Andre La Gerche

Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes

AIMS Endurance training may be associated with arrhythmogenic cardiac remodelling of the right ventricle (RV). We examined whether myocardial dysfunction following intense endurance exercise affects the RV more than the left ventricle (LV) and whether cumulative exposure to endurance competition influences cardiac remodelling (including fibrosis) in well-trained athletes. METHODS AND RESULTS Forty athletes were studied at baseline, immediately following an endurance race (3-11 h duration) and 1-week post-race. Evaluation included cardiac troponin (cTnI), B-type natriuretic peptide, and echocardiography [including three-dimensional volumes, ejection fraction (EF), and systolic strain rate]. Delayed gadolinium enhancement (DGE) on cardiac magnetic resonance imaging (CMR) was assessed as a marker of myocardial fibrosis. Relative to baseline, RV volumes increased and all functional measures decreased post-race, whereas LV volumes reduced and function was preserved. B-type natriuretic peptide (13.1 ± 14.0 vs. 25.4 ± 21.4 ng/L, P = 0.003) and cTnI (0.01 ± .03 vs. 0.14 ± .17 μg/L, P < 0.0001) increased post-race and correlated with reductions in RVEF (r = 0.52, P = 0.001 and r = 0.49, P = 0.002, respectively), but not LVEF. Right ventricular ejection fraction decreased with increasing race duration (r = -0.501, P < 0.0001) and VO(2)max (r = -0.359, P = 0.011). Right ventricular function mostly recovered by 1 week. On CMR, DGE localized to the interventricular septum was identified in 5 of 39 athletes who had greater cumulative exercise exposure and lower RVEF (47.1 ± 5.9 vs. 51.1 ± 3.7%, P = 0.042) than those with normal CMR. CONCLUSION Intense endurance exercise causes acute dysfunction of the RV, but not the LV. Although short-term recovery appears complete, chronic structural changes and reduced RV function are evident in some of the most practiced athletes, the long-term clinical significance of which warrants further study.

Disproportionate Exercise Load and Remodeling of the Athlete's Right Ventricle

PURPOSE There is evolving evidence that intense exercise may place a disproportionate load on the right ventricle (RV) when compared with the left ventricle (LV) of the heart. Using a novel method of estimating end-systolic wall stress (ES-σ), we compared the RV and LV during exercise and assessed whether this influenced chronic ventricular remodeling in athletes. METHODS For this study, 39 endurance athletes (EA) and 14 nonathletes (NA) underwent resting cardiac magnetic resonance (CMR), maximal oxygen uptake (VO2), and exercise echocardiography studies. LV and RV end-systolic wall stress (ES-σ) were calculated using the Laplace relation (ES-σ = Pr/(2h)). Ventricular size and wall thickness were determined by CMR; invasive and Doppler echo estimates were used to measure systemic and pulmonary ventricular pressures, respectively; and stroke volume was quantified by Doppler echocardiography and used to calculate changes in ventricular geometry during exercise. RESULTS In EA, compared with NA, resting CMR measures showed greater RV than LV remodeling. The ratios RV ESV/LV ESV (1.40 ± 0.23 vs 1.26 ± 0.12, P = 0.007) and RV mass/LV mass (0.29 ± 0.04 vs 0.25 ± 0.03, P = 0.012) were greater in EA than in NA. RVES-σ was lower at rest than LVES-σ (143 ± 44 vs 252 ± 49 kdyn · cm, P < 0.001) but increased more with strenuous exercise (125% vs 14%, P < 0.001), resulting in similar peak exercise ES-σ (321 ± 106 vs 286 ± 77 kdyn · cm, P = 0.058). Peak exercise RVES-σ was greater in EA than in NA (340 ± 107 vs 266 ± 82 kdyn · cm, P = 0.028), whereas RVES-σ at matched absolute workloads did not differ (P = 0.79). CONCLUSIONS Exercise induces a relative increase in RVES-σ which exceeds LVES-σ. In athletes, greater RV enlargement and greater wall thickening may be a product of this disproportionate load excess.

The Fontan circulation: who controls cardiac output?

In a Fontan circuit the mechanisms involved in control of cardiac output at rest and during exercise differ significantly from normal. The classical model presumes an unlimited preload which is not available in the Fontan circuit. This review critically analyses the role of contractility, heart rate, and afterload and highlights the importance of pulmonary vascular resistance (PVR) in determining adequate preload and, therefore, cardiac output in these patients. A conceptual model of the determinants of cardiac output in Fontan patients is presented.

Left ventricular strain and strain rate: characterization of the effect of load in human subjects.

AIMS Left ventricular (LV) strain and strain rate have been proposed as novel indices of systolic function; however, there are limited data about the effect of acute changes on these parameters. METHODS AND RESULTS Simultaneous Millar micromanometer LV pressure and echocardiographic assessment were performed on 18 patients. Loading was altered sequentially by the administration of glyceryl trinitrate (GTN) and saline fluid loading. Echocardiographic speckle tracking imaging was used to quantify the peak systolic strain (S) and peak systolic strain rate (SR S) and dp/dt max was recorded from the micromanometer data. GTN administration decreased preload (LV end diastolic pressure [LVEDP]: 15.7 vs. 8.4 mmHg, P < 0.001) and afterload (end systolic wall stress: 74 vs. 43 x 10(3)dyn/cm(2), P < 0.001). Administration of fluid increased preload (LVEDP: 11.3 vs. 18.1 mmHg, P < 0.001) and increased wall stress (53 vs. 62 x 10(3)dyn/cm(2), P < 0.003). Administration of GTN resulted in increased circumferential SR S (-1.2 vs. -1.7s(-1), P < 0.01) and longitudinal SR S (-0.9 vs. -1.0 s(-1), P < 0.001). The administration of fluid resulted in decreased circumferential SR S (-1.5 vs. -1.3s(-1), P < 0.01) and longitudinal SR S (-1.0 vs. -0.9s(-1), P < 0.01). As preload and afterload increased, decrease in circumferential SR S (r = 0.63, P < 0.001; r = 0.56, P<0.001) and longitudinal SR S were observed (r = 0.42, P < 0.003; r = 0.49 P < 0.001). CONCLUSION Circumferential and longitudinal peak strain and systolic strain rate are sensitive to acute changes in load, an important factor that needs to be considered in their application as indices of systolic function.

Pulmonary transit of agitated contrast is associated with enhanced pulmonary vascular reserve and right ventricular function during exercise

Pulmonary transit of agitated contrast (PTAC) occurs to variable extents during exercise. We tested the hypothesis that the onset of PTAC signifies flow through larger-caliber vessels, resulting in improved pulmonary vascular reserve during exercise. Forty athletes and fifteen nonathletes performed maximal exercise with continuous echocardiographic Doppler measures [cardiac output (CO), pulmonary artery systolic pressure (PASP), and myocardial velocities] and invasive blood pressure (BP). Arterial gases and B-type natriuretic peptide (BNP) were measured at baseline and peak exercise. Pulmonary vascular resistance (PVR) was determined as the regression of PASP/CO and was compared according to athletic and PTAC status. At peak exercise, athletes had greater CO (16.0 ± 2.9 vs. 12.4 ± 3.2 l/min, P < 0.001) and higher PASP (60.8 ± 12.6 vs. 47.0 ± 6.5 mmHg, P < 0.001), but PVR was similar to nonathletes (P = 0.71). High PTAC (defined by contrast filling of the left ventricle) occurred in a similar proportion of athletes and nonathletes (18/40 vs. 10/15, P = 0.35) and was associated with higher peak-exercise CO (16.1 ± 3.4 vs. 13.9 ± 2.9 l/min, P = 0.010), lower PASP (52.3 ± 9.8 vs. 62.6 ± 13.7 mmHg, P = 0.003), and 37% lower PVR (P < 0.0001) relative to low PTAC. Right ventricular (RV) myocardial velocities increased more and BNP increased less in high vs. low PTAC subjects. On multivariate analysis, maximal oxygen consumption (VO(2max)) (P = 0.009) and maximal exercise output (P = 0.049) were greater in high PTAC subjects. An exercise-induced decrease in arterial oxygen saturation (98.0 ± 0.4 vs. 96.7 ± 1.4%, P < 0.0001) was not influenced by PTAC status (P = 0.96). Increased PTAC during exercise is a marker of pulmonary vascular reserve reflected by greater flow, reduced PVR, and enhanced RV function.

Left Ventricular Untwisting Is an Important Determinant of Early Diastolic Function

OBJECTIVES We sought to establish the relationship between invasive measures of diastolic function and untwisting parameters measured with speckle tracking imaging. BACKGROUND Left ventricular (LV) diastolic function is determined by early diastolic relaxation (which creates suction gradients for LV filling) and myocardial stiffness. Assessment of LV torsion has shown that untwisting begins before aortic valve closure and, in animals, might be an important component of normal diastolic filling. Studies in human subjects using indirect indexes derived from right heart catheterization have suggested a relationship between tau and measures of untwisting, but the relationship between directly measured diastolic function indexes with micromanometer catheters and untwisting parameters has not been established in human subjects. METHODS Simultaneous Millar micromanometer LV pressure and echocardiographic assessment was performed on 18 patients (10 male, mean age 66 years) with normal systolic function and a spectrum of diastolic function. Invasive rate of the rise of LV pressure, dp/dt minimum and tau were recorded as measures of active relaxation, and the LV minimum diastolic pressure was recorded as an index of diastolic suction. The LV stiffness constant and functional chamber stiffness were estimated from hybrid pressure-volume loops. Echocardiographic speckle tracking imaging was used to quantify torsion. RESULTS As relaxation was impaired, (prolonged tau) untwisting was delayed (r = 0.35, p < 0.01). There were nonsignificant associations between reduced untwisting and longer values of tau and lower dp/dt minimum. Reduction in the extent of untwisting before mitral valve opening was associated with increased LV minimum diastolic pressure (r = -0.30, p < 0.034). No relation was observed between the LV stiffness constant (beta: r = 0.11, p = NS) or the functional LV chamber stiffness (b: r = 0.11, p = NS) and untwisting. CONCLUSIONS Untwisting parameters are related to invasive indexes of LV relaxation and suction but not to LV stiffness. These data suggest that untwisting is an important component of early diastolic LV filling but not later diastolic events.

Exercise Strain Rate Imaging Demonstrates Normal Right Ventricular Contractile Reserve and Clarifies Ambiguous Resting Measures in Endurance Athletes

BACKGROUND The significance of reduced right ventricular (RV) deformation reported in endurance athletes (EAs) is unclear, highlighting the ambiguities between physiologic RV remodeling and pathology. The aim of this study was to test the hypothesis that RV functional reserve would be normal in EAs despite reduced deformation measures at rest. METHODS Forty EAs and 15 nonathletes (NAs) performed maximal incremental exercise with simultaneous echocardiographic measures of RV function. Two-dimensional (2D) and color-coded Doppler acquisitions were used to quantify peak systolic strain and strain rate (SRs) for the basal, mid, and apical RV free wall. A second surrogate of contractility, the RV end-systolic pressure-area relationship, was calculated from the tricuspid regurgitant velocity and the RV end-systolic area. Changes in multiple measures obtained throughout exercise were used to assess the affect of exercise on RV contractility. RESULTS Compared with NAs at rest, basal RV strain and SRs were reduced in EAs, with good agreement between 2D and Doppler methods. During exercise, there was a strong linear correlation between heart rate and global SRs (r = -0.74 and r = -0.84 for Doppler and 2D methods, respectively, P < .0001), which was similar for EAs and NAs (P = .21 and P = .97 for differences in mean regression slopes by Doppler and 2D echocardiography, respectively). Exercise-induced increases in the RV end-systolic pressure-area relationship were also similar for EAs and NAs (P = .42). There was a strong correlation between RV global SRs and the RV end-systolic pressure-area relationship during exercise (r = 0.71, P < .0001). CONCLUSIONS Comparable RV contractile reserve for EAs and NAs suggests that the lower resting values of RV in EAs may represent physiologic changes rather than subclinical myocardial damage.

Cardiac MRI A New Gold Standard for Ventricular Volume Quantification During High-Intensity Exercise

Background— 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. Methods and Results— 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<0.0001) 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<0.01). 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). Conclusions— 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.Background— 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. Methods and Results— 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 <0.0001) 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 <0.01). 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). Conclusions— 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.

The Seattle Criteria increase the specificity of preparticipation ECG screening among elite athletes

Background In 2010, the European Society of Cardiology (ESC) released recommendations for the interpretation of the 12-lead ECG in athletes, dividing changes into group 1 (training related) and group 2 (training unrelated). Recently, the ‘Seattle Criteria’, a series of revisions to these recommendations, was published, with the aim of improving the specificity of ECG screening in athletes. Objectives First, to assess the prevalence of ECG abnormalities in a cohort of elite Australian athletes using the 2010 ESC recommendations and determine how often group 2 ECG changes correlate with the evidence of significant cardiac pathology on further investigation. Second, to assess the impact of the ‘Seattle Criteria’ in reducing the number of athletes with ECG abnormalities in whom further cardiac testing is unremarkable (‘false positives’). Design 1197 elite athletes underwent cardiovascular screening between 2011 and 2012, of whom 1078 aged 16–35 years volunteered and were eligible to participate. Results 186 (17.3%) had an abnormal ECG according to ESC recommendations and a further 30 (2.8)% had unclassified changes. Three athletes (0.3%) were found to have a cardiac abnormality on further investigation. Using the Seattle Criteria, the number of athletes classified as abnormal fell to 48 (4.5%, p<0.0001) and the three with an underlying cardiac abnormality were still identified. The improved specificity was due to reclassification of 71 athletes (6.6%) with an equivocal QTc interval, 42 (3.9%) with T wave inversion isolated to V1–2 and 22 (2%) with either isolated right axis deviation or right ventricular hypertrophy on voltage criteria. Conclusions The ‘Seattle Criteria’ reduced the false-positive rate of ECG screening from 17% to 4.2%, while still identifying the 0.3% of athletes with a cardiac abnormality.

Ventricular arrhythmias associated with long-term endurance sports: what is the evidence?

Athletic performance tests the limits of the human body and mind. Awe-inspiring achievements is what makes sports so fascinating. It is well appreciated however that top-level sports may sometimes overtax the body, and can lead to injuries, most notably of musculo-skeletal nature. This paper defends the thesis that the heart can also develop sports injuries at the ventricular level. We will elaborate on our hypothesis, originally put forward in 2003, that intense endurance activities put a particularly high strain on the right ventricle (RV), which over time, may lead to a proarrhythmic state resembling right (or less often) left ventricular cardiomyopathy. This can develop even in the absence of underlying demonstrable genetic abnormalities, probably just as a result of excessive RV wall stress during exercise. The syndrome of ‘exercise-induced arrhythmogenic RV cardiomyopathy’ may easily be overlooked. Sports cardiologists, like orthopaedic specialists, should be prepared to realise that excessive sports activity can lead to cardiac sports injuries in some, which will help to council on safe participation in all.