Right Heart Score for Predicting Outcome in Idiopathic, Familial, or Drug- and Toxin-Associated Pulmonary Arterial Hypertension

Abstract

Objectives: This study sought to determine whether a simple score combining indexes of right ventricular (RV) function and right atrial (RA) size would offer good discrimination of outcome in patients with pulmonary arterial hypertension (PAH).

Background: Identifying a simple score of outcome could simplify risk stratification of patients with PAH and potentially lead to improved tailored monitoring or therapy.

Methods: We recruited patients from both Stanford University (derivation cohort) and VU University Medical Center (validation cohort). The composite endpoint for the study was death or lung transplantation. A Cox proportional hazard with bootstrap CI adjustment model was used to determine independent correlates of death or transplantation. A predictive score was developed using the beta coefficients of the multivariable models.

Results: For the derivation cohort (n = 95), the majority of patients were female (79%), average age was 43 ± 11 years, mean pulmonary arterial pressure was 54 ± 14 mm Hg, and pulmonary vascular resistance index was 25 ± 12 Wood units × m(2). Over an average follow-up of 5 years, the composite endpoint occurred in 34 patients, including 26 deaths and 8 patients requiring lung transplant. On multivariable analysis, RV systolic dysfunction grade (hazard ratio [HR]: 3.4 per grade; 95% confidence interval [CI]: 2.0 to 7.8; p < 0.001), severe RA enlargement (HR: 3.0; 95% CI: 1.3 to 8.1; p = 0.009), and systemic blood pressure <110 mm Hg (HR: 3.3; 95% CI: 1.5 to 9.4; p < 0.001) were independently associated with outcome. A right heart (RH) score constructed on the basis of these 3 parameters compared favorably with the National Institutes of Health survival equation (0.88; 95% CI: 0.79 to 0.94 vs. 0.60; 95% CI: 0.49 to 0.71; p < 0.001) but was not statistically different than the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) score c-statistic of 0.80 (95% CI: 0.69 to 0.88) with p = 0.097. In the validation cohort (n = 87), the RH score remained the strongest independent correlate of outcome.

Conclusions: In patients with prevalent PAH, a simple RH score may offer good discrimination of long-term outcome.

Keywords: atrial function; heart failure; outcome; pulmonary hypertension; right heart.

Figure 1. Representative measures of right heart size and functional parameters

Section A shows measures of RVEDA, section B measures of RVESA and 2D TAPSE, section C and D measures of TR duration and RV ejection time respectively.

Figure 2. Right atrial emptying fractions

The figure depicts the different concepts related to right atrial volumes and the related concepts of total, passive and RA emptying fractions.

Figure 3. Ventricular and atrial remodeling and function in our study population

Section A presents the box and whisker plots of comparing indexed RA and RV areas between patients with PAH and healthy controls. Section B presents the box and whisker plots of indexed RA area according to the predefined categories of RV dysfunction. Section C presents the box and whisker plots of comparing total, active and passive RAEF between patients with PAH and healthy controls, and section D present the bar graph with 95% confidence interval for mean value for RAEF active stratified according to the pre-defined categories of RA size. In the box- and-whisker plots, the central box represents the values from the lower to upper quartile (25 to 75 percentile); the middle line represents the median and the line extends from the minimum to the maximum value, excluding outlier values.

Figure 4

C-statistics and Kaplan-Meier curves for selected parameters of RV and RA function. Section A illustrates the c-statistic between indices of RV function. Section B represents the 5-year Kaplan-Meier curves of RV systolic dysfunction based on RVFAC. Section C illustrates the c-statistic curves between indices of RA indices and section D shows the associated 5-year Kaplan-Meier curves and severe RA enlargement.

Figure 5

The Right heart (RH) score in relation to the REVEAL and NIH scores. Section A shows the 5-year Kaplan-Meier curves based on the Right heart score; Section B compares the c-statistic of the right heart score with the REVEAL score and the 5 year predicted NIH survival. Section C and D illustrates the strong relationship between the right heart score and the REVEAL and NIH scores, respectively with 95% confidence interval for mean value.