Heart Failure and Transplantation

Preclinical Research

Cedars-Sinai researchers aim to prevent heart failure and, in case of occurrence, improve heart function. The major focus points of their preclinical projects are:

  • Sodium calcium exchanges
  • Connexin43
  • Ischemia and reperfusion
  • Stem cells

Sodium Calcium Exchanges
Researchers understand the causes of abnormal heart pump function at the molecular and cellular levels by studying specific proteins regulating heart contraction through manipulation of intracellular calcium, known as sodium calcium exchanges (NCX). Using an advanced, high-speed, laser-scanning confocal microscope, researchers study these calcium movements inside single heart cells of genetically modified mice while recording their electrical activity. The belief is that we can manipulate NCX by using drugs or genetic therapies to strengthen the heart’s pump function and thereby treat heart failure.

Researchers aim to develop therapies to restore cell-to-cell communication in diseased hearts by studying the Connexin43 (Cx43) life cycle and how the pathways in these processes become amenable to pharmaceutical manipulation. Using Cx43 as a model of intracellular channel movement, researchers identified that the reason L-type calcium channels can traffic to cardiomyocyte T-tubules is that the microtubule cytoskeleton delivers the channels to BIN1-enriched membrane at T-tubules. Research further shows that BIN1 — a membrane scaffolding protein that helps determine the strength of each heartbeat — is decreased in diseased and failing hearts and blood. Researchers are learning how blood-based BIN1 is a marker of myocardial reserve in patients with chronic heart failure.

Ischemia and Reperfusion
In cell, rodent and porcine models, researchers investigate and mitigate ischemic injury to develop treatments. Cedars-Sinai researchers are pioneers in autography in cardioprotection and the use of mitochondria-targeted recombinant proteins for cardiac therapy. Currently, they are investigating the impact of age and metabolic syndrome on autophagy and cardioprotection.

Mechanism of Heart Regeneration by Cardiosphere-Derived Cells
Cedars-Sinai investigators seek to understand the basic mechanisms of coronary artery disease in preclinical disease models. They hope to gather novel mechanistic insights enabling us to boost the efficacy of stem cell-based treatments by bolstering the regeneration of injured heart muscle.

Clinical Research

Cedars-Sinai is are participating in multicenter trials that will help determine the optimal course of therapy for patients with heart failure. The objective is to advance new therapeutics and devices to assist patients in advanced stages of heart disease. Clinical research includes clinical trials and observational studies in:

  • Heart failure
  • Heart transplant
  • Mechanical circulatory support devices

Heart Failure
Cedars-Sinai investigators are testing new drugs and cardiac stem cell therapeutics for end-stage (advanced) heart failure in patients. Researchers seek to improve outcomes and quality of life. These clinical trials include:

  • Left Atrial Pressure (LAP) Monitoring to Optimize Heart Failure Therapy study
  • Observational review of clinical outcomes in heart failure patients undergoing bariatric surgery

Heart Transplant
Researchers are identifying noninvasive methods to detect rejection and are discovering more effective immunosuppressant drugs with fewer side effects to fight organ rejection in transplant patients. The clinical trials are:

  • ACE Inhibition and Cardiac Allograft Vasculopathy
  • The DeNovo Use of Eculizumab

Mechanical Circulatory Support Research
Researchers seek to improve total artificial heart and mechanical circulatory support devices, which are bridges to heart transplantation. They hope to improve outcomes and quality of life in patients with mechanical circulatory support devices in these clinical trials:

  • Interagency Registry of Mechanically Assisted Circulatory Support (INTERMAC): A National Registry for Mechanical Assist Device Patients
  • HeartWare: Endurance – A Prospective Randomized, Controlled, Unblended, Multicenter Clinical Trial to Evaluate the HeartWare Ventricular Assist Device For Destination Therapy of Advanced Heart Failure