Sam Esfandiari

Left atrial phasic function interacts to support left ventricular filling during exercise in healthy athletes

We studied the contribution of phasic left atrial (LA) function to left ventricular (LV) filling during exercise. We hypothesized that reduced LV filling time at moderate-intensity exercise limits LA passive emptying and increases LA active emptying. Twenty endurance-trained males (55 ± 6 yr) were studied at rest and during light- (∼100 beats/min) and moderate-intensity (∼130 beats/min) exercise. Two-dimensional and Doppler echocardiography were used to assess phasic volumes and diastolic function. LV end-diastolic volume increased from rest to light exercise (54 ± 6 to 58 ± 5 ml/m(2), P < 0.01) and from light to moderate exercise (58 ± 5 to 62 ± 6 ml/m(2), P < 0.01). LA maximal volume increased from rest to light exercise (26 ± 4 to 30 ± 5 ml/m(2), P < 0.01) related to atrioventricular plane displacement (r = 0.55, P < 0.005), without further change at moderate exercise. LA passive emptying increased at light exercise (9 ± 2 to 13 ± 3 ml/m(2), P < 0.01) and then returned to baseline at moderate exercise, whereas LA active emptying increased appreciably only at moderate exercise (6 ± 2 to 14 ± 3 ml/m(2), P < 0.01). Thus, the total atrial emptying volume did not increase beyond light exercise, and the increase in LV filling at moderate exercise could be attributed primarily to an increase in the conduit flow volume (19 ± 3 to 25 ± 5 ml/m(2), P < 0.01). LA filling increases during exercise in relation to augmented LV longitudinal contraction. Conduit flow increases progressively with exercise in athletes, although this is driven by LV properties rather than intrinsic LA function. The pump function of the LA augments only at moderate exercise due to a reduced diastolic filling time and the Frank-Starling mechanism.

The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults.

A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship. This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP. We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise‐associated increases in PAWP. Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP. Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle.

The pulmonary artery wedge pressure response to sustained exercise is time-variant in healthy adults

Objectives The clinical and prognostic significance of ‘exaggerated’ elevations in pulmonary artery wedge pressure (PAWP) during symptom-limited exercise testing is increasingly recognised. However, the paucity of normative data makes the identification of abnormal responses challenging. Our objectives was to describe haemodynamic responses that reflect normal adaptation to submaximal exercise in a group of community-dwelling, older, non-dyspnoeic adults. Methods Twenty-eight healthy volunteers (16 men/12 women; 55±6 years) were studied during rest and two consecutive stages of cycle ergometry, at targeted heart rates of 100 bpm (light exercise) and 120 bpm (moderate exercise). Right-heart catheterisation was performed to measure pulmonary artery pressures, both early (2 min) and after sustained (7 min) exercise at each intensity. Results End-expiratory PAWP at baseline was 11±3 mm Hg and increased to 22±5 mm Hg at early-light exercise (p<0.01). At sustained-light exercise, PAWP declined to 17±5 mm Hg, remaining elevated versus baseline (p<0.01). PAWP increased again at early-moderate exercise to 20±6 mm Hg but did not exceed the values observed at early-light exercise, and declined further to 15±5 mm Hg at sustained-moderate exercise (p<0.01 vs baseline). When analysed at 30 s intervals, mean and diastolic pulmonary artery pressures peaked at 180 (IQR=30) s and 130 (IQR=90) s, respectively, and both declined significantly by 420 (IQR=30) s (both p<0.01) of light exercise. Similar temporal patterns were observed at moderate exercise. Conclusions The range of PAWP responses to submaximal exercise is broad in health, but also time-variant. PAWP may routinely exceed 20 mm Hg early in exercise. Initial increases in PAWP and mean pulmonary artery pressures do not necessarily reflect abnormal cardiopulmonary physiology, as pressures may normalise within a period of minutes.

Heart Rate–Dependent Left Ventricular Diastolic Function in Patients With and Without Heart Failure

BACKGROUND Chronic heart rate (HR) reduction in the treatment of heart failure (HF) with systolic dysfunction is beneficial, but the immediate mechanical advantages or disadvantages of altering HR are incompletely understood. We examined the effects of increasing HR on early and late diastole in humans with and without HF. METHODS AND RESULTS We studied force-interval relationships of the left ventricle (LV) in 11 HF patients and 14 control subjects. HR was controlled by right atrial pacing, and LV pressure was recorded by a micromanometer-tipped catheter. The time constant of isovolumic relaxation (tau) was calculated, and simultaneous sonographic images were analyzed for LV volumes. The end-diastolic pressure-volume relationship (EDPVR) was analyzed with the use of a single-beat method. Tau was shortened in response to increasing HR in both groups; the slope of this relationship was steeper in HF than in control subjects. The predicted volume at a theoretic pressure of 0 mm Hg (V30) increased at higher HRs compared with baseline, shifting the predicted EDPVR compliance curve to the right in HF patients but not in control subjects. CONCLUSIONS In HF, changes in HR affect early relaxation and diastolic compliance to a greater extent than in control subjects. Our study reinforces current recommendations for HR-lowering drug treatment in HF.

Cardiac function following prolonged exercise: influence of age

This study sought to determine the influence of age on the left ventricular (LV) response to prolonged exercise (PE; 150 min). LV systolic and diastolic performance was assessed using echocardiography (ECHO) before (pre) and 60 min following (post) exercise performed at 80% maximal aerobic power in young (28 ± 4.5 years; n = 18; mean ± SD) and middle-aged (52 ± 3.9 years; n = 18) participants. LV performance was assessed using two-dimensional ECHO, including speckle-tracking imaging, to determine LV strain (LV S) and LV S rate (LV SR), in addition to Doppler measures of diastolic function. We observed a postexercise elevation in LV S (young: -19.5 ± 2.1% vs. -21.6 ± 2.1%; middle-aged: -19.9 ± 2.3% vs. -20.8 ± 2.1%; P < 0.05) and LV SR (young: -1.19 ± 0.1 vs. -1.37 ± 0.2; middle-aged: -1.20 ± 0.2 vs. -1.38 ± 0.2; P < 0.05) during recovery in both groups. Diastolic function was reduced during recovery, including the LV SR ratio of early-to-late atrial diastolic filling (SR(e/a)), in young (2.35 ± 0.7 vs. 1.89 ± 0.5; P < 0.01) and middle-aged (1.51 ± 0.5 vs. 1.05 ± 0.2; P < 0.01) participants, as were conventional indices including the E/A ratio. Dobutamine stress ECHO revealed a postexercise depression in LV S in response to increasing dobutamine dose, which was similar in both young (pre-exercise dobutamine 0 vs. 20 μg·kg(-1)·min(-1): -19.5 ± 2.1 vs. -27.2 ± 2.2%; postexercise dobutamine 0 vs. 20 μg·kg(-1)·min(-1): -21.6 ± 2.1 vs. -23.7 ± 2.2%; P < 0.05) and middle-aged participants (pre: -19.9 ± 2.3 vs. -25.3 ± 2.7%; post: -20.8 ± 2.1 vs. -23.5 ± 2.7; P < 0.05). This was despite higher noradrenaline concentrations immediately postexercise in the middle-aged participants compared with young (4.26 ± 2.7 nmol/L vs. 3.00 ± 1.4 nmol/L; P = 0.12). These data indicate that LV dysfunction is observed following PE and that advancing age does not increase the magnitude of this response.

Pulmonary Artery Wedge Pressure Relative to Exercise Work Rate in Older Men and Women

Purpose An augmented pulmonary artery wedge pressure (PAWP) response may explain exercise intolerance in some humans. However, routine use of exercise hemodynamic testing is limited by a lack of data from normal older men and women. Our objective was to evaluate the exercise PAWP response and the potential for sexual dimorphism in healthy, nondyspneic older adults. Methods Thirty-six healthy volunteers (18 men [54 ± 7 yr] and 18 women [58 ± 6 yr]) were studied at rest (control) and during two stages of semi-upright cycle ergometry, at heart rates of 100 bpm (light exercise) and 120 bpm (moderate exercise). Right heart catheterization was performed to measure pulmonary pressures. The PAWP response to exercise was assessed in context of exercise work rate and body size. Results At control, PAWP was similar between men and women. Work rates were significantly smaller in women at comparable HR (P < 0.001). PAWP increased similarly at light exercise, with no further increase at moderate exercise. When indexed to work rate alone or work rate adjusted to body weight and height, the PAWP response at light and moderate exercise was significantly elevated in women compared with men (P < 0.05 condition–sex interaction). The change in PAWP relative to the increase in cardiac output did not exceed 2 mm Hg·L−1·min−1 in any volunteer at moderate exercise. Conclusions The similar rise in the PAWP response to submaximal exercise occurs despite lower work rate in healthy older women compared with men, even when adjusted for smaller body size. It is important to consider sex in the development of normal reference ranges for exercise hemodynamic testing.

Getting at the heart of the issue: advanced imaging and stem cell-based therapy offer a novel approach to cardiac resynchronization.

The pump function of the left ventricle (LV) is dependent on synchronous depolarization and contraction to expel blood efficiently. The propagation of the apical-to-basal ventricular contraction pattern is controlled by electrical signalling of the fibre system down the interventricular septum and woven through the free walls of the ventricular myocardium. Dyssynchronous contraction results in mechanical inefficiency, decreased external work, and reduced cardiac output. Myocardial infarction (MI) may cause wall motion abnormalities not only through disturbed electrical conduction, but also through myocardial damage and non-viable tissue. Therapy targeted at preventing adverse remodelling and improving the viability of non-contracting tissue may have the potential for great improvement in ventricular synchronization by addressing mechanical disturbances in the myocardium. Recent advances in stem cell therapy hold promise for regenerative cardiac interventions, as the use of undifferentiated stem cells delivered to the myocardium may be effective in forming functional cardiac tissue and restoring global heart function. While the potential use of such therapies has gained recent attention, the administration of stem cell therapy to ameliorate regional dyssynchrony related to MI has not been examined.

Flow-related Right Ventricular – Pulmonary Arterial Pressure Gradients during Exercise

Aims The assumption of equivalence between right ventricular (RV) and pulmonary arterial systolic pressure is fundamental to several assessments of RV or pulmonary vascular haemodynamic function. Our aims were to (i) determine whether systolic pressure gradients develop across the RV outflow tract in healthy adults during exercise, (ii) examine the potential correlates of such gradients, and (iii) consider the effect of such gradients on calculated indices of RV function. Methods and results Healthy untrained and endurance-trained adult volunteers were studied using right-heart catheterization at rest and during submaximal cycle ergometry. RV and pulmonary artery (PA) pressures were simultaneously transduced, and the cardiac output was determined by thermodilution. Systolic pressures, peak and mean gradients, and indices of chamber, vascular, and valve function were analysed offline. Summary data are reported as mean ± standard deviation or median (interquartile range). No significant RV outflow tract gradients were observed at rest [mean gradient = 4 (3-5) mmHg], and the calculated effective orifice area was 3.6 ± 1.0 cm2. The increase in right ventricular systolic pressure during exercise was greater than the PA systolic pressure. Accordingly, mean gradients were developed during light exercise [8 (7-9) mmHg] and increased during moderate exercise [12 (9-14) mmHg, P < 0.001]. The magnitude of the mean gradient was linearly related to the cardiac output (r2 = 0.70, P < 0.001). Conclusions In healthy adults without pulmonic stenosis, systolic pressure gradients develop during exercise, and the magnitude is related to the blood flow rate.