Shigeki Shibata

Cardiovascular Effects of 1 Year of Progressive and Vigorous Exercise Training in Previously Sedentary Individuals Older Than 65 Years of Age

Background— Healthy but sedentary aging leads to cardiovascular stiffening, whereas life-long endurance training preserves left ventricular (LV) compliance. However, it is unknown whether exercise training started later in life can reverse the effects of sedentary behavior on the heart. Methods and Results— Twelve sedentary seniors and 12 Masters athletes were thoroughly screened for comorbidities. Subjects underwent invasive hemodynamic measurements with pulmonary artery catheterization to define Starling and LV pressure-volume curves; secondary functional outcomes included Doppler echocardiography, magnetic resonance imaging assessment of cardiac morphology, arterial stiffness (total aortic compliance and arterial elastance), and maximal exercise testing. Nine of 12 sedentary seniors (70.6±3 years; 6 male, 3 female) 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 cardiac filling with lower-body negative pressure, and increased filling with saline infusion. LV compliance was assessed by the slope of the pressure-volume curve. Before training, &OV0312;o2max, LV mass, LV end-diastolic volume, and stroke volume were significantly smaller and the LV was less compliant in sedentary seniors than Masters athletes. One year of exercise training had little effect on cardiac compliance. However, it reduced arterial elastance and improved &OV0312;o2max by 19% (22.8±3.4 versus 27.2±4.3 mL/kg/mL; P<0.001). LV mass increased (10%, 64.5±7.9 versus 71.2±12.3 g/m2; P=0.037) with no change in the mass-volume ratio. Conclusions— Although 1 year of vigorous exercise training did not appear to favorably reverse cardiac stiffening in sedentary seniors, it nonetheless induced physiological LV remodeling and imparted favorable effects on arterial function and aerobic exercise capacity.

The Relationship of Right- and Left-sided Filling Pressures in Patients with Heart Failure and a Preserved Ejection Fraction

BACKGROUNDnAlthough right-sided filling pressures often mirror left-sided filling pressures in systolic heart failure, it is not known whether a similar relationship exists in heart failure with preserved ejection fraction.nnnMETHODS AND RESULTSnEleven subjects with heart failure with preserved ejection fraction underwent right heart catheterization at rest and under loading conditions manipulated by lower body negative pressure and saline infusion. Right atrial pressure (RAP) was classified as elevated when >or=10 mm Hg and pulmonary capillary wedge pressure (PCWP) when >or=22 mm Hg. If both the RAP and the PCWP were elevated or both not elevated, they were classified as concordant; otherwise, they were classified as discordant. Correlation of RAP and PCWP was determined by a repeated measures model. Among 66 paired measurements of RAP and PCWP, 44 (67%) had a low RAP and PCWP and 8 (12%) a high RAP and PCWP, yielding a concordance rate of 79%. In a sensitivity analysis performed by varying the definition of elevated RAP (from 8 to 12 mm Hg) and PCWP (from 15 to 25 mm Hg), the mean+/-SD concordance of RAP and PCWP was 76+/-10%. The correlation coefficient of RAP and PCWP for the overall cohort was r=0.86 (P<0.0001).nnnCONCLUSIONSnRight-sided filling pressures often reflect left-sided filling pressures in heart failure with preserved ejection fraction, supporting the role of estimation of jugular venous pressure to assess volume status in this condition.

Vasomotor sympathetic neural control is maintained during sustained upright posture in humans

Vasomotor sympathetic activity plays an important role in arterial pressure maintenance via the baroreflex during acute orthostasis in humans. If orthostasis is prolonged, blood pressure may be supported additionally by humoral factors with a possible reduction in sympathetic baroreflex sensitivity. We tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) decreases during prolonged upright posture. MSNA and haemodynamics were measured supine and during 45 min 60 deg upright tilt in 13 healthy individuals. Sympathetic baroreflex sensitivity was quantified using the slope of the linear correlation between MSNA and diastolic pressure during spontaneous breathing. It was further assessed as the relationship between MSNA and stroke volume, with stroke volume derived from cardiac output (C2H2 rebreathing) and heart rate. Total peripheral resistance was calculated from mean arterial pressure and cardiac output. We found that MSNA increased from supine to upright (17 ± 8 (s.d.) versus 38 ± 12 bursts min−1; P < 0.01), and continued to increase to a smaller degree during sustained tilt (39 ± 11, 41 ± 12, 43 ± 13 and 46 ± 15 bursts min−1 after 10, 20, 30 and 45 min of tilt; between treatments P < 0.01). Sympathetic baroreflex sensitivity increased from supine to upright (−292 ± 180 versus−718 ± 362 units beat−1 mmHg−1; P < 0.01), but remained unchanged as tilting continued (−611 ± 342 and −521 ± 221 units beat−1 mmHg−1 after 20 and 45 min of tilt; P= 0.49). For each subject, changes in MSNA were associated with changes in stroke volume (r= 0.88 ± 0.13, P < 0.05), while total peripheral resistance was related to MSNA during 45 min upright tilt (r= 0.82 ± 0.15, P < 0.05). These results suggest that the vasoconstriction initiated by sympathetic adrenergic nerves is maintained by ongoing sympathetic activation during sustained (i.e. 45 min) orthostasis without obvious changes in vasomotor sympathetic neural control.

Cardiac systolic and diastolic function during whole body heat stress

During a whole body heat stress, stroke volume is either maintained or slightly elevated despite reduced ventricular filling pressures and central blood volume, suggestive of improved cardiac diastolic and/or systolic function. Heat stress improves cardiac systolic and diastolic function in patients with congestive heart failure, although it remains unknown whether similar responses occur in healthy individuals, which is the hypothesis to be tested. Nine male volunteers underwent a whole body heat stress. Echocardiographic indexes of diastolic and systolic function were performed following a supine resting period, and again following an increase in internal temperature of approximately 1.0 degrees C via passive heat stress. Despite previous reports of heat stress-induced decreases in ventricular filling pressures and central blood volume, no changes in indexes of diastolic function were identified during heating [i.e., unchanged early diastolic mitral annular tissue velocity (E), mitral inflow during the early diastolic phase (E), the E/E ratio, and isovolumetric relaxation time]. Heat stress increased late diastolic septal (P = 0.03) and lateral (P = 0.01) mitral annular tissue velocities (A), mitral inflow velocity during atrial contraction (P < 0.001), and the relative contribution of atrial contraction to left ventricular filling during diastole (P = 0.01), all indicative of improved atrial systolic function. Furthermore, indexes of ventricular systolic function were increased by heat stress [i.e., increased septal (P = 0.001) and lateral (P = 0.01) mitral annular systolic velocities and isovolumic acceleration at the septal (P = 0.03) and lateral (P < 0.001) mitral annulus]. These data are suggestive of improved atrial and ventricular systolic function by the heat stress. Together these data support previous findings, which used the less precise measure of ejection fraction, that heat stress improves indexes of systolic function, while diastolic function is maintained.

Effects of pericardial constraint and ventricular interaction on left ventricular hemodynamics in the unloaded heart

Pericardial constraint and ventricular interaction influence left ventricular (LV) performance when preload is high. However, it is unclear if these constraining forces modulate LV filling when the heart is unloaded, such as during upright posture, in humans. Fifty healthy individuals underwent right heart catheterization to measure pulmonary capillary wedge (PCWP) and right atrial pressure (RAP). To evaluate the effects of pericardial constraint on hemodynamics, transmural filling pressure (LVTMP) was defined as PCWP-RAP. Beat-to-beat blood pressure (BP) waveforms were recorded, and stroke volume (SV) was derived from the Modelflow method. After measurements at -30 mmHg lower body negative pressure (LBNP), which approximates the upright position, LBNP was released, and beat-to-beat measurements were performed for 15 heartbeats. At -30 mmHg LBNP, RAP and PCWP were significantly decreased. During the first six beats of LBNP release, heart rate (HR) was unchanged, while BP increased from the fourth beat. RAP increased faster than PCWP resulting in an acute decrease in LVTMP from the fourth beat. A corresponding drop in SV by 3% was observed with no change in pulse pressure. From the 7th to 15th beats, LVTMP and SV increased steadily, followed by a decreased HR due to the baroreflex. A decreased TMP, but not PCWP, caused a transient drop in SV with no changes in HR or pulse pressure during LBNP release. These results suggest that the pericardium constrains LV filling during LBNP release, enough to cause a small but significant drop of SV, even at low cardiac filling pressure in healthy humans.

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.

Effects of sex and hypertension subtype on haemodynamics and left ventricular diastolic function in older patients with stage 1 hypertension

Background: Hypertension is associated with cardiovascular stiffening and left ventricular diastolic dysfunction, leading to comorbidities such as heart failure with preserved ejection fraction (HFpEF). It is unknown whether sex and hypertension subtype affect haemodynamics and left ventricular function in older individuals. Methods: Ninety-five older patients with Stage 1 hypertension (ambulatory awake SBP135–159u200ammHg) and 56 normotensive controls were enrolled. Patients were stratified prospectively into isolated systolic hypertension (ISH, DBP <85u200ammHg) or systolic-diastolic hypertension (SDH, DBP ≥85u200ammHg). Haemodynamics and Doppler variables including early filling (E) and averaged mitral annular (E′mean) velocities were measured during supine rest. Results: Ambulatory awake blood pressures (BPs) were the highest in SDH, whereas supine SBP was similar in both hypertensive groups. No sex difference was observed in supine or ambulatory awake BPs in all groups. Stroke volume was similar among groups within the same sex, but smaller in women. Women exhibited faster E, slower E′mean and greater E/E′mean, whereas no group difference was observed in E within the same sex. In women, E′mean was significantly slower in SDH (5.9u200a±u200a1.6 vs. 7.4u200a±u200a1.1u200acm/s, Pu200a<u200a0.01) and ISH (6.6u200a±u200a1.6u200acm/s, Pu200a=u200a0.07) than controls, resulting in the highest E/E′mean in SDH. In men, E′mean and E/E′mean were similar among the three groups. Conclusion: These results suggest that elderly hypertensive women may have left ventricular early diastolic dysfunction and higher estimated filling pressure, consistent with their susceptibility to HFpEF. Women with SDH seemed to have more left ventricular diastolic dysfunction, which might be explained by the greater cumulative afterload when ambulatory.