Gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) is emerging as a new potentially important cause of increased cardiovascular risk. The purpose of this meta-analysis was to systematically estimate and quantify the association between TMAO plasma levels, mortality, and major adverse cardio and cerebrovascular events (MACCE). MEDLINE, ISI Web of Science, and SCOPUS databases were searched for ad hoc studies published up to April 2017. Associations between TMAO plasma levels, all-cause mortality (primary outcome) and MACCE (secondary outcome) were systematically addressed. A total of 17 clinical studies were included in the analytic synthesis, enrolling 26 167 subjects. The mean follow-up in our study population was 4.3 ± 1.5 years. High TMAO plasma levels were associated with increased incidence of all-cause mortality [14 studies for 16 cohorts enrolling 15 662 subjects, hazard ratio (HR): 1.91; 95% confidence interval (CI): 1.40–2.61, P < 0.0001, I² = 94%] and MACCE (5 studies for 6 cohorts enrolling 13 944 subjects, HR: 1.67, 95% CI: 1.33–2.11, P < 0.00001, I² = 46%,). Dose-response meta-analysis revealed that the relative risk (RR) for all-cause mortality increased by 7.6% per each 10 μmol/L increment of TMAO [summary RR: 1.07, 95% CI (1.04–1.11), P < 0.0001; based on seven studies]. Association of TMAO and mortality persisted in all examined subgroups and across all subject populations. This is the first systematic review and meta-analysis demonstrating the positive dose-dependent association between TMAO plasma levels and increased cardiovascular risk and mortality.

Secondary mitral regurgitation (SMR) occurs when normal or almost normal mitral leaflets are prevented from adequate coaptation by underlying left ventricular (LV) dysfunction, mitral annular dilation, or both. It is the most common valve disease, with an incidence of less than 1% before age 55 years but reaching 9% after age 75 years.¹ Secondary mitral regurgitation is generally divided into SMR due to ischemic heart disease or nonischemic cardiomyopathies, although it can also be a consequence of chronic atrial enlargement. In ischemic heart disease, even mild SMR has been shown to increase mortality.^2-4 In the Survival and Ventricular Enlargement (SAVE)⁵ trial, patients with SMR were more likely to experience cardiovascular mortality and severe heart failure (HF) than those without SMR. Grigioni et al² showed adjusted relative risks of total and cardiac mortality associated with the presence of ischemic mitral regurgitation (MR) of 1.88 and 1.83, respectively, compared with patients without ischemic MR. The results from an MR substudy of the Surgical Treatment for Ischemic Heart Failure (STICH)⁶ trial confirmed the previous observational studies, demonstrating an adverse prognosis of untreated ischemic MR in a cohort of patients with ischemic cardiomyopathy treated with current guideline-directed medical therapy. However, several other studies^7-11 did not find that SMR predicted worse survival among patients with ischemia. Similarly, in patients with nonischemic cardiomyopathy, the presence of SMR has been linked to different outcomes, such as death, HF hospitalization, or transplant. In the Beta-blocker Evaluation of Survival Trial (BEST),¹² an MR vena contracta width less than 0.4 cm predicted worse outcomes. Similarly, Cioffi et al¹³ and Rossi et al¹⁴ found that SMR was an independent predictor of mortality even in patients without ischemia. On the other hand, studies by Patel et al¹⁵ and Boriani et al¹⁶ did not confirm these results. In the setting of such conflicting findings, we performed a meta-analysis to clarify whether patients with ischemic or idiopathic cardiomyopathies and SMR have an adverse prognosis.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

The comparative benefits and harms of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for patients with aortic stenosis are unclear. To compare clinical outcomes, including early (≤30-day) and midterm (≤1-year) mortality, in adults with severe aortic stenosis undergoing either TAVI or SAVR. MEDLINE, Cochrane, and Scopus databases (without language restrictions) from April 2002 to 5 April 2016; multiple registries and Web sites; scientific meeting presentations. Five randomized trials and 31 observational matched studies comparing mortality outcomes after TAVI or SAVR. Two investigators independently extracted study data and rated risk of bias. 16 638 patients were analyzed. Overall, there was no statistically significant difference between TAVI and SAVR in early (odds ratio [OR], 1.01 [95% CI, 0.81 to 1.26]) or midterm (OR, 0.96 [CI, 0.81 to 1.14]) all-cause mortality. Analyses restricted to trials (early: OR, 0.80 [CI, 0.51 to 1.25]; midterm: OR, 0.90 [CI, 0.64 to 1.26]) were inconclusive, with wide CIs, whereas analyses of matched studies were similar to the overall results. Transfemoral TAVI provided mortality benefits over SAVR in trials. Analyses restricted to studies of patients at low to intermediate risk showed statistically nonsignificant reductions in early (OR, 0.67 [CI, 0.42 to 1.07]) and midterm (OR, 0.91 [CI, 0.67 to 1.23]) mortality with TAVI. Incidence of periprocedural myocardial infarction, major bleeding, acute kidney injury, and new-onset atrial fibrillation was lower with TAVI, but risk for pacemaker implantation, vascular complications, and paravalvular leak increased. Overall, there was a statistically nonsignificant increased risk in long-term (2- to 5-year) all-cause mortality with TAVI (OR, 1.28 [CI, 0.97 to 1.69]), whereas long-term mortality outcomes in patients at low to intermediate risk were inconclusive, with wide CIs (OR, 1.06 [CI, 0.59 to 1.91]). The number of trials was limited, and study designs and patient characteristics were heterogeneous. Compared with SAVR, TAVI may have similar or better early and midterm outcomes for adults with aortic stenosis, including those at low to intermediate risk. None.

The Official Journal of EuroPCR and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)