Impact of arterial load and loading sequence on left ventricular tissue velocities in humans.

OBJECTIVES: The aim of this study was to examine the relationship between individual components of left ventricular (LV) afterload and tissue Doppler echocardiography (TDE) velocities in humans. BACKGROUND: Acute increases in afterload slow diastolic relaxation as assessed invasively, yet little is known about chronic effects of load and loading sequence on LV TDE velocities. METHODS: Forty-eight subjects underwent echo Doppler and color-coded TDE with comprehensive noninvasive vascular assessment. Arterial afterload was measured by effective arterial elastance (Ea) and systemic vascular resistance index (SVRI), and loading sequence was quantified by early- (carotid characteristic impedance [Zc]) and late-systolic loads (augmentation index [cAI]; late pressure-time integral [PTI3]). Vascular stiffness was measured by carotid-femoral pulse wave velocity (PWV) and total arterial compliance. RESULTS: Early-diastolic velocity (E') varied inversely with Zc, SVRI, Ea, and PWV (r = -0.4 to 0.5; beta = 1.0 to 1.2; p < or = 0.004), but late-systolic load (cAI and PTI3 r = -0.6; beta = 1.6; both p < 0.0001) and arterial compliance (r = 0.6; beta = 1.4; p < 0.0001) had the strongest associations with E'. Load dependence was not altered by the presence of hypertension, and in multivariate analysis only cAI and Zc significantly predicted E', even after adjusting for age (p < 0.05). Peak systolic velocity was additionally found to be inversely related to afterload, whereas other measures of contractility were not. CONCLUSIONS: Diastolic and systolic tissue velocities vary inversely with arterial afterload, with late-systolic load having the greatest influence on E'. These findings may partly explain the decrease in early relaxation velocity noted with aging, hypertension, and patients with heart failure. Strategies to reduce afterload, vascular stiffening, and wave reflections may prove useful to enhance early diastolic relaxation.

Estimation of central pressure augmentation using automated radial artery tonometry.

BACKGROUND: Peripheral wave reflection augments central blood pressure and contributes to cardiac load. This pressure augmentation is not quantifiable from brachial cuff pressure but can be determined from carotid pulsations using the augmentation index (AI). However, carotid tonometry is technically challenging and difficult to standardize in practice. We tested whether automated radial pressure analysis provides a viable alternative. METHODS AND RESULTS: Carotid and radial AI (cAI, rAI) were measured in 46 volunteers with a broad range of arterial properties. Data were assessed at rest, during a cold-pressor test, and following 0.4 mg of sublingual nitroglycerin. cAI correlated with rAI independent of age, mean blood pressure (BP), gender or body mass (cAI = 0.79 x rAI - 0.467, r = 0.81, P < 0.00001), with zero mean bias. There was individual variability in the prediction (difference of -4 +/- 23%), though 65% of the estimates fell within 15% of each other. Change in rAI and cAI with provocative maneuvers also correlated (r = 0.77, P < 0.001). Both cAI and rAI were nonlinearly related to late-systolic pressure-time integral (PTI), an index of cardiac load. At cAI < 0.1 or rAI < 0.69, PTI was unaltered, while greater values correlated with increased PTI. rAI accurately predicted this cut-off in 88% of cases, with a 5.5% false negative rate. CONCLUSIONS: Automated rAI analysis is an easily applied method to assess basal and dynamic central pressure augmentation. While individual predictive accuracy of cAI was variable, overall population results were consistent, supporting use of rAI in clinical trials. Its prediction of when AI is associated with greater LV loading (i.e. cardiac risk) is good and may help stratify individual risk along with brachial cuff pressure.

Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction.

BACKGROUND: Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role. METHODS AND RESULTS: Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180+/-71 versus 455+/-184 seconds; peak oxygen consumption 9.0+/-3.4 versus 14.4+/-3.4 mL x kg(-1) x min(-1); both P<0.001). At matched low-level workload, HFpEF subjects displayed approximately 40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P<0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups. CONCLUSIONS: HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.