Characterization of static and dynamic left ventricular diastolic function in patients with heart failure with a preserved ejection fraction

Abstract

Background: Congestive heart failure in the setting of a preserved left ventricular (LV) ejection fraction is increasing in prevalence among the senior population. The underlying pathophysiologic abnormalities in ventricular function and structure remain unclear for this disorder. We hypothesized that patients with heart failure with preserved ejection fraction (HFPEF) would have marked abnormalities in LV diastolic function with increased static diastolic stiffness and slowed myocardial relaxation compared with age-matched healthy controls.

Methods and results: Eleven highly screened patients (4 men, 7 women) aged 73±7 years with HFPEF were recruited to participate in this study. Thirteen sedentary healthy controls (7 men, 6 women) aged 70±4 years also were recruited. All subjects underwent pulmonary artery catheterization with measurement of cardiac output, end-diastolic volumes, and pulmonary capillary wedge pressures at baseline; cardiac unloading (lower-body negative pressure or upright tilt); and cardiac loading (rapid saline infusion). The data were used to define the Frank-Starling and LV end-diastolic pressure-volume relationships. Doppler echocardiographic data (tissue Doppler velocities, isovolumic relaxation time, propagation velocity of early mitral inflow , E/A-wave ratio) were obtained at each level of cardiac preload. Compared with healthy controls, patients with HFPEF had similar LV contractile function and static LV compliance but reduced LV chamber distensibility with elevated filling pressures and slower myocardial relaxation as assessed by tissue Doppler imaging.

Conclusions: In this small, highly screened patient population with hemodynamically confirmed HFPEF, increased end-diastolic static ventricular stiffness relative to age-matched controls was not a universal finding. Nevertheless, patients with HFPEF, even when well compensated, had elevated filling pressures, reduced distensibility, and increased diastolic wall stress compared with controls. In contrast, LV relaxation as assessed by tissue Doppler variables appeared consistently impaired in patients with HFPEF.

Figure 1

Patient enrollment flowchart. CABG indicates coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction.

Figure 2

A, Frank-Starling relationship. Overall contractile function was similar between the patients with HFPEF and controls (second-order regression analysis, r=0.99 for both groups; P=0.664). B, PRSW. No differences were noted in PRSW (linear regression analysis, r=0.97 and r=0.98 for patients with HFPEF and controls, respectively; P=0.421).

Figure 3

A, End-diastolic pressure-volume relationships showing decreased distensibility in the patients with HFPEF versus controls, with no significant differences in overall chamber compliance. B, End-diastolic transmural pressure-volume relationships. The relationship is maintained even when PCWP is substituted for by estimated transmural pressure (PCWP–right atrial pressure).

Figure 4

End-diastolic stress-strain relationship. Baseline circumferential wall stress was higher in the patients with HFPEF than in controls (P<0.001). For any equivalent degree of ventricular deformation, the patients with HFPEF had a higher wall stress during cardiac unloading (P=0.024), but not during saline loading (P=0.339), than controls.

Figure 5

A, Mean of lateral and septal TDI mitral annular velocities (TDI E_mean), which were significantly slower in the patients with HFPEF than in controls across loading conditions (P=0.013). B, E/A ratio showing no difference across loading conditions between the patients with HFPEF and controls (P=0.431). C, IVRT was prolonged in the controls versus the patients with HFPEF across loading conditions (P=0.002). D, V_p was faster in the controls than in the patients with HFPEF across loading conditions (P=0.023).

Figure 6

A. Sex-based differences in IVRT. IVRT was shortest in the female patients with HFPEF across loading conditions than in female controls (P=0.008), male controls (P<0.001), and male patients with HFPEF (P=0.030). B, Sex-based differences in TDI E_mean velocities. TDI E_mean velocities were slower in the female patients with HFPEF than in the female controls (P=0.017) and slower in the male patients with HFPEF than in all other subjects (P<0.001). C, Sex differences in end-diastolic pressure-volume relationships. Male patients with HFPEF had a leftward shift of their end-diastolic pressure-volume relationship compared with female patients with HFPEF. In contrast, female controls and female patients with HFPEF had little difference in static LV compliance.