Phillip Sasse M.D.
Cardiac arrhythmias are common disorders affecting the rhythmicity of the heartbeat and can lead to hypotension, syncope, and even sudden cardiac death. My current research focuses on identification of new methods for diagnosis, treatment and understanding the mechanisms of cardiac arrhythmias using optogenetics and patient-specific induced pluripotent stem cells. Bradycardic arrhythmias are typically treated by the implantation of a cardiac pacemaker, which stimulates the heart electrically. My group has developed an alternative, optogenetic method to stimulate cardiomyocytes by light (Bruegmann T et al. Nature Methods 2010). We showed that light can be used for artifact-free, uniform and long-lasting stimulation with ...Read More
Paul G.A. Volders M.D., Ph.D., F.E.S.C.
David J. Christini Ph.D.
Atrial fibrillation (AF) is very difficult to study comprehensively in large-animal models, in part because it has several variants, is multi-factorial, and evolves over time and also because of the inherent technical difficulties of maging whole-atria electrophysiology in vivo. Predictive multiscale computational modeling can help to overcome such hurdles and help to evaluate potential pharmacological and device-based AF therapies. Because a multiscale atrial model is only as strong as its underlying cellular model, we are working to improve atrial cell model fidelity. To do so, we are applying dynamically rich electrophysiology protocols to human atrial cells and then using automated ...Read More
John M. Miller M.D.
Jonathan R. Silva Ph.D.
Guy Salama Ph.D.
Women have a longer baseline QTc than men, and are at higher risk (60-75%) for long QT syndrome (LQTS) than men. LQTS is characterized by sudden syncopal attacks, seizures, and sudden death. LQTS is associated with a form of polymorphic ventricular tachycardia, called Torsade de Pointes (TdP) which often leads to sudden death and remains a major health problem. TdP caused by the suppression of the fast component of the delayed rectifying K+ current, IKr results in repolarization delay and QT prolongation, called Long QT type 2 (LQT2). Sex differences in the propensity to LQT2 have been attributed to a ...Read More
Stacey Rentschler M.D., Ph.D
Timothy J. Kamp M.D., Ph.D., F.A.C.C.
Changes in the repolarization properties of cardiac muscle frequently underlie the increased susceptibility to ventricular arrhythmias in a variety of heart diseases, but the control of cardiac repolarization is incompletely understood. Abnormalities of repolarization resulting in action potential duration prolongation or shortening can be pro-arrhythmic. Multiple different ion channels in cardiomyocytes impact action potential repolarization, and the diversity of ion channels and regulatory pathways involved in repolarization is highlighted by the association of at least 13 distinct genes with the inherited long QT syndrome which is due to delayed repolarization. For example, mutations in the gene encoding caveolin-3 (Cav-3) have ...Read More
Xander Wehrens M.D., Ph.D., F.A.H.A., F.H.R.S.
Atrial fibrillation (AF) is the most common atrial arrhythmia in clinical practice. A combination of electrical, structural, and calcium handling remodeling contributes to the progression of AF from selfterminating episodes (paroxysmal AF) towards more persistent states (chronic AF). Dr. Wehrens will present new insights into the cellular mechanisms underlying arrhythmogenesis during the early phases of AF development. This work revealed distinct changes in calcium handling proteins as compared to those seen in more advanced (chronic) AF. In addition, new evidence will be presented implicating calcium leak from the sarcoplasmic reticulum as a key signal underlying some aspects of atrial remodeling ...Read More
Lior Gepstein M.D, Ph.D
Eli Rothenberg Ph.D.
James Weiss M.D.
Lori L. Isom Ph.D.
Calum A. MacRae M.D, Ph.D
Björn C. Knollmann M.D, Ph.D
Connexin43, plakophilin-2 and the sodium channel complex: Partners in a heartbeat. Arrhythmia mechanisms in ARVC
Mario Delmar M.D, Ph.D