Safety and efficacy of transitioning from selexipag to oral treprostinil in pulmonary arterial hypertension: Findings from the ADAPT registry.

PURPOSE: Oral treprostinil and selexipag are drugs targeting the prostacyclin pathway and are approved for treatment of pulmonary arterial hypertension (PAH). In the setting of unsatisfactory clinical response or tolerability issues while on selexipag, there is little data on clinical benefit, safety, or strategies on transitioning to oral treprostinil. Using prospective data from the ADAPT registry, we aimed to evaluate clinical outcomes, safety, and transition strategies in ten patients with PAH transitioning from selexipag to oral treprostinil. METHODS: ADAPT was a prospective, real-world, multicenter, United States-based registry of patients with PAH newly started on oral treprostinil, with a cohort of patients (n = 10) transitioning from selexipag to oral treprostinil. PAH variables of interest were collected from standard-of-care clinic visits. Clinical improvement was defined by modified REPLACE criterion, and risk was assessed by REVEAL Lite 2 from baseline to last follow-up. Real world transition strategies were recorded. Healthcare utilization or worsening PAH was evaluated within 30 days of transitions. RESULTS: Seven patients transitioned due to worsening PAH or lack of efficacy on selexipag, and three patients transitioned due to tolerability issues. Based on the modified REPLACE criterion, five patients demonstrated clinical improvement after transition from selexipag to oral treprostinil. Using REVEAL Lite 2 to assess risk, three patients improved and five patients maintained risk category from baseline to last follow-up. All transitions occurred in an outpatient setting either as abrupt stop/start or cross-titration, without parenteral treprostinil bridging. CONCLUSION: Transition from selexipag to oral treprostinil was safe, performed without parenteral prostacyclin bridging, and resulted in clinical and categorical risk improvements in some patients.

Reversible cardiomyopathies--a review.

End-stage renal disease, cirrhosis, obesity, tachycardia, and extreme stress have all been shown to result in impaired left ventricular function. It is becoming clear, however, that the cardiomyopathies associated with these states are reversible after resolution of the underlying process. In this article, we present the current data demonstrating that renal transplantation, liver transplantation, and bariatric surgery can lead to reversal of uremic, cirrhotic, and obesity cardiomyopathies, respectively. We also discuss the reversibility of tachycardia-induced cardiomyopathy after radiofrequency ablation or pharmacologic therapy for rate or rhythm control and the reversibility of stress-induced cardiomyopathy with supportive care.

Severe left ventricular systolic dysfunction may reverse with renal transplantation: uremic cardiomyopathy and cardiorenal syndrome.

Chronic heart failure (CHF) and chronic kidney disease (CKD) are serious medical conditions with significant morbidity and mortality. Emerging evidence indicates that the function of these two organ systems are affected by each other in a complex interplay. Most patients with CKD suffer frequently from cardiac abnormalities including left ventricular hypertrophy (LVH), left ventricular dilatation (LVD), left ventricular (LV) diastolic and/or systolic dysfunction. Although previously thought that LV systolic dysfunction was an absolute contraindication to renal transplantation, several observational studies have shown this not to be true and that transplantation can lead to significant improvement in LV systolic function. Furthermore, correction of the uremic state by renal transplantation leads to improvement of LVD and possibly regression of LVH. In fact, the reduction of LVH postkidney transplantation was shown to be dependent on adequate renal function and hypertension control. Diabetes mellitus does not seem to be a confounding factor in the improvement of uremic cardiomyopathy with renal transplantation.