Persistent Pulmonary Hypertension in Corrected Valvular Heart Disease: Hemodynamic Insights and Long-Term Survival

Abstract

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long-term follow-up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32-44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18-26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow-up of 4.5 years, 91 deaths accounted for 4.21 higher-than-expected mortality in the age-matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance-either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six-month changes in the composite clinical score and in the 6-minute walk test distance were related to survival. Conclusions Persistent valvular heart disease-pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.

Keywords: heart failure; pulmonary hypertension; valvular heart disease.

Conflict of interest statement

None.

Figures

Figure 1. Enrollment of the study cohort.

The confirmatory catheterization procedure excluded pulmonary hypertension (PH) (mean pulmonary arterial pressure [mPAP]

Figure 2. Hemodynamic characterization at enrollment.

CpcPH indicates combined postcapillary pulmonary hypertension; IpcPH, isolated postcapillary pulmonary hypertension; PAWP, pulmonary capillary pressure; PH, pulmonary hypertension; and PVR, pulmonary vascular resistance

Figure 3. Survival curves of the study cohort.

(A) Global survival of the full cohort compared with the Spanish age‐matched control population. (B) Survival without cardiovascular mortality. (C, D) Stratification based on the role in the clinical trial and pulmonary hypertension (PH) classification group, respectively. CpcPH indicates combined postcapillary pulmonary hypertension; IpcPH, isolated postcapillary pulmonary hypertension; mPAP, mean pulmonary arterial pressure; PH, pulmonary hypertension; SIOVAC Sildenafil for Improving Outcomes After Valvular Correction; and SMR, standard mortality ratio.

Figure 4. The relationship between pulmonary vascular resistance (PVR) and outcomes.

(A) Kaplan‐Meir survival curves based on the PVR quartile distribution. (B) Per‐quartile hazard ratio (HR) analysis. When analyzed by quantiles of the distribution, only quartile 4 vs quartile 1 was significant (HR not including 1), without significant differences in the intermediate categories.

Figure 5. Results of the multivariable regression fitting for predicting pulmonary vascular resistance (PVR) from ultrasound data.

AccTimePV indicates Doppler acceleration time as measured by pulsed‐wave Doppler at the level of the pulmonary valve (ms); BSA, body surface area (m2); HR, heart rate (min‐1); PVR, pulmonary vascular resistance (Wood units [WU]); SysDTI_RV, peak systolic myocardial velocity as measured by Doppler tissue imaging of the right ventricular free wall (cm/s); TVILVOT, left ventricular outflow‐tract pulsed‐wave Doppler time velocity integral (cm); and VmaxTR, peak jet velocity of the tricuspid regurgitation jet (m/s).

Figure 6. Kaplan‐Meier overall‐survival curves based on most relevant predictors.

Stratification based on sex (A), World Health Organization (WHO) functional class (B), and pulmonary vascular resistance (PVR), either measured (C) or estimated by ultrasound (D).

Figure 7. Survival curves of the 6‐month end points of the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial.

(A, B, C) Split survival curves based on the clinical composite score, median change in brain natriuretic peptide (BNP) levels, and median change in the 6‐minute walk test (6MWT) distance, respectively. HR indicates hazard ratio.