Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation

Abstract

Background: Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs.

Methods: Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure-volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls.

Results: Healed myocardial infarction was associated with preserved echocardiographic left ventricular ejection fraction (0.57 +/- 0.01, mean +/- SEM) and altered Doppler mitral indices of diastolic function. NT-proBNP was increased, aldosterone was decreased, and norepinephrine was unchanged. Invasive measurements showed a markedly decreased end-systolic elastance (2.1 +/- 0.2 vs 6.1 +/- 0.8, mmHg/ml, p < 0.001) and end-systolic elastance to effective arterial elastance ratio (0.6 +/- 0.1 vs 1.4 +/- 0.2, p < 0.001), with altered active relaxation (dP/dtmin -1992 +/- 71 vs -2821 +/- 305, mmHg/s, p < 0.01) but preserved left ventricular capacitance (70 +/- 6 vs 61 +/- 3, ml at 20 mmHg, p = NS) and stiffness constant. Among echocardiographic variables, the wall motion score index was the most reliable indicator of cardiac contractility while E', E/A and E'/A' were correlated to dP/dtmin.

Conclusions: In the canine model of healed myocardial infarction induced by coronary ligation, heart failure is essentially characterized by an altered contractility with left ventricular-arterial uncoupling despite vascular compensation rather than by abnormal diastolic function.

Figure 1

PV loops under preload reduction. Representative left ventricular (LV) pressure-volume (PV) loops during vena cava occlusion in a control dog and in a dog 2 months after recovery from a myocardial infarction. Recovery from myocardial infarction was associated with a decreased end-systolic elastance (decreased contractility, altered systolic function) but unchanged/slightly decreased diastolic elastance (unchanged diastolic function). Ees: end-systolic pressure volume relationship; Ea: effective arterial elastance; MI:myocardial infarction; ESP: end-systolic pressure; EDV: end-diastolic volume.

Figure 2

Correlations between hemodynamic and echocardiographic data: systolic function. A: Scatterplot of Ees as a function of WMSI. B: Scatterplot of Ees/Ea as a function of S'. Ees: left ventricular end-systolic elastance; WMSI: wall motion score index; Ea: arterial elastance; S': Tissue Doppler mitral annulus S wave.

Figure 3

Correlations between hemodynamic and echocardiographic data: active relaxation. A: Scatterplot of dP/dtmin as a function of tissue Doppler mitral annulus velocity E' wave. B: Scatterplot of dP/dtmin as a function of mitral Doppler flow ratio of E and A waves.