High-Sensitivity Cardiac Troponin and New-Onset Heart Failure: A Systematic Review and Meta-Analysis of 67,063 Patients With 4,165 Incident Heart Failure Events.

OBJECTIVES: The aim of this study was to systematically collate and appraise the available evidence regarding the association between high-sensitivity cardiac troponin (hs-cTn) and incident heart failure (HF) and the added value of hs-cTn in HF prediction. BACKGROUND: Identification of subjects at high risk for HF and early risk factor modification with medications such as angiotensin-converting enzyme inhibitors may delay the onset of HF. Hs-cTn has been suggested as a prognostic marker for the incidence of first-ever HF in asymptomatic subjects. METHODS: PubMed, Embase, and Web of Science were systematically searched for prospective cohort studies published before January 2017 that reported associations between hs-cTn and incident HF in subjects without baseline HF. Study-specific multivariate-adjusted hazard ratios (HRs) were pooled using random-effects meta-analysis. RESULTS: Data were collated from 16 studies with a total of 67,063 subjects and 4,165 incident HF events. The average age was 57 years, and 47% were women. Study quality was high (Newcastle-Ottawa score 8.2 of 9). In a comparison of participants in the top third with those in the bottom third of baseline values of hs-cTn, the pooled multivariate-adjusted HR for incident HF was 2.09 (95% confidence interval [CI]: 1.76 to 2.48; p < 0.001). Between-study heterogeneity was high, with an I2 value of 80%. HRs were similar in men and women (2.29 [95% CI: 1.64 to 3.21] vs. 2.18 [95% CI: 1.68 to 2.81]) and for hs-cTnI and hs-cTnT (2.09 [95% CI: 1.53 to 2.85] vs. 2.11 [95% CI: 1.69 to 2.63]) and across other study-level characteristics. Further adjustment for B-type natriuretic peptide yielded a similar HR of 2.08 (95% CI: 1.64 to 2.65). Assay of hs-cTn in addition to conventional risk factors provided improvements in the C index of 1% to 3%. CONCLUSIONS: Available prospective studies indicate a strong association of hs-cTn with the risk of first-ever HF and significant improvements in HF prediction

A systematic review and meta-analysis of the effect of intravitreal VEGF inhibitors on cardiorenal outcomes.

BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFi) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects. METHODS: Systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed-effects meta-analyses were conducted where possible. RESULTS: There were 78 trials (81 comparisons; 13 175 participants) that met criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups (7.3 versus 5.4%; RR 1.08 [0.91; 1.28]). New or worsening heart failure (10 trials; 3384 participants) had similar incidence in VEGFi and control groups (RR 1.03 [0.70; 1.51]). Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls (0.0%; RR 4.43 [0.49; 40.0]). Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, risk of all-cause mortality was higher in VEGFi-treated participants (RR 1.62 [1.04; 2.46]). CONCLUSION: In trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, though these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve recognition of safety concerns in VEGFi-treated patients