Contrasting haemodynamic effects of exercise and saline infusion in older adults with pulmonary arterial hypertension.

In this study, among patients with pulmonary arterial hypertension, exercise was more potent in eliciting pulmonary vascular abnormalities and demonstrated paradoxical increase in RC-time https://bit.ly/35Mb0dv.

Normal and Abnormal Relationships of Pulmonary Artery to Wedge Pressure During Exercise.

Background Resting right heart catheterization can assess both left heart filling and pulmonary artery (PA) pressures to identify and classify pulmonary hypertension. Although exercise may further elucidate hemodynamic abnormalities, current pulmonary hypertension classifications do not consider the expected interrelationship between PA and left heart filling pressures. This study explored the utility of this relationship to enhance the classification of exercise hemodynamic phenotypes in pulmonary hypertension. Methods and Results Data from 36 healthy individuals (55, 50-60 years, 50% male) and 85 consecutive patients (60, 49-71 years, 48% male) with dyspnea and/or suspected pulmonary hypertension of uncertain etiology were analyzed. Right heart catheterization was performed at rest and during semiupright submaximal cycling. To classify exercise phenotypes in patients, upper 95% CIs were identified from the healthy individuals for the change from rest to exercise in mean PA pressure over cardiac output (ΔmPAP/ΔCO ≤3.2 Wood units [WU]), pulmonary artery wedge pressure over CO (ΔPAWP/ΔCO ≤2 mm Hg/L per minute), and exercise PA pulse pressure over PAWP (PP/PAWP ≤2.5). Among patients with a ΔmPAP/ΔCO ≤3.2 WU, the majority (84%) demonstrated a ΔPAWP/ΔCO ≤2 mm Hg/L per minute, yet 23% demonstrated an exercise PP/PAWP >2.5. Among patients with a ΔmPAP/ΔCO >3.2 WU, 37% had an exercise PP/PAWP >2.5 split between ΔPAWP/ΔCO groups. Patients with normal hemodynamic classification declined from 52% at rest to 36% with exercise. Conclusions The addition of PP/PAWP to classify exercise hemodynamics uncovers previously unrecognized abnormal phenotypes within each ΔmPAP/ΔCO group. Our study refines abnormal exercise hemodynamic phenotypes based on an understanding of the interrelationship between PA and left heart filling pressures.

Flow-related right ventricular to 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.

Pulmonary Arterial Wedge Pressure at Rest and During Exercise in Healthy Adults: A Systematic Review and Meta-analysis.

BACKGROUND: The pulmonary arterial wedge pressure (PAWP) response to exercise may unmask latent heart failure with preserved ejection fraction. There remains a lack of consensus over threshold values for PAWP during exercise. A systematic review of studies examining PAWP by means of right heart catheterization at rest and during exercise in healthy individuals was performed. METHODS AND RESULTS: Relevant data derived from healthy volunteers were stratified by age (older than 40 years vs 40 years or younger) and sex. Three exercise intensities were predefined: light, moderate, and strenuous. Weighted means and weighted 95% confidence intervals (CIs) for the aggregate data were calculated. A total of 424 individuals from 32 unique studies were included, of which 19% (n = 82) were female. PAWP reached weighted mean and 95% CI values of 19 (17-21) and 17 (16-18) mm Hg at light and moderate exercise, respectively. The PAWP response to exercise was similar between men and women >40 years of age. However, exercise intensities were lower in women. CONCLUSIONS: PAWP increases during exercise, reaching up to 20 mm Hg in adults >40 years of age. Older women achieve PAWP values similar to those of older men, but at lower intensities. Findings support a threshold of at least 25 mm Hg as an absolute cutoff value for "normal" PAWP response to exercise in individuals >40 years old.

Pulmonary hemodynamic and right ventricular responses to brief and prolonged exercise in middle-aged endurance athletes.

Right ventricular (RV) function is closely coupled to pulmonary arterial (PA) hemodynamics and is believed to decline with prolonged exercise. A linear pressure-flow relationship is thought to exist between PA pressures and increasing exercise intensity in athletes, yet a paucity of directly measured pulmonary hemodynamic data exists supporting this contention. We sought to describe the PA pressure, PA wedge pressure (PAWP), and RV functional responses to brief and prolonged exercise in endurance-trained athletes. Twenty-one healthy athletes (54 ± 5 yr) underwent right heart catheterization to assess pulmonary hemodynamics during graded, submaximal exercise. Measurements were made at rest and during three stages of steady-state, semiupright cycle ergometry at heart rates of 100 beats/min (EX1), 130 beats/min (EX2), and 150 beats/min (EX3). Five athletes completed an additional 34 min at 130 beats/min for a total exercise time of 60 min [prolonged exercise (PLG)]. PA pressures and PAWP increased significantly at EX1 without a further rise at EX2, EX3, or PLG. PAWP adjusted for absolute work rate demonstrated a significant decline as exercise intensity increased from EX1 to EX2. The resistance compliance time constant decreased at EX1 without further changes at EX2, EX3, and prolonged exercise. RV function did not decline during PLG. After an initial rise in PA pressure and PAWP during early, nonsteady-state exercise, values remained constant despite increases in exercise intensity and duration. These data indicate that in healthy, middle-aged endurance-trained athletes, the PA and pulmonary venous/left atrial compartments rapidly accommodate high conduit flows produced during intensive and prolonged exercise while maintaining RV function. NEW & NOTEWORTHY The right ventricular (RV)-pulmonary arterial (PA) circulatory unit has not been well studied during prolonged exercise, and this study provides an ecological approach that reflects a typical bout of endurance training integrating a transition from rest to exercise with successive increases in intensity, progressing to steady-state, sustained exercise. We demonstrated a remarkably constant response of the PA and PA wedge pressure during incremental, steady-state exercise and that no changes occur in pulmonary pressures throughout prolonged exercise, concomitant to a preservation of RV performance.

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·min 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.

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

KEY POINTS: 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. ABSTRACT: The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp-time. The RpCp-time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp-time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non-athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8-10 min stages of cycle ergometry, at targeted heart-rates of 100 beats min(-1) (Light) and 120 beats min(-1) (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate exercise. RpCp-time decreased for Light exercise (0.39 ± 0.08 to 0.25 ± 0.08, P < 0.001) without any further change for Moderate exercise, and the decrease in RpCp-time was related to changes in PAWP (r(2)  = 0.26, P < 0.001). Changes in PASP (r(2)  = 0.43, P < 0.001), PADP (r(2)  = 0.47, P < 0.001) and mPAP (r(2)  = 0.50, P < 0.001) were linearly correlated with changes in PAWP, although they were not significantly related to changes in cardiac output. In healthy adults, exercise is associated with decreases in Cp and a resultant decline in RpCp-time, indicating increased pulsatile right ventricular afterload. Changes in RpCp-time, PASP, PADP and mPAP were systematically related to increases in PAWP.

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.

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.

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.

Left atrial functional changes following short-term exercise training.

BACKGROUND: Exercise-induced adaptations of the human atria remain understudied, particularly early in the training process. We examined the effects of short-term high-intensity interval training (HIT) and continuous moderate-intensity training (CMT) on left atrial (LA) systolic and diastolic function, relative to left ventricular (LV) function in young, healthy men, by speckle tracking echocardiography (STE). METHODS: Fourteen untrained men (mean age = 25 ± 4 years) were randomized to HIT or CMT, and assessed before and after six training sessions over a 12-day period. HIT included 8-12 intervals of cycling for 60 s at 95-100% of maximal aerobic power (VO2MAX), interspersed by 75 s of cycling at 10 % VO2MAX. CMT consisted of 90-120 min of cycling at 65% VO2MAX. RESULTS: VO2MAX increased following HIT and CMT by 11.5 and 5.5%, respectively (p < 0.05). Calculated plasma volume expanded 11 % following HIT and 10% following CMT (p < 0.005). Resting LV volumes and ejection fraction were unaltered following training. Peak atrial longitudinal strain increased following HIT (41.8 ± 5.2%-47.1 ± 3.7%, p < 0.01) and CMT (38.5 ± 4.6%-41.7 ± 6.0%, p < 0.01). Atrial systolic strain rate increased following HIT (1.6 ± 0.2%/s-2.0 ± 0.3%/s, p < 0.01) and CMT (1.6 ± 0.2%/s-1.9 ± 0.2%/s, p < 0.01). CONCLUSIONS: LA function assessed by STE improves rapidly during short-term intensive exercise training.

Short-term high-intensity interval and continuous moderate-intensity training improve maximal aerobic power and diastolic filling during exercise.

PURPOSE: This study examined the effects of short-term high-intensity interval training (HIT) and continuous moderate-intensity training (CMT) on cardiac function in young, healthy men. METHODS: Sixteen previously untrained men (mean age of 25.1 ± 4.1 years) were randomly assigned to HIT and CMT (n = 8 each) and assessed before and after six sessions over a 12-day training period. HIT consisted of 8-12 intervals of cycling for 60 s at 95-100% of pre-training maximal aerobic power (VO(2max)), interspersed by 75 s of cycling at 10% VO(2max). CMT involved 90-120 min of cycling at 65% pre-training VO(2max). Left ventricular (LV) function was determined at rest and during submaximal exercise (heart rate ~105 bpm) using two-dimensional and Doppler echocardiography. RESULTS: Training resulted in increased calculated plasma volume (PV) in both groups, accompanied by improved VO(2max) in HIT (HIT: from 39.5 ± 7.1 to 43.9 ± 5.5 mL kg(-1) min(-1); CMT: from 39.9 ± 5.9 to 41.7 ± 5.3 mL kg(-1) min(-1); P < 0.001). Resting LV function was not altered. However, increased exercise stroke volume (P = 0.02) and cardiac output (P = 0.02) were observed, secondary to increases in end-diastolic volume (P < 0.001). Numerous Doppler and speckle tracking indices of diastolic function were similarly enhanced during exercise in both training groups and were related to changes in PV. CONCLUSION: Short-term HIT and CMT elicit rapid improvements in VO2max and LV filling without global changes in cardiac performance at rest.

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.