ORCID Profile
0000-0001-8261-6666
Current Organisations
KU Leuven
,
Universitaire Ziekenhuizen Leuven
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Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Oxford University Press (OUP)
Date: 07-03-2022
Abstract: Cardiac output limitation is a fundamental feature of heart failure with preserved ejection fraction (HFpEF) but the relative contribution of its determinants in symptomatic vs. asymptomatic stages are not well characterized. We aimed to gain insight into disease mechanisms by performing comprehensive comparative non-invasive exercise imaging in patients across the disease spectrum. We performed bicycle stress echocardiography in 10 healthy controls, 13 patients with hypertensive left ventricular (LV) concentric remodelling and asymptomatic diastolic dysfunction (HTDD), 15 HFpEF patients, and 15 subjects with isolated right ventricular (RV) dysfunction secondary to chronic thromboembolic pulmonary hypertension (CTEPH). During exercise, ventricular performance differed across the groups (all P ≤ 0.01 for interaction). Notably in controls, LV and RV function significantly increased (all P & 0.05) while both LV systolic and diastolic reserve were significantly reduced in HFpEF patients. Likewise, RV systolic reserve was also impaired in HFpEF but not to the extent of CTEPH patients (P & 0.001 between groups). HTDD patients behaved as an intermediary group with borderline LV systolic and diastolic reserve and reduced RV systolic reserve. The increased pulmonary vascular (PV) load in HFpEF and CTEPH patients in combination with impaired RV reserve resulted in RV–pulmonary artery uncoupling during exercise. The multifaceted decline of cardiac and PV function accompanying disease progression in HFpEF is unmasked by exercise and already emerges in preclinical disease. The revelation of these subtle abnormalities during exercise illustrates the benefit of exercise imaging and creates new prospects for early diagnosis and management.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-10-2018
Abstract: Reduced ventricular function and decreased exercise capacity are widespread in adults with complete transposition of the great arteries after atrial switch ( TGA ‐Mustard/Senning) and congenitally corrected TGA (cc TGA ). Advanced imaging techniques may help to better phenotype these patients and evaluate exercise cardiac response. Thirty‐three adults with a systemic right ventricle (70% TGA ‐Mustard/Senning, 37±9 years of age, 24% female, 94% New York Heart Association class I‐ II ) underwent echocardiogram, cardiopulmonary exercise testing, and cardiovascular magnetic resonance imaging at rest and during a 4‐stage free‐breathing bicycle test. They were compared with 12 healthy controls (39±10 years of age, 25% female, all New York Heart Association class I). TGA ‐Mustard/Senning patients had a higher global circumferential strain (−15.8±3.6 versus −11.2±5.2%, P =0.008) when compared with cc TGA , whereas global longitudinal strain and systemic right ventricle contractility during exercise were similar in both groups. Septal extracellular volume ( ECV ) in cc TGA was significantly higher than in TGA ‐Mustard/Senning (30.2±2.0 versus 27.1±2.7%, P =0.005). During exercise, TGA ‐Mustard/Senning had a fall in end‐diastolic volume and stroke volume (11% and 8%, respectively both P ≤0.002), whereas cc TGA could increase their stroke volume in the same way as healthy controls. Because of a greater heart rate reserve in TGA ‐Mustard/Senning ( P for interaction=0.010), cardiac index and peak oxygen uptake were similar between both patient groups. Caution should be exercised when evaluating pooled analyses of systemic right ventricle patients, given the differences in myocardial contraction pattern, septal extracellular volume, and the exercise response of TGA ‐Mustard/Senning versus cc TGA patients. Longitudinal follow‐up will determine whether abnormal exercise cardiac response is a marker of earlier failure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
Publisher: Oxford University Press (OUP)
Date: 26-03-2018
DOI: 10.1093/EHJCI/JEY050
Abstract: The distinction between left ventricular (LV) dilation with mildly reduced LV ejection fraction (EF) in response to regular endurance exercise training and an early cardiomyopathy is a frequently encountered and difficult clinical conundrum. We hypothesized that exercise rather than resting measures would provide better discrimination between physiological and pathological LV remodelling and that preserved exercise capacity does not exclude significant LV damage. We prospectively included 19 subjects with LVEF between 40 and 52%, comprising 10 ostensibly healthy endurance athletes (EA-healthy) and nine patients with dilated cardiomyopathy (DCM). In addition, we recruited five EAs with a region of subepicardial LV. Receiver operating characteristic fibrosis (EA-fibrosis). Cardiac magnetic resonance (CMR) imaging was performed at rest and during supine bicycle exercise. Invasive afterload measures were obtained to enable calculations of biventricular function relative to load (an estimate of contractility). In DCM and EA-fibrosis subjects there was diminished augmentation of LVEF (5 ± 6% vs. 4 ± 3% vs. 14 ± 3% P = 0.001) and contractility [LV end-systolic pressure-volume ratio, LVESPVR 1.4 (1.3-1.6) vs. 1.5 (1.3-1.6) vs. 1.8 (1.7-2.7) P < 0.001] during exercise relative to EA-healthy. Receiver-operator characteristic curves demonstrated that a cut-off value of 11.2% for ΔLVEF differentiated DCM and EA-fibrosis patients from EA-healthy [area under the curve (AUC) = 0.92, P < 0.001], whereas resting LVEF and VO2max were not predictive. The AUC value for LVESPVR ratio was similar to that of ΔLVEF. Functional cardiac evaluation during exercise is a promising tool in differentiating healthy athletes with borderline LVEF from those with an underlying cardiomyopathy. Excellent exercise capacity does not exclude significant LV damage.
Publisher: BMJ
Date: 29-07-2015
DOI: 10.1136/BJSPORTS-2014-094546
Abstract: Subepicardial delayed gadolinium enhancement (DGE) patches without underlying cardiomyopathy is poorly understood. It is often reported as the result of prior silent myocarditis. Its prognostic relevance in asymptomatic athletes is unknown therefore, medical clearance for competitive sports participation is debated. This case series aims to relate this pattern of DGE in athletes to outcome. We report on seven young asymptomatic athletes with isolated subepicardial DGE detected during workup of abnormalities on their regular screening examination, that is, pathological T-wave inversions on ECG (n=4) or ventricular arrhythmias on exercise test (n=3). All underwent a comprehensive initial investigation in order to assess left ventricular (LV) function at rest and exercise (exercise cardiac MRI and/or exercise echocardiography) and occurrence of arrhythmias (exercise test, 24 h-ECG Holter, electrophysiological study). All underwent a careful follow-up with biannual evaluation. All athletes had extensive subepicardial DGE (12.0±4.8% of LV mass), predominantly in the lateral wall. Three athletes had non-sustained ventricular arrhythmias, whereas two of them had LV ejection fraction <50% at rest with no contractile reserve at exercise. During a follow-up of 3.0±1.5 years in the four remaining athletes, two had symptomatic ventricular tachycardia and one demonstrated progressive LV dysfunction. Hence, six of seven athletes had to be excluded from competitive sports participation. Isolated large areas of subepicardial DGE in an asymptomatic athlete are not benign and require a careful evaluation at exercise and a strict follow-up. These findings question whether extreme exercise during silent myocarditis may facilitate fibrosis generation and adverse remodelling.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2023
DOI: 10.1161/ATVBAHA.122.317262
Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model. We aimed to compare whether intrathrombus administration of an antifibrinolytic agent, tranexamic acid, or an inhibitor of angiogenesis, SU5416, would contribute to CTEPH progression. Both products were administered on a weekly basis by autologous clot embolization in rabbits. Right ventricular pressure was monitored by telemetry, right ventricular function by transthoracic echocardiography, and a complete pulmonary hemodynamic evaluation was obtained through right heart catheterization. Markers of inflammation, endothelial dysfunction, heart failure, and fibrinolysis were measured in plasma. Pulmonary vessel remodeling was analyzed by immunohistochemistry. Impairing intrathrombus angiogenesis by repeatedly embolizing autologous blood clots containing SU5416 resulted in elevated mean pulmonary arterial pressure (38 mm Hg), increased indexed pulmonary vascular resistance, and enhanced right ventricular hypertrophy (80%, 1.9-fold, 36%, respectively, compared with rabbits embolized with clots containing an antifibrinolytic agent). This was caused by both obstruction of large pulmonary arteries with fibrothrombotic material and muscularization of pulmonary microvessels, and accompanied by inflammatory cell infiltration and increased circulating endothelin-1. The key role of angiogenesis-driven clot resolution was validated in a reliable small-animal model reproducing the major pathophysiological hallmarks of CTEPH.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-11-2021
Publisher: Elsevier BV
Date: 10-2015
Publisher: IOP Publishing
Date: 08-03-2019
Abstract: We propose and evaluate a method to estimate a respiratory signal from ungated cardiac magnetic resonance (CMR) images. Ungated CMR images were acquired in five subjects who performed exercise at different intensity levels under different physiological conditions while breathing freely. The respiratory motion was estimated by applying principal components analysis (PCA). A sign correction procedure was developed to correctly define inspiration and expiration, based on either tracking of the diaphragmatic motion or estimation of the lung volume or a combination of both. Evaluation was done using a plethysmograph signal as reference. There was a good correspondence between the plethysmograph and the estimated respiratory signals. Respiratory motion was effectively captured by one of the PCA components in 88% of the cases. Moreover, the proposed method successfully estimated the respiratory phase in 91% of the evaluated slices. The pipeline is robust, admitting a slight decline in performance with increased exercise intensity. Respiratory motion was accurately estimated by means of PCA and the application of a sign correction procedure. Our method showed promising results even for acquisitions during exercise where excessive body motion occurs. The proposed method provides a way to extract the respiratory signal from ungated CMR images, at rest as well as during exercise, in a fully unsupervised fashion, which may reduce the clinician's workload drastically.
Publisher: Oxford University Press (OUP)
Date: 02-06-2015
Abstract: Intense exercise places disproportionate strain on the right ventricle (RV) which may promote pro-arrhythmic remodelling in some athletes. RV exercise imaging may enable early identification of athletes at risk of arrhythmias. Exercise imaging was performed in 17 athletes with RV ventricular arrhythmias (EA-VAs), of which eight (47%) had an implantable cardiac defibrillator (ICD), 10 healthy endurance athletes (EAs), and seven non-athletes (NAs). Echocardiographic measures included the RV end-systolic pressure-area ratio (ESPAR), RV fractional area change (RVFAC), and systolic tricuspid annular velocity (RV S'). Cardiac magnetic resonance (CMR) measures combined with invasive measurements of pulmonary and systemic artery pressures provided left-ventricular (LV) and RV end-systolic pressure-volume ratios (SP/ESV), biventricular volumes, and ejection fraction (EF) at rest and during intense exercise. Resting measures of cardiac function were similar in all groups, as was LV function during exercise. In contrast, exercise-induced increases in RVFAC, RV S', and RVESPAR were attenuated in EA-VAs during exercise when compared with EAs and NAs (P < 0.0001 for interaction group × workload). During exercise-CMR, decreases in RVESV and augmentation of both RVEF and RV SP/ESV were significantly less in EA-VAs relative to EAs and NAs (P < 0.01 for the respective interactions). Receiver-operator characteristic curves demonstrated that RV exercise measures could accurately differentiate EA-VAs from subjects without arrhythmias [AUC for ΔRVESPAR = 0.96 (0.89-1.00), P < 0.0001]. Among athletes with normal cardiac function at rest, exercise testing reveals RV contractile dysfunction among athletes with RV arrhythmias. RV stress testing shows promise as a non-invasive means of risk-stratifying athletes.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.CJCA.2015.01.022
Abstract: There is substantial evidence supporting the prescription of exercise training in patients with left-sided heart disease, but data on the effects of exercise are far more limited for conditions that primarily affect the right ventricle. There is evolving evidence that right ventricular (RV) function is of critical importance to circulatory function during exercise. Even in healthy in iduals with normal pulmonary vascular function, the hemodynamic load on the right ventricle increases relatively more during exercise than that of the left ventricle, and this disproportionate load is far greater in patients with pulmonary hypertension. Exercise-induced increases in pulmonary artery pressures can exceed RV contractile reserve (so-called arterioventricular uncoupling), resulting in attenuated cardiac output and exercise intolerance. In this review, we explore the spectrum of RV reserve-from transient RV dysfunction observed in athletes after extreme bouts of intense endurance exercise to RV failure with minimal exertion in patients with advanced pulmonary hypertension. Recent advances and novel approaches to echocardiographic and cardiac magnetic resonance imaging have provided more accurate means of assessing the right ventricle and pulmonary circulation during exercise such that quantification of exercise reserve may provide a valuable means of assessing prognosis and response to therapies. We discuss the potential benefits and risks of exercise training in both health and disease while recognizing the need for prospective studies that assess the long-term efficacy and safety of exercise interventions in patients with pulmonary vascular and RV pathologic conditions.
Publisher: American Physiological Society
Date: 15-03-2014
DOI: 10.1152/AJPHEART.00752.2013
Abstract: Breathing-induced changes in intrathoracic pressures influence left ventricular (LV) and right ventricular (RV) volumes, the exact nature and extent of which have not previously been evaluated in humans. We sought to examine this “respiratory pump” using novel real-time cardiac magnetic resonance (CMR) imaging. Eight healthy subjects underwent serial multislice real-time CMR during normal breathing, breath holding, and the Valsalva maneuver. Subsequently, a separate cohort of nine subjects underwent real-time CMR at rest and during incremental exercise. LV and RV end-diastolic volume (EDV) and end-systolic volume (ESV) and diastolic and systolic eccentricity indexes were determined at peak inspiration and expiration. During normal breathing, inspiration resulted in an increase in RV volumes [RVEDV: +18 ± 8%, RVESV: +14 ± 12%, and RV stroke volume (SV): +21 ± 10%, P 0.01] and an opposing decrease in LV volumes ( P 0.0001 for interaction). During end-inspiratory breath holding, RV SV decreased by 9 ± 10% ( P = 0.046), whereas LV SV did not change. During the Valsalva maneuver, volumes decreased in both ventricles (RVEDV: −29 ± 11%, RVESV: −16 ± 14%, RV SV: −36 ± 14%, LVEDV: −22 ± 17%, and LV SV: −25 ± 17%, P 0.01). The reciprocal effect of respiration on LV and RV volumes was maintained throughout exercise. The diastolic and systolic eccentricity indexes were greater during inspiration than during expiration, both at rest and during exercise ( P 0.0001 for both). In conclusion, ventricular volumes oscillate with respiratory phase such that RV and LV volumes are maximal at peak inspiration and expiration, respectively. Thus, interpretation of RV versus LV volumes requires careful definition of the exact respiratory time point for proper interpretation, both at rest and during exercise.
Publisher: Oxford University Press (OUP)
Date: 23-10-2018
DOI: 10.1093/EHJCI/JEX245
Publisher: Human Kinetics
Date: 09-2023
Publisher: Wiley
Date: 06-2016
DOI: 10.1113/JP272168
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.JACEP.2015.03.007
Abstract: The objective of this study was to test the hypothesis that T-wave inversion in the right precordial leads (TWI TWI Sixty-eight EAs and 41 nonathletic control subjects underwent ECG and cardiac magnetic resonance imaging (CMRI). In addition to standard measurements of biventricular function and volume, novel measurements of cardiac displacement and orientation were analyzed from horizontal long-axis images. These included RV wall thickness in diastole (RV All cardiac volume, RV In healthy EAs, TWI
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-03-2015
Abstract: Patients with normalized mean pulmonary artery pressure ( mPAP ) after pulmonary endarterectomy ( PEA ) for chronic thromboembolic pulmonary hypertension ( CTEPH ) do not always regain normal exercise capacity. We evaluated right ventricular function, its interaction with both pulsatile and resistive afterload, and the effect of sildenafil during exercise in these patients. Fourteen healthy controls, 15 CTEPH patients, and 7 patients with normalized resting mPAP (≤25 mm Hg) post‐ PEA underwent cardiopulmonary exercise testing, followed by cardiac magnetic resonance imaging with simultaneous invasive mPAP measurement during incremental supine cycling exercise. Peak oxygen consumption and peak heart rate were significantly reduced in post‐ PEA and CTEPH patients compared to controls. The mPAP –cardiac output slope was steeper in post‐ PEA patients than in controls and similar to CTEPH . Relative to controls, resting right ventricular ejection fraction was reduced in CTEPH , but not in post‐ PEA patients. In contrast, peak exercise right ventricular ejection fraction was reduced both in post‐ PEA and CTEPH patients. Exercise led to reduction of pulmonary arterial compliance in all groups. Nevertheless, resting pulmonary arterial compliance values in CTEPH and post‐ PEA patients were even lower than those in controls at peak exercise. In post‐ PEA patients, sildenafil did not affect resting hemodynamics nor right ventricular function, but decreased the mPAP /cardiac output slope and increased peak exercise right ventricular ejection fraction. Exercise intolerance in post‐ PEA patients is explained by abnormal pulmonary vascular reserve and chronotropic incompetence. The mPAP /cardiac output slope and pulmonary arterial compliance are sensitive measures demonstrating abnormal resistive and pulsatile pulmonary vascular function in post‐ PEA patients. These abnormalities are partially attenuated with sildenafil.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.JELECTROCARD.2015.03.001
Abstract: There is increasing evidence that regular intense endurance exercise can promote structural and electrical remodeling of the right ventricle (RV). These physiological changes can be profound and are frequently accompanied by ECG changes in the right precordial leads, thereby mimicking features observed in arrhythmogenic right ventricular cardiomyopathy (ARVC). Because the 12-lead ECG is used as both a screening and diagnostic tool for the detection of conditions associated with sudden death in athletes, it is of fundamental importance to have a good understanding of the ECG features that distinguish physiological adaptations to endurance exercise from those related to RV pathology as well as their potential overlap. This article describes ECG findings observed in healthy endurance athletes versus athletes with underlying RV pathology and illustrates their differentiation using 4 case presentations.
Publisher: Wiley
Date: 09-2014
DOI: 10.1086/677355
Abstract: There is unequivocal evidence that exercise results in considerable health benefits. These are the result of positive hormonal, metabolic, neuronal, and structural changes brought about by the intermittent physiological challenge of exercise. However, there is evolving evidence that intense exercise may place disproportionate physiological stress on the right ventricle (RV) and the pulmonary circulation. Both echocardiographic and invasive studies are consistent in demonstrating that pulmonary arterial pressures increase progressively with exercise intensity, such that the harder one exercises, the greater the load on the RV. This disproportionate load can result in fatigue or damage of the RV if the intensity and duration of exercise is sufficiently prolonged. This is distinctly different from the load imposed by exercise on the left ventricle (LV), which is moderated by a greater capacity for reductions in systemic afterload. Finally, given the increasing RV demand during exercise, it may be hypothesized that chronic exercise–induced cardiac remodeling (the so‐called athlete's heart) may also disproportionately affect the RV. Indeed, there is evidence, although somewhat inconsistent, that RV volume increases may be relatively greater than those for the LV. Perhaps more importantly, there is a suggestion that chronic endurance exercise may cause electrical remodeling, predisposing some athletes to serious arrhythmias originating from the RV. Thus, a relatively consistent picture is emerging of acute stress, prolonged fatigue, and long‐term remodeling, which all disproportionately affect the RV. Thus, we contend that the RV should be considered a potential Achilles' heel of the exercising heart.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-10-2016
Publisher: Elsevier BV
Date: 12-2015
Publisher: Oxford University Press (OUP)
Date: 03-10-2019
DOI: 10.1093/EHJCI/JEZ228
Abstract: Athletes with right ventricular (RV) arrhythmias, even in the absence of desmosomal mutations, may have subtle RV abnormalities which can be unmasked by deformation imaging. As exercise places a disproportionate stress on the right ventricle, evaluation of cardiac function and deformation during exercise might improve diagnostic performance. We performed bicycle stress echocardiography in 17 apparently healthy endurance athletes (EAs), 12 non-athletic controls (NAs), and 17 athletes with RV arrhythmias without desmosomal mutations (EI-ARVCs) and compared biventricular function at rest and during low (25% of upright peak power) and moderate intensity (60%). At rest, we observed no differences in left ventricular (LV) or RV function between groups. During exercise, however, the increase in RV fractional area change (RVFAC), RV free wall strain (RVFWSL), and strain rate (RVFWSRL) were significantly attenuated in EI-ARVCs as compared to EAs and NAs. At moderate exercise intensity, EI-ARVCs had a lower RVFAC, RVFWSL, and RVFWSRL (all P 0.01) compared to the control groups. Exercise-related increases in LV ejection fraction, strain, and strain rate were also attenuated in EI-ARVCs (P 0.05 for interaction). Exercise but not resting parameters identified EI-ARVCs and RVFWSRL with a cut-off value of −2.35 at moderate exercise intensity had the greatest accuracy to detect EI-ARVCs (area under the curve 0.95). Exercise deformation imaging holds promise as a non-invasive diagnostic tool to identify intrinsic RV dysfunction concealed at rest. Strain rate appears to be the most accurate parameter and should be incorporated in future, prospective studies to identify subclinical disease in an early stage.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2014
Publisher: BMJ
Date: 16-02-2015
DOI: 10.1136/HEARTJNL-2014-306851
Abstract: Symptoms in patients with chronic thromboembolic pulmonary hypertension (CTEPH) predominantly occur during exercise, while haemodynamic assessment is generally performed at rest. We hypothesised that exercise imaging of RV function would better explain exercise limitation and the acute effects of pulmonary vasodilator administration than resting measurements. Fourteen patients with CTEPH and seven healthy control subjects underwent cardiopulmonary testing to determine peak exercise oxygen consumption (VO2peak) and ventilatory equivalent for carbon dioxide (VE/VCO2) at the anaerobic threshold. Subsequently, cardiac MRI was performed at rest and during supine bicycle exercise with simultaneous invasive measurement of mean pulmonary arterial pressure (mPAP) before and after sildenafil. During exercise, patients with CTEPH had a greater increase in the ratio of mPAP relative to cardiac output (CO) than controls (6.7 (5.1-8.7) vs 0.94 (0.86-1.8) mm Hg/L/min p < 0.001). Stroke volume index (SVi) and RVEF increased during exercise in controls, but not in patients with CTEPH (interaction p < 0.001). Sildenafil decreased the mPAP/CO slope and increased SVi and RVEF in patients with CTEPH (p < 0.05) but not in controls. In patients with CTEPH, RVEF reserve correlated moderately with VO2peak (r = 0.60 p = 0.030) and VE/VCO2 (r = -0.67 p = 0.012). By contrast, neither VO2peak nor VE/VCO2 correlated with resting RVEF. Exercise measures of RV function explain much of the variance in the exercise capacity of patients with CTEPH while resting measures do not. Sildenafil increases SVi during exercise in patients with CTEPH, but not in healthy subjects.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-05-2021
DOI: 10.1161/CIRCULATIONAHA.120.052899
Abstract: Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the pathogenesis has been attributed to central factors, including ventilation erfusion mismatch, increased pulmonary vascular resistance, and right heart dysfunction and uncoupling. Pulmonary endarterectomy and balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. However, despite normalization of pulmonary hemodynamics, exercise capacity often does not return to age-predicted levels. By systematically evaluating the oxygen pathway, we aimed to elucidate the causes of functional limitations in patients with CTEPH before and after pulmonary vascular intervention. Using exercise cardiac magnetic resonance imaging with simultaneous invasive hemodynamic monitoring, we sought to quantify the steps of the O 2 transport cascade from the mouth to the mitochondria in patients with CTEPH (n=20) as compared with healthy participants (n=10). Furthermore, we evaluated the effect of pulmonary vascular intervention (pulmonary endarterectomy or balloon angioplasty) on the in idual components of the cascade (n=10). Peak V o 2 (oxygen uptake) was significantly reduced in patients with CTEPH relative to controls (56±17 versus 112±20% of predicted P .0001). The difference was attributable to impairments in multiple steps of the O 2 cascade, including O 2 delivery (product of cardiac output and arterial O 2 content), skeletal muscle diffusion capacity, and pulmonary diffusion. The total O 2 extracted in the periphery (ie, ΔAV o 2 [arteriovenous O 2 content difference]) was not different. After pulmonary vascular intervention, peak V o 2 increased significantly (from 12.5±4.0 to 17.8±7.5 mL/[kg·min] P =0.036) but remained below age-predicted levels (70±11%). The O 2 delivery was improved owing to an increase in peak cardiac output and lung diffusion capacity. However, peak exercise ΔAV o 2 was unchanged, as was skeletal muscle diffusion capacity. We demonstrated that patients with CTEPH have significant impairment of all steps in the O 2 use cascade, resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increased peak V o 2 by partly correcting O 2 delivery but had no effect on abnormalities in peripheral O 2 extraction. This suggests that current interventions only partially address patients’ limitations and that additional therapies may improve functional capacity.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 12-2016
Publisher: Wiley
Date: 07-2013
Publisher: BMJ
Date: 06-06-2023
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.IJCARD.2018.03.029
Abstract: To evaluate the relationship between right ventricular (RV) systolic dysfunction at rest and reduced exercise capacity in patients with a systemic RV (sRV). All patients with congenitally corrected transposition of the great arteries (ccTGA) or complete TGA after atrial switch (TGA-Mustard/Senning) followed in our institution between July 2011 and September 2017 who underwent cardiac imaging within a six-month time period of cardiopulmonary exercise testing (CPET) were analyzed. We assessed sRV systolic function with TAPSE and fractional area change on echocardiogram and, if possible, with ejection fraction, global longitudinal and circumferential strain on cardiac magnetic resonance (CMR) imaging. We studied 105 patients with an sRV (median age 34 [IQR 28-42] years, 29% ccTGA and 71% TGA-Mustard/Senning) of which 39% had either a pacemaker (n = 17), Eisenmenger physiology (n = 6), severe systemic atrioventricular valve regurgitation (n = 14), or peak exercise arterial oxygen saturation < 92% (n = 17). Most patients were asymptomatic or mildly symptomatic (NYHA class I/II/III in 71/23/6%). Sixty-four percent had evidence of moderate or severe sRV dysfunction on cardiac imaging. Mean peak oxygen uptake (pVO2) was 24.1 ± 7.4 mL/kg/min, corresponding to a percentage of predicted pVO2 (%ppVO2) of 69 ± 17%. No parameter of sRV systolic function as evaluated on echocardiography (n = 105) or CMR (n = 46) was correlated with the %ppVO2, even after adjusting for associated cardiac defects or pacemakers. In adults with an sRV, there is no relation between echocardiographic or CMR-derived sRV systolic function parameters at rest and peak oxygen uptake. Exercise imaging may be superior to evaluate whether sRV contractility limits exercise capacity.
Publisher: European Respiratory Society (ERS)
Date: 27-07-2023
DOI: 10.1183/23120541.00229-2023
Abstract: Pulmonary hypertension due to left heart disease (PH-LHD) is the most frequent form of PH. As differential diagnosis with pulmonary arterial hypertension (PAH) has therapeutic implications, it is important to accurately and non-invasively differentiate PH-LHD from PAH before referral to PH centres. The aim was to develop and validate a machine learning (ML) model to improve prediction of PH-LHD in a population of PAH and PH-LHD patients. Non-invasive PH-LHD predictors from 172 PAH and 172 PH-LHD patients from the PH centre database at the University Hospitals of Leuven were used to develop a ML model. Jacobs score [1] was used as performance benchmark. The dataset was split into a training and test set (70:30) and the best model was selected after 10-fold cross-validation on the training dataset (n=240). The final model was externally validated using 165 patients (91 PAH, 74 PH-LHD) from Erasme Hospital Brussels. In the internal test dataset (n=104), a random forest-based model correctly diagnosed 70% of PH-LHD patients (sensitivity: n=35/50), with 100% PPV, 78% NPV and 100% specificity. The model outperformed the Jacobs score that identified 18% (n=9/50) of the patients with PH-LHD without false positives. In external validation, the model had 64% sensitivity at 100% specificity while Jacobs score had a sensitivity of 3% for no false positives. ML significantly improves the sensitivity of PH-LHD prediction at 100% specificity. Such a model may substantially reduce the number of patients referred for invasive diagnostics without missing PAH diagnoses.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.JCMG.2018.07.021
Abstract: This study was a comprehensive evaluation of cardiopulmonary function in patients with chronic thromboembolic (pulmonary vascular) disease (CTED) during exercise. Exertional dyspnea is frequent following pulmonary embolism, but only a minority of patients eventually develops chronic thromboembolic pulmonary hypertension (CTEPH). Better understanding of the factors that limit exercise capacity in patients with persistent pulmonary artery obstruction could help to further define the entity of CTED. Fifty-two subjects (13 healthy control subjects, 14 CTED patients, and 25 CTEPH patients) underwent cardiopulmonary exercise testing and exercise cardiac magnetic resonance with simultaneous invasive pressure registration. Pulmonary vascular function and right ventricular contractile reserve were assessed through combined invasive pressure measurements and magnetic resonance imaging volume measures. Exercise capacity was reduced by 29% and 57% in patients with CTED and CTEPH respectively, compared with control subjects. Both CTED (3.48 [interquartile range: 2.24 to 4.36] mm Hg × l CTED represents an intermediate clinical phenotype. Exercise imaging unmasks cardiovascular dysfunction not evident at rest and identifies hemodynamically significant disease that results from reduced contractile reserve or increased vascular load.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
DOI: 10.1161/CIRCIMAGING.112.980037
Abstract: Accurate measures are critical when attempting to distinguish normal from pathological changes in cardiac function during exercise, yet imaging modalities have seldom been assessed against invasive exercise standards. We sought to validate a novel method of biventricular volume quantification by cardiac MRI (CMR) during maximal exercise. CMR was performed on 34 subjects during exercise and free-breathing with the use of an ungated real-time (RT-ungated) CMR sequence. ECG and respiratory movements were retrospectively synchronized, enabling compensation for cardiac cycle and respiratory phase. Feasibility of RT-ungated imaging was compared with standard exercise CMR imaging with ECG gating (gated) accuracy of RT-ungated CMR was assessed against an invasive standard (direct Fick) and reproducibility was determined after a second bout of maximal exercise. Ventricular volumes were analyzed more frequently during high-intensity exercise with RT-ungated compared with gated CMR (100% versus 47% P .0001) and with better interobserver variability for RT-ungated (coefficient of variation=1.9% and 2.0% for left and right ventricular stroke volumes, respectively) than gated (coefficient of variation=15.2% and 13.6% P .01). Cardiac output determined by RT-ungated CMR proved accurate against the direct Fick method with excellent agreement (intraclass correlation coefficient, R =0.96), which was highly reproducible during a second bout of maximal exercise ( R =0.98). When RT-ungated CMR is combined with post hoc analysis incorporating compensation for respiratory motion, highly reproducible and accurate biventricular volumes can be measured during maximal exercise.
Publisher: Oxford University Press (OUP)
Date: 14-08-2017
DOI: 10.1093/CVR/CVX156
Abstract: Exercise is associated with unequivocal health benefits and results in many structural and functional changes of the myocardium that enhance performance and prevent heart failure. However, intense exercise also presents a significant hemodynamic challenge in which the right-sided heart chambers are exposed to a disproportionate increase in afterload and wall stress that can manifest as myocardial fatigue or even damage if intense exercise is sustained for prolonged periods. This review focuses on the physiological factors that result in a disproportionate load on the right ventricle during exercise and the long-term consequences. The changes in cardiac structure and function that define 'athlete's heart' disproportionately affect the right-sided heart chambers and this can raise important diagnostic overlap with some cardiac pathologies, particularly some inherited cardiomyopathies. The interaction between exercise and arrhythmogenic right ventricular cardiomyopathy (ARVC) will be highlighted as an important ex le of how hemodynamic stressors can combine with deficiencies in cardiac structural elements to cause cardiac dysfunction predisposing to arrhythmias. The extent to which extreme exercise can cause adverse remodelling in the absence of a genetic predisposition remains controversial. In the athlete with profound changes in heart structure, it can be extremely challenging to determine whether common symptoms such as palpitations may be a marker of more sinister arrhythmias. This review discusses some of the techniques that have recently been proposed to identify pathology in these circumstances. Finally, we will discuss recent evidence defining the role of exercise restriction as a therapeutic intervention in in iduals predisposed to arrhythmogenic cardiomyopathy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2014
DOI: 10.1161/CIRCIMAGING.113.001243
Abstract: Patients with Fontan circulation have reduced exercise capacity. The absence of a presystemic pump may limit flow through the pulmonary circulation, restricting ventricular filling and cardiac output. We evaluated exercise hemodynamics and the effect of sildenafil on exercise hemodynamics in Fontan patients. Ten Fontan patients (6 men, 20±4 years) underwent cardiac magnetic resonance imaging at rest and during supine bicycle exercise before and after sildenafil. Systemic ventricular volumes were obtained at rest and during low- (34±15 W), moderate- (69±29 W), and high-intensity (97±36 W) exercise using an ungated, free-breathing cardiac magnetic resonance sequence and analyzed correcting for cardiac phase and respiratory translation. Radial and pulmonary artery pressures and cGMP were measured. Before sildenafil, cardiac index increased throughout exercise (4.0±0.9, 5.9±1.1, 7.0±1.6, 7.4±1.7 L/(min·m 2 ) P .0001) with 106±49% increase in heart rate. Stroke volume index ( P =0.015) and end-diastolic volume index ( P =0.001) decreased during exercise. End-systolic volume index remained unchanged ( P =0.8). Total pulmonary resistance index ( P =0.005) increased, whereas systemic vascular resistance index decreased during exercise ( P .0001). Sildenafil increased cardiac index ( P .0001) and stroke volume index ( P =0.003), especially at high-intensity exercise (interaction P =0.004 and P =0.003, respectively). Systemic vascular resistance index was reduced ( P .0001–interaction P =0.1), whereas total pulmonary resistance index was reduced at rest and reduced further during exercise ( P =0.008–interaction P =0.029). cGMP remained unchanged before sildenafil ( P =0.9), whereas it increased significantly after sildenafil ( P =0.019). In Fontan patients, sildenafil improved cardiac index during exercise with a decrease in total pulmonary resistance index and an increase in stroke volume index. This implies that pulmonary vasculature represents a physiological limitation, which can be attenuated by sildenafil, the clinical significance of which warrants further study.
Publisher: Oxford University Press (OUP)
Date: 06-03-2023
DOI: 10.1093/EURHEARTJ/EHAD152
Abstract: The impact of long-term endurance sport participation (on top of a healthy lifestyle) on coronary atherosclerosis and acute cardiac events remains controversial. The Master@Heart study is a well-balanced prospective observational cohort study. Overall, 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile, were included. Peak oxygen uptake quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on computed tomography coronary angiography. Analyses were corrected for multiple cardiovascular risk factors. The median age was 55 (50–60) years in all groups. Lifelong and late-onset athletes had higher peak oxygen uptake than non-athletes [159 (143–177) vs. 155 (138–169) vs. 122 (108–138) % predicted]. Lifelong endurance sports was associated with having ≥1 coronary plaque [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.17–2.94], ≥ 1 proximal plaque (OR 1.96, 95% CI 1.24–3.11), ≥ 1 calcified plaques (OR 1.58, 95% CI 1.01–2.49), ≥ 1 calcified proximal plaque (OR 2.07, 95% CI 1.28–3.35), ≥ 1 non-calcified plaque (OR 1.95, 95% CI 1.12–3.40), ≥ 1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39–5.65), and ≥1 mixed plaque (OR 1.78, 95% CI 1.06–2.99) as compared to a healthy non-athletic lifestyle. Lifelong endurance sport participation is not associated with a more favourable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy in iduals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum.
Publisher: BMJ
Date: 11-10-2016
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.HEALUN.2016.06.018
Abstract: Non-invasive estimates have suggested that asymptomatic BMPR2 mutation carriers may have an abnormal pulmonary vascular response to exercise and hypoxia. However, this has not been assessed with "gold standard" invasive measures. Eight controls and 8 asymptomatic BMPR2 mutation carriers underwent cardiac magnetic resonance imaging with simultaneous invasive pressure recording during bicycle exercise in normoxia, hypoxia and after sildenafil administration. Abnormal pulmonary vascular reserve was defined as an increase in mean pulmonary artery pressure relative to cardiac output (P/Q slope) >3 mm Hg/liter/min. During normoxic exercise, BMPR2 mutation carriers had a similar P/Q slope when compared with healthy subjects. Only 1 of 8 BMPR2 mutation carriers had a P/Q slope >3 mm Hg/liter/min. During exercise in hypoxia, 3 of 8 BMPR2 mutation carriers had P/Q slopes >3 mm Hg/liter/min compared with none of the controls. Sildenafil decreased the P/Q slope both in controls and BMPR2 mutation carriers. The exercise-induced increase in right ventricular ejection fraction was similar between groups. None of the BMPR2 mutation carriers developed pulmonary arterial hypertension within 2 (range 1.3 to 2.8) years. The presence of a BMPR2 mutation, per se, is not associated with an abnormal pulmonary vascular and right ventricular functional response to exercise in asymptomatic in iduals. Longer follow-up will be required to determine whether a P/Q slope of >3 mm Hg/liter/min during exercise in normoxia or hypoxia is a sign of pre-clinical disease expression.
Publisher: BMJ
Date: 12-03-2011
Abstract: To evaluate whether in a population of patients with 'lone atrial flutter', the proportion of those engaged in long-term endurance sports is higher than that observed in the general population. An age and sex-matched retrospective case-control study. A database with 638 consecutive patients who underwent ablation for atrial flutter at the University of Leuven. Sixty-one patients (55 men, 90%) fitted the inclusion criteria of 'lone atrial flutter', ie, aged 65 years or less, without documented atrial fibrillation and without identifiable underlying disease (including hypertension). Sex, age and inclusion criteria-matched controls, two for each flutter patient, were selected in a general practice in the same geographical region. Sports activity was evaluated by detailed questionnaires, which were available in 58 flutter patients (95%). A transthoracic echocardiogram was performed in all lone flutter patients. Types of sports, number of years of participation and average number of hours per week. The proportion of regular sportsmen (≥3 h of sports practice per week) among patients with lone atrial flutter was significantly higher than that observed in the general population (50% vs 17% p<0.0001). The proportion of sportsmen engaged in long-term endurance sports (participation in cycling, running or swimming for ≥3 h/week) was also significantly higher in lone flutter patients than in controls (31% vs 8% p=0.0003). Those flutter patients performing endurance sports had a larger left atrium than non-sportsmen (p=0.04, by one-way analysis of variance). A history of endurance sports and subsequent left atrial remodelling may be a risk factor for the development of atrial flutter.
Start Date: 2017
End Date: 2021
Funder: FWO Vlaanderen
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