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

Abstract

Objectives The objective of our study was to determine whether a simple score combining indices 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 end-point for the study was death or lung transplantation. A Cox proportional hazard with bootstrap confidence interval adjustment model was used to determine independent correlates of death or transplantation. A predictive score was developed using the β- coefficients of the multivariate 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 mmHg, and indexed pulmonary vascular resistance was 25±12 WU m2. Over an average follow-up of 5 years, the composite end-point occurred in 34 patients consisting of 26 deaths and 8 patients undergoing lung transplantation. On multivariate analysis, RV systolic dysfunction grade [HR 3.4, 2.0 to 7.8, P<0.001], severe RA enlargement [HR 3.0, 1.3 to 8.1, P=0.009] and systemic blood pressure <110 mmHg [HR 3.3, 1.5 to 9,4, P<0.001] were independently associated with outcome. A right heart (RH) score was constructed based on these 3 parameters compared favorably to the NIH survival equation (0.88[0.79 to 0.94] vs. 0.60[0.49 to 0.710], P< 0.001) but not statistically different than the REVEAL score c-statistic of 0.80[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. Conclusion In patients with prevalent PAH, a simple RH score may offer good discrimination of long term outcome in PAH.

Right atrial emptying fraction non-invasively predicts mortality in pulmonary hypertension

“…I ndexed RAEDV, by contrast, was associated with survival in this study only in univariate analyses but not using KaplanMeier or multivariate analyses. This is in contrast to a recent report from Haddad et al where they found RAEDV more useful than RAEF in deriving a prognostic echocardiographic 'right heart score' for IPAH patients [6]. While the difference in results between our studies may possibly be explained by the different patient populations or different imaging modalities used (cMRI may more accurately determine the RAEF, for example, and Haddad et al did not use cMRI for their derivation cohort of patients), this should not distract from the important general conclusion that RA structure and function are important predictors for hard patient outcomes in patients with PH.…”

“…Stroke volume index, RV ejection fraction (RVEF), and indexed RV end-diastolic and end-systolic volumes, as assessed by cMRI , have been shown previously as important non-invasive prognostic markers in I PAH [27][28][29][30][31]. There has even been recent work examining the added benefit of RA functional and structural measurements in prognostic scores for I PAH patients [6,32,33]. I n the absence of primary abnormalities of the tricuspid valve, RA enlargement is generally viewed as a manifestation of high RA pressure due to functional tricuspid regurgitation (TR) or elevated RV diastolic pressure, both consequences of RV failure.…”

“…However, the association between RA structure and function and RV failure and death in all types of PH has not been well-described. Moreover, prognostic classification for idiopathic IPAH patients remains imperfect [2,5,6] and prognostic classification for other types of PH patients is even less well defined. The purpose of our study is to evaluate the association of RA structure and function with RVEF as well as with time to death in PH patients.…”

“…PH-associated morbidity and mortality remain high despite available treatments including oral medications, continuous intravenous therapy, lung transplantation, and additional interventions aimed to counteract the specific causes of the various forms of PH [2][3][4]. Although prognostic scores have been developed for idiopathic PH (I PAH) [2,5,6], diagnostic and treatment algorithms for patients with PH at large remain cumbersome while the ability of individual tests to inform clinical decision-making remain limited.…”

Predicting Mortality in Pulmonary Arterial Hypertension

“…It is also apparent that these tools have recently been applied to the RA(10,11), and therefore, a greater depth of knowledge pertaining to the RA-RV relationship is rapidly becoming reality.The next logical step should aim to use the advances in echocardiography without detracting from the "simple" nature of the index. It is important to commend Haddad et al(6) for this work and for reminding us that "simple" can still reflect complexity but also to be aware that any index needs to be sensitive to responses to therapy and disease progression while remaining valid and reproducible.REPRINT REQUESTS AND CORRESPONDENCE: Dr. David Oxborough, Research Institute for Sport and Exercise Sciences, Tom Reilly Building, Liverpool John Moores University, Liverpool L3 3AF, UnitedKingdom. E-mail: d.l.oxborough@ljmu.ac.uk.…”