Cardiology Research Team Builds on Arthur Moss’ Legacy of Discovery
Thursday, September 12, 2019
More than a year after his passing, Arthur Moss’ research continues to fuel discoveries related to the treatment of heart disease, and his dedication to teaching and mentoring carries on in the training of a new generation of researchers.
Moss, M.D., founding director of URMC’s Heart Research Follow-up Program who passed away in February 2018, made some of the most significant discoveries in sudden-cardiac-death prevention and treatment. His research improved the standard of care for people with heart disease and helped them to live longer, better lives.
“Arthur’s mission was to identify people at risk of sudden cardiac death and to find a way to prevent it,” said Charles J. Lowenstein, M.D., chief of Cardiology. “His mission led to landmark clinical trials and the groundbreaking discovery that implantable defibrillators save lives. Hundreds of thousands of lives worldwide were saved by Arthur’s research.”
The Multicenter Automatic Defibrillator Implantation Trial (MADIT) series of clinical trials in the 1990s showed that the implantable cardioverter defibrillator–a device that detects arrhythmias and shocks the heart back into a normal rhythm–significantly improves survival in patients with a high risk of sudden death. These findings directly led to new medical guidelines in the U.S. and around the world.
Moss’ legacy endures in the ongoing work of URMC’s team of cardiologists and electrophysiologists, through the expansion of the MADIT trials, a formal research training program, and broader collaboration and teamwork.
Expanding clinical trials
Building on the Heart Research Follow-up Program, URMC established the Clinical Cardiovascular Research Center (CCRC) to consolidate all clinical cardiology research into one team. The world's leading research group for clinical trials of sudden death, the CCRC team is led by center director Ilan Goldenberg, M.D., and includes faculty Wojciech Zareba, M.D., Ph.D., professor of Cardiology, Valentina Kutyifa, M.D., Ph.D., associate professor of Cardiology Heart Research, and Jean-Philippe Couderc, Ph.D., M.B.A., associate professor of Cardiology.
According to Goldenberg, center researchers are now looking to identify the patients in the more general population who are at risk of sudden cardiac death and to help them live longer using device and implantable monitor therapy. “Our initial series of MADIT trials focused on the sickest patients with more advanced cardiac dysfunction,” Goldenberg said. “We are planning the next series of MADIT studies to expand and explore sudden cardiac death among a more general population.”
One new study led by Kutyifa will analyze sex-specific outcomes in patients with non-ischemic cardiomyopathy treated with cardiac defibrillator device therapy. With a particular emphasis on women, the BIO-LIBRA study will explore whether women respond to defibrillator therapy differently than men. The target group is 1,000 patients in 50 sites in the U.S., with a goal of at least 40 percent female enrollment.
Goldenberg was recently awarded the highly prestigious American Heart Association grant on arrhythmia and sudden cardiac death, in collaboration with the University of Washington and Johns Hopkins. This project will focus on how to prevent sudden cardiac death using genomics and innovative digital technology, particularly among such underrepresented populations as women and children.
Continuing Moss’ legacy of National Institutes of Health-funded research, Zareba obtained NIH grants to conduct multicenter studies on: 1) the risk stratification in nonischemic cardiomyopathy to test ECG and cardiac magnetic resonance parameters in predicting ventricular arrhythmias; and 2) new therapy in the arrhythmogenic right ventricular cardiomyopathy.
In addition to continuing international clinical trials on sudden cardiac death, center researchers are expanding trials into other areas, including novel technologies for heart failure, ventricular tachycardia and thrombosis. Examples range from telemedicine and the next generation of defibrillators, to new pacemakers and new monitoring devices. Couderc conducts NIH-funded studies with new monitoring technologies including video cameras and CardioMat to monitor heart rate and ECG.
A passion for teaching and mentoring
Besides conducting research, Moss’ other passion was advancing the careers of his students. He trained one or two fellows per year in his clinical research methods. Today, his enthusiasm for teaching and mentoring lives on in a structured training program led by Goldenberg and Kutyifa that involves all URMC Cardiology fellows.
Fellows receive hands-on training, and they are assigned an individual research project. The CCRC team also is offering clinical research training to other URMC divisions, such as Pulmonary and Critical Care and the Wilmot Cancer Institute.
A center for collaboration
CCRC researchers are furthering Moss’ commitment to teamwork by fostering greater collaboration among university faculty as well as among other centers around the globe. Faculty members are working together to prepare for the next phase of clinical trials, and the worldwide research network is expanding to other centers in the U.S. and Europe.
“Arthur Moss helped build our heart research program into a worldwide hub of international studies on medical interventions for sudden death, cardiac arrhythmias, heart attack and heart failure,” Lowenstein added. “Today, Ilan Goldenberg and his team–all of whom worked with and were inspired by Arthur–are taking cardiovascular research to the next level, building on his legacy.”
AHA Grant Fuels Study of Sex Differences in Sudden Cardiac Arrest
Wednesday, July 3, 2019
The Clinical Cardiovascular Research Center (CCRC) at URMC is partnering with investigators from the University of Washington and Johns Hopkins University to study sex-specific differences in arrhythmias and sudden cardiac arrest. With a new $3.8 million grant from the American Heart Association, the group will work to improve sudden cardiac arrest risk stratification and resuscitation strategies among women and men.
In the United States, more than 350,000 people experience sudden cardiac arrest every year, and about 90 percent of them die. Women have different risk factors than men; they have a lower incidence in the general population, but a higher incidence among certain subgroups.
Rochester’s portion of the project will focus on sex hormones and arrhythmias and aim to answer the following questions:
- What is the association between female sex hormones and arrhythmic risk?
- Can sex-specific risk factors improve risk stratification for sudden cardiac arrest in patients with long QT syndrome (LQTS)? LQTS is an inherited arrhythmic disorder that predisposes children and young adults to sudden cardiac arrest.
- Are there sex differences in response to medical and defibrillator therapy in LQTS?
“We know that there are associations between the menstrual cycle and risk for sudden cardiac arrest beginning in adolescence in females with inherited arrhythmic disorder, as well as in women who are exposed to a large number of drugs that predispose to arrhythmic risk (such as certain antibiotics). Furthermore, in these women the risk of sudden cardiac arrest increases after pregnancy and during the peri-menopausal period,” says Ilan Goldenberg, M.D., principal investigator on the Rochester study and professor and director of the CCRC. “Understanding the relationship between sex hormones, genetics and risk for sudden cardiac arrest may lead to new hormone-based treatment options for women with inherited and acquired arrhythmic disorders.”
Goldenberg will work closely with co-principal investigator Wojciech Zareba, M.D., Ph.D., professor of Medicine, Cardiology and Derick Peterson, Ph.D., professor of Biostatistics and Computational Biology to lead the project. The team will analyze data from more than 6,000 individuals included in the international LQTS Registry, which is based at URMC. They’ll also partner with clinicians at UR Medicine and Rochester General Hospital to enroll women in various sub-studies that will involve ECG monitoring and hormone level testing.
Johns Hopkins researchers will explore the genes and biologic processes associated with sudden cardiac arrest in women and men. They plan to use this information to formulate a genetic risk score to predict who is at high risk of sudden cardiac arrest. The team at the University of Washington will work to understand why some people fail to respond to resuscitation efforts or implantable cardioverter defibrillator (ICD) therapy. The goal is to improve sex-specific resuscitation strategies for cardiac arrest through the creation of a computer-generated algorithm that would yield more precise resuscitation strategies.
The grant also includes a training program, coordinated by the University of Washington. All three centers will recruit and work with trainees to develop expertise in sudden cardiac arrest research.