Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction

Abstract

Objectives: We sought to compare left ventricular (LV) systolic stiffness and contractility in normal subjects, hypertensive patients without heart failure, and patients with heart failure and preserved ejection fraction (HFpEF) and to determine whether LV systolic stiffness or myocardial contractility is associated with the rate of mortality in patients with HFpEF.

Background: Arterial load is increased in patients with hypertension and is matched by increased end-systolic LV stiffness (ventricular-arterial coupling). Increased end-systolic LV stiffness may be mediated by enhanced myocardial contractility or processes that increase passive myocardial stiffness.

Methods: Healthy control patients (n = 617), hypertensive patients (no heart failure, n = 719), and patients with HFpEF (n = 244, 96% hypertensive) underwent echo-Doppler characterization of arterial (Ea) and LV end-systolic (Ees) stiffness (elastance), ventricular-arterial coupling (Ea/Ees ratio), and chamber-level and myocardial contractility (stress-corrected midwall shortening).

Results: We found that Ea and Ees were similarly increased in hypertensive patients with or without HFpEF compared with control patients, but ventricular-arterial coupling was similar across groups. In hypertensive patients, increased Ees was associated with enhanced chamber-level and myocardial contractility, whereas in patients with HFpEF, chamber and myocardial contractility were depressed compared with both hypertensive and control patients. Group differences persisted after adjusting for geometry. In patients with HFpEF, impaired myocardial contractility (but not Ees) was associated with increased age-adjusted mortality.

Conclusions: Although arterial load is increased and matched by increased LV systolic stiffness in hypertensive patients with or without HFpEF, the mechanisms of systolic LV stiffening differ substantially. These data suggest that myocardial contractility increases to match arterial load in asymptomatic hypertensive heart disease, but that progression to HFpEF may be mediated by processes that simultaneously impair myocardial contractility and increase passive myocardial stiffness.

Figure 1. VA coupling and contractility

[A] The relationship between Ees and Ea was similar among each group (dashed lines show 95% prediction bands). [B-D] Load-independent chamber contractility (PRSW and sc-eFS) and myocardial contractility (sc-mFS) were elevated in hypertensives without HF and decreased in HFpEF compared with hypertensives and controls. Data are mean ± standard deviation.

Figure 2. Myocardial contractility

[A] The relationship between midwall myofiber shortening (mFS) and end-systolic wall stress (log cESS) showing mean regression (solid) line and 95% confidence limits (dotted) in controls (black) with data points and regression line for hypertensives (blue) shifted upward, indicating enhanced myocardial contractility in hypertension. [B-C] In HFpEF (red), the data points and regression line are shifted down as compared to both controls and hypertensives, indicating depressed contractility. [D] Cumulative distribution plot for sc-mFS show that compared to healthy controls (black), myocardial contractility is depressed in HFpEF (red) and enhanced in hypertensives without HF (blue).

Figure 3. Geometry and its effect on end-systolic elastance and contractility indices

[A] The distributions of LV geometry differed among controls, hypertensives and HFpEF. Even within the healthy control group, Ees varied according to geometry pattern [B], as did PRSW, sc-eFS and sc-mFS [C]. See text for discussion. Data are mean ± standard error.

Figure 4. VA coupling and contractility according to group and geometry

[A] Ees was elevated in HFpEF (red) and hypertensives (blue) compared with controls (black) for each pattern of geometry. In contrast, PRSW [B], sc-eFS [C] and sc-mFS [D] were each consistently depressed in HFpEF and elevated in hypertensives compared with controls. CR, concentric remodeling; CH, concentric hypertrophy; EH, eccentric hypertrophy. See text for discussion. Data are mean ± standard error.

Figure 5. Kaplan-Meier plot of survival in HFpEF patients

Stress-corrected midwall myofiber shortening (sc-mFS) below the median value is associated with reduced survival in HFpEF.