Reporting and interpretation of subgroup analyses in heart failure randomized controlled trials.

AIMS: This study aimed to investigate the reporting of subgroup analyses in heart failure (HF) randomized controlled trials (RCTs) and to determine the strength and credibility of subgroup claims. METHODS AND RESULTS: All primary HF RCTs published in nine high-impact journals from 1 January 2008 to 31 December 2017 were included. Multivariable regression analysis was used to identify factors that may favour the reporting of results in specific subgroups. Strength of the subgroup effect claimed was classified into (i) strong, (ii) likely, or (iii) suggestive. Credibility of subgroup claim was scored using a pre-specified 10 pointer criteria. Of the 261 HF RCTs studied, 107 (41%) reported subgroup analyses. Twenty-five (23%) RCTs claimed a subgroup effect for the primary outcome of which six (24%) made a strong claim, eight (32%) claimed a likely effect, and 11 (44%) suggested a possible subgroup effect. Seven of the 25 RCTs did not employ interaction testing for subgroup claims of the primary outcome. Three out of 10 pre-specified credibility criteria were satisfied by half of the trials. Fourteen trials justified the choice of subgroups, and 10 explicitly stated they were underpowered to detect differences within subgroups. Source of funding did not influence the frequency of reporting subgroup analyses (OR 0.53, 95% CI 0.78-3.62, P = 0.52). CONCLUSIONS: Appropriate credibility criteria were rarely met even by HF RCTs that held strong subgroup claims. Subgroup analyses should be pre-specified, be adequately powered, present interaction terms, and be replicated in independent data before being integrated into clinical decision making.

Restless Leg Syndrome in Patients with Liver Cirrhosis! Its Frequency, Severity, and Correlation.

BACKGROUND: Restless leg syndrome (RLS) has been recognized as a typical additional manifestation among patients with cirrhosis of the liver. RLS prevalence in liver cirrhosis further worsens the quality of life, which has already been compromised with the disease-related complications of cirrhosis itself. AIMS: The study aimed to determine the frequency and severity of Restless Leg Syndrome (RLS) among patients with cirrhosis of the liver and to correlate its severity with the severity of cirrhosis. METHODS: This prospective cross-sectional study was carried out at Ruth K.M. Pfau Civil Hospital (Karachi, Pakistan) from December 2019 to February 2020. Three hundred and fifteen cirrhotic patients with any etiology were included in the study after informed written consent. Restless leg syndrome with its severity was determined in all cirrhotic patients. For continuous variables, means and medians with standard deviations were calculated, while percentages and proportions were used for discrete variables. Spearman correlation was used to find significance between RLS Severity Score (RSS) and Model of End-stage Liver Disease MELD Score. A p value of < 0.05 was considered significant for all analyses. RESULTS: The frequency of RLS among cirrhotic patients was 38.4%. More than half (54.5%) of the patients had severe RLS. Viral related hepatitis C and hepatitis B were the most common cause of cirrhosis of the liver (57.8% and 30.8%). A significant difference was found between as patients both with or without RLS in terms of age (p=0.003), gender (p=0.005), hemoglobin (p=0.00), and serum albumin (p=0.01). No significant association was found between RLS severity score and MELD Score (p=0.693). CONCLUSION: Prevalence of RLS is very high among cirrhotic patients, but no correlation was found between the severity of RLS and cirrhosis. Further studies should be carried out to assess the quality of life in cirrhotic patients having RLS.

Systematic review and meta-analysis of current risk models in predicting short-term mortality after transcatheter aortic valve replacement.

AIMS: The aim of this study was to evaluate the performance of risk stratification models (RSMs) in predicting short-term mortality after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: MEDLINE and Scopus were queried to identify studies which validated RSMs designed to assess 30-day or in-hospital mortality after TAVR. Discrimination and calibration were assessed using C-statistics and observed/expected ratios (OERs), respectively. C-statistics were pooled using a random-effects inverse-variance method, while OERs were pooled using the Peto odds ratio. A good RSM is defined as one with a C-statistic >0.7 and an OER close to 1.0. Twenty-four studies (n=68,215 patients) testing 11 different RSMs were identified. Discrimination of all RSMs was poor (C-statistic <0.7); however, certain TAVR-specific RSMs such as the in-hospital STS/ACC TVT (C-statistic=0.65) and STT (C-statistic=0.66) predicted individual mortality more reliably than surgical models (C-statistic range=0.59-0.61). A good calibration was demonstrated by the in-hospital STS/ACC TVT (OER=0.99), 30-day STS/ACC TVT (OER=1.08) and STS (OER=1.01) models. Baseline dialysis (OER: 2.64 [1.88, 3.70]; p<0.001) was the strongest predictor of mortality. CONCLUSIONS: This study demonstrates that the STS/ACC TVT model (in-hospital and 30-day) and the STS model have accurate calibration, making them useful for comparison of centre-level risk-adjusted mortality. In contrast, the discriminative ability of currently available models is limited.

Percutaneous Mitral Valve Repair versus Optimal Medical Therapy in Patients with Functional Mitral Regurgitation: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare percutaneous mitral valve repair (PMVR) with optimal medical therapy (OMT) in patients with heart failure (HF) and severe functional mitral regurgitation (FMR). BACKGROUND: Many patients with HF and FMR are not suitable for surgical valve replacement and remain symptomatic despite maximal OMT. PMVR has recently emerged as an alternative solution. METHODS: We performed a systematic review and a meta-analysis to address this question. Cochrane CENTRAL, MEDLINE, and Scopus were searched for randomized (RCT) and nonrandomized studies comparing PMVR with OMT in patients with HF and FMR. Primary endpoint was all-cause midterm mortality (at 1 and 2 years). Secondary endpoints were 30-day mortality and cardiovascular mortality and HF hospitalizations, at maximum follow-up. Studies including mixed cohort of degenerative and functional MR were allowed initially but were excluded in a secondary sensitivity analysis for each of the study's end points. This meta-analysis was performed following the publication of two RCTs (MITRA-FR and COAPT). RESULTS: Eight studies (six observational, two RCTs) comprising 3,009 patients were included in the meta-analysis. In comparison with OMT, PMVR significantly reduced 1-year mortality (RR: 0.70 [0.56, 0.87]; p=0.002; I2=47.6%), 2-year mortality (RR: 0.63 [0.55, 0.73]; p<0.001; I2=0%), and cardiovascular mortality (RR: 0.32 [0.23, 0.44]; p<0.001; I2=0%). No significant difference between PMVR+OMT and OMT was noted in HF hospitalization (HR: 0.69 [0.40, 1.20]; p=0.19; I2=85%) and 30-day mortality (RR: 1.13 [0.68, 1.87]; p=0.16; I2=0%). CONCLUSIONS: In comparison with OMT, PMVR significantly reduces 1-year mortality, 2-year mortality, and cardiovascular mortality in patients with HF and severe MR.