Publications by authors named "Guido Claessen"

51 Publications

Magnetic resonance relaxometry of the liver - a new imaging biomarker to assess right heart failure in pulmonary hypertension.

J Heart Lung Transplant 2021 Sep 16. Epub 2021 Sep 16.

Dept of Imaging and Pathology, KU Leuven and Dept of Radiology, University Hospitals Leuven, Leuven, Belgium.

Background: Right heart failure (RHF) in pulmonary hypertension (PH) patients is manifested by increased right atrial (RA) pressure. We hypothesized liver relaxation times measured at cardiovascular magnetic resonance (CMR) can be used to noninvasively assess increased right-sided filling pressure.

Methods: Forty-five consecutive patients, that is, 37 PH patients and 8 chronic thromboembolic pulmonary disease patients without PH underwent right heart catheterization and CMR. CMR findings were compared to 40 control subjects. Native T1, T2, and extracellular volume (ECV) liver values were measured on the cardiac maps.

Results: Patients with increased RA pressure (i.e.,≥8 mm Hg)(n = 19, RA+ group) showed higher NT-proBNP and CRP values, lower LVEF, MAPSE values, larger atrial size, and higher native T1 and T2 values of the myocardium than patients with normal RA pressure (RA- group, n = 26). Liver T1, T2 and ECV was significantly higher in RA+ than RA- patients and controls, that is, T1: 684 ± 129 ms vs 563 ± 72 ms and 540 ± 34 ms; T2: 60 ± 10 ms vs 49 ± 6 ms and 46 ± 4 ms; ECV: 36 ± 8% vs 29 ± 4% and 30 ± 3%. A positive correlation was found between liver T1, T2 and ECV and RA pressure, that is, r of 0.61, 0.82, and 0.58, respectively (p < 0.001). ROC analysis to depict increased RA pressure showed an AUC of 0.847, 0.904, 0.816, and 0.645 for liver T1, T2, NT-proNBP and gamma-glutamyl transpeptidase, respectively. Excellent intra- and inter-observer agreement was found for assessment of T1/T2/ECV liver values.

Conclusions: Assessment of liver relaxation times as part of a comprehensive CMR exam in PH patients may provide valuable information with regard to the presence of passive liver congestion.
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http://dx.doi.org/10.1016/j.healun.2021.09.005DOI Listing
September 2021

Exercise capacity, muscle strength and objectively measured physical activity in patients after heart transplantation.

Transpl Int 2021 Oct 13. Epub 2021 Oct 13.

Department of Cardiovascular Sciences, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium.

Maximal exercise capacity of patients after heart transplantation (HTX) remains limited, affecting their quality of life. Evidence on the evolution of muscle strength and physical activity (PA) post-HTX is lacking, but a prerequisite to tailor cardiac rehabilitation programmes. Forty-five consecutive patients were evaluated every 3 months during the first year post-HTX. Functional exercise capacity (Six minutes walking distance test (6MWD)), peripheral (Quadriceps strength (QF)) and respiratory (Maximal inspiratory strength (MIP)) muscle strength were evaluated. PA (number of steps (PAsteps), active time (PAactive) and sedentary time (PAsed)) was objectively measured. 6MWD, QF, MIP, PAsteps and PAactive significantly improved over time (P < 0.001). No change in PAsed was noticed (P = 0.129). Despite improvements in 6MWD and QF, results remained substantially below those of age-and gender-matched healthy subjects. One year post-HTX, 30% of patients presented with peripheral muscle weakness. Baseline levels of 6MWD and QF were significantly higher in patients with pretransplant LVAD-implantation and this difference was maintained during follow-up. cardiac rehabilitation, combining aerobic exercise training and peripheral muscle strength training, is mandatory in patients post-HTX. Inspiratory muscle training should be implemented when respiratory muscle weakness is present. Programmes improving physical activity and reducing sedentary time post-HTX are essential.
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http://dx.doi.org/10.1111/tri.14139DOI Listing
October 2021

Right ventricular and cyclic guanosine monophosphate signalling abnormalities in stages B and C of heart failure with preserved ejection fraction.

ESC Heart Fail 2021 Sep 3. Epub 2021 Sep 3.

Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.

Aims: Identifying early right ventricular (RV) dysfunction and impaired vasodilator reserve is challenging in heart failure with preserved ejection fraction (HFpEF). We hypothesized that cardiac magnetic resonance (CMR)-based exercise imaging and serial cyclic guanosine monophosphate (cGMP) measurements can identify dynamic RV-arterial uncoupling and responsiveness to pulmonary vasodilators at early stages of the HFpEF syndrome.

Methods And Results: Patients with HFpEF (n = 16), impaired left ventricular relaxation due to concentric remodelling (LVCR, n = 7), and healthy controls (n = 8) underwent CMR at rest and during supine bicycle exercise with simultaneous measurements of central haemodynamics and circulating cGMP levels, before and after oral administration of 50 mg sildenafil. At rest, mean pulmonary artery pressures (mPAP) were higher in HFpEF, compared with LVCR and controls (27 ± 2, 18 ± 1, and 11 ± 1, respectively; P = 0.01), whereas biventricular volumes, heart rate, and stroke volume were similar. During exercise, LVCR and HFpEF had a greater increase in the ratio of mPAP over cardiac output than controls (5.50 ± 0.77 and 6.34 ± 0.86 vs. 2.24 ± 0.55 in controls, P = 0.005). The ratio of peak exercise to rest RV end-systolic pressure-volume, a surrogate of RV contractility, was significantly reduced in LVCR and HFpEF (2.32 ± 0.17 and 1.56 ± 0.08 vs. 3.49 ± 0.35 in controls, P < 0.001) and correlated with peak exercise VO (R  = 0.648, P < 0.001). cGMP levels increased with exercise across the HFpEF spectrum (P < 0.05 vs. baseline), except when postcapillary pulmonary hypertension was present at rest (P = 0.73 vs. baseline). A single sildenafil administration failed to increase circulating cGMP levels and did not improve RV performance.

Conclusion: Exercise CMR identifies impaired RV-arterial coupling at an early stage of HFpEF. Circulating cGMP levels phenocopy the haemodynamic spectrum in HFpEF but fail to increase after phosphodiesterase type 5 inhibition, endorsing the need for alternative interventions to increase cGMP signalling in HFpEF.
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http://dx.doi.org/10.1002/ehf2.13514DOI Listing
September 2021

Ultrasound Diagnosis of Cardiac Arrest in an 81-Year-Old Postoperative Patient.

Chest 2021 Aug;160(2):e233-e236

Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiac Intensive Care, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1016/j.chest.2020.07.105DOI Listing
August 2021

Endurance exercise and the risk of cardiovascular pathology in men: a comparison between lifelong and late-onset endurance training and a non-athletic lifestyle - rationale and design of the [email protected] study, a prospective cohort trial.

BMJ Open Sport Exerc Med 2021 16;7(2):e001048. Epub 2021 Apr 16.

Cardiovascular Sciences, KU Leuven University Hospitals Leuven, Leuven, Flanders, Belgium.

Introduction: Low and moderate endurance exercise is associated with better control of cardiovascular risk factors, a decreased risk of coronary artery disease and atrial fibrillation (AF). There is, however, a growing proportion of individuals regularly performing strenuous and prolonged endurance exercise in which the health benefits have been challenged. Higher doses of endurance exercise have been associated with a greater coronary atherosclerotic plaque burden, risk of AF and myocardial fibrosis (MF).

Methods And Analysis: [email protected] is a multicentre prospective cohort study aiming to assess the incidence of coronary atherosclerosis, AF and MF in lifelong endurance athletes compared to late-onset endurance athletes (initiation of regular endurance exercise after the age of 30 years) and healthy non-athletes.The primary endpoint is the incidence of mixed coronary plaques. Secondary endpoints include coronary calcium scores, coronary stenosis >50%, the prevalence of calcified and soft plaques and AF and MF presence. Tertiary endpoints include ventricular arrhythmias, left and right ventricular function at rest and during exercise, arterial stiffness and carotid artery intima media thickness.Two hundred male lifelong athletes, 200 late-onset athletes and 200 healthy non-athletes aged 45-70 will undergo comprehensive cardiovascular phenotyping using CT, coronary angiography, echocardiography, cardiac MRI, 12-lead ECG, exercise ECG and 24-hour Holter monitoring at baseline. Follow-up will include online tracking of sports activities, telephone calls to assess clinical events and a 7-day ECG recording after 1 year.

Ethics And Dissemination: Local ethics committees approved the [email protected] study. The trial was launched on 18 October 2018, recruitment is complete and inclusions are ongoing.

Trial Registration Number: NCT03711539.
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http://dx.doi.org/10.1136/bmjsem-2021-001048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055127PMC
April 2021

Oxygen Pathway Limitations in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Circulation 2021 May 15;143(21):2061-2073. Epub 2021 Apr 15.

Baker Heart and Diabetes Institute (E.J.H., S.R.-C., A.L.G., G.C.), Melbourne, Australia.

Background: 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/perfusion 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.

Methods: Using exercise cardiac magnetic resonance imaging with simultaneous invasive hemodynamic monitoring, we sought to quantify the steps of the O 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 individual components of the cascade (n=10).

Results: Peak Vo (oxygen uptake) was significantly reduced in patients with CTEPH relative to controls (56±17 versus 112±20% of predicted; <0.0001). The difference was attributable to impairments in multiple steps of the O cascade, including O delivery (product of cardiac output and arterial O content), skeletal muscle diffusion capacity, and pulmonary diffusion. The total O extracted in the periphery (ie, ΔAVo [arteriovenous O content difference]) was not different. After pulmonary vascular intervention, peak Vo increased significantly (from 12.5±4.0 to 17.8±7.5 mL/[kg·min]; =0.036) but remained below age-predicted levels (70±11%). The O delivery was improved owing to an increase in peak cardiac output and lung diffusion capacity. However, peak exercise ΔAVo was unchanged, as was skeletal muscle diffusion capacity.

Conclusions: We demonstrated that patients with CTEPH have significant impairment of all steps in the O use cascade, resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increased peak Vo by partly correcting O delivery but had no effect on abnormalities in peripheral O extraction. This suggests that current interventions only partially address patients' limitations and that additional therapies may improve functional capacity.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052899DOI Listing
May 2021

Iron Deficiency Is Associated With Impaired Biventricular Reserve and Reduced Exercise Capacity in Patients With Unexplained Dyspnea.

J Card Fail 2021 07 7;27(7):766-776. Epub 2021 Apr 7.

Department of Cardiology, Hartcentrum, Jessa Hospital, Hasselt, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.

Background: Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear.

Methods And Results: Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography in a tertiary care dyspnea clinic. ID was defined as ferritin of <300 µg/L and a transferrin saturation of <20% and its impact on peak oxygen uptake (peakVO), biventricular response to exercise, and peripheral oxygen extraction was assessed. Of 272 patients who underwent cardiopulmonary exercise testing with echocardiography, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO (14.6 ± 7.6 mL/kg/minvs 17.8 ± 8.8 mL/kg/min; P = .009) and maximal workload (89 ± 50 watt vs 108 ± 56 watt P = .047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (P < .05) and depressed RV function by tricuspid s' (P = .004), tricuspid annular plane systolic excursion (P = .034), and RV end-systolic pressure-area ratio (P = .038), with more RV-pulmonary artery uncoupling measured by tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure ratio (P = .023). RV end-systolic pressure-area ratio change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09 ± 0.72 mm Hg/cm vs 2.58 ± 1.14 mm Hg/cm; P < .001). ID was associated with impaired peripheral oxygen extraction (peakVO/peak cardiac output; P = .036). Cardiopulmonary exercise testing with echocardiography resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio of >14, with equal distribution in patients with (28.6%) or without ID (25.4%, P = .611). None of these findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea.

Conclusions: In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with decreased exercise capacity, diminished biventricular contractile reserve, and decreased peripheral oxygen extraction.
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http://dx.doi.org/10.1016/j.cardfail.2021.03.010DOI Listing
July 2021

Response to Sanchis-Gomar et al. 'Atrial fibrillation in athletes and non-athletes: evidence of different causative mechanisms'.

Eur Heart J Cardiovasc Imaging 2021 05;22(6):722

Department of Cardiology, Westmead Hospital, Sydney, Australia.

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http://dx.doi.org/10.1093/ehjci/jeab060DOI Listing
May 2021

The effect of posture on maximal oxygen uptake in active healthy individuals.

Eur J Appl Physiol 2021 May 27;121(5):1487-1498. Epub 2021 Feb 27.

Sports Cardiology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia.

Purpose: Semi-supine and supine cardiopulmonary exercise testing (CPET) with concurrent cardiac imaging has emerged as a valuable tool for evaluating patients with cardiovascular disease. Yet, it is unclear how posture effects CPET measures. We aimed to discern the effect of posture on maximal oxygen uptake (VOmax) and its determinants using three clinically relevant cycle ergometers.

Methods: In random order, 10 healthy, active males (Age 27 ± 7 years; BMI 23 ± 2 kg m) underwent a ramp CPET and subsequent constant workload verification test performed at 105% peak ramp power to quantify VOmax on upright, semi-supine and supine cycle ergometers. Doppler echocardiography was conducted at peak exercise to measure stroke volume (SV) which was multiplied by heart rate (HR) to calculate cardiac output (CO).

Results: Compared to upright (46.8 ± 11.2 ml/kg/min), VOmax was progressively reduced in semi-supine (43.8 ± 10.6 ml/kg/min) and supine (38.2 ± 9.3 ml/kg/min; upright vs. semi-supine vs. supine; all p ≤ 0.005). Similarly, peak power was highest in upright (325 ± 80 W), followed by semi-supine (298 ± 72 W) and supine (200 ± 51 W; upright vs. semi-supine vs. supine; all p < 0.01). Peak HR decreased progressively from upright to semi-supine to supine (186 ± 11 vs. 176 ± 13 vs. 169 ± 12 bpm; all p < 0.05). Peak SV and CO were lower in supine relative to semi-supine and upright (82 ± 22 vs. 92 ± 26 vs. 91 ± 24 ml and 14 ± 3 vs. 16 ± 4 vs. 17 ± 4 l/min; all p < 0.01), but not different between semi-supine and upright.

Conclusion: VOmax is progressively reduced in reclined postures. Thus, posture should be considered when comparing VOmax results between different testing modalities.
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http://dx.doi.org/10.1007/s00421-021-04630-7DOI Listing
May 2021

Exercise with End-expiratory Breath Holding Induces Large Increase in Stroke Volume.

Int J Sports Med 2021 Jan 25;42(1):56-65. Epub 2020 Aug 25.

UFR de Santé, Médecine et Biologie Humaine, Université Paris 13, Bobigny, France.

Eight well-trained male cyclists participated in two testing sessions each including two sets of 10 cycle exercise bouts at 150% of maximal aerobic power. In the first session, subjects performed the exercise bouts with end-expiratory breath holding (EEBH) of maximal duration. Each exercise bout started at the onset of EEBH and ended at its release (mean duration: 9.6±0.9 s; range: 8.6-11.1 s). At the second testing session, subjects performed the exercise bouts (same duration as in the first session) with normal breathing. Heart rate, left ventricular stroke volume (LVSV), and cardiac output were continuously measured through bio-impedancemetry. Data were analysed for the 4 s preceding and following the end of each exercise bout. LVSV (peak values: 163±33 vs. 124±17 mL, p<0.01) was higher and heart rate lower both in the end phase and in the early recovery of the exercise bouts with EEBH as compared with exercise with normal breathing. Cardiac output was generally not different between exercise conditions. This study showed that performing maximal EEBH during high-intensity exercise led to a large increase in LVSV. This phenomenon is likely explained by greater left ventricular filling as a result of an augmented filling time and decreased right ventricular volume at peak EEBH.
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http://dx.doi.org/10.1055/a-1179-6093DOI Listing
January 2021

Differing mechanisms of atrial fibrillation in athletes and non-athletes: alterations in atrial structure and function.

Eur Heart J Cardiovasc Imaging 2020 12;21(12):1374-1383

Sports Cardiology Lab, Baker Heart and Diabetes Institute, Melbourne, Australia.

Aims: Atrial fibrillation (AF) is more common in athletes and may be associated with adverse left atrial (LA) remodelling. We compared LA structure and function in athletes and non-athletes with and without AF.

Methods And Results: Individuals (144) were recruited from four groups (each n = 36): (i) endurance athletes with paroxysmal AF, (ii) endurance athletes without AF, (iii) non-athletes with paroxysmal AF, and (iv) non-athletic healthy controls. Detailed echocardiograms were performed. Athletes had 35% larger LA volumes and 51% larger left ventricular (LV) volumes vs. non-athletes. Non-athletes with AF had increased LA size compared with controls. LA/LV volume ratios were similar in both athlete groups and non-athlete controls, but LA volumes were differentially increased in non-athletes with AF. Diastolic function was impaired in non-athletes with AF vs. non-athletes without, while athletes with and without AF had normal diastolic function. Compared with non-AF athletes, athletes with AF had increased LA minimum volumes (22.6 ± 5.6 vs. 19.2 ± 6.7 mL/m2, P = 0.033), with reduced LA emptying fraction (0.49 ± 0.06 vs. 0.55 ± 0.12, P = 0.02), and LA expansion index (1.0 ± 0.3 vs. 1.2 ± 0.5, P = 0.03). LA reservoir and contractile strain were decreased in athletes and similar to non-athletes with AF.

Conclusion: Functional associations differed between athletes and non-athletes with AF, suggesting different pathophysiological mechanisms. Diastolic dysfunction and reduced strain defined non-athletes with AF. Athletes had low atrial strain and those with AF had enlarged LA volumes and reduced atrial emptying, but preserved LV diastolic parameters. Thus, AF in athletes may be triggered by an atrial myopathy from exercise-induced haemodynamic stretch consequent to increased cardiac output.
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http://dx.doi.org/10.1093/ehjci/jeaa183DOI Listing
December 2020

The Utility of Cardiac Reserve for the Early Detection of Cancer Treatment-Related Cardiac Dysfunction: A Comprehensive Overview.

Front Cardiovasc Med 2020 10;7:32. Epub 2020 Mar 10.

Department of Sports Cardiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

With progressive advancements in cancer detection and treatment, cancer-specific survival has improved dramatically over the past decades. Consequently, long-term health outcomes are increasingly defined by comorbidities such as cardiovascular disease. Importantly, a number of well-established and emerging cancer treatments have been associated with varying degrees of cardiovascular injury that may not emerge until years following the completion of cancer treatment. Of particular concern is the development of cancer treatment related cardiac dysfunction (CTRCD) which is associated with an increased risk of heart failure and high risk of morbidity and mortality. Early detection of CTRCD appears critical for preventing long-term cardiovascular morbidity in cancer survivors. However, current clinical standards for the identification of CTRCD rely on assessments of cardiac function in the resting state. This provides incomplete information about the heart's reserve capacity and may reduce the sensitivity for detecting sub-clinical myocardial injury. Advances in non-invasive imaging techniques have enabled cardiac function to be quantified during exercise thereby providing a novel means of identifying early cardiac dysfunction that has proved useful in several cardiovascular pathologies. The purpose of this narrative review is (1) to discuss the different non-invasive imaging techniques that can be used for quantifying different aspects of cardiac reserve; (2) discuss the findings from studies of cancer patients that have measured cardiac reserve as a marker of CTRCD; and (3) highlight the future directions important knowledge gaps that need to be addressed for cardiac reserve to be effectively integrated into routine monitoring for cancer patients exposed to cardiotoxic therapies.
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http://dx.doi.org/10.3389/fcvm.2020.00032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076049PMC
March 2020

Right ventricular strain rate during exercise accurately identifies male athletes with right ventricular arrhythmias.

Eur Heart J Cardiovasc Imaging 2020 03;21(3):282-290

Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, BE-3000 Leuven, Belgium.

Aims: 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.

Methods And Results: 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).

Conclusion: 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.
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http://dx.doi.org/10.1093/ehjci/jez228DOI Listing
March 2020

Heart Rate Reserve in Fontan Patients: Chronotropic Incompetence or Hemodynamic Limitation?

J Am Heart Assoc 2019 05;8(9):e012008

1 Department of Cardiovascular Sciences KU Leuven Leuven Belgium.

Background Patients with a Fontan circulation achieve lower peak heart rates ( HR ) during exercise. Whether this impaired chronotropic response reflects pathology of the sinoatrial node or is a consequence of altered cardiac hemodynamics is uncertain. We evaluated the adequacy of HR acceleration throughout exercise relative to metabolic demand and cardiac output in patients with a Fontan circulation relative to healthy controls. Methods and Results Thirty subjects (20 healthy controls and 10 Fontan patients) underwent cardiac magnetic resonance imaging with simultaneous invasive pressure recording via a pulmonary and radial artery catheter during supine bicycle exercise to near maximal exertion. Adequacy of cardiac index, stroke volume, and HR reserve was assessed by determining the exercise-induced increase (∆) in cardiac index, stroke volume, and HR relative to the increase in oxygen consumption ( VO ). HR reserve was lower in Fontan patients compared with controls (71±21 versus 92±15 bpm; P=0.001). In contrast, increases in HR relative to workload and VO were higher than in controls. The change in cardiac index relative to the change in VO (∆cardiac index/∆ VO ) was similar between groups, but Fontan patients had increased ∆ HR /∆ VO and reduced ∆ stroke volume/∆ VO compared with controls. There was an early and marked reduction in stroke volume during exercise in Fontan patients corresponding with a plateau in cardiac output at a low peak HR . Conclusions In Fontan patients, the chronotropic response is appropriate relative to exercise intensity, implying normal sinoatrial function. However, premature reductions in ventricular filling and stroke volume cause an early plateau in cardiac output beyond which further increases in HR would be physiologically implausible. Thus, abnormal cardiac filling rather than sinoatrial node dysfunction explains the diminished HR reserve in Fontan patients.
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http://dx.doi.org/10.1161/JAHA.119.012008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512107PMC
May 2019

The effect of minimally invasive surgical aortic valve replacement on postoperative pulmonary and skeletal muscle function.

Exp Physiol 2019 06 19;104(6):855-865. Epub 2019 Apr 19.

BIOMED - Biomedical Research Center, and REVAL - Rehabilitation Research Center, Faculty of Medicine and Life Sciences, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium.

New Findings: What is the central question of this study? How does surgical aortic valve replacement affect cardiopulmonary and muscle function during exercise? What is the main finding and its importance? Early after the surgical replacement of the aortic valve a significant decline in pulmonary function was observed, which was followed by a decline in skeletal muscle function in the subsequent weeks of recovery. These date reiterate, despite restoration of aortic valve function, the need for a tailored rehabilitation programme for the respiratory and peripheral muscular system.

Abstract: Suboptimal post-operative improvements in functional capacity are often observed after minimally invasive aortic valve replacement (mini-AVR). It remains to be studied how AVR affects the cardiopulmonary and skeletal muscle function during exercise to explain these clinical observations and to provide a basis for improved/tailored post-operative rehabilitation. Twenty-two patients with severe aortic stenosis (AS) (aortic valve area (AVA) <1.0 cm²) were pre-operatively compared to 22 healthy controls during submaximal constant-workload endurance-type exercise for oxygen uptake ( ), carbon dioxide output ( ), respiratory gas exchange ratio, expiratory volume ( ), ventilatory equivalents for O ( / ) and CO ( / ), respiratory rate (RR), tidal volume (V ), heart rate (HR), oxygen pulse ( /HR), blood lactate, Borg ratings of perceived exertion (RPE) and exercise-onset kinetics. These exercise tests were repeated at 5 and 21 days after AVR surgery (n = 14), along with echocardiographic examinations. Respiratory exchange ratio and ventilatory equivalents ( / and / ) were significantly elevated, and /HR were significantly lowered, and exercise-onset kinetics were significantly slower in AS patients vs. healthy controls (P < 0.05). Although the AVA was restored by mini-AVR in AS patients, / and / further worsened significantly within 5 days after surgery, accompanied by elevations in Borg RPE, and RR, and lowered V . At 21 days after mini-AVR, exercise-onset kinetics further slowed significantly (P < 0.05). A decline in pulmonary function was observed early after mini-AVR surgery, which was followed by a decline in skeletal muscle function in the subsequent weeks of recovery. Therefore, a tailored rehabilitation programme should include training modalities for the respiratory and peripheral muscular system.
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http://dx.doi.org/10.1113/EP087407DOI Listing
June 2019

Right Ventricular Function: The Barometer of All That Lies Ahead.

JACC Cardiovasc Imaging 2019 12 13;12(12):2386-2388. Epub 2019 Feb 13.

Clinical Research Domain, Baker Heart and Diabetes Institute, Melbourne, Australia; Division of Cardiology, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1016/j.jcmg.2018.12.018DOI Listing
December 2019

Unsupervised respiratory signal extraction from ungated cardiac magnetic resonance imaging at rest and during exercise.

Phys Med Biol 2019 03 8;64(6):065001. Epub 2019 Mar 8.

KU Leuven, Department of Cardiovascular Sciences, Cardiovascular Imaging and Dynamics, Leuven, Belgium.

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.
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http://dx.doi.org/10.1088/1361-6560/ab02cdDOI Listing
March 2019

Robust motion correction for cardiac T1 and ECV mapping using a T1 relaxation model approach.

Med Image Anal 2019 02 18;52:212-227. Epub 2018 Dec 18.

Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium; Medical Imaging Research Center, UZ Leuven, Herestraat 49 - 7003, Leuven, 3000, Belgium.

T1 and ECV mapping are quantitative methods for myocardial tissue characterization using cardiac MRI, and are highly relevant for the diagnosis of diffuse myocardial diseases. Since the maps are calculated pixel-by-pixel from a set of MRI images with different T1-weighting, it is critical to assure exact spatial correspondence between these images. However, in practice, different sources of motion e.g. cardiac motion, respiratory motion or patient motion, hamper accurate T1 and ECV calculation such that retrospective motion correction is required. We propose a new robust non-rigid registration framework combining a data-driven initialization with a model-based registration approach, which uses a model for T1 relaxation to avoid direct registration of images with highly varying contrast. The registration between native T1 and enhanced T1 to obtain a motion free ECV map is also calculated using information from T1 model-fitting. The method was validated on three datasets recorded with two substantially different acquisition protocols (MOLLI (dataset 1 (n=15) and dataset 2 (n=29)) and STONE (dataset 3 (n = 210))), one in breath-hold condition and one free-breathing. The average Dice coefficient increased from 72.6 ± 12.1% to 82.3 ± 7.4% (P < 0.05) and mean boundary error decreased from 2.91 ± 1.51mm to 1.62 ± 0.80mm (P < 0.05) for motion correction in a single T1-weighted image sequence (3 datasets) while average Dice coefficient increased from 63.4 ± 22.5% to 79.2 ± 8.5% (P < 0.05) and mean boundary error decreased from 3.26 ± 2.64mm to 1.77 ± 0.86mm (P < 0.05) between native and enhanced sequences (dataset 1 and 2). Overall, the native T1 SD error decreased from 67.32 ± 32.57ms to 58.11 ± 21.59ms (P < 0.05), enhanced SD error from 30.15 ± 25ms to 22.74 ± 8.94ms (P < 0.05) and ECV SD error from 10.08 ± 9.59% to 5.42 ± 3.21% (P < 0.05) (dataset 1 and 2).
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http://dx.doi.org/10.1016/j.media.2018.12.004DOI Listing
February 2019

Advanced Imaging to Phenotype Patients With a Systemic Right Ventricle.

J Am Heart Assoc 2018 10;7(20):e009185

1 Department of Cardiovascular Sciences KU Leuven-University of Leuven Belgium.

Background 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. Methods and Results 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. Conclusions 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.
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http://dx.doi.org/10.1161/JAHA.118.009185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474967PMC
October 2018

Impaired Cardiac Reserve and Abnormal Vascular Load Limit Exercise Capacity in Chronic Thromboembolic Disease.

JACC Cardiovasc Imaging 2019 08 12;12(8 Pt 1):1444-1456. Epub 2018 Sep 12.

Department of Pneumology, University Hospitals Leuven, Leuven, Belgium; Division of Pneumology, Department of Chronic Diseases, Metabolism and Aging, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.

Objectives: This study was a comprehensive evaluation of cardiopulmonary function in patients with chronic thromboembolic (pulmonary vascular) disease (CTED) during exercise.

Background: 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.

Methods: 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.

Results: 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 × min) and CTEPH patients (8.85 [interquartile range: 7.18 to 10.4] mm Hg × l × min) had abnormal total pulmonary vascular resistance. Right ventricular contractile reserve was reduced in CTED patients compared with control subjects (2.23 ± 0.55 vs. 3.72 ± 0.94), but was still higher than that in CTEPH patients (1.34 ± 0.24; p < 0.001). As opposed to patients with CTEPH in whom right ventricular ejection fraction declined with exercise, right ventricular ejection fraction still increased in patients with CTED, albeit to a lesser extent than in healthy control subjects (interaction p < 0.001), which illustrated the distinct patterns of ventricular-arterial coupling.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.jcmg.2018.07.021DOI Listing
August 2019

Exercise cardiac magnetic resonance to differentiate athlete's heart from structural heart disease.

Eur Heart J Cardiovasc Imaging 2018 09;19(9):1062-1070

University Hospital Antwerp, Antwerp, Belgium.

Aims: 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.

Methods And Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1093/ehjci/jey050DOI Listing
September 2018

Right ventricular systolic dysfunction at rest is not related to decreased exercise capacity in patients with a systemic right ventricle.

Int J Cardiol 2018 06 8;260:66-71. Epub 2018 Mar 8.

Unit of Cardiology, Department of Cardiovascular Sciences, KU Leuven - University of Leuven, Leuven, Belgium; Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Background: To evaluate the relationship between right ventricular (RV) systolic dysfunction at rest and reduced exercise capacity in patients with a systemic RV (sRV).

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.ijcard.2018.03.029DOI Listing
June 2018

Atrial volume and function during exercise in health and disease.

J Cardiovasc Magn Reson 2017 Dec 18;19(1):104. Epub 2017 Dec 18.

Department of Cardiology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium.

Background: Although atrial function has prognostic significance in many cardiovascular conditions, changes during exercise have not previously been assessed. The aim of this study was to evaluate left atrial (LA) and right atrial (RA) volume and function during incremental exercise, both in normal individuals, healthy athletes, and in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Methods: Fifteen healthy non-athletes, 15 athletes and 15 CTEPH patients underwent multi-slice real-time cardiovascular magnetic resonance imaging at rest and during supine bicycle exercise with simultaneous invasive hemodynamic measurements.

Results: At rest, athletes had larger indexed maximal RA and LA volumes (iRAVmax, iLAVmax) than CTEPH patients and non-athletes, the latter two groups having similar values. CTEPH patients had lower RA and LA emptying functions (EmF) at rest. During exercise, RA volumes (maximum and minimum) increased in CTEPH patients, whilst decreasing in athletes and non-athletes (P < 0.001). The exercise-induced change in iLAVmax was similar between groups, but iLAVmin did not decrease in CTEPH patients. Thus exercise-induced increases in RAEmF and LAEmF, as seen in normal physiology, were significantly impaired in CTEPH patients. At peak exercise, RA volumes (maximum and minimum) and EmF correlated strongly with RA pressure (R = 0.70; P = 0.005; R = 0.83; P < 0.001; R = -0.87; P < 0.001). On multivariate analysis, peak exercise RAEmF and iLAVmin were independent predictors of VOpeak in CTEPH patients and together explained 72% of the variance in VOpeak (ß =0.581 and ß = -0.515, respectively).

Conclusions: In normal physiology, RAEmF and LAEmF increase with exercise, whereas CTEPH patients have impaired LAEmF and RAEmF, which becomes more apparent during exercise. Therefore, the changes in atrial volumes and function during exercise enable a far better distinction between physiological and pathological atrial remodeling than resting measures of volumes which are prone to confounding factors (e.g. endurance training). Peak exercise RAEmF is a good marker of poor functional state in CTEPH patients.
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http://dx.doi.org/10.1186/s12968-017-0416-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735907PMC
December 2017

Atrial deformation in athletes with AF: chronic adverse remodelling or transient mechanical stunning?

Eur Heart J Cardiovasc Imaging 2018 02;19(2):154-156

Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, Leuven B-3000, Belgium.

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http://dx.doi.org/10.1093/ehjci/jex245DOI Listing
February 2018

Exercise and the right ventricle: a potential Achilles' heel.

Cardiovasc Res 2017 Oct;113(12):1499-1508

Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.

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 example 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 individuals predisposed to arrhythmogenic cardiomyopathy.
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http://dx.doi.org/10.1093/cvr/cvx156DOI Listing
October 2017

Pulmonary Vascular Function During Exercise: Progressing Toward Routine Clinical Use.

Circ Cardiovasc Imaging 2017 04;10(4)

From the Department of Cardiovascular Sciences, KU Leuven, Belgium (G.C., A.L.G.); Department of Cardiovascular Medicine, University Hospitals Leuven, Belgium (G.C.); and Baker Heart and Diabetes Institute, Melbourne, Australia (A.L.G.).

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http://dx.doi.org/10.1161/CIRCIMAGING.117.006326DOI Listing
April 2017

Letter by Heidbuchel et al Regarding Article, "Right and Left Ventricular Function and Mass in Male Elite Master Athletes: A Controlled Contrast-Enhanced Cardiovascular Magnetic Resonance Study".

Circulation 2016 10;134(16):e360-e361

From University Hospital and University of Antwerp, Antwerp, Belgium (H.H.); Department of Cardiovascular Sciences and University Hospital, University of Leuven, Leuven, Belgium (G.C.); and Baker IDI Heart and Diabetes Institute, Melbourne, Australia (A.L.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024071DOI Listing
October 2016

Stressing the right ventricular-pulmonary vascular unit: beyond pulmonary vascular resistance.

Heart 2017 03 11;103(6):404-406. Epub 2016 Oct 11.

Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1136/heartjnl-2016-310360DOI Listing
March 2017

Increased Flow, Dam Walls, and Upstream Pressure: The Physiological Challenges and Atrial Consequences of Intense Exercise.

JACC Cardiovasc Imaging 2016 12 17;9(12):1389-1391. Epub 2016 Aug 17.

Department of Cardiovascular Medicine, University Hospital Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1016/j.jcmg.2016.06.008DOI Listing
December 2016
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