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QUARTERLY FOCUS ISSUE: HEART FAILURE: HEART FAILURE WITH PRESERVED EJECTION FRACTION

Contractility and Ventricular Systolic Stiffening in Hypertensive Heart Disease

Insights Into the Pathogenesis of Heart Failure With Preserved Ejection Fraction

Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, Minnesota

Manuscript received February 14, 2009; revised manuscript received April 9, 2009, accepted May 5, 2009.

^_* Reprint requests and correspondence: Dr. Margaret M. Redfield, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905 (Email: redfield.margaret{at}mayo.edu).

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.

Key Words: contractility • heart failure • hypertension • pathophysiology

Abbreviations and Acronyms   cESS = circumferential end-systolic stress   Ea = effective arterial elastance (stiffness)   Ees = end-systolic elastance (stiffness)   EF = ejection fraction   HF = heart failure   HFpEF = heart failure with preserved ejection fraction   LV = left ventricle   PRSW = pre-load recruitable stroke work   sc-eFS = stress-corrected endocardial fractional shortening   sc-mFS = stress-corrected midwall fractional shortening

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