Combined Ventricular Systolic and Arterial Stiffening in Patients With Heart Failure and Preserved Ejection Fraction

Abstract

Background-Heart failure with preserved ejection fraction (HF-nlEF) is common in aged individuals with systolic hypertension and is frequently ascribed to diastolic dysfunction. We hypothesized that such patients also display combined ventricular-systolic and arterial stiffening that can exacerbate blood pressure lability and diastolic dysfunction under stress. Methods and Results-Left ventricular pressure-volume relations were measured in patients with HF-nlEF (nϭ10) and contrasted with asymptomatic age-matched (nϭ9) and young (nϭ14) normotensives and age-and blood pressurematched controls (nϭ25). End-systolic elastance (stiffness) was higher in patients with HF-nlEF (4.7Ϯ1.5 mm Hg/mL) than in controls (2.1Ϯ0.9 mm Hg/mL for normotensives and 3.3Ϯ1.0 mm Hg/mL for hypertensives; PϽ0.001).Effective arterial elastance was also higher (2.6Ϯ0.5 versus 1.9Ϯ0.5 mm Hg/mL) due to reduced total arterial compliance; the latter inversely correlated with end-systolic elastance (Pϭ0.0001). Body size and stroke volumes were similar and could not explain differences in ventricular-arterial stiffening. HF-nlEF patients also displayed diastolic abnormalities, including higher left ventricular end-diastolic pressures (24.3Ϯ4.6 versus 12.9Ϯ5.5 mm Hg), caused by an upward-shifted diastolic pressure-volume curve. However, isovolumic relaxation and the early-to-late filling ratio were similar in age-and blood pressure-matched controls. Ventricular-arterial stiffening amplified stress-induced hypertension, which worsened diastolic function, and predicted higher cardiac energy costs to provide reserve output. Conclusion-Patients

Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

“…The major effect of age on the vasculature is systolic hypertension with widening of the pulse pressure that results from age‐related increase in arterial stiffness and early wave reflections 43, 44. Arterial stiffening and early wave reflections are steady vascular features in HFpEF 45, 46, 47, 48, 49, 50, 51, 52. In the proximal arterial tree, vascular smooth cell loss of elastin increases systolic arterial pressure by lessening the “windkessel” effect 44, 45, 53.…”

Echocardiographic evaluation of diastolic heart failure

“…LV filling is impaired (abnormalities of active relaxation and passive stiffness of the myocardium) in combination with abnormal ventriculo‐arterial coupling 12 , 13 . However, with emerging technologies that question the accuracy of normal systolic function, the pathophysiology of HFNEF remains controversial 14 .…”

“…The traditional concept of HFNEF is based on sophisticated catheter based conductance studies 15 , 16 demonstrating haemodynamically that HFNEF patients exhibit an upward and leftward shift in end‐diastolic pressure‐volume relationship, whereas the end‐systolic pressure‐volume relationship (end‐systolic elastance) is unaltered or even steeper than in subjects without HF 17 , 18 . Zile, et al 19 demonstrated that HFNEF patients have abnormalities of active LV relaxation (prolonged time constant of relaxation, tau (t), and LV stiffness (increased LV passive stiffness constant (β)) with a resultant increase in left ventricular end‐diastolic pressure (LVEDP) and pulmonary venous pressure even with small changes in LV end‐diastolic volumes, resulting in exertional dyspnoea and even pulmonary oedema 20 .…”

Association between sleep‐disordered breathing and arterial stiffness in heart failure patients with reduced or preserved ejection fraction

“…In HFpEF patients, LV diastolic relaxation abnormalities were revealed by pressure–volume analysis and echocardiographic examination 7, 8, 28. Moreover, both ventricular stiffness and arterial stiffness increase with advancing age; further, ventricular–arterial stiffening, compliance, and relaxation abnormalities are common in patients with HFpEF 7, 10, 11, 12. In HFrEF patients, myocardial loss or degeneration and dysfunction play essential pathophysiological roles.…”

“…Crucial pathophysiological conditions in the development of HFpEF include prolonged isovolumic left ventricular (LV) relaxation, slow LV filling, increased diastolic LV stiffness, and LV diastolic dysfunction 4, 5, 6. These pathophysiological characteristics are associated with increased ventricular–arterial stiffness and exaggerated blood pressure response to changes in ventricular loading in HFpEF patients 7, 8, 9. In particular, in HFpEF patients, central aortic stiffness is increased, and arterial stiffness modulates ventricular loading conditions as well as LV diastolic function 10, 11, 12.…”