Diminished contractile response to increased heart rate in intact human left ventricular hypertrophy. Systolic versus diastolic determinants.

Abstract

BACKGROUND Experimental studies indicate that in addition to diastolic dysfunction, hypertrophied myocardium can display depressed contractile responses, particularly at rapid heart rates, compounding reserve limitations. This study tests whether such abnormalities exist in intact human subjects at physiological paced rates and, if so, whether they are linked to simultaneous rate-dependent deterioration in diastolic function. METHODS AND RESULTS Ten subjects with left ventricular hypertrophy (LVH) and 8 normal control subjects were studied. Most LVH patients presented with dyspnea and/or pulmonary edema and had concentric hypertrophy. Since rapid pacing simultaneously alters cardiac filling volumes and pressures, pressure-volume relation analysis was used to better define changes in contractile response. Patients were instrumented with a conductance catheter and micromanometer for pressure-volume data recording and a balloon occluder at the right atrial-inferior vena caval junction to vary filling and thus generate function relations. Data were obtained at baseline and at three atrial pacing rates (100, 120, 150 min-1). In addition, single-beat force-interval data were used to indirectly examine calcium cycling kinetics. LVH subjects demonstrated baseline diastolic abnormalities, including prolonged relaxation, elevated end-diastolic pressure, and reduced chamber compliance. However, systolic function was similar to that in control subjects. With rapid pacing, normal subjects displayed a positive contractile response, whereas this was markedly diminished in LVH subjects. With abrupt termination of pacing and return to slower sinus rhythm, LVH subjects displayed greater initial potentiation followed by a more rapid decline than control subjects, suggesting abnormalities of calcium handling. Despite contractile abnormalities, diastolic function did not further deteriorate with rapid pacing and thus did not appear to be tightly linked to the systolic changes. CONCLUSIONS Pacing stress in intact human LVH can result in systolic impairment superimposed on preexisting but not worsened diastolic dysfunction. Abnormal calcium handling probably contributes prominently to this response.

Reduced Myocardial Sarcoplasmic Reticulum Ca 2+ -ATPase mRNA Expression and Biphasic Force-Frequency Relations in Patients With Hypertrophic Cardiomyopathy

“…In fact, T 1/2 , which was prolonged at rest in HCM, shortened progressively in both HCM and control subjects. Similar findings were observed previously by Liu et al 6 in patients with LVH. The mechanism of the preserved relaxation-frequency relation despite reduced SERCA2 gene expression in patients with severe HCM is not clear.…”

Ventricular Structure and Function in Aged Dogs With Renal Hypertension

“…We did not find increases in ␤ or ␣ despite the presence of LV hypertrophy and fibrosis in ExDHF, a finding similar to that reported recently in patients with DHF 5 but in contrast to other studies in human hypertensive heart disease 25,26 and a recent study in human DHF. 4 There are several potential explanations for this observation.…”

Hypertension and heart failure: a dysfunction of systole, diastole or both?

“…70,73 Furthermore, HFNEF is frequently referred to as diastolic heart failure as slow LV relaxation and high LV stiffness were further confirmed from invasive haemodynamic studies. [74][75][76][77] On the basis of the above data acquired at rest, three different pathophysiologic theories have been postulated for HFNEF. First, an increase in intrinsic muscle stiffness and impaired relaxation in diastole result in higher left atrial pressures to fill adequately, predisposing these patients to pulmonary venous congestion and dyspnoea especially on exertion.…”

“…First, an increase in intrinsic muscle stiffness and impaired relaxation in diastole result in higher left atrial pressures to fill adequately, predisposing these patients to pulmonary venous congestion and dyspnoea especially on exertion. 74,75,77 Second, increased systolic ventricular and arterial stiffening, that is, deranged ventriculoarterial coupling, may contribute to the pathophysiology of HFNEF by exaggerating hypertensive response with increased systolic load and inducing load-dependent diastolic dysfunction especially during exercise or other stresses. 78 Third, an enhanced sensitivity to volume overload from increased LV remodelling and dilation with volumedependent elevation of filling pressures was observed by Maurer et al 79 in a subgroup of hypertensive HFNEF patients from the Cardiovascular Health Study who had renal impairment and larger LV volumes but normal systolic ventricular and vascular stiffness.…”