Abstract 4143194: Clinical predictors of right ventricular contractile depression among patients with pulmonary hypertension

Background: Right ventricular (RV) dysfunction in patients with pulmonary hypertension (PH) leads to drastically worse clinical outcomes. It remains difficult to find the best clinical correlates of intrinsic RV contractile dysfunction given the load dependent nature of these measures. Here, we evaluate which clinical indices may identify poor RV myocyte contractility among PH patients. Methods: Single-center cohort study of 14 patients with PH (10 with group 1 pulmonary arterial hypertension, 4 with group 2 secondary to heart failure). Clinical evaluation included transthoracic echocardiogram and RV pressure-volume loops measured at rest and during supine bike exercise. Myocyte mechanics were measured using frozen, permeabilized RV myocardium samples. Poor RV myocyte contractility was defined as >2 standard deviations below the mean of normal controls. Results: Among 14 PH subjects, we identified 6 and 8 patients with normal and depressed RV myocyte function, respectively. By area under the receiver operator curve (AUROC) analysis, we found that common clinical measures did not capture those with reduced RV myocyte contractile function: TAPSE (AUROC 0.70, P- value 0.26), RAP (AUROC 0.58, P- value 0.61), RAP/PCWP (AUROC 0.50, P- value >0.99), and PAPi (AUROC 0.52, P -value 0.90) (Figure 1A). We next investigated more sensitive methods of detecting RV dysfunction, such as RV contractile reserve measured during exercise. Changes in RV contractility and RV dilation during exercise were worse in those with poor RV myocyte contractility (Figure 1B). Using AUROC analysis, these measures of RV contractile reserve post-exercise were better able to identify those with intrinsic poor RV myocyte contractility: RV contractile reserve (AUROC 0.94, P -value <0.01) and RV exercise dilation (AUROC 0.85, P -value 0.03) (Figure 1C). Conclusion: Measures of RV contractile reserve are better than commonly obtained clinical measures of resting RV dysfunction at identifying underlying RV myocyte contractile weakness.