VanCART Research

At the forefront of basic and clinical discovery 

Vanderbilt University Medical Center is an internationally recognized leader in the field of arrhythmia research and therapeutics. Vanderbilt investigators have been at the forefront of basic and clinical discovery in mechanisms underlying arrhythmias and their variable responses to treatments, notably the development of proarrhythmia defined by CAST (in which Vanderbilt was a leading participant) and by studies of QT prolongation. 

More recently, Vanderbilt investigators have pioneered mechanistic research in drug-induced and genetic heart rhythm disorders, including the identification of rare and common genetic variants associated with arrhythmia risk, and the development of the first molecularly-targeted anti-arrhythmic drug therapy in a rare genetic arrhythmia disorder. 

The next frontier in arrhythmia research and therapeutics is to translate the detailed genetic information into mechanisms at the molecular and cellular level, and to translate the basic discoveries into optimal personalized care for patients with abnormal heart rhythms and to new drug development. This will require multidisciplinary research teams that include geneticists, bioinformatics specialists, structural biologists, cell biologists, basic ion channel biologists and clinical electrophysiologists as well as an infrastructure in basic electrophysiology equipment, research cores for sample processing and storage, bioinformatics, electronic patient databases, and clinical trial support.

Clinical Research Studies

 

Comparison of (R) and (S) Propafenone for Prevention of Atrial Fibrillation Induction 

  • A double-blind randomized active-controlled clinical trial that will determine the efficacy of R-propafenone for suppressing inducible atrial fibrillation in patients with a history of paroxysmal AF undergoing ablation. This is a single center study conducted at Vanderbilt University Medical Center by VanCART members Bjorn Knollmann, MD, PhD, and Benjamin Shoemaker, MD, MSCI. 

Arrhythmia Genetics Network (AGENT) - Vanderbilt Cohort 

  • Multicenter observational registry and DNA biorepository for inherited arrhythmia syndromes. Currently participating centers: Vanderbilt, MGH, U of Washington, Stanford, Cedars Sinai. GS-6615 

Late Sodium Current Blocker for Long QT Type 3 

  • Phase 3 clinical trial of GS-6615 to reduce QT interval in LQT3 patients. This is a study conducted at Vanderbilt University by VanCART member Benjamin Shoemaker, MD, MSCI. 

Sudden Unexplained Death DNA/Tissue Repository

  • Post-mortem DNA and tissue biorepository of victims of sudden unexplained death or evidence of arrhythmogenic cardiomyopathy. Collaboration with local medical examiner 

LIVE-LQTS 

  • Multicenter observational study of activity level (measured by Fitbit) and arrhythmic events in LQTS (PI: Rachel Lampert, Yale)

IHD Registry 

  • Observational registry and DNA biorepository for patients with inherited cardiomyopathies seen in the VUH Inherited Arrhythmia Clinic.

LIVE-HCM 

  • Multicenter observational study of activity level (measured by a Fitbit) and arrhythmic events in HCM (PI: Rachel Lampert, Yale)

HCM Pacing Study 

  • Prospective study of QT response to cardiac pacing interval in patients with HCM versus controls. Performed in CRC. 

LIBERTY-HCM 

  • Phase 3 clinical trial of GS-6615 late sodium current blocker to improve peak VO2 in HCM (measured at baseline and 24 weeks) 

Arrhythmia and Cardiomyopathy Phenotypes from eMERGE-3 (Electric Medical Records and Genomics Networks) 

  • A current project of the eMERGE network that will study the issue surrounding the return-of-result to providers of incidentally detected, potentially pathogenic mutations including those found in arrhythmia and cardiomyopathy associated genes. 

A New Paradigm for Identifying Patients and Drugs at Risk for QT Prolongation (Improving Prediction of Drug Action- PGRN IV) 

  • A current project of PGRN that will create iPSC-derived cardiomyocytes from patients with a history of drug-induced TdP. 

The Vanderbilt AF Electrophysiology Phenotyping Project 

  • A prospective observational registry with DNA and EP data from patients with AF undergoing AF ablation. Standardized data collection includes: baseline intervals, AV block cycle length, AV node ERP, LA ERP, pulmonary vein ERP, LA voltage, LA conduction velocity, and PV myocardial sleeve measurements. 

Prospective Identification of Long QT Syndrome in Fetal Life 

  • This study is a multicenter, international, observational study lead by Dr. Bettina Cuneo, University of Colorado and Dr. Peter Schwartz, Milan Italy. The research aim is to identify individuals prior to birth who have long QT syndrome (LQTS).