Recent Trends in Infective Endocarditis Among Patients with and Without Injection Drug Use: An Eight-Year Single Center Study.

BACKGROUND: Infective endocarditis (IE) is associated with considerable morbidity and mortality. Given the opioid crisis and emergence of drug-resistant organisms, we sought to examine annual trends in hospitalization rates for IE and potential epidemiologic shift in the causative microorganisms among patients with and without injection drug use (IDU). METHODS: This was a single-center retrospective cohort study of hospitalized adults with IE. Annual trends in hospitalization rates were calculated (2011-2018), and patient characteristics and clinical outcomes were compared according to IDU status. RESULTS: Our cohort of 244 hospitalized patients with IE had a subset of 112 with IDU. The annual hospitalization rate for IE increased almost four-fold and was most notable among patients with IDU. The highest increase occurred in patients with Staphylococcus aureus-associated IE. Patients with IDU were younger, and more likely to be women with tricuspid valve vegetations and have IE due to methicillin-sensitive and methicillin-resistant Staphylococcus aureus. Patients without IDU were more likely to have central venous catheters with mitral and aortic valve vegetations and have IE due to Streptococcus and coagulase-negative Staphylococcus species. Patients without IDU had a higher requirement for cardiac surgery and higher 90-day mortality. Age was the only independent variable associated with 90-day mortality. CONCLUSIONS: The rising incidence of IE in younger and older persons is driven in part by the opioid public health crisis and higher prevalence of indwelling central venous catheters, respectively. Timely treatment of opioid use disorders and stewardship surrounding use of central venous catheters is urgently needed.

Usefulness of Single Nucleotide Polymorphisms as Predictors of Sudden Cardiac Death.

The pathophysiology of sudden cardiac death (SCD) remains incompletely understood. Genetic mutations can create a favorable substrate for SCD. Our aim is to evaluate the evidence of single nucleotide polymorphisms (SNPs) as predictors of SCD. We searched the Medline database (2000 to 2017) and selected all case-control or cohort studies that reported associations between SNPs and SCD. Our search terms included "polymorphisms" and "sudden death." We collected the study design, population ethnic background, gene testing strategy, the association between the SNP and SCD, and the cardiovascular comorbidities of the population. Our search yielded 723 studies, of which we included 24 based upon our inclusion criteria. The studies had a total population of 78,165 participants, with a median age of 62.5 years (IQR 56 to 66) and 35% (IQR 13 to 32) were female. Almost all studies were conducted in white patients of European descent and the most commonly used genetic strategy was candidate gene panels. Fifteen of the studies had a case-control design that included SCD patients without known heart disease as the comparison group and the other 9 studies included patients with heart failure and coronary artery disease. The studies evaluated 53 SNPs and the most common genetic loci were SCN5A, RyR2, CASQ2, NOSA1P, and AGTR. SNPs with the 3 strongest statistically significant ORs >1 were: rs6684209 of CASQ2 (odds ratio [OR] 19), rs3814843 of CALM1 (OR 5.5), and rs35594137 of GJA5 (OR 3.6). In Conclusion, many SNPs are associated with SCD, with the strongest associations seen in SNPs of genes related to intracellular calcium handling. These findings were generated primarily using a candidate gene strategy in white patients with European descent.

Febuxostat and Cardiovascular Events: A Systematic Review and Meta-Analysis.

BACKGROUND: Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial. OBJECTIVE: To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group. METHODS: We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI). RESULTS: Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03). CONCLUSIONS: Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.