By Ariaratnam Gobikrishna –

Ariaratnam Gobikrishna MD

“I aced the test with flying colors” is a phrase we hear often from patients when asked about their understanding of prior stress tests or cardiac catheterizations. While this impression may occasionally be accurate, in many cases it is misleading—if not entirely incorrect. The misunderstanding arises partly from the nature of the tests themselves and partly from how results are often communicated at the end of the procedure.

The consequence is predictable. Patients may come away believing their hearts are entirely healthy and, reassured by this perception, may ease up on medications or lifestyle changes. At times, clinicians too may become less aggressive with preventive care, especially when a patient’s short-term risk appears modest.

The key issue is this: these tests are designed to find major blockages, not early or moderate disease. A stress test usually becomes abnormal only when an artery is narrowed by about 50 percent or more, and in many cases closer to 70 percent. Likewise, a catheterization may be described as “normal” if there are no severe blockages requiring a stent or surgery, even though significant plaque build-up is often present. These plaques may remain silent for years, but they can still grow or suddenly become unstable, rupture and cause heart attacks.

In fact, more than 70% of heart attacks arise from plaques causing less than 50% blockage. Before a major heart attack, these plaques often undergo repeated cycles of rupture and self-healing, with each cycle leaving behind scar tissue that gradually enlarges the plaque to more than 70% blockage. A major heart attack occurs on the day this self-healing process fails completely. Notably, this often happens at rest, contrary to the common belief that cardiac chest pain coinciding with a major heart attack occurs with exertion or significant emotional stress.

When we say “healing,” this refers to the body’s urgent effort to dissolve the clot that forms at the site of plaque rupture. During this phase, most patients remain symptom free, but some may experience vague, non-specific symptoms—feeling unusually tired, unwell, nauseated, or simply “not themselves.” If the body successfully dissolves the clot, a major catastrophe is averted. Even if a stress test is performed soon after, the results may appear normal.

On the other end of the spectrum, even for those whose arteries we might consider severely narrowed (>70%), stress tests are not foolproof. To start with, there are practical limitations to the different types of stress testing. Not everyone is able to walk long enough or fast enough on a treadmill to adequately stress the heart. For those who cannot walk at all —an increasingly large portion of the population for a variety of reasons—medications are given through a vein to simulate stress. These medications either make the heart beat faster or widen the healthy blood vessels, directing more blood through them, so that areas supplied by narrowed arteries receive relatively less blood. Consequently, the areas supplied by those narrowed arteries appear sluggish on imaging, making the test abnormal. While helpful and effective in theory, this is not the same as natural exercise and can often produce less reliable results. Unfortunately, more and more stress tests are now performed this way. In addition, technical challenges during imaging and differences in how results are interpreted can further add to the uncertainty.

For these reasons, a normal stress test or a “clean” catheterization should not be taken as a clean bill of health. It simply suggests that there is probably no major blockage at that moment.

If stress tests and EKGs are not sufficient for early detection, then what should we rely on?

Even before modern coronary CT scans (CCTA) became widely available, a physician in Florida—Arthur Agatston—helped shape two important approaches to cardiovascular disease — prevention and early detection. He is widely known for developing the South Beach Diet, and also for introducing the coronary calcium score, a tool that helps detect atherosclerosis before symptoms appear.

The South Beach Diet emerged from his clinical observations that American low-fat, high-carbohydrate diets were not producing the desired cardiovascular improvements in his patients. In response, he proposed a more balanced approach that emphasizes reducing refined carbohydrates and sugars while encouraging healthier fats, lean proteins, and fiber-rich foods.

In parallel, Agatston contributed to the development and popularization of coronary calcium scoring. A coronary calcium scan is a simple CT scan of the chest that detects calcium deposits in the coronary arteries. These deposits represent cholesterol that has been present long enough to harden. The computer then calculates a score based on the amount of calcium present.

This information can be very useful. In younger individuals, the presence of calcium is concerning, as it suggests early atherosclerosis. In older individuals, the absence of calcium is reassuring. However, a zero score does not completely rule out disease, because cholesterol buildup is a dynamic process, and so-called “soft plaques” may still be present but not yet calcified. These soft plaques are, in fact, more dangerous, as they are more prone to rupture and cause heart attacks. Because this test cannot detect them, the conventional assumption is that a higher calcium score reflects a greater overall plaque burden, including the likely presence of more soft plaques. Moreover, certain groups—such as younger individuals, women, and those with diabetes—tend to harbor relatively more soft plaques at any given calcium score. As coronary artery disease remains the leading cause of death, there is growing consensus that every chest CT scan, done for any reason, should, by default, include AI-assisted detection and reporting of coronary artery calcium.

Building on this, Coronary Computed Tomography Angiography (CCTA) takes things a step further. With the use of injectable contrast dye, it provides a detailed look at the coronary arteries. It can show how much plaque is present, whether it is “soft plaque” or calcified, whether it is narrowing the artery and, if so, whether it may require a stent, and in some cases whether it has features that suggest higher likelihood of rupture. There are still technical challenges. Heavy calcification can sometimes make arteries appear more narrowed than they truly are—a phenomenon known as “blooming.” However, advances such as photon-counting CT are improving image clarity and helping to overcome these limitations. In addition, AI-assisted CT-derived fractional flow reserve (CT-FFR) can help determine whether a severe narrowing truly requires stenting and may, in time, help address the longstanding criticism that coronary CT angiography leads to too many invasive catheterizations. Moreover, this technology doesn’t just look at the coronary arteries—it evaluates the heart as a whole, including chamber size, the pericardium for fluid, and the major vessels for aneurysms. It also looks beyond the heart, picking up lung abnormalities (especially in smokers), fatty liver, and even obvious bone thinning.

Taken together, these advances are reshaping how we detect coronary artery disease, often allowing for earlier and more direct assessment than traditional stress testing. Conventional stress tests—particularly those using nuclear imaging—carry the additional drawback of radiation exposure and, in some cases, may involve higher doses than contemporary CT-based techniques. The most commonly used nuclear modality, Single Photon Emission Computed Tomography (SPECT), not only delivers relatively higher radiation but also provides suboptimal anatomical detail—talk about a double whammy.

That said, nuclear stress testing continues to play an important, albeit limited, role. It remains particularly valuable in patients with significant kidney disease who cannot safely receive the contrast agents required for CT imaging. In situations where CT image quality is compromised—such as in individuals with morbid obesity—Positron Emission Tomography (PET) offers a distinct advantage, providing superior image quality with lower radiation exposure than SPECT.

For those who have had the misfortune of dealing with cancer, PET is often a familiar technology. By using radiolabeled sugars—most commonly fluorodeoxyglucose (FDG) —PET imaging detects areas of increased metabolic activity, allowing sites of cancer involvement and spread to “light up” on the scanner. This same technology can be applied in cardiology. When evaluating blood flow to the heart during stress test, a different tracer—rubidium—is usually used instead of FDG.

However, PET imaging is not without its limitations. High cost, limited availability, and the logistical challenges of handling special radioactive isotopes make these studies less accessible and more cumbersome to perform. The ultra–short half-lives of commonly used PET tracers also preclude true exercise-based protocols, often necessitating pharmacologic stress, with its limitations as already discussed. The use of PET to assess whether heart muscle is still alive (not scar tissue )before heart bypass surgery has also fallen out of favor, largely because major clinical trials have not shown benefits.

Overall, its role in cardiology—particularly in the evaluation of coronary artery disease—is limited, much like its counterpart, SPECT. There are, however, important exceptions. PET can be useful in detecting abnormalities in the heart’s smallest blood vessels—the tiny branches that penetrate deep into the myocardium. This so-called “microvascular disease”—more academic than actionable, yet one that bodes poorly for patients—is something coronary CT angiography cannot reliably detect. Meanwhile, SPECT has seen a resurgence in the diagnosis of ATTR amyloidosis, ( one of many causes of a stiff heart) although the details are beyond the scope of this article.

As you can see, we have come a long way, though the path has not always been straightforward. Yet we are moving in the right direction, with steady advances in the direct imaging of the coronary arteries—the very vessels at the center of the leading cause of death.

Conventional testing prior to the advent of CCTA often operated under the implicit assumption that what was not seen did not exist. Stress testing—whether a treadmill exercise test, nuclear SPECT or PET, or a stress echocardiogram—by design detects only flow-limiting disease and therefore misses nonobstructive cholesterol deposits. Similarly, cardiac catheterization may fail to identify plaque-laden arterial walls unless lesions produce luminal irregularities that are conspicuous along the path of the injected dye. This limitation is further compounded by the infrequent use of intravascular imaging from the tip of the catheter, such as ultrasound or near-infrared light (IVUS/OCT), which can magnify and reveal the different stages of cholesterol buildup and the vulnerability of plaques to rupture within the coronary arteries.

As a practicing physician, and as someone with a strong family history who lost both parents to this disease after long battles, I find myself seeking clarity.  In my view, we are still only scratching the surface, with far too many unknowns. But one thing is clear: unless we actively look for harmful changes in the coronary arteries with the tools currently available, we risk being falsely reassured by what we fail to see. In coronary artery disease, what we fail to see is often what proves deadly.