Benjamin D. Levine

Echocardiographic Indices Do Not Reliably Track Changes in Left-Sided Filling Pressure in Healthy Subjects or Patients with Heart Failure with Preserved Ejection Fraction

Background— In select patient populations, Doppler echocardiographic indices may be used to estimate left-sided filling pressures. It is not known, however, whether changes in these indices track changes in left-sided filling pressures within individual healthy subjects or patients with heart failure with preserved ejection fraction (HFpEF). This knowledge is important because it would support, or refute, the serial use of these indices to estimate changes in filling pressures associated with the titration of medical therapy in patients with heart failure. Methods and Results— Forty-seven volunteers were enrolled: 11 highly screened elderly outpatients with a clear diagnosis of HFpEF, 24 healthy elderly subjects, and 12 healthy young subjects. Each patient underwent right heart catheterization with simultaneous transthoracic echo. Pulmonary capillary wedge pressure (PCWP) and key echo indices (E/e′ and E/Vp) were measured at two baselines and during 4 preload altering maneuvers: lower body negative pressure −15 mm Hg; lower body negative pressure −30 mm Hg; rapid saline infusion of 10 to 15 mL/kg; and rapid saline infusion of 20 to 30 mL/kg. A random coefficient mixed model regression of PCWP versus E/e′ and PCWP versus E/Vp was performed for (1) a composite of all data points and (2) a composite of all data points within each of the 3 groups. Linear regression analysis was performed for individual subjects. With this protocol, PCWP was manipulated from 0.8 to 28.8 mm Hg. For E/e′, the composite random effects mixed model regression was PCWP=0.58×E/e′+7.02 (P<0.001), confirming the weak but significant relationship between these 2 variables. Individual subject linear regression slopes (range, −6.76 to 11.03) and r 2 (0.00 to 0.94) were highly variable and often very different than those derived for the composite and group regressions. For E/Vp, the composite random coefficient mixed model regression was PCWP=1.95×E/Vp+7.48 (P=0.005); once again, individual subject linear regression slopes (range, −16.42 to 25.39) and r 2 (range, 0.02 to 0.94) were highly variable and often very different than those derived for the composite and group regressions. Conclusions— Within individual subjects the noninvasive indices E/e′ and E/Vp do not reliably track changes in left-sided filling pressures as these pressures vary, precluding the use of these techniques in research studies with healthy volunteers or the titration of medical therapy in patients with HFpEF.