The effect of lifelong endurance exercise on cardiovascular structure and exercise function in women.

KEY POINTS: The beneficial effects of sustained or lifelong (>25 years) endurance exercise on cardiovascular structure and exercise function have been largely established in men. The current findings indicate that committed (≥4 weekly exercise sessions) lifelong exercise results in substantial benefits in exercise capacity ( V̇O2max ), cardiovascular function at submaximal and maximal exercise, left ventricular mass and compliance, and blood volume compared to similarly aged or even younger (middle-age) untrained women. Endurance exercise training should be considered a key strategy to prevent cardiovascular disease with ageing in women as well as men. ABSTRACT: This study was a retrospective, cross-sectional analysis of exercise performance and left ventricular (LV) morphology in 70 women to examine whether women who have performed regular, lifelong endurance exercise acquire the same beneficial adaptations in cardiovascular structure and function and exercise performance that have been reported previously in men. Three groups of women were examined: (1) 35 older (>60 years) untrained women (older untrained, OU), (2) 13 older women who had consistently performed four or more endurance exercise sessions weekly for at least 25 years (older trained, OT), and (3) 22 middle-aged (range 35-59 years) untrained women (middle-aged untrained, MU) as a reference control for the appropriate age-related changes. Oxygen uptake ( V̇O2 ) and cardiovascular function (cardiac output ( Q̇ ); stroke volume (SV) acetylene rebreathing) were examined at rest, steady-state submaximal exercise and maximal exercise (maximal oxygen uptake, V̇O2max ). Blood volume (CO rebreathing) and LV mass (cardiac magnetic resonance imaging), plus invasive measures of static and dynamic chamber compliance were also examined. V̇O2max (p < 0.001) and maximal exercise Q̇ and SV were larger in older trained women compared to the two untrained groups (∼17% and ∼27% for Q̇ and SV, respectively, versus MU; ∼40% and ∼38% versus OU, all p < 0.001). Blood volume (mL kg-1 ) and LV mass index (g m-2 ) were larger in OT versus OU (∼11% and ∼16%, respectively, both P ≤ 0.015) Static LV chamber compliance was greater in OT compared to both untrained groups (median (25-75%): MU: 0.065 (0.049-0.080); OU: 0.085 (0.061-0.138); OT: 0.047 (0.031-0.054), P ≤ 0.053). Collectively, these findings indicate that lifetime endurance exercise appears to be extremely effective at preserving or even enhancing cardiovascular structure and function with advanced age in women.

Plasma matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs and aging and lifelong exercise adaptations in ventricular and arterial stiffness.

The age-associated increase in cardiac and central arterial stiffness is attenuated with lifelong (>25 years) endurance exercise in a dose-dependent manner. Remodelling of the extracellular matrix of cardiovascular structures may underpin these lifelong exercise adaptations in structural stiffness. The primary aim was to examine whether matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) levels are associated with aging and lifelong exercise-related changes in cardiac and central arterial stiffness. Plasma MMPs and TIMPs, left ventricular (LV) (LV stiffness constant) and central arterial stiffness (pulse wave velocity) were examined in healthy adults stratified into five groups based on age and lifelong weekly exercise frequency: (1) young sedentary adults (28-50 years), and older adults (>60 years) who had performed either: (a) sedentary (0-1 sessions/week), (b) casual (2-3 sessions/week), (c) committed (4-5 sessions/week) or (d) athletic (≥6 sessions/week) frequency of exercise. MMP-1 was significantly lower in young compared to older sedentary (p = 0.049). Except for TIMP-2 (p = 0.018 versus committed) and the ratio of MMP-2/TIMP-4 (p = 0.047 versus committed), MMP and TIMP expression was not significantly different in lifelong exercise groups (≥casual) compared to the older sedentary group. MMP-1, -3 had a weak positive relationship with central PWV (r = 0.17-0.25, p ≤ 0.050) but there were no significant relationships between MMPs or TIMPs and LV stiffness constant (p ≥ 0.148). In conclusion, there was not a clear or consistent difference in plasma MMPs and TIMPs with lifelong exercise dose despite exhibiting lower cardiovascular stiffness at the highest exercise levels.

Impact of Lifelong Exercise Training Dose on Ventricular-Arterial Coupling.

BACKGROUND: The dynamic Starling mechanism, as assessed by beat-by-beat changes in stroke volume and left ventricular end-diastolic pressure, reflects ventricular-arterial coupling. It deteriorates with age, and is preserved in highly trained masters athletes. Currently, it remains unclear how much exercise over a lifetime is necessary to preserve efficient ventricular-arterial coupling. The purpose of this study was to assess the dose-dependent relationship between lifelong exercise training and the dynamic Starling mechanism in healthy seniors. METHODS: One hundred two seniors were recruited and stratified into 4 groups based on 25 years of exercise training history: sedentary subjects (n=27, <2 sessions/week), casual exercisers (n=25, 2-3 sessions/week), committed exercisers (n=25, 4-5 sessions/week), and competitive Masters Athletes (n=25, 6-7 sessions/week). The dynamic Starling mechanism was estimated by transfer function gain between beat-by-beat changes in diastolic pulmonary artery pressure, a surrogate for left ventricular end-diastolic pressure, and stroke volume index. RESULTS: The transfer function gain of pulmonary artery pressure-stroke volume index was markedly enhanced in committed and competitive exercisers compared with more sedentary seniors and correlated with higher peak oxygen uptake (Vo2) and lower left ventricular stiffness. The power spectral density of pulmonary artery pressure was greater in sedentary adults than in committed and competitive exercisers, whereas the power spectral density of stroke volume index was greater in competitive exercisers than in the other groups. CONCLUSIONS: There is a graded, dose-dependent improvement in ventricular-arterial coupling with increasing amounts of lifelong regular exercise in healthy older individuals. Our data suggest that the optimal dose of lifelong endurance exercise to preserve ventricular-arterial coupling with age appears to be at least 4 to 5 sessions per week.

The effect of lifelong exercise frequency on arterial stiffness.

KEY POINTS: This study examined the effect of different 'doses' of lifelong (>25 years) exercise on arterial stiffening (a hallmark of vascular ageing) in older adults. There are clear dose-dependent effects of lifelong exercise training on human arterial stiffness that vary according to the site and size of the arteries. Similar to what we have observed previously with ventricular stiffening, 4-5 days week-1 of committed exercise over a lifetime are necessary to preserve 'youthful' vascular compliance, especially of the large central arteries. Casual exercise training of two to three times per week may be sufficient for middle-sized arteries like the carotid to minimize arterial stiffening with ageing. However, there is little effect of exercise training on the small-sized peripheral arteries at any dose. ABSTRACT: Central arterial stiffness increases with sedentary ageing. While near-daily, vigorous lifelong (>25 years) endurance exercise training prevents arterial stiffening with ageing, this rigorous routine of exercise training over a lifetime is impractical for most individuals. The aim was to examine whether a less frequent 'dose' of lifelong exercise training (four to five sessions per week for > 30 min) that is consistent with current physical activity recommendations elicits similar benefits on central arterial stiffening with ageing. A cross-sectional examination of 102 seniors (>60 years old) who had a consistent lifelong exercise history was performed. Subjects were stratified into four groups based on exercise frequency as an index of exercise 'dose': sedentary: fewer than two sessions per week; casual exercisers: two to three sessions per week; committed exercisers: four to five sessions per week; and Masters athletes: six to seven sessions per week plus regular competitions. Detailed measurements of arterial stiffness and left ventricular afterload were collected. Biological aortic age and central pulse wave velocity were younger in committed exercisers and Masters athletes compared to sedentary seniors. Total arterial compliance index (TACi) was lower, while carotid ß-stiffness index and effective arterial elastance were higher in sedentary seniors compared to the other groups. There appeared to be a dose-response threshold for carotid ß-stiffness index and TACi. Peripheral arterial stiffness was not significantly different among the groups. These data suggest that four to five weekly exercise sessions over a lifetime is associated with reduced central arterial stiffness in the elderly. A less frequent dose of lifelong exercise (two to three sessions per week) is associated with decreased ventricular afterload and peripheral resistance, while peripheral arterial stiffness is unaffected by any dose of exercise.

Left Ventricular Volume-Time Relation in Patients With Heart Failure With Preserved Ejection Fraction.

Elevated left ventricular (LV) filling pressures are commonly reported in patients with heart failure with preserved ejection fraction (HFpEF) and are associated with impaired relaxation in diastole. Relaxation has been assessed by Doppler, but the methods for doing so are indirect and heavily influenced by loading conditions. The aim of this study is to assess LV volume-time relation in patients with HFpEF, when correcting for left atrial driving pressure and chamber size, using cardiac magnetic resonance imaging (cMRI). Cine short-axis views by cMRI (1.5T-magnet) at 26 Hz were used for measurement of LV volume. We compared the following diastolic parameters: peak filling rate/end-diastolic volume (PFR/EDV); PFR/EDV/pulmonary capillary wedge pressure (PFR/EDV/PCWP); time to PFR (TPFR); and %TPFR for cardiac cycle calculated by cMRI between patients with HFpEF (n = 10, 73 ± 7 years) and age-matched controls (n = 12, 70 ± 3 years). PCWP was significantly greater in the HFpEF group than in controls (HFpEF vs controls: 15.6 ± 5.2 vs 11.2 ± 1.3 mmHg, p = 0.0092). PFR/EDV was significantly slower in the HFpEF group than in controls (2.68 ± 0.85 vs 3.59 ± 0.87/s, p = 0.03), and was nearly 50% slower when corrected for left atrial driving pressure: PFR/EDV/PCWP (0.18 ± 0.07 vs 0.33 ± 0.10/s/mmHg, p = 0.002). In addition, TPFR (246 ± 17.2 vs 188 ± 15.7 ms, p = 0.04) and %TPFR of cardiac cycle (36.4 ± 10.4 vs 25.6 ± 5.9%, p = 0.012) were significantly longer in the HFpEF group than in controls. Patients with HFpEF have an abnormal volume-time relation, including lower PFR/EDV (PFR/EDV/PCWP) and prolonged TPFR, due to the impairment of active relaxation during early diastole.

Isometric handgrip echocardiography: A noninvasive stress test to assess left ventricular diastolic function.

BACKGROUND: Cycle exercise echocardiography is a useful tool to "unmask" diastolic dysfunction; however, this approach can be limited by respiratory and movement artifacts. Isometric handgrip avoids these issues while reproducibly increasing afterload and myocardial oxygen demand. HYPOTHESIS: Isometric handgrip echocardiography (IHE) can differentiate normal from abnormal diastolic function. METHODS: First recruited 19 young healthy individuals (mean age, 24 ± 4 years) to establish the "normal" response. To extend these observations to a more at-risk population, we performed IHE on 17 elderly individuals (mean age, 72 ± 6 years) with age-related diastolic dysfunction. The change in the ratio of mitral valve inflow velocity to lateral wall tissue velocity (E/e'), a surrogate for left ventricular filling pressure, was used to assess the diastolic stress response in each group. RESULTS: In the young subjects, isometric handgrip increased heart rate and mean arterial pressure (25 ± 12 bpm and 26 ± 17 mmHg, respectively), whereas E/e' changed minimally (0.6 ± 0.9). In the elderly subjects, heart rate and mean arterial pressure were similarly increased with isometric handgrip (19 ± 16 bpm and 25 ± 11 mmHg, respectively), whereas E/e' increased more dramatically (2.3 ± 1.7). Remarkably, 11 of the 17 elderly subjects had an abnormal diastolic response (ΔE/e': 3.4 ± 1.1), whereas the remaining 6 elderly subjects showed very little change (ΔE/e': 0.3 ± 0.7), independent of age or the change in myocardial oxygen demand. CONCLUSIONS: IHE is a simple, effective tool for evaluating diastolic function during simulated activities of daily living.

Heart rate, blood pressure and repolarization effects of an energy drink as compared to coffee.

The goal of this study was to investigate the impact of energy drinks on haemodynamic and cardiac physiology. Comparisons were made to coffee as well as water consumption. In Protocol #1 the caffeine content was normalized to body weight to represent a controlled environment. Heart rate, blood pressure and cardiac QTc interval were assessed in 15 participants, on 4 days, prior to and for 6·5 h postconsumption of (i) energy drink (2 mg caffeine per kg body weight; low dose), (ii) energy drink (3 mg caffeine per kg body weight; medium dose), (iii) coffee (2 mg caffeine per kg body weight) and (iv) 250 ml water. In Protocol #2, the beverages were consumed in volumes that they are purchased to represent real-life conditions. The aforementioned measurements were repeated in 15 participants following (i) 1 16 oz can of energy drink (16 oz Monster), (ii) 1 24 oz can of energy drink (24 oz Monster), (iii) 1 packet of Keurig K-Cup Starbucks coffee (coffee) and (iv) 250 ml water. The order of the beverages was performed in a randomized double-blinded fashion. For both protocols, QTc interval, heart rate and systolic blood pressure were unchanged in any condition (P>0·05). Diastolic blood pressure and mean blood pressure were slightly elevated in Protocol #1 (P<0·05, main effect of time) with no difference between beverages (P<0·05, interaction of beverage × time); however, they were unaffected in Protocol #2 (P>0·05). These findings suggest that acute consumption of these commonly consumed beverages has no negative effect on cardiac QTc interval.

Lifelong Physical Activity Regardless of Dose Is Not Associated With Myocardial Fibrosis.

BACKGROUND: Recent reports have suggested that long-term, intensive physical training may be associated with adverse cardiovascular effects, including the development of myocardial fibrosis. However, the dose-response association of different levels of lifelong physical activity on myocardial fibrosis has not been evaluated. METHODS AND RESULTS: Seniors free of major chronic illnesses were recruited from predefined populations based on the consistent documentation of stable physical activity over >25 years and were classified into 4 groups by the number of sessions/week of aerobic activities ≥30 minutes: sedentary (group 1), <2 sessions; casual (group 2), 2 to 3 sessions; committed (group 3), 4 to 5 sessions; and Masters athletes (group 4), 6 to 7 sessions plus regular competitions. All subjects underwent cardiopulmonary exercise testing and cardiac magnetic resonance imaging, including late gadolinium enhancement assessment of fibrosis. Ninety-two subjects (mean age 69 years, 27% women) were enrolled. No significant differences in age or sex were seen between groups. Median peak oxygen uptake was 25, 26, 32, and 40 mL/kg/min for groups 1, 2, 3, and 4, respectively. Cardiac magnetic resonance imaging demonstrated increasing left ventricular end-diastolic volumes, end-systolic volumes, stroke volumes, and masses with increasing doses of lifelong physical activity. One subject in group 2 had late gadolinium enhancement in a noncoronary distribution, and no subjects in groups 3 and 4 had evidence of late gadolinium enhancement. CONCLUSIONS: A lifelong history of consistent physical activity, regardless of dose ranging from sedentary to competitive marathon running, was not associated with the development of focal myocardial fibrosis.

Heart Failure: Exercise-Based Cardiac Rehabilitation: Who, When, and How Intense?

The primary chronic symptom in patients with clinically stable heart failure (HF) is reduced exercise tolerance, measured as decreased peak aerobic power (peak oxygen consumption [Vo2]), and is associated with reduced quality of life and survival. Exercise-based cardiac rehabilitation (EBCR) is a safe and effective intervention to improve peak Vo2, muscle strength, physical functional performance, and quality of life and is associated with a reduction in overall and HF-specific hospitalization in clinically stable patients with HF. Despite these salient benefits, fewer than one-tenth of eligible patients with HF are referred for EBCR after hospitalization. In this review, selection for and timing of EBCR for patients with HF, as well as exercise prescription guidelines with special emphasis on the optimal exercise training intensity to improve peak Vo2, are discussed.

Impact of lifelong exercise "dose" on left ventricular compliance and distensibility.

BACKGROUND: Sedentary aging has deleterious effects on the cardiovascular system, including decreased left ventricular compliance and distensibility (LVCD). Conversely, Masters level athletes, who train intensively throughout adulthood, retain youthful LVCD. OBJECTIVES: The purpose of this study was to test the hypothesis that preservation of LVCD may be possible with moderate lifelong exercise training. METHODS: Healthy seniors (n = 102) were recruited from predefined populations, screened for lifelong patterns of exercise training, and stratified into 4 groups: "sedentary" (<2 sessions/week); "casual" (2 to 3 sessions/week); "committed" (4 to 5 sessions/week); and "competitive" Masters level athletes (6 to 7 sessions/week). Right heart catheterization and echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion to define LV pressure-volume relationships and Frank-Starling curves. RESULTS: Peak oxygen uptake and LV mass increased with escalating doses of lifelong exercise, with little change in systolic function. At baseline, LV distensibility was greater in committed (21%) and competitive (36%) exercisers than in sedentary subjects. Group LV stiffness constants (sedentary: 0.062 ± 0.039; casual: 0.079 ± 0.052; committed: 0.055 ± 0.033; and competitive: 0.035 ± 0.033) revealed: 1) increased stiffness in sedentary subjects compared to competitive athletes, whereas lifelong casual exercise had no effect; and 2) greater compliance in committed exercisers than in sedentary or casual exercisers. CONCLUSIONS: Low doses of casual, lifelong exercise do not prevent the decreased compliance and distensibility observed with healthy, sedentary aging. In contrast, 4 to 5 exercise sessions/week throughout adulthood prevent most of these age-related changes. As LV stiffening has been implicated in the pathophysiology of many cardiovascular conditions affecting the elderly, this "dose" of exercise training may have important implications for prevention of cardiovascular disease.

The effect of lifelong exercise dose on cardiovascular function during exercise.

An increased "dose" of endurance exercise training is associated with a greater maximal oxygen uptake (Vo2max), a larger left ventricular (LV) mass, and improved heart rate and blood pressure control. However, the effect of lifelong exercise dose on metabolic and hemodynamic response during exercise has not been previously examined. We performed a cross-sectional study on 101 (69 men) seniors (60 yr and older) focusing on lifelong exercise frequency as an index of exercise dose. These included 27 who had performed ≤ 2 exercise sessions/wk (sedentary), 25 who performed 2-3 sessions/wk (casual), 24 who performed 4-5 sessions/wk (committed) and 25 who performed ≥ 6 sessions/wk plus regular competitions (Masters athletes) over at least the last 25 yr. Oxygen uptake and hemodynamics [cardiac output, stroke volume (SV)] were collected at rest, two levels of steady-state submaximal exercise, and maximal exercise. Doppler ultrasound measures of LV diastolic filling were assessed at rest and during LV loading (saline infusion) to simulate increased LV filling. Body composition, total blood volume, and heart rate recovery after maximal exercise were also examined. Vo2max increased in a dose-dependent manner (P < 0.05). At maximal exercise, cardiac output and SV were largest in committed exercisers and Masters athletes (P < 0.05), while arteriovenous oxygen difference was greater in all trained groups (P < 0.05). At maximal exercise, effective arterial elastance, an index of ventricular-arterial coupling, was lower in committed exercisers and Masters athletes (P < 0.05). Doppler measures of LV filling were not enhanced at any condition, irrespective of lifelong exercise frequency. These data suggest that performing four or more weekly endurance exercise sessions over a lifetime results in significant gains in Vo2max, SV, and heart rate regulation during exercise; however, improved SV regulation during exercise is not coupled with favorable effects on LV filling, even when the heart is fully loaded.

Cardiovascular effects of 1 year of alagebrium and endurance exercise training in healthy older individuals.

BACKGROUND: Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise combined with alagebrium would improve LV stiffness in sedentary older humans. METHODS AND RESULTS: Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define LV pressure-volume curves; secondary functional outcomes included cardiopulmonary exercise testing and arterial compliance. A total of 57 of 62 subjects (67 ± 6 years; 37 f/20 m) completed 1 year of intervention followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the slope of LV pressure-volume curve. After intervention, LV mass and end-diastolic volume increased and exercise capacity improved (by ≈8%) only in the exercise groups. Neither LV mass nor exercise capacity was affected by alagebrium. Exercise training had little impact on LV stiffness (training × time effect, P=0.46), whereas alagebrium showed a modest improvement in LV stiffness compared with placebo (medication × time effect, P=0.04). CONCLUSIONS: Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening. CLINICAL TRIAL REGISTRATION- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01014572.

Effects of age and aerobic fitness on myocardial lipid content.

BACKGROUND: Aging and sedentary lifestyles lead to cardiac atrophy, ventricular stiffening, and impaired diastolic function. Both conditions are marked by increased adiposity, which can lead to ectopic fat deposition in nonadipocyte tissues including the myocardium. The effect of excess intramyocardial fat on cardiac function in nonobese individuals is unknown. METHODS AND RESULTS: Cardiac lipid content was measured by magnetic resonance spectroscopy in 153 healthy nonobese subjects with varying fitness levels quantified by peak oxygen uptake during treadmill exercise. Cardiac function (echo) and left ventricular (LV) filling pressures (right heart catheterization) were measured under varying preloads. LV stiffness was calculated from a curve fit of the diastolic portion of the pressure-volume curve. The strongest clinical predictors of lipid content were body mass index (ß=+0.03; 95% confidence interval, 0.001-0.06) and peak oxygen uptake (ß=-0.02; 95% confidence interval, -0.03 to -0.009; R(2)=0.14; P<0.001). Subjects in the highest quintile had smaller LV end-diastolic volumes (68±13 versus 58±12 mL/m(2); P<0.01) and decreased peak early mitral annular and increased peak late mitral inflow velocities. There were no differences in LV stiffness, but a leftward shift in the pressure-volume curve suggested a less distensible ventricle with increasing myocardial lipid levels. After adjusting for age, fitness, and body mass index, echocardiographic and morphometric differences among groups were attenuated and no longer significant. CONCLUSIONS: Body mass index and fitness levels are the strongest predictors of myocardial lipid content in nonobese humans. Cardiac lipid content is associated with decreased ventricular distensibility, and it may provide a causal mechanism linking changes in LV function related to age and fitness.

The effect of exercise training on left ventricular relaxation and diastolic suction at rest and during orthostatic stress after bed rest.

A marked reduction in upright stroke volume (SV) contributes substantially to orthostatic intolerance after exposure to spaceflight or bed rest. It is unclear whether slowed left ventricular (LV) relaxation and diastolic suction contribute to the reduction in SV or whether these changes are influenced by exercise training while in bed. Twenty-seven healthy adults completed 5 weeks of -6 deg head-down bed rest (HDBR). During HDBR, nine subjects were sedentary (NOEX), while 18 performed near-daily rowing ergometry (EX). Left ventricular mass, SV, LV end-diastolic volume (LVEDV), pulmonary capillary wedge pressure and Doppler ultrasound indices of LV function were collected pre- and post-HDBR during supine rest (twice) and during reduced LV loading (lower body negative pressure; LBNP) and increased LV loading (saline infusion). Post-HDBR, LV mass increased in the EX group, but decreased in the NOEX group. The reduction in SV and LVEDV during supine rest and LBNP were greater with NOEX in comparison to EX after HDBR. Peak early mitral annular velocity, isovolumic relaxation time, early propagation velocity, a non-invasive index of early diastolic filling and ventricular diastolic suction, and peak global longitudinal early strain rate were slowed during supine rest after HDBR with NOEX; however, these variables were either unaltered or the reduction was less prominent with EX. Doppler ultrasound measures of early diastolic filling, ventricular relaxation and diastolic suction were not significantly affected during LV unloading by LBNP after HDBR in either group. All Doppler indices were restored to pre-HDBR levels in both groups during saline infusion to normalize LV filling pressure after HDBR. It is concluded that Doppler indices of dynamic LV filling were reduced in both groups after HDBR; however, these effects were more pronounced in the NOEX group. Irrespective of group, post-HDBR Doppler parameters were restored when LV filling pressure was increased to pre-HDBR levels during saline infusion. Therefore, the reduction in upright SV after HDBR is more influenced by changes in LV loading conditions, namely left atrial pressure in the setting of LV remodelling, rather than ventricular relaxation and diastolic suction.

Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure.

BACKGROUND: Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction. However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remain unknown. METHODS AND RESULTS: Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure and mean pulmonary arterial pressure to volume loading with rapid saline infusion (100-200 mL/min). Hemodynamic responses to saline infusion in heart failure with preserved ejection fraction (n=11) were then compared with those of healthy young (<50 years of age) and older (≥50 years of age) subjects. In healthy subjects, pulmonary capillary wedge pressure increased from 10±2 to 16±3 mm Hg after ~1 L and to 20±3 mm Hg after ~2 L of saline infusion. Older women displayed a steeper increase in pulmonary capillary wedge pressure relative to volume infused (16±4 mm Hg·L(-1)·m(2)) than the other 3 groups (P≤0.019). Saline infusion resulted in a greater increase in mean pulmonary arterial pressure relative to cardiac output in women compared with men regardless of age. Subjects with heart failure with preserved ejection fraction exhibited a steeper increase in pulmonary capillary wedge pressure relative to infused volume (25±12 mm Hg·L(-1)·m(2)) than healthy young and older subjects (P≤0.005). CONCLUSIONS: Filling pressures rise significantly with volume loading, even in healthy volunteers. Older women and patients with heart failure with preserved ejection fraction exhibit the largest increases in pulmonary capillary wedge pressure and mean pulmonary arterial pressure.

The effect of age-related differences in body size and composition on cardiovascular determinants of VO2max.

BACKGROUND: A reduction in maximal stroke volume (SVmax) and total blood volume (TBV) has been hypothesized to contribute to the decline in maximal oxygen uptake (VO2max) with healthy aging. However, these variables have rarely been collected simultaneously in a board age range to support or refute this hypothesis. It is also unclear to what extent scaling size-related cardiovascular determinants of VO2max affects the interpretation of age-related differences. METHODS: A retrospective analysis of VO2max, maximal cardiac output (QCmax), TBV, and body composition including fat-free mass (FFM) in 95 (51% M) healthy adults ranging from 19-86 years. RESULTS: Absolute and indexed VO2max, QCmax, and maximal heart rate decreased in both sexes with age (p ≤ .031). SVmax declined with age when scaled to total body mass or body surface area (p ≤ .047) but not when expressed in absolute levels (p = .120) or relative to FFM (p = .464). Absolute and indexed TBVs (mL/kg; mL/m(2)) were not significantly affected by age but increased with age in both sexes when scaled to FFM (p ≤ .013). A lower arteriovenous oxygen difference (a-vO2diff) contributed to the reduction in VO2max with age in treadmill exercisers (p = .004) but not in the entire cohort (p = .128). CONCLUSION: These results suggest (a) a reduction in absolute SVmax, and TBV do not contribute substantially to the age-related reduction in VO2max, which instead results from a smaller QCmax due to a lower maximal heart rate, and (b) body composition scaling methods should be used to accurately describe the effect of aging on physical function and cardiovascular variables.

Cardiovascular effects of 1 year of progressive endurance exercise training in patients with heart failure with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a disease of the elderly with cardiovascular stiffening and reduced exercise capacity. Exercise training appears to improve exercise capacity and cardiovascular function in heart failure with reduced ejection fraction. However, it is unclear whether exercise training could improve cardiovascular stiffness, exercise capacity, and ventricular-arterial coupling in HFpEF. METHODS: Eleven HFpEF patients and 13 healthy controls underwent invasive measurements with right heart catheterization to define Starling and left ventricular (LV) pressure-volume curves; secondary functional outcomes included Doppler echocardiography, arterial stiffness, cardiopulmonary exercise testing with cardiac output measurement, and ventricular-arterial coupling assessed by the dynamic Starling mechanism. Seven of 11 HFpEF patients (74.9 ± 6 years; 3 men/4 women) completed 1 year of endurance training followed by repeat measurements. Pulmonary capillary wedge pressures and LV end-diastolic volumes were measured at baseline during decreased and increased cardiac filling. LV compliance was assessed by the slope of the pressure-volume curve. Beat-to-beat LV end-diastolic pressure (estimated from pulmonary arterial diastolic pressure) and stroke volume index were obtained, and spectral transfer function analysis was used to assess the dynamic Starling mechanism. RESULTS: Before training, HFpEF patients had reduced exercise capacity, distensibility and dynamic Starling mechanism but similar LV compliance and end-diastolic volumes compared to controls albeit with elevated filling pressure and increased wall stress. One year of training had little effect on LV compliance and volumes, arterial stiffness, exercise capacity or ventricular-arterial coupling. CONCLUSION: Contrary to our hypothesis, 1 year of endurance training failed to impart favorable effects on cardiovascular stiffness or function in HFpEF.

Effect of healthy aging on left ventricular relaxation and diastolic suction.

Doppler ultrasound measures of left ventricular (LV) active relaxation and diastolic suction are slowed with healthy aging. It is unclear to what extent these changes are related to alterations in intrinsic LV properties and/or cardiovascular loading conditions. Seventy carefully screened individuals (38 female, 32 male) aged 21-77 were recruited into four age groups (young: <35; early middle age: 35-49; late middle age: 50-64 and seniors: ≥65 yr). Pulmonary capillary wedge pressure (PCWP), stroke volume, LV end-diastolic volume, and Doppler measures of LV diastolic filling were collected at multiple loading conditions, including supine baseline, lower body negative pressure to reduce LV filling, and saline infusion to increase LV filling. LV mass, supine PCWP, and heart rate were not affected significantly by aging. Measures of LV relaxation, including isovolumic relaxation time and the time constant of isovolumic pressure decay increased progressively, whereas peak early mitral annular longitudinal velocity decreased with advancing age (P < 0.001). The propagation velocity of early mitral inflow, a noninvasive measure of LV suction, decreased with aging with the greatest reduction in seniors (P < 0.001). Age-related differences in LV relaxation and diastolic suction were not attenuated significantly when PCWP was increased in older subjects or reduced in the younger subjects. There is an early slowing of LV relaxation and diastolic suction beginning in early middle age, with the greatest reduction observed in seniors. Because age-related differences in LV dynamic diastolic filling parameters were not diminished significantly with significant changes in LV loading conditions, a decline in ventricular relaxation is likely responsible for the alterations in LV diastolic filling with senescence.

Effect of ageing on left ventricular compliance and distensibility in healthy sedentary humans.

Healthy, but sedentary ageing leads to marked atrophy and stiffening of the heart, with substantially reduced cardiac compliance; but the time course of when this process occurs during normal ageing is unknown. Seventy healthy sedentary subjects (39 female; 21­77 years) were recruited from the Dallas Heart Study, a population-based, random community sample and enriched by a second random sample from employees of Texas Health Resources. Subjects were highly screened for co-morbidities and stratified into four groups according to age: G(21−34): 21­34 years, G(35−49): 35­49 years, G5(0−64): 50­64 years, G(≥65): ≥65 years. All subjects underwent invasive haemodynamic measurements with right heart catheterization to define Starling and left ventricular (LV) pressure­volume curves. LV end-diastolic volumes (EDV) were measured by echocardiography at baseline, −15 and −30 mmHg lower-body negative pressure, and 15 and 30 ml kg(−1) saline infusion with simultaneous measurements of pulmonary capillary wedge pressure. There were no differences in heart rate or blood pressures among the four groups at baseline. Baseline EDV index was smaller in G(≥65) than other groups. LV diastolic pressure­volume curves confirmed a substantially greater LV compliance in G(21−34) compared with G(50−64) and G(≥65), resulting in greater LV volume changes with preload manipulations. Although LV chamber compliance in G(50−64) and G(≥65) appeared identical, pressure­volume curves were shifted leftward, toward a decreased distensibility, with increasing age. These results suggest that LV stiffening in healthy ageing occurs during the transition between youth and middle-age and becomes manifest between the ages of 50 to 64. Thereafter, this LV stiffening is followed by LV volume contraction and remodelling after the age of 65.

Effect of rowing ergometry and oral volume loading on cardiovascular structure and function during bed rest.

This study examined the effectiveness of a short-duration but high-intensity exercise countermeasure in combination with a novel oral volume load in preventing bed rest deconditioning and orthostatic intolerance. Bed rest reduces work capacity and orthostatic tolerance due in part to cardiac atrophy and decreased stroke volume. Twenty seven healthy subjects completed 5 wk of -6 degree head down bed rest. Eighteen were randomized to daily rowing ergometry and biweekly strength training while nine remained sedentary. Measurements included cardiac mass, invasive pressure-volume relations, maximal upright exercise capacity, and orthostatic tolerance. Before post-bed rest orthostatic tolerance and exercise testing, nine exercise subjects were given 2 days of fludrocortisone and increased salt. Sedentary bed rest led to cardiac atrophy (125 ± 23 vs. 115 ± 20 g; P < 0.001); however, exercise preserved cardiac mass (128 ± 38 vs. 137 ± 34 g; P = 0.002). Exercise training preserved left ventricular chamber compliance, whereas sedentary bed rest increased stiffness (180 ± 170%, P = 0.032). Orthostatic tolerance was preserved only when exercise was combined with volume loading (-10 ± 22%, P = 0.169) but not with exercise (-14 ± 43%, P = 0.047) or sedentary bed rest (-24 ± 26%, P = 0.035) alone. Rowing and supplemental strength training prevent cardiovascular deconditioning during prolonged bed rest. When combined with an oral volume load, orthostatic tolerance is also preserved. This combined countermeasure may be an ideal strategy for prolonged spaceflight, or patients with orthostatic intolerance.