Andrew T. Burns

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.

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.

Doin’ the twist: new tools for an old concept of myocardial function

It has been known for some time that the heart rotates during the cardiac cycle in concert with radial and longitudinal motion. With advances in imaging technology, it has been appreciated that the apex and base of the heart rotate in different directions, resulting in a twisting or torsional motion. A new echocardiographic technique, “speckle tracking imaging”, permits accurate quantification of this motion. Torsion as well as the timing and magnitude of the rate of torsion (torsional velocity) may provide important new insights into cardiac physiology and disease.

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.

Left Ventricular Torsion Parameters are Affected by Acute Changes in Load

Background: Quantification of left ventricular torsion may provide new indices of systolic and diastolic function. We sought to characterize the effect of acute manipulation of load on cardiac torsion, plecotropy in human subjects. Methods: Simultaneous Millar LV pressure, micromanometry, and echocardiograms were performed on 18 patients (10 male, mean age 66 years) with normal systolic function. Loading was altered sequentially by the administration of glyceryl trinitrate (GTN) and saline fluid loading. Echocardiographic speckle tracking imaging was used to quantify LV torsion and event timing was recorded relative to mitral valve opening (MVO). Results: GTN administration decreased preload (LV end diastolic pressure: 15.7 vs 8.4 mmHg, P < 0.001), and afterload (wall stress: 140 vs 84 ×103dyn/cm2, P < 0.02). Administration of fluid increased preload (LVEDP 11.3 vs 18.1 mmHg, P < 0.001) and increased wall stress, but to a lesser extent (102 vs 117 ×103dyn/cm2, P < 0.003). GTN administration augmented peak torsion (8.4 vs 11.0 deg, P < 0.05), increased systolic torsion velocity (46.6 vs 65.3deg/sec, P < 0.01) and resulted in earlier onset of untwisting (–105 vs –127ms, P < 0.05). Fluid loading decreased the proportion of untwisting prior to MVO (39.0 vs 31.0%, P < 0.05), untwisting acceleration (–750 vs –592deg/sec/sec, P < 0.05) and delayed the timing of peak untwisting (–37.0 vs 9.1ms, P < 0.01), but did not affect systolic torsion parameters. Conclusions: Left ventricular torsion parameters are sensitive to acute changes in load and therefore need to be interpreted in the context of current loading conditions. (ECHOCARDIOGRAPHY 2010;27:407‐414)

Effect of Heart Rate on Tissue Doppler Measures of Diastolic Function

Background: Our aim was to study the independent effect of heart rate (HR) on parameters of diastolic function, particularly mitral annular velocities measured by tissue Doppler imaging (TDI), an effect which is not well understood. Methods: Sixteen patients with dual chamber pacemakers attending for routine pacemaker review underwent detailed echocardiographic assessment during atrial pacing with intact atrioventricular conduction at baseline and accelerated HRs. Mitral inflow and annular tissue Doppler velocities and systolic strain parameters were compared. Results: Parameters of systolic function were unaffected by increased HR. When these parameters were compared at baseline (mean 67 bpm) and accelerated HR (mean 80 bpm), the following was observed: a significant decrease in early mitral inflow (E) wave (70.5 ± 5.5 cm/s vs 63.5 ± 4.9 cm/s, P < 0.02) and early mitral annular (E′) velocities (7.0 ± 0.5 cm/s vs 6.3 ± 0.6 cm/s, P < 0.003) and a significant increase in mitral inflow A wave (70.3 ± 4.5 cm/s vs 77.3 ± 4.4 cm/s, P < 0.05) and late mitral annular (A′) velocities (9.3 ± 0.6 cm/s vs 10.8 ± 0.5, P < 0.00004). Conclusion: Changes in HR have previously unrecognized significant effects on tissue Doppler parameters of diastolic function. Further study is required to determine if tissue Doppler derived annular velocities should be corrected for HR.

When Collateral Supply is Accounted For Epicardial Stenosis Does Not Increase Microvascular Resistance

Background— The relationship between epicardial stenosis and microvascular resistance remains controversial. Exploring the relationship is critical, as many tools used in interventional cardiology imply minimal and constant resistance. However, variable collateralization may impact well on these measures. We hypothesized that when collateral supply was accounted for, microvascular resistance would be independent of epicardial stenosis. Methods and Results— Forty patients with stable angina were studied before and following percutaneous intervention. A temperature and pressure sensing guide wire was used to derive microvascular resistance using the index of microcirculatory resistance (IMR), defined as the hyperemic distal pressure multiplied by the hyperemic mean transit time. Lesion severity was assessed using fractional flow reserve. For comparison, evaluation of an angiographically normal reference vessel from the same subject also was undertaken. Both simple IMR (sIMR) and IMR corrected for collateral flow (cIMR) were calculated. When collateral supply was not accounted for, there was a significant difference in IMR values between the culprit, the post PCI, and nonculprit values (culprit sIMR 26.68±2.06, nonculprit sIMR 18.37±1.89, P=0.002; post percutaneous intervention sIMR 18.5±1.94 versus culprit sIMR 26.68±2.06, P<0.0001). However, when collateral supply was accounted for there was no difference observed (cIMR 16.96±1.78 versus nonculprit sIMR 18.37±1.89, P=0.52; post percutaneous intervention sIMR 18.5±1.94 versus cIMR 16.96±1.78, P=0.42). Conclusions— When collateral supply is accounted for, epicardial stenosis does not increase microvascular resistance in patients with stable angina.