Pioneering cardiologist James Muller, MD, cardiology specialist with Brigham and Women’s Hospital and winner of the Nobel Peace Prize, was one of the chief researchers that developed the concept of vulnerable plaques causing heart attacks. He was recognized for his contributions in cardiology with the honor of Distinguished Scientist at the American College of Cardiology (ACC) 2023 meeting. He spoke with Cardiology Business at the meeting about his accomplishments.
Muller said he has two lives, one as a cardiologist/clinical researcher one as an advocate for peace and nuclear non-proliferation. It was the combination of those two lives that led to the term "vulnerable plaque" in the mid-1980s. That was when he was among a group of recipients of the Nobel Peace Prize and his cardiac research led to key questions.
His research originally focused on circadian variation of cardiac events, where a larger number of heart attacks were found to occur in the morning. His research group then looked at anger and heavy exertion as triggers of heart attacks.
"We then asked why would an activity trigger a heart attack, and we came up with the idea that maybe the patient has a vulnerable plaque that could rupture and a clot could form," Muller explained.
The term "vulnerable" actually came out of a discussion Muller had with a Pentagon official in 1985, he said.
"The Pentagon said our nuclear weapons in North Dakota are vulnerable to the Russians who will take them out in the first strike. I said well they might be vulnerable, but the ones on the submarines are not vulnerable," Muller explained. "That was in 1985, the same year we found the circadian variation of heart attacks and we were thinking about why some plaques would rupture, and I thought let's call them vulnerable. So that term vulnerable plaque actually comes from the nuclear arms race. "
Controversy over the idea of vulnerable plaque
Today, it is generally accepted that coronary plaque morphology plays a key role in the development of a heart attack and there is a difference between stable and unstable plaques. Plaques with a thick fibers cap are considered stable, but thin-capped atheromas with a lipid rich core, macrophages and a necrotic core are considered unstable. These are often the culprit lesions in myocardial infections, when they rupture and it causes a clotting cascade inside the vessel.
It took years of research to show the connection between changes in the plaques and the resulting heart attacks. However, it was a long road to acceptance of this idea, and Muller was often the target of ridicule.
"There was a lot of controversy and I was called Einstein's fool for doing the same thing over and over again searching for a vulnerable plaque and never finding one. My reply was that some day the data will speak," Muller said.
Today, there are nine prospective cardiac imaging trials done with inter vascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS) where patients were followed for at least two years.
"Low and behold, in each of the nine trials, it's now possible to predict that a plaque is going to cause of a heart attack. So the vulnerable plaque field, diagnostically, has matured," Muller said. "It has now reached a point that a plaque that has a 20% risk of rupture can be identified."
Muller was also involved in the development of intravascular NIRS imaging technology. He said it was created to what was hoped to be a vulnerable plaque detector, where the spectroscopy analysis from infrared light from the plaque can tell you what is the chemical composition of the plaque. The color-coded image it creates shows area of the vessel wall with high concentrations of lipids. This technology is currently commercialized by Infraredx and is combined with co-registered IVUS. He is also involved with another startup, SpectraWave, which gained FDA clearance in March 2023 for a NIRS-OCT system.
To treat or not to treat a detected vulnerable plaque
Once it is possible to identify a vulnerable plaque, the next step is deciding whether to preemptively treat the lesion with a procedure to possibly prevent a heart attack or just treat the patient with medication and monitor the lesion over time.
"The diagnostic part is the hard part, and I feel we are about 92% there now, but it is good enough now where we can find vulnerable plaques," Muller said. "So now the question is, should they be stented?"
Stents themselves can carry long-term risks, he noted, so more data is needed before cardiologists begin preemptively stenting these lesions.
Additionally, Muller emphasized that stenting a non-stenotic lesion because it is a vulnerable plaque and billing Medicare for it is illegal. But, it can be done in randomized trials, of which three are ongoing to look at this question. Muller said the first of these studies, the PREVENT trial, where 1,600 patients were randomized in South Korea and Japan, might be finished soon and possibly presented as early as 2024. He said that trial will be the capstone on the vulnerable plaque question.
Cardiologists win the Nobel Peace Prize
During the height of the Cold War, Muller was a co-founder of a group of U.S. and Russian doctors who created the International Physicians for the Prevention of Nuclear War (IPPNW). The group leveraged the existing international cooperation between physicians and their clout in society to draw attention to what the catastrophic outcomes would be of a nuclear war. The group lobbied their governments and spoke out publicly for nuclear arms reductions. For those efforts, the IPPNW as an organization was awarded the Nobel Peace Prize in 1985.
In 1985, when his group received the prize, there were 55,000 nuclear weapons. Today, there are 15,000. He said some progress has been made on that front since the 1980s to reduce the number of nukes.
Nearly 40 years later, Muller is still active with delivering the message to reduce and eliminate nuclear weapons. He was invited to speak on vulnerable plaque in Moscow in early 2022 prior to the Russian invasion of Ukraine. He and the Russian doctors he was working with took the opportunity of his visit to issue a public statement to protest nuclear arms.
The IPPNW was co-founded on the American side by four medical thought-leaders. These included cardiologists Bernard Lown, Muller, radiologist and cardiac imager Herbert Abrams, and psychiatrist Eric Chivian. All four were colleagues at Brigham and Women’s Hospital and at Harvard. Lown developed the defibrillator for cardiac resuscitation. Abrams was a pioneer in invasive coronary angiography and other areas of vascular imaging. Chivian went on to become the founder and director of the Center for Health and the Global Environment at Harvard Medical School.
Muller shares more details in the video at the top of the page.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com