three significant predictors of LVH: rural Māori (p=0.0001) age (p<0.0001) and gender (p=0.0048). Structural and functional heart abnormalities are more prevalent in Māori compared to non-Māori, and especially rural Māori. Early identification should lead to better management, ultimately improving life expectancy and quality of life.
Publisher: Elsevier BV
Date: 06-2011
Publisher: Elsevier BV
Date: 2015
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.CARDFAIL.2015.04.012
Abstract: Daily measurements of left atrial pressure (LAP) may be useful for guiding adjustments in medical therapy that prevent clinical decompensation in patients with severe heart failure (HF). LAPTOP-HF is a prospective, multicenter, randomized, controlled clinical trial in ambulatory patients with advanced heart failure in which the safety and clinical effectiveness of a physician-directed patient self-management therapeutic strategy based on LAP measured twice daily by means of an implantable sensor will be compared with a control group receiving optimal medical therapy. The trial will enroll up to 730 patients with New York Heart Association functional class III symptoms and either a hospitalization for HF during the previous 12 months or an elevated B-type natriuretic peptide level, regardless of ejection fraction, at up to 75 investigational centers. Randomization to the treatment group or control group will be at a 1:1 ratio in 3 strata based on the ejection fraction (EF > or ≤35%) and the presence of a de novo CRT device indication. LAPTOP-HF will provide essential information about the role of implantable LAP monitoring in conjunction with a new HF treatment paradigm across the spectrum of HF patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-01-2018
DOI: 10.1161/CIRCULATIONAHA.117.031984
Abstract: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation There were 11 529 participants in the preimplementation phase (range, 284–3465) and 19 803 in the postimplementation phase (range, 395–5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%–37.7%) to 18.4% (6.8%–43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3–2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4–3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44% P =0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. URL: www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.JCHF.2015.07.015
Abstract: The study sought to investigate the association between soluble growth stimulation expressed gene 2 (sST2) level and adverse outcomes in acute heart failure (HF). Several studies have demonstrated the prognostic utility of sST2 levels in HF. sST2 levels were measured in sequential baseline and follow-up (48 to 72 h and 30 days) plasma s les from 858 acute HF subjects enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial biomarker substudy and were related to in-hospital and post-discharge clinical outcomes. Higher sST2 levels were associated with increased death risk at 180 days (baseline hazard ratio [HR]: 2.21 follow-up HR: 2.64 both p 60 ng/ml) sST2 levels at follow-up had higher 180-day death rates than those with lower follow-up sST2 levels (adjusted HR: 2.91, p = 0.004). Neither baseline nor follow-up sST2 levels were associated with dyspnea improvement. Changes in sST2 from baseline were less in the nesiritide versus placebo group at follow-up, but were similar at 30 days. Elevated levels of sST2 were associated with an increased risk of adverse clinical events in acute HF, but prognostic value of baseline sST2 diminished after adjusting for clinical covariates and aminoterminal pro-B-type natriuretic peptide. In those with elevated baseline sST2 levels, persistently elevated sST2 levels at follow-up were associated with increased mortality risk. In addition, nesiritide did not demonstrate an incremental impact on sST2 levels over standard therapy.
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1111/J.1753-6405.2011.00777.X
Abstract: To document levels of cardiovascular disease (CVD), diagnosed and undiagnosed risk factors and clinical management of CVD risk in rural Māori. Participants (aged 20-64 years), of Māori descent and self-report, were randomly s led to be representative of age and gender profiles of the community. Screening clinics included health questionnaires, fasting blood s les, blood pressure and anthropometric measures. Data were obtained from participants' primary care physicians regarding prior diagnoses and current clinical management. New Zealand Cardiovascular Guidelines were used to identify new diagnoses at screening and Bestpractice electronic-decision support software used to estimate 5-year CVD risk. Mean age of participants (n=252) was 45.7 ± 0.7, 8% reported a history of cardiac disease, 43% were current smokers, 22% had a healthy BMI, 30% were overweight and 48% obese. Hypertension was previously diagnosed in 25% an additional 22% were hypertensive at screening. Dyslipidaemia was previously diagnosed in 14% and an additional 43% were dyslipidaemic at screening. Type-2 diabetes was previously diagnosed in 11%. Glycaemic control was achieved in only 21% of those with type-2 diabetes. Blood pressure and cholesterol were above recommended targets in more than half of those with diagnosed CVD risk factors. High levels of diagnosed and undiagnosed CVD risk factors, especially hypertension, dyslipidaemia and diabetes were identified in this rural Māori community. There is a need for opportunistic screening and intensified management of CVD risk factors in this indigenous population group.
Publisher: Springer Science and Business Media LLC
Date: 14-10-2010
Publisher: Wiley
Date: 09-01-2020
DOI: 10.1002/EJHF.1701
Abstract: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT) and soluble suppression of tumorigenesis-2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. In idual data from 5301 patients with chronic HF and NT-proBNP, hs-TnT, and sST2 data were evaluated. Patients were stratified according to age: <60 years (n = 1332, 25%), 60-69 years (n = 1628, 31%), 70-79 years (n = 1662, 31%), and ≥ 80 years (n = 679, 13%). Patients (median age 66 years, 75% men, median left ventricular ejection fraction 28%, 64% with ischaemic HF) had median NT-proBNP 1564 ng/L, hs-TnT 21 ng/L, and sST2 29 ng/mL. Age independently predicted NT-proBNP and hs-TnT, but not sST2. The best NT-proBNP and hs-TnT cut-offs for 1-year and 5-year all-cause and cardiovascular mortality and 1- to 12-month HF hospitalization increased with age, while the best sST2 cut-offs did not. When stratifying patients according to age- and outcome-specific cut-offs, this stratification yielded independent prognostic significance over NT-proBNP levels only, or the composite of NT-proBNP and hs-TnT, and improved risk prediction for most endpoints. Finally, absolute NT-proBNP, hs-TnT, and sST2 levels predicted outcomes independent of age, sex, left ventricular ejection fraction category, ethnic group, and other variables. Soluble ST2 is less influenced by age than NT-proBNP or hs-TnT all these biomarkers predict outcome regardless of age. The use of age- and outcome-specific cut-offs of NT-proBNP, hs-TnT and sST2 allows more accurate risk stratification than NT-proBNP alone or the combination of NT-proBNP and hs-TnT.
Publisher: Wiley
Date: 29-08-2019
DOI: 10.1002/ART.41007
Abstract: To determine whether gout and serum urate (SU) levels are associated with increased risk of death, time to first readmission for any cardiovascular event, or incident heart failure in in iduals with cardiovascular disease. In iduals presenting with an acute coronary syndrome (ACS) were enrolled in the Coronary Disease Cohort Study. Clinical data were collected from the medical records at the index hospital admission, and clinical, echocardiographic, and biochemical data were collected postdischarge. Gout was defined by self-report, use of urate-lowering therapy, or use of colchicine with evidence of gout on review of the medical record. The primary end points were all-cause mortality, time to readmission for a cardiac ischemic event, and time to readmission for heart failure. Data from 1,514 participants were available. During the follow-up period, 53 of 160 participants with gout (33.1%) and 298 of 1,354 participants without gout (22.0%) died. After adjustment for other factors known to be associated with mortality, there was no gout-specific increase in risk of mortality (adjusted hazard ratio 0.98 [95% confidence interval 0.69-1.38]). Time to readmission for heart failure was significantly briefer in those with, compared to those without, gout (adjusted hazard ratio 1.42 [95% confidence interval 1.02-1.97]). Irrespective of whether a participant had gout or not, as SU level increased, there was an increased risk of death and readmission for either a cardiovascular event or heart failure. Survival post-ACS is similar with and without the presence of gout. People with gout are at an increased risk of readmission for heart failure and have longer hospital stays. Risk of these events increases in parallel with increases in SU levels.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.CLINBIOCHEM.2013.11.019
Abstract: Concentrations of troponin measured with high sensitivity troponin assays are raised in a number of emergency department (ED) patients however many are not diagnosed with acute myocardial infarction (AMI). Clinical comparisons between the early use (2h after presentation) of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) assays for the diagnosis of AMI have not been reported. Early (0 h and 2 h) hs-cTnT and hs-cTnI assay results in 1571 ED patients with potential acute coronary syndrome (ACS) without ST elevation on electrocardiograph (ECG) were evaluated. The primary outcome was diagnosis of index AMI adjudicated by cardiologists using the local cTnI assay results taken ≥6 h after presentation, ECGs and clinical information. Stored s les were later analysed with hs-cTnT and hs-cTnI assays. The ROC analysis for AMI (204 patients 13.0%) for hs-cTnT and hs-cTnI after 2h was 0.95 (95% CI: 0.94-0.97) and 0.98 (95% CI: 0.97-0.99) respectively. The sensitivity, specificity, PLR, and NLR of hs-cTnT and hs-cTnI for AMI after 2h were 94.1% (95% CI: 90.0-96.6) and 95.6% (95% CI: 91.8-97.7), 79.0% (95% CI: 76.8-81.1) and 92.5% (95% CI: 90.9-93.7), 4.48 (95% CI: 4.02-5.00) and 12.86 (95% CI: 10.51-15.31), and 0.07 (95% CI: 0.04-0.13) and 0.05 (95% CI:0.03-0.09) respectively. Exclusion of AMI 2h after presentation in emergency patients with possible ACS can be achieved using hs-cTnT or hs-cTnI assays. Significant differences in specificity of these assays are relevant and if using the hs-cTnT assay, further clinical assessment in a larger proportion of patients would be required.
Publisher: Informa UK Limited
Date: 2001
DOI: 10.3109/07853890108995955
Abstract: The drug treatment of heart failure, once simple, has become complex. Apart from a loop diuretic and digoxin, most patients should now be receiving an angiotensin-converting enzyme inhibitor (or angiotensin II receptor blocker), a beta-blocker and spironolactone. Newer drugs, such as endothelin-receptor antagonists and combined blockers of converting-enzyme and neutral endopeptidase, might soon become available. When to introduce these drugs and what dose is optimal for any in idual, are questions that currently vex clinicians. We proposed that plasma levels of the cardiac hormone brain natriuretic peptide (BNP, or better, its 1-76 amino-acid N-terminal fragment, N-BNP), would provide an objective index for guiding drug treatment in patients with established, stable cardiac failure. In a pilot study, 69 patients were randomized to drug treatment based on clinical criteria, or based on plasma levels of N-BNP. After a median follow-up of 9.6 months, those in the N-BNP group had fewer clinical end-points than those in the group managed by clinical criteria alone (19 vs 54 P= 0.02). These preliminary data encourage the concept that the increasingly complex pharmacotherapy for heart failure, both chronic (as in this trial) and acute, might best be guided by an objective measure such as plasma levels of BNP or N-BNP.
Publisher: Wiley
Date: 15-01-2014
Abstract: Risk scores and accelerated diagnostic protocols can identify chest pain patients with low risk of major adverse cardiac event who could be discharged early from the ED, saving time and costs. We aimed to derive and validate a chest pain score and accelerated diagnostic protocol (ADP) that could safely increase the proportion of patients suitable for early discharge. Logistic regression identified statistical predictors for major adverse cardiac events in a derivation cohort. Statistical coefficients were converted to whole numbers to create a score. Clinician feedback was used to improve the clinical plausibility and the usability of the final score (Emergency Department Assessment of Chest pain Score [EDACS]). EDACS was combined with electrocardiogram results and troponin results at 0 and 2 h to develop an ADP (EDACS-ADP). The score and EDACS-ADP were validated and tested for reproducibility in separate cohorts of patients. In the derivation (n = 1974) and validation (n = 608) cohorts, the EDACS-ADP classified 42.2% (sensitivity 99.0%, specificity 49.9%) and 51.3% (sensitivity 100.0%, specificity 59.0%) as low risk of major adverse cardiac events, respectively. The intra-class correlation coefficient for categorisation of patients as low risk was 0.87. The EDACS-ADP identified approximately half of the patients presenting to the ED with possible cardiac chest pain as having low risk of short-term major adverse cardiac events, with high sensitivity. This is a significant improvement on similar, previously reported protocols. The EDACS-ADP is reproducible and has the potential to make considerable cost reductions to health systems.
Location: United States of America
Location: New Zealand
Start Date: 2020
End Date: 2024
Funder: Health Research Council of New Zealand
View Funded ActivityStart Date: 2018
End Date: 2022
Funder: Health Research Council of New Zealand
View Funded ActivityStart Date: 2020
End Date: 2025
Funder: Health Research Council of New Zealand
View Funded ActivityStart Date: 2012
End Date: 2014
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2020
Funder: Health Research Council of New Zealand
View Funded ActivityStart Date: 2017
End Date: 2020
Funder: Health Research Council of New Zealand
View Funded ActivityStart Date: 2020
End Date: 2023
Funder: Health Research Council of New Zealand
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