No abstract

Pulmonary hypertension (PH) complicating chronic obstructive pulmonary disease (COPD-PH) and interstitial lung disease (ILD-PH) (World Health Organization [WHO] Group III PH) increases medical costs and reduces survival. Despite limited data, many clinicians are using pulmonary arterial hypertension (PAH)-specific therapy to treat WHO Group III PH patients. To further investigate the utility of PAH-specific therapy in WHO Group III PH, we performed a systematic review and meta-analysis. Relevant studies from January 2000 through May 2016 were identified in the MEDLINE, EMBASE, and COCHRANE electronic databases and www.clinicaltrials.gov. Change in six-minute walk distance (6MWD) was estimated using random effects meta-analysis techniques. Five randomized controlled trials (RCTs) in COPD-PH (128 placebo or standard treatment and 129 PAH-medication treated patients), two RCTs in ILD-PH (23 placebo and 46 treated patients), and four single-arm clinical trials (50 patients) in ILD-PH were identified. Treatment in both COPD-PH and ILD-PH did not worsen hypoxemia. Symptomatic burden was not consistently reduced but there were trends for reduced pulmonary artery pressures and pulmonary vascular resistance with PAH-specific therapy. As compared to placebo, 6MWD was not significantly improved with PAH-specific therapy in the five COPD-PH RCTs (42.7 m; 95% confidence interval [CI], –1.0 – 86.3). In the four single-arm studies in ILD-PH patients, there was a significant improvement in 6MWD after PAH-specific treatment (46.2 m; 95% CI, 27.9–64.4), but in the two ILD-PH RCTs there was not an improvement (21.6 m; 95% CI, –17.8 – 61.0) in exercise capacity when compared to placebo. Due to the small numbers of patients evaluated and inconsistent beneficial effects, the utility of PAH-specific therapy in WHO Group III PH remains unproven. A future clinical trial that is appropriately powered is needed to definitively determine the efficacy of this widely implemented treatment approach.

Background: Implantable cardioverter-defibrillators are used to prevent sudden cardiac death in patients with cardiac sarcoidosis. The most recent recommendations for implantable cardioverter-defibrillator implantation in these patients are in the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. These recommendations, based on observational studies or expert opinion, have not been assessed. We aimed to assess them. Methods: We performed a large retrospective cohort study of patients with biopsy-proven sarcoidosis and known or suspected cardiac sarcoidosis that underwent cardiovascular magnetic resonance imaging. Patients were followed for a composite end point of significant ventricular arrhythmia or sudden cardiac death. The discriminatory performance of the Guideline recommendations was tested using time-dependent receiver operating characteristic analyses. The optimal cutoff for the extent of late gadolinium enhancement predictive of the composite end point was determined using the Youden index. Results: In 290 patients, the class I and IIa recommendations identified all patients who experienced the composite end point during a median follow-up of 3.0 years. Patients meeting class I recommendations had a significantly higher incidence of the composite end point than those meeting class IIa recommendations. Left ventricular ejection fraction (LVEF) >35% with >5.7% late gadolinium enhancement on cardiovascular magnetic resonance imaging was as sensitive as and significantly more specific than LVEF >35% with any late gadolinium enhancement. Patients meeting 2 class IIa recommendations, LVEF >35% with the need for a permanent pacemaker and LVEF >35% with late gadolinium enhancement >5.7%, had high annualized event rates. Excluding 2 class IIa recommendations, LVEF >35% with syncope and LVEF >35% with inducible ventricular arrhythmia, resulted in improved discrimination for the composite end point. Conclusions: We assessed the Guideline recommendations for implantable cardioverter-defibrillator implantation in patients with known or suspected cardiac sarcoidosis and identified topics for future research.

No abstract