Questions grow about the need for cardiac stress tests

The pandemic quieted stress-test treadmills and heart catheterization suites, which for decades have been part of a growing enterprise seeking to detect and treat heart disease. Yet everywhere over the past couple of months, such elective tests and procedures, prescribed by doctors for stable patients, were put on hold, deferring them until we had the virus under control.

But in April the world of testing and interventions in cardiology shifted, perhaps permanently. As all attention was directed toward the pandemic, the New England Journal of Medicine published an exceptionally important study that might reset everything about the future of how we detect and treat heart disease.

Although it was published to little fanfare as all eyes focused on news about covid-19, the disease caused by the novel coronavirus, the study will probably change cardiology. The study found that many people with heart artery blockages that restrict blood flow during stress testing did not live longer, or avoid future heart attacks, after they got procedures to characterize and improve that blood flow. This finding throws into question the value of doing screening tests as a way to identify people who should undergo these procedures, which has been a common, but in recent years increasingly debated, approach.

Heart attacks most commonly occur when the blood flow to the heart is suddenly interrupted. When people have a heart attack from a suddenly blocked artery, we cardiologists know that treating them quickly with medications or procedures to open the artery and restore the blood flow can save their life. We even know that doctors can avert damage to the heart if they treat people quickly enough, which could be within 30 minutes of the onset of pain. One of the great breakthroughs in the past 20 years is the ability to reduce the damage and risk of heart attacks with such rapid intervention.

For people who are not in the midst of a heart attack, but who had a positive stress test showing inadequate blood flow or an imaging test showing narrowed arteries — the conventional wisdom for many years was that those narrowed arteries should be opened — and that evidence of compromised blood flow to the heart, what we call ischemia, needed to be addressed.

It made sense. If you had blockages that compromised blood flow with exertion, you would be better off with a procedure that unclogged the arteries. This logic led to doctors to order increasing numbers of stress tests to detect ischemia and cardiac procedures to open blockages or bypass them. The idea was that these blockages represented impending heart attacks — and that the ischemia was damaging the heart.

This approach made an industry of screening for heart artery blockages and reduced blood flow. Doctors treated heart ischemia like Smokey Bear treated abandoned campfires — something to be found and extinguished. Even the slightest indication of ischemia — or even just risk factors such as high cholesterol or high blood pressure — might precipitate a referral for a stress test and then procedures even for people without symptoms. As more advanced nuclear imaging spread, doctors sought to use increasingly sensitive imaging tests to ensure that ischemia would not be missed.

As the intensive attention toward the detection and elimination of ischemia grew, the science began to reassess this mental plumbing-like model of the heart as having pipes — with the idea that when pipes become blocked, we need to open them. Yet, evidence started to indicate that propping open arteries as a preventive measure in people who were not experiencing a heart attack might not produce much benefit.

The issue is important because all the invasive cardiac interventions also have risks and costs — and in many cases, require people to take medications that can also cause problems.

As early as 1988, as the notion of opening arteries was gaining traction, John Ambrose, a cardiologist then at Mount Sinai in New York, and colleagues made a seminal observation that rocked the cardiology community.

They studied people who had an examination of their heart arteries before and at the time of a heart attack. They found that the heart attack often did not occur where the blockages had been most severe. They often occurred in places where the artery was previously quite open. The finding threw into doubt the idea that opening narrowed arteries might prevent heart attacks.

Several studies that followed reinforced the concern that, for stable patients, opening blocked arteries had little value — although the findings did not have a dramatic effect on medical practice.

In 2007, the COURAGE trial reported the results of a study of over 2,000 people with ischemia. They randomly gave study participants the best medical therapy at the time, which included statins and other effective drugs alone or in combination with a procedure to place a stent and open the blocked arteries. They found that the procedure failed to reduce the risk of death or heart attacks of other heart events. In the more recent 2018 ORBITA study, the opening of blockages with stents did not even increase exercise time.

These prior studies were a prelude to the larger 2020 ISCHEMIA trial reported in the New England Journal of Medicine in March. Funded by the National Institutes of Health, the investigators randomized more than 5,000 people with moderate or severe ischemia to medical therapy or a procedure to evaluate the heart arteries and to address blockages.

They studied people whose stress test indicated inadequate blood flow to their heart and a further imaging test showed blockages of the heart arteries. They excluded the few people with a narrowing of the main heart artery because it is known that these people do better with a procedure to improve blood flow.

What they found was that, with more than three years of follow-up, the procedure strategy did not decrease the risk of death or heart attacks compared with the best medical therapy alone. The only benefit accrued to those with the most symptoms — and they had a modest reduction in angina, the chest discomfort that sometimes accompanies ischemia.

There is still some controversy, with stalwarts holding onto to older beliefs. Nevertheless, all seem to agree that people with mild or no symptoms experienced no substantive benefit, even if other tests indicated that their heart had compromised blood flow.

Now, the pandemic has forced a change in practice, at least for the past few months. Some people have deferred needed tests. But there may be others who tests may no longer be useful. In the midst of one the most dramatic reversals of practice that we have seen in a long time, there may be an opportunity to improve clinical care. There are still some reasons for stress testing and procedures for stable patients, such as determining risk levels or diagnosing the cause of chest pain, but the ISCHEMIA trial, if we act on the evidence, should reduce the use of treadmills and other testing that were previously done on many patients as a glidepath to procedures.

The pandemic may have led the publication of the ISCHEMIA trial to be underreported (and to be fair, the investigators released the preliminary findings last November), but ultimately this trial should have an enduring groundbreaking effect. As a result, those quiet treadmills may never return to their prior level of use — and that may be a good thing to come of the pandemic.

Harlan Krumholz is the Harold H. Hines Jr. professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research and Evaluation, one of the nation’s first research units dedicated to improving patient outcomes and promoting better population health.

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