Giannakoulas, George

Abstract Rationale Pulmonary hypertension (PH) in interstitial lung disease (ILD) lacks approved therapies. Objectives The Pulmonary Vascular Research Institute GoDeep metaregistry collects real-world data of patients with PH from international PH referral centers. Methods Patients with ILD-PH and relevant subgroups (idiopathic interstitial pneumonia [IIP], idiopathic pulmonary fibrosis [IPF]) were stratified by pulmonary vascular resistance (PVR). Kaplan-Meier survival analyses and adjusted Cox proportional hazards models were employed, additionally accounting for immortal time bias, sensitivity analyses, Heller explained relative risk statistics, and target trial emulation framework analysis. Measurements and Main Results Among 34,482 patients, 940 with hemodynamically fully characterized incident ILD-PH (median age, 67 [IQR, 59–74] yr) were identified. A total of 62% had severe ILD-PH with PVR >5 Wood units (WU) and poor survival rates (29% and 18% at 3 and 5 yr), significantly worse than patients with ILD-PH with PVR ≤5 WU and patients with pulmonary arterial hypertension. Survival was poorest in severe IPF-PH. A total of 59% of all patients ILD-PH received PH-targeted therapy, predominantly phosphodiesterase-5 inhibitors (PDE5is). PDE5i treatment was consistently associated with significantly improved survival in patients with severe PH (hazard ratios of 0.537 [0.370–0.781], 0.461 [0.233–0.913], and 0.435 [0.215–0.8] for IIP-PH, IPF-PH, and IIP-PH with nintedanib/pirfenidone background therapy), but not in patients with less severe hemodynamic impairment, supported by sensitivity analyses, Heller statistics, and target trial emulation framework analysis. The survival statistics of patients with PDE5i-treated IIP-PH or IPF-PH were validated in the independent COMPERA registry. Combination therapy with PDE5is and inhaled prostacyclin analogues was superior to monotherapy using PDE5is (hazard ratio, 0.341; 0.205–0.566). Conclusions Prognosis in ILD-PH was generally very poor and was related to PH severity. PDE5i treatment in severe IIP-PH and IPF-PH was associated with improved survival, which is to be further verified in controlled trials.

Abstract Background Although a rhythm control strategy is associated with an overall better prognosis in atrial fibrillation (AF), current guidelines suggest that only highly selected asymptomatic patients may be considered candidates for AF catheter ablation. Therefore, this study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF. Methods A comprehensive search of Medline, the Cochrane Library, and Scopus was conducted up until September 30, 2024. Study selection, data extraction, and quality assessment were performed independently by three reviewers. Random-effects meta-analyses were used to pool the evidence. Results A total of 36 studies, comprising 217,850 participants, were included. Frequentist analysis revealed no significant difference between symptomatic and asymptomatic AF patients in terms of all-cause mortality [hazard ratio (HR) = 0.97, 95% confidence interval (CI)= (0.80, 1.17)], cardiovascular mortality (HR= 1.04, 95% CI= [0.72, 1.49]), thromboembolism (HR= 1.06, 95% CI= [0.87, 1.28]), stroke (HR= 1.06, 95% CI= [0.84, 1.34]), hospitalization (HR= 1.34, 95% CI= [0.89, 2.02]), and myocardial infarction (HR= 0.98, 95% CI= [0.70, 1.36]). However, symptomatic patients exhibited a 33% increased risk of new-onset heart failure (HR= 1.33, 95% CI= [1.19, 1.49]) and a 30% reduced risk of progression to permanent AF (HR= 0.70, 95% CI= [0.54, 0.89]). Bayesian analysis produced similar results, although the association between symptom status and new-onset heart failure was not statistically significant [HR = 1.27, 95% credible interval (CrI)= (0.76, 1.93); Bayes factor (BF10)= 1.2]. Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR]= 1.64, 95% CI= [1.33, 2.03]) and ablation therapy (OR= 1.47, 95% CI= [1.06, 2.05]) compared to their asymptomatic counterparts. Conclusions The risk of major clinical outcomes does not significantly differ between AF patients with and without symptoms. However, asymptomatic patients have a higher risk of progressing to permanent AF.