Cedars-Sinai is at the forefront of advancing biological therapies and minimally invasive approaches, and of gaining deeper knowledge of the molecular and cellular mechanisms underlying heart rhythm and dysfunction.
Cedars-Sinai researchers are developing gene- and cell-based therapeutics to offer alternatives or adjuncts to conventional treatments. Using an engineered virus carrying T-box (TBx18), researchers are reprogramming heart muscle cells (cardiomyoctes) into induced sinoatrial node (iSAN) cells in pigs.
Cedars-Sinai research shows that these new cells generate electrical impulses spontaneously and are indistinguishable from SAN (native pacemaker) cells. Researchers believe this could be a viable therapeutic avenue for pacemaker-dependent patients afflicted with device-related complications.
- Principal investigators: Eduardo Marbán, MD, PhD
Also, Cedars-Sinai is developing a clinically applicable, gene-based biological as a bridge-to-device solution for patients with bacterial infections who need temporary pacing during antibiotic treatment. In a porcine, preclinical model of complete heart block, investigators are able to successfully deliver an adenoviral vector genetic cocktail that provides physiologically relevant pacing over a 14-day period. The approach offers external pacing assistance to allow effective clearance of infection prior to reimplantation of a definitive electronic pacemaker or other situations that require temporary, off-the-shelf pacing.
- Principal investigator: Eugenio Cingolani, MD
Minimally Invasive Approach
In addition to the temporary biopacers, Cedars-Sinai is testing minimally invasive percutaneous venous catheter delivery systems to translate the current, highly invasive approaches — such as open-chest and left-sided delivery techniques — into minimally invasive outpatient procedures.
The first to successfully deliver the genetic biopacer via the femoral vein to the atrioventricular node region, Cedars-Sinai investigators continue to study optimal location and system deliveries. Plans are underway for an immediate clinical trial for patients who cannot have an electronic pacemaker implanted due to infection.
Molecular and Cellular Mechanisms of Heart Rhythm and Dysfunction
Cedars-Sinai research targets a more complete understanding of the molecular basis of contractile dysfunction of heart muscle associated with acute myocardial infarction and systolic heart failure.
Cedars-Sinai researchers are studying:
- Cardiac ion channel formation and trafficking with a particular emphasis on Connexin43 gap junctions and L-type calcium channels
- How ion channels are targeted to specific subdomains of cardiac cell membrane in both healthy and failing heart muscle
- Regulation of cardiac excitation-contraction coupling in health and disease, with a particular focus on the effects of metabolic inhibition, ischemia and heart failure on sodium-calcium exchange
- Mechanisms of RNA translation
- Cytoskeleton-based delivery of channels
- Calcium channels and biomarkers that prognosticate heart failure outcomes
Investigators work to enhance their understanding of mechanisms of defective electrical activity in the heart and advancing percutaneous catheter ablation techniques. Projects include observational studies and clinical trials.
- Principal investigator: Sumeet S. Chugh, MD
Clinical research interests include:
- Evaluating novel treatment modalities for heart rhythm disorders
- Catheter ablation of atrial fibrillation and other complex arrhythmias, including atypical atrial flutter and ventricular arrhythmias
- Identifying novel determinants of sudden cardiac arrest that will facilitate the identification of subjects at risk, with the overall goal of improving prevention
- Evaluating newly developed modalities for arrhythmia management
- Cardiac arrest prevention, including the Oregon Sudden Unexpected Death Study, an investigation of sudden cardiac arrests that occur among residents of the Portland metropolitan area.