After a seemingly healthy 17-year-old lacrosse player passed out on the field, her frightened family turned to cardiologist Matthew Martinez for help. Imaging confirmed she had hypertrophic cardiomyopathy (HCM), a genetic disorder that causes heart muscle to become abnormally thick. Affecting as many as one in 250 Americans, HCM is a leading structural cause of sudden death in young athletes.
One month earlier, however, she had been cleared to play by her primary care doctor, who didn’t detect any heart problems during a sports physical. The case highlights the limitations of current approaches to screening student-athletes for cardiac threats such as HCM, says Martinez, director of sports cardiology at Morristown Medical Center (MMC), part of Atlantic Health System. He and other researchers are looking for better tools to identify young athletes with HCM, a disorder that goes undiagnosed in more than 85% of those who have it1.
Martinez’s study is one of dozens underway at MMC, one of the nation’s top hospitals for cardiology, and home to New Jersey’s largest cardiac surgery programme. Every year, its physician-scientists conduct major clinical trials focused on discovering treatments and diagnostic tools for a wide range of cardiovascular conditions. Here are three intriguing initiatives, in HCM, valvular disorders and other structural heart diseases, that showcase how researchers at Atlantic Health are influencing approaches to treatment to potentially save millions, of lives.
Early intervention for aortic stenosis
In November 2021, MMC investigators launched PROGRESS, a large, multicentre clinical trial in aortic stenosis. Around 2.5 million Americans have this condition where the heart’s aortic valve narrows and cannot fully open, reducing the flow of oxygenated blood to the rest of the body.
Patients with aortic stenosis are closely monitored by their cardiologists. Current guidelines recommend valve replacement surgery only if the disease becomes severe, says Philippe Généreux, the trial’s principal investigator and a director of the Structural Heart Program at MMC’s Gagnon Cardiovascular Institute. “It’s become obvious to me that some patients need help earlier than what’s recommended now — because they can develop irreversible heart damage, go into heart failure or even die — before the guidelines say that valves should be replaced.”
One reason why valve replacement is reserved for those with severe aortic stenosis is that it used to always require open-heart surgery, which has a long recovery time and many potential risks for patients, most of whom are elderly. Now there is a minimally invasive, FDA-approved procedure called transcatheter aortic valve replacement (TAVR), in which a narrow tube is threaded through a leg artery up to the aorta and used to implant the replacement valve. In PROGRESS, patients aged 65 and older with moderate aortic stenosis and either symptoms or evidence of cardiac damage/dysfunction will be randomly assigned to receive either traditional care or TAVR to compare their outcomes.
“This is an extremely important study because it could change how we approach these patients,” says Linda Gillam, medical director of Atlantic Health’s cardiovascular service line. “If early intervention turns out to be the way to go, that will translate to new guidelines. If results are similar in both groups, that’s also a guideline change. And if TAVR is not the way to go, which would surprise me, the results will strengthen scientific support for the current approach.”
Cardiologists who treat mitral regurgitation — blood flowing the wrong way through the left chambers due to a leaky mitral valve — face a clinical conundrum: the two imaging methods used to evaluate this condition, echocardiography and cardiac MRI, frequently provide conflicting information as to whether the leakage is severe enough to require surgery.
“If echo says mitral regurgitation is severe and MRI says it’s mild, which one is right?” asks Seth Uretsky, Atlantic Health’s medical director of cardiovascular imaging. Cardiologists need reliable imaging data, he says. “Otherwise you could be sending patients to surgery who may not need it, and missing those who do.”
These are critical decisions. Mitral regurgitation, which affects about four million Americans2, can have serious complications, including heart failure, pulmonary artery hypertension and atrial fibrillation.
Over the past decade, Uretsky has led several clinical trials to compare the two imaging tools using an innovative method. “As mitral regurgitant volume gets bigger, so does the left ventricle (LV) to keep up with output,” he says. “If someone with severe mitral regurgitation underwent surgery, we’d expect LV size to shrink afterwards, indicating that the patient was appropriately treated.” Lack of LV shrinkage could indicate that surgery was unnecessary because the disease was mild.
In 2015, his team reported3 a strong correlation between MRI assessment of mitral regurgitation severity and a postsurgical decrease in LV size, and poor correlation between these factors with echocardiography. A second trial confirmed the results4. These findings suggest that MRI quantitation may be more accurate and should be used more widely to guide important clinical decisions, such as which patients should undergo surgery.
Cardiac danger for young athletes
Martinez continues to monitor the lacrosse player, who is now doing well with appropriate therapy and surveillance. In 2020, he served on an expert committee that wrote new cardiology guidelines5 for the diagnosis and management of HCM, which recommend several ways to make a diagnosis including ECG, echocardiography or cardiac MRI for the initial workup. However, these tests may not be readily available, can be costly, and will always require expert interpretation, making them impractical for screening millions of student athletes, Martinez notes.
Instead, his team is ‘re-exploring’ the potential of a more broadly available method to identify young athletes at risk of sudden death from HCM. They are using artificial intelligence to analyse cardiac imaging data from thousands of male and female athletes, most of whom are Black or Hispanic — groups that have been underrepresented in HCM research — to search for previously unrecognized signals that could indicate HCM. The goal is to develop a rapid, accurate and inexpensive computerized tool to identify specific abnormalities linked to HCM. If successful, this will not only improve diagnostic capabilities but could improve access for people in remote and underserved populations.
The potential outcomes of the research are significant, as they are for all of MMC’s exploratory work. “If we can accomplish this, it’s going to change the way we take care of athletes, increase diagnostic yield of HCM and contribute to the next set of guidelines for HCM diagnosis and treatment,” says Martinez. “And most importantly, it may help save lives.”