Atrial Fibrillation Genomics: Discovery and Translation.

PURPOSE OF REVIEW: Our understanding of the fundamental cellular and molecular factors leading to atrial fibrillation (AF) remains stagnant despite significant advancement in ablation and device technologies. Diagnosis and prevention strategies fall behind that of treatment, but expanding knowledge in AF genetics holds the potential to drive progress. We aim to review how an understanding of the genetic contributions to AF can guide an approach to individualized risk stratification and novel avenues in drug discovery. RECENT FINDINGS: Rare familial forms of AF identified monogenic contributions to the development of AF. Genome-wide association studies (GWAS) further identified single-nucleotide polymorphisms (SNPs) suggesting polygenic and multiplex nature of this common disease. Polygenic risk scores accounting for the multitude of associated SNPs that each confer mildly elevated risk have been developed to translate genetic information into clinical practice, though shortcomings remain. Additionally, novel laboratory methods have been empowered by recent genetic findings to enhance drug discovery efforts. AF is increasingly recognized as a disease with a significant genetic component. With expanding sequencing technologies and accessibility, polygenic risk scores can help identify high risk individuals. Advancement in digital health tools, artificial intelligence and machine learning based on standard electrocardiograms, and genomic driven drug discovery may be integrated to deliver a sophisticated level of precision medicine in this modern era of emphasis on prevention. Randomized, prospective studies to demonstrate clinical benefits of these available tools are needed to validate this approach.

Novel doses of sacubitril/valsartan in patients unable to tolerate traditional therapy: Effects on N-terminal pro B-type natriuretic peptide levels.

BACKGROUND: Widespread use of angiotensin receptor blocker and neprilysin inhibitor (ARNI) remains low, and many patients are unable to tolerate the medication due to hypotension at the currently recommended starting dose. HYPOTHESIS: The aim of this study is to assess if lower than standard doses of ARNI, sacubitril/valsartan (S/V), significantly reduces NT-proBNP and leads to any change in diuretic dose, serum potassium, or creatinine. METHODS: In a retrospective study of 278 patients who were started on a low dose S/V at a single medical center, 45 patients were selected for the study cohort. Patients were subcategorized to Group 1 (n = 10): very low dose S/V (half a tab of 24/26 mg BID), Group 2 (n = 10): very low dose titrated to low dose S/V, and Group 3 (n = 25): low dose S/V (24/26 mg BID). NT-proBNP, diuretic dose, serum potassium, and creatinine were compared before and after initiation of S/V. RESULTS: Among all groups, there was a significant reduction in NT-proBNP level (Group 1: p < .01, Group 2: p < .01, and Group 3: p < .001). In addition, there was a significant reduction in diuretic dose across all groups combined (furosemide 53 mg/day vs. 73 mg/day; p = .03), with 17.8% (8/45) patients being able to discontinue their diuretic completely. There was no significant change in potassium or creatinine. CONCLUSIONS: Lower than standard dose of S/V significantly reduces NT-proBNP and diuretic requirement without change in potassium or creatinine, which provides hope that patients who cannot tolerate standard doses of S/V due to hypotension may be able to receive the benefits of S/V therapy.

Left atrial thrombus two years after placement of a left atrial appendage closure device: Unexplored area of the Watchman.

A 72-year-old man who underwent a left atrial appendage (LAA) closure device 2 years ago presented with atrial flutter with rapid ventricular rate and was referred for cardioversion. Precardioversion transesophageal echocardiogram showed left atrial thrombus and therefore the procedure was aborted. Currently, there is no guideline on imaging surveillance or anticoagulation in patients with LAA closure device who develop intracardiac thrombus after the initial 6-month surveillance period.