Changing Strategy: Edging Stable Chest Pain Diagnosis Out of ‘a Primitive Age of Evidence’

Four million stress tests are conducted each year on patients with stable chest pain, and yet the cardiology community has reached little consensus about how best to identify patients who will benefit from a trip to the cath lab. That may be changing, however, as cardiologists consider new data indicating the value of coronary computed tomographic angiography (CCTA) for diagnosing these patients.

Diagnostic dilemma

Cardiologists have long struggled with the thorny problem of evaluating chest pain. In general, the physicians “do not do very well in having the right patient go to the cath lab with the underlying diagnosis of suspected coronary artery disease [CAD],” says Ralph G. Brindis, MD, MPH, clinical professor of medicine at the University of California, San Francisco, and senior medical officer of external affairs at the American College of Cardiology (ACC) National Cardiovascular Data Registry.

The root of the diagnostic dilemma is lack of evidence. Only about 1 percent of the more than 700 recommendations related to cardiovascular imaging in ACC/American Heart Association guidelines are classified as Class I Level of Evidence A because relatively few large, randomized, controlled trials have examined the issue. One recent study found only a weak correlation between most noninvasive diagnostic tests and the likelihood of obstructive CAD (Am Heart J 2014;167[6]:846-852). The researchers reported that about 58 percent of patients who had elective angiography did not actually have obstructive CAD.

Cardiologists are in “a primitive age of evidence when we talk about stable chest pain,” Valentin Fuster, MD, PhD, said in a Journal of the American College of Cardiology

audio-commentary on an article reviewing the implications of SCOT-HEART and PROMISE, the two largest and most comprehensive cardiovascular imaging trials of stable angina (2016;67[7]:843-52). Fuster underscored the review author’s conclusion: “Both trials show that coronary computed tomography angiography should have a greater role in the diagnostic pathway of patients with stable chest pain.”

Clearer pathway with CCTA?

The SCOT-HEART (Scottish COmputed Tomography of the HEART) trial compared the effectiveness of CCTA along with usual care with conventional stress testing alone (usually including exercise electrocardiography) to evaluate suspected angina due to coronary heart disease (Lancet 2015;385:2383-2391). The investigators found that adding information obtained from a 64-slice CCTA to standard clinical care clarified the diagnosis of angina due to coronary heart disease. The strategy resulted in reduced need for further stress testing and a modest net increase in the use of invasive coronary angiography. Event rates were low in both arms of the trial. At 20 months, there was a 38 percent reduction in cardiovascular death and nonfatal myocardial infarction (MI) in the CCTA arm compared with standard care, but the finding was not statistically significant.

The PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) trial randomized 10,003 patients who had symptoms suspicious for significant CAD that required non-emergent noninvasive testing to either an anatomic strategy using 64-slice CCTA or a functional strategy that included exercise electrocardiography, exercise or pharmacologic nuclear stress testing, or stress echocardiography (N Engl J Med 2015;372:1291-1300). The investigators found no significant differences in outcomes related to death, MI, unstable angina or major procedural complications between patients randomized to the initial anatomic strategy vs. the functional testing strategy. Use of the initial CCTA strategy was associated with fewer catheterizations showing no obstructive CAD when compared with catheterizations performed on patients in the functional testing groups.

In statements issued after the PROMISE and SCOT-HEART trials were presented at the ACC.15 Scientific Sessions, Ricardo C. Cury, MD, then-president of the Society of Cardiovascular Computed Tomography (SCCT), said, “PROMISE appears to demonstrate that coronary CTA uniquely identifies patients who have non-obstructive atherosclerosis and who will benefit from medical therapy” and “SCOT-HEART demonstrated that CCTA provided a clearer and more precise diagnosis of coronary heart disease [compared with conventional stress testing], reclassifying the diagnosis in one of every 4 patients.”

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Cost & radiation tradeoffs?

Also at the ACC.15 Scientific Sessions, Daniel B. Mark, MD, MPH, professor of medicine and vice chief for academic affairs at Duke University Medical Center, presented a PROMISE economic substudy comparing initial testing costs per person (based on costs in the Premier database) plus Medicare reimbursements for physician fees for each of the diagnostic imaging tests. At a total of $404, CCTA was more costly than an ECG-only stress test but less costly than echocardiography with either pharmacologic stress or exercise stress or than nuclear imaging with either exercise stress or pharmacologic stress.

In the PROMISE trial, using CCTA increased costs by a small, statistically nonsignificant amount when compared with a functional diagnostic testing strategy. Calculation of the cumulative total costs by intention to treat and mean cost difference showed that the total costs for CCTA ranged from $279 higher than functional testing at three months to about $694 higher at 36 months. One reason, Mark says, was that more patients in the CCTA arm underwent invasive catheterization and revascularization. In contrast, CCTA was associated with fewer catheterizations that found no obstructive CAD.

CCTA “may not be the ‘holy grail’ of diagnostic testing once hoped for, but its more liberal use following PROMISE standards will improve some aspects of care without causing a major new economic burden on the healthcare system,” Mark says.

In a white paper published by SCCT in late 2015, Kenneth Eric Stone, MD, a cardiologist at the Heart Clinic of San Antonio, reported that multiple peer-reviewed manuscripts have demonstrated cost savings and reduced downstream resource utilization when CCTA was used to evaluate low- to intermediate-risk, symptomatic patients with possible CAD (www.scct.org/tools/CT_WhitePaper_Nov2015.pdf).

The initial cost of a CT scanner is certainly high, but most hospitals already have invested in CT technology and most have 64-slice scanners. If more facilities turn to CCTA for evaluation of stable chest pain, there may be some workflow changes needed, but the overall staffing numbers should not change, according to Pamela S. Douglas, MD, director of the imaging program and professor of cardiology at Duke University Medical Center and principal investigator of the PROMISE trial.

In the past, concerns have been raised about whether the benefits of CT technology are overshadowed by concerns about radiation exposure. There has been “marked improvement in terms of radiation exposure over time, so now it is substantially less of an issue,” Brindis says. The mean radiation exposure of patients in the CCTA arm of the PROMISE trial was 0.7 mSv higher than that of patients who underwent functional testing. “There is a substantial amount of radiation with nuclear testing,” Brindis adds.

According to SCCT, the threshold for radiation exposure has dropped as CCTA systems have improved. In 2006, the threshold for low-dose exposure was 100 mSv. Current scanners deliver between 1 and 10 mSv, which SCCT says “is comparable to the average annual exposure in the US from natural sources (3 mSv)” and is “significantly less than that historically required for nuclear myocardial imaging (15-60 mSv) or invasive angiography.”

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CCTA plus?

Computed tomography with fractional flow reserve (FFRCT), another diagnostic strategy on the horizon, could “be close to giving us the total picture,” Fuster said in his JACC audio-commentary. By providing both functional and anatomic information about patients’ CAD, FFRCT allows cardiologists to analyze blockages detected by CT on blood flow. “Such an approach might become ideal in those patients with pre-testing, low-probability and/or coronary artery disease assumed to be at low risk,” Fuster said.

In the PLATFORM (Prospective Longitudinal Trial of FFRCT Outcome and Resource Impacts) trial, web-based FFRCT technology resulted in the safe cancellation of 61 percent of planned invasive catheterizations and a lower rate of catheterizations that found no obstructive CAD (Eur Heart J 2015;36[47]:3359-67). Speaking at the 2015 European Society of Cardiology Congress, Douglas—PLATFORM’s principal investigator—said the prospective data provided by the trial were “essential to evaluating and optimizing the role of noninvasive testing as a gatekeeper to catheterization.” 

FFRCT also might be a pathway to reduced costs. In an analysis of outcome and resource impacts in the PLATFORM trial, researchers compared resource utilization among the patients who received usual care vs. FFRCT -guided care. Among patients in a group planned for invasive coronary angiography, mean costs were $4,112 higher in the patients who underwent usual care vs. those who received FFRCT -guided care. The costs remained higher even when costs were calculated with FFR priced at seven times that of CCTA. In the patients planned to receive noninvasive usual care, costs were similar, at $2,329 for usual care vs. $2,833 for the FFRCT-guided care group (J Am Coll Cardiol 2016;67[13_S]:1589).

FFRCT is a “significant advance in the diagnosis and treatment of patients with stable chest pain, who previously may have been sent for unnecessary invasive testing to determine appropriate treatment pathways,” Douglas says. 

In light of the latest clinical trial data, some cardiologists have suggested that practice guidelines should be reexamined. The latest U.S. guidelines recommend exercise tolerance as the first diagnostic test of choice for diagnosing stable chest pain. CCTA is recommended only in patients who cannot undergo stress testing.

The strategies used to evaluate patients with chest pain may be changing, but Douglas thinks tests will always be used “side by side in different groups of patients and with different needs.” For example, she says, exercise testing allows physicians to derive “a picture from the treadmill, seeing what [a patient’s] exercise capacity is and whether or not you have reproduced their symptoms by that exercise.” That information cannot be obtained with CCTA. 

It’s unlikely, Douglas adds, that cardiologists will “ever be in a position to say one or the other is a better mouse trap and will replace or eclipse the other.”