Prevalence and prognostic value of left ventricular diastolic dysfunction in idiopathic and heritable pulmonary arterial hypertension

Abstract

Background: Little is known about the association between left ventricular (LV) diastolic dysfunction and outcomes in patients with idiopathic or heritable pulmonary arterial hypertension (PAH). Our rationale was to investigate the prevalence of LV diastolic dysfunction, and its association with disease severity and outcomes, in patients with idiopathic or heritable PAH.

Methods: Using the Cleveland Clinic Pulmonary Hypertension Registry, we identified subjects with heritable or idiopathic PAH who underwent Doppler echocardiography and right-sided heart catheterization. Echocardiographic diastolic parameters were assessed in each patient.

Results: A total of 61 patients met the inclusion criteria (idiopathic 85%, heritable 15%). The age at the time of echocardiography was 48.3 ± 18 years, 84% of the subjects were women, and 48% were on PAH-targeted therapies. Normal LV diastolic function, impaired relaxation, and pseudonormalization were seen in 10%, 88%, and 2% of the patients, respectively. Peak early diastolic (peak E) velocity was directly associated with LV end-diastolic volume and cardiac index and inversely associated with the degree of right ventricular dilation, right atrial pressure, and pulmonary vascular resistance. Peak E velocity was associated with mortality adjusted for age and sex (hazard ratio [HR], 1.5; 95% CI, 1.1-2 per 10 cm/s decrease; P = .015) and age, sex, 6-min walk distance, and cardiac output (HR, 1.8; 95% CI, 1.2-2.9 per 10 cm/s decrease; P = .01).

Conclusions: LV diastolic dysfunction of the impaired relaxation type is observed in the majority of patients with advanced idiopathic or heritable PAH. A decrease in transmitral flow peak E velocity is associated with worse hemodynamics and outcome.

Figure 1.

Eccentricity index. A, M mode at the level of LV papillary muscles in parasternal long axis view. There is marked RV dilation, early diastolic septal flattening, and PE. B-D, Measurements of eccentricity index in the parasternal short axis view at the level of the LV papillary muscles. B, End diastole; C, end systole; D, early diastole. Arrowheads in each panel point the interventricular septum. bpm = beats/min; HR = heart rate; LV = left ventricular; PE = pericardial effusion; RV = right ventricular.

Figure 2.

Diastolic function evaluated with pulse Doppler of the mitral inflow. A, Normal diastolic function (peak E wave velocity [E] over peak A wave velocity [A] ratio > 1). B, Impaired LV relaxation (E/A ratio < 1). C, Pseudonormal LV filling pattern (during normal respiration E/A ratio > 1). D, During Valsalva maneuver there is reversal of the ratio (E/A ratio < 1) due to LV preload reduction. See Figure 1 legend for expansion of abbreviations.

Figure 3.

Kaplan-Meier survival analysis. Kaplan-Meier survival analysis using peak E wave velocity of < 60 and ≥ 60 cm/s. Log rank statistics showed P = .03. Cum = cumulative.