NHLBI TOPMed: Defining the Time-Dependent Genetic and Transcriptomic Responses to Cardiac Injury Among Patients with Arrhythmias

The UMMS miRhythm Study is an ongoing study of adult patients undergoing an elective electrophysiology study or arrhythmia ablation procedure for a supraventricular or ventricular arrhythmia, including atrial fibrillation (AF). Atrial fibrillation is a major clinical and public health problem that is related to atrial pathologic remodeling. Few tools are available to quantify the activity or extent of this remodeling, rendering it difficult to identify individuals at risk for AF. Previous studies have suggested an important role for miRNA in cardiovascular disease through gene expression regulation, making this a promising avenue for studying AF mechanisms. The aim of the study is to determine the time-dependent changes to key circulating miRNAs in a model of planned atrial injury and remodeling via ablation. Such knowledge might provide additional insight into the biology and activity of the acute atrial injury response, and furthermore, inform new targets for development of preventative interventions or allow for better AF risk stratification. To assess pathways regulating atrial pathological remodeling, patient blood samples are collected prior to their ablation procedures and also at a regularly scheduled 1-month follow-up appointment. Plasma expression of miRNA is measured using high-throughput quantitative reverse transcriptase polymerase chain reaction (RT-qPCR), providing novel insights into the regulatory processes underlying AF, as well as acute atrial injury in vivo. Additionally, data collected from whole-genome sequencing (WGS) is used to supplement miRNA analyses and further explore new relations between genes and abnormal heart rhythm.]]>
TOPMed Whole Genome Sequencing Methods: Freeze 9TOPMed Whole Genome Sequencing Methods: Freeze 10Inclusion Criteria for this Enrollment: Any adult patient ≥18 years of age undergoing an elective electrophysiology study or arrhythmia ablation procedure for a supraventricular or ventricular arrhythmia, including atrial fibrillation (AF) Patients may be in sinus rhythm or atrial fibrillation at the time of the procedure. The patient must be able to give signed, informed consent. Exclusion Criteria for Enrollment: Age <18, known pregnancy, inability to consent, cardiac surgery within the last 2 months.]]>
This study started in 2011 and now includes over 600 participants recruited from the UMass Memorial HealthCare Center (UMMHC). As of June 2017, approximately 100 study participants have had their plasma miRNA levels quantified, with an additional 110 miRNA results available from control patients with no known history of AF. Beginning in Fall 2016, the miRhythm study was expanded to include patients undergoing electrophysiology studies or ablation procedures for arrhythmias other than atrial fibrillation such as atrial flutter, SVT, and ventricular tachycardia. Expansion of the miRhythm study will allow for a broader understanding of the genetic mechanisms contributing to the development of various abnormal heart rhythms.]]>