Heart of the matter - PET/CT scanning

On a warm July day, Merneptah, king of upper and lower Egypt, exalted by the strength of Horus, and dread of the Nine Bows, the Libyans and the Israelites, was laid upon a slab to have his innards examined. After carefully removing the delicate shroud wrapped around the pharaoh’s body, archaeologist Grafton Elliott Smith discovered that most of the internal organs had been removed, apart from one. “I was able to recognise part of the heart pushed far up into the thorax, but still attached to the aorta,” wrote Smith in his 1907 account of the examination. On closer inspection, he found that the largest artery in the human body “was affected with severe atheromatous disease [and] large calcified patches being distinctly visible”.

The consensus among Egyptologists today is that Merneptah suffered from a debilitating form of atherosclerosis. Consisting of a build-up of calcium plaques and fatty deposits along the arterial walls of the patient, the Pharaoh’s case was not anomalous. Typically thought of as a modern disease tied to the diet and specific lifestyle of the patient, a study published in The Lancet in 2013 found that, of 137 mummies from across a wide sample size of cultures revealed, atherosclerosis was not uncommon among pre-industrial populations.

It has remained as such today, with the proviso that modern medicine has transformed heart disease from an unknown ailment into one of which the progress can be charted and, contingent on changes to one’s diet and lifestyle, reversed. Yet, our ability to predict the specific susceptibility of patients to cardiovascular problems remains limited. One of the most popular methods by which doctors chart the progress of heart disease – the cardiac stress test – provides, at best, a snapshot of arterial integrity, and although scanning techniques exist to provide more accurate prognosis, many have shied away from their use for fear of inflicting unnecessarily high doses of radiation upon patients. At the Intermountain Heart Institute in Salt Lake City, however, physician’s assistant Viet Le is hoping that advances in CT and PET scanning can complement existing stress testing procedures to provide long-term predictions for cardiac health.

Heartbreak hotel

Le’s interest in heart disease stems back to his days at medical school.

“I came out of the PA programme in 2004 and went directly into cardiology,” he recalls. “[In] occupational medicine, you read up on a lot of research to make determinations for causality and association of certain activities with injury. I thought it’d be nice to actually be on the creative end of that, and compile the information and the knowledge that others refer to. That’s what brought me back to research, and, in particular, cardiology.”

Le eventually wound up at Intermountain Heart Institute, in its cardiovascular research department. It was there that he came into contact with the facility’s PET/CT scanner, a hybrid nuclear imaging technology that allows for more accurate anatomical imaging. “We are unique in the sense that we scan more patients here using this machine than anywhere else in the US,” explains Le. “And I would say that, internationally, there’s probably no one else who does as many cardiac PET scans as we do on any given day.”

In March 2013, Le and his colleagues began to use the machine to detect the presence of calcium in the arteries of patients who had just undergone a standard cardiac stress test. They already knew that the detection of calcium was a good indication of plaque build-up, which if left unchecked could lead to a major cardiac event later on in life. Usually, however, doctors could only detect calcium using a SPECT scanner, which was widely considered to expose patients to excess doses of radiation. By contrast, a PET/CT imager allowed patients to experience a dose equivalent to their yearly intake of ambient radiation.

Le and his colleagues would take advantage of this fact by investigating precisely why a small number of patients who had received a positive result from their stress test went on to have major cardiac events within months. They suspected it had something to do with the basic modus operandi of the stress test itself. “In cardiology, we tend to look at atherosclerosis as important if it obstructs the arteries,” says Le. “So, we look at stenosis – the amount of narrowing – to the extent that we have identified a decrease in blood flow. That’s what a stress test is designed to do.”

There is, of course, a major drawback to this approach, something that Le likes to explain using a somewhat surreal analogy involving a man asked to walk to the end of a long corridor where cardboard boxes are falling from the ceiling at random, each respectively representing blood, the artery and calcium deposits. A standard cardiac stress test is the equivalent of measuring the ability of the man to walk to the end of the corridor.

The test is not overly concerned with how many boxes he has to kick out of his way, or how long it would eventually take for him to be buried alive by packaging.

Most of the time, patients simply aren’t briefed on these considerations, and, as such, they’re often jubilant if they receive a positive result at the end of their stress test. “They think they’re Superman,” explains Le. “[They think] they can eat anything now and they’ll never have an event. And time and time again, what we’ve seen is that people do have subsequent events, and then the lamentation is, ‘Why me? What happened? I passed my stress test and I was supposed to be invincible.’”

Le and his colleagues were eager to prove that these misconceptions could be easily avoided. “Stress testing won’t guarantee that you’ll never have obstruction in and around the heart from that point on,” he says. “I want to be able to tell them that, in the next year or in subsequent years, ‘You’ll be fine’ or ‘Hey, there’s something a little wonky here. We probably ought to do something.’”

Acute care

In the resulting study, conducted between 2013 and 2015, and presented to the American Heart Association last year, 658 men and women aged between 57 and 77, who had passed stress testing for blocked arteries, underwent a calcium scan, and were then monitored for any subsequent cardiac events. 33 subjects were discovered to have little or no calcification and would go on to have no cardiac events after their initial stress test and scan. However, another 31 who tested high for calcium in their arteries did go on to suffer a cardiac event within the span of a year.

This correlation, between calcification and the long-term risk of a heart attack or stroke, was mirrored in a previous study conducted at Intermountain that hadn’t used a PET/CT scanner. “It actually proved itself out in our Utah population among diabetics, in that if you had a coronary calcium [level] of zero, your event rate was very, very low within a follow-up period of six months. Now that we have a PET/CT machine at our disposal, which we know is highly sensitive; we can let people leave the ER with prognosis [of a cardiac event] for the rest of their lives.”

Broadly speaking, Le and his colleagues were encouraged by the knowledge that, by matching a calcium scan to a standard stress test, they had effectively uncovered a whole new diseased population. “The coronary calcium scan allows us to identify individuals who should, perhaps, have a full court press on their high blood pressure,” he explains. “[They] should be told, ‘Start exercising and watch your diet. We need to have a really serious conversation about lipid-lowering therapies.’ That way, we will recapture them before they leave the ER. Perhaps this [test] will identify individuals who should go to their primary care provider that week, or the following week, so that they can have that more in-depth conversation.”

Le admits there is still work to be done. Intermountain plans to expand the study to 1,500 individuals, and measure the overall amount of time that elapses between the scan and a cardiac event, instead of simply counting those who have had one occur within a 12-month window. “From my perspective, we’re now getting an idea of moving the paradigm from just looking at obstruction, where we know that arteriosclerosis is, by itself, a risk,” he explains. “And that is the disease that we’re looking at. Yet, simply defining coronary disease as whether you have an obstruction or not doesn’t make a lot of sense to me, because events occur in those that have a continuum of the disease.”

While on the face of it, Le and his colleagues have already provided compelling evidence as to the necessity of additional calcium scans on top of existing stress tests, there is one lingering doubt in the former’s mind that also compels the expansion of their original study. “I have to play devil’s advocate and dampen my enthusiasm just a little bit,” he admits. “The sticking point in this, indeed with any diagnostic imaging, is whether it will make a difference. Are we just identifying individuals who are going to have an event anyway, and will earlier and more aggressive medical therapy reduce the number of those events?”

Strangely, it’s a presumption that echoes back to the conclusion of the study on the presence of atherosclerosis in mummies published in 2013; namely, that humans could simply have a ‘basic predisposition’ to the disease. Moreover, calcification of the arteries cannot be reversed.

It may be the case that Le and his colleagues have just hit upon a way to provide a countdown. The next big challenge may just be to find a cure, he says: “We have perhaps sounded the alarm, but we want to be able to get people a solution as well.”