BMI and Treatment Response in Patients With Pulmonary Arterial Hypertension: A Meta-analysis.

BACKGROUND: Obesity is increasingly prevalent in pulmonary arterial hypertension (PAH) but is associated with improved survival, creating an "obesity paradox" in PAH. It is unknown if the improved outcomes could be attributable to obese patients deriving a greater benefit from PAH therapies. RESEARCH QUESTION: Does BMI modify treatment effectiveness in PAH? STUDY DESIGN AND METHODS: Using individual participant data, a meta-analysis was conducted of phase III, randomized, placebo-controlled trials of treatments for PAH submitted for approval to the U.S. Food and Drug Administration from 2000 to 2015. Primary outcomes were change in 6-min walk distance (6MWD) and World Health Organization (WHO) functional class. RESULTS: A total of 5,440 participants from 17 trials were included. Patients with overweight and obesity had lower baseline 6MWD and were more likely to be WHO functional class III or IV. Treatment was associated with a 27.01-m increase in 6MWD (95% CI, 21.58-32.45; P < .001) and lower odds of worse WHO functional class (OR, 0.58; 95% CI, 0.48-0.70; P < .001). For every 1 kg/m2 increase in BMI, 6MWD was reduced by 0.66 m (P = .07); there was no significant effect modification of treatment response in 6MWD according to BMI (P for interaction = .34). Higher BMI was not associated with odds of WHO functional class at end of follow-up; however, higher BMI attenuated the treatment response such that every 1 kg/m2 increase in BMI increased odds of worse WHO functional class by 3% (OR, 1.03; P for interaction = .06). INTERPRETATION: Patients with overweight and obesity had lower baseline 6MWD and worse WHO functional class than patients with normal weight with PAH. Higher BMI did not modify the treatment response for change in 6MWD, but it attenuated the treatment response for WHO functional class. PAH trials should include participants representative of all weight groups to allow for assessment of treatment heterogeneity and mechanisms.

Predicting Long Term Outcome in Patients Treated With Continuous Flow Left Ventricular Assist Device: The Penn-Columbia Risk Score.

BACKGROUND: Predicting which patients are unlikely to benefit from continuous flow left ventricular assist device (LVAD) treatment is crucial for the identification of appropriate patients. Previously developed scoring systems are limited to past eras of device or restricted to specific devices. Our objective was to create a risk model for patients treated with continuous flow LVAD based on the preimplant variables. METHODS AND RESULTS: We performed a retrospective analysis of all patients implanted with a continuous flow LVAD between 2006 and 2014 at the University of Pennsylvania and included a total of 210 patients (male 78%; mean age, 56±15; mean follow-up, 465±486 days). From all plausible preoperative covariates, we performed univariate Cox regression analysis for covariates affecting the odds of 1-year survival following implantation (P<0.2). These variables were included in a multivariable model and dropped if significance rose above P=0.2. From this base model, we performed step-wise forward and backward selection for other covariates that improved power by minimizing Akaike Information Criteria while maximizing the Harrell Concordance Index. We then used Kaplan-Meier curves, the log-rank test, and Cox proportional hazard models to assess internal validity of the scoring system and its ability to stratify survival. A final optimized model was identified based on clinical and echocardiographic parameters preceding LVAD implantation. One-year mortality was significantly higher in patients with higher risk scores (hazard ratio, 1.38; P=0.004). This hazard ratio represents the multiplied risk of death for every increase of 1 point in the risk score. The risk score was validated in a separate patient cohort of 260 patients at Columbia University, which confirmed the prognostic utility of this risk score (P=0.0237). CONCLUSION: We present a novel risk score and its validation for prediction of long-term survival in patients with current types of continuous flow LVAD support.