Improving Diagnosis and Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: Integrating Clinical and Basic Science

• Applicant: Professorin Dr. Kaomei Guan
• Subject Area: Human Genetics ; Cardiology, Angiology
• Term: from 2016 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 287718088

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia syndrome with a prevalence of 1 in 10 000 that causes sudden cardiac death. It is one of the most lethal pathologies involving ion channels and is most commonly due to mutations in the ryanodine receptor 2 (RYR2). CPVT is characterized by exercise- or emotion-induced ventricular arrhythmias without abnormalities in resting ECG and cardiac structure, which makes the diagnosis difficult. At present, neither optimal risk stratification tools nor effective interventions for CPVT are available to the treating cardiologists. This proposal brings together global clinical leaders and basic scientists with expertise in inherited arrhythmia conditions and national and international registries. The overall objective of this CPVT research program is to develop an effective strategy for rationalizing therapies based on the risk profile of an individual, thereby reducing morbidity and preventing sudden cardiac death. To achieve this objective, we will establish an international CPVT registry and a corresponding biobank to enable identification of relevant new genes, to correlate genotype with phenotype, and to generate risk prediction algorithms for clinical use. Further, we will enhance our understanding of RYR2 mutations in CPVT by performing basic research including the development of patient-specific pluripotent stem cell-derived cardiomyocytes that can recapitulate the CPVT phenotype in vitro. By treating CPVT patients according to risk stratification based on demographics, family history, clinical presentation, genetics, and functional characteristics, we aim to improve patient outcomes and save lives.

• DFG Programme: Research Grants
• International Connection: Canada, France, Netherlands, Romania, Spain
• Cooperation Partners: Dr. Ramon Brugada; Professor Dr. S.R. Wayne Chen; Professor Dr. Antoine Leenhardt; Professor Dr. Shubhayan Sanatani; Dr. Calin Siliste; Professor Dr. Arthur A.M. Wilde