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PARIS -- Whether a person had chest pains resolved by angioplasty hinged on the nature, not the severity, of their presenting symptoms, an ORBITA-2 analysis showed.

Investigators found two groups more likely to benefit from percutaneous coronary intervention (PCI) for angina relief in stable coronary artery disease (CAD): those with Rose pattern angina (OR 1.9, 95% CrI 1.6-2.1) and those with guideline-based typical angina (OR 1.8, 95% CrI 1.6-2.1).

"Rose angina and typical angina are excellent predictors of the placebo-controlled efficacy of PCI," said Florentina Simader, MD, of Imperial College London, presenting the study's results at the annual EuroPCR meeting. Results were published simultaneously in the Journal of the American College of Cardiology.

Among study patients, 64% had Rose angina, as assessed by the Rose angina questionnaire. Rose angina describes chest pain – coming from within the sternum and/or within both the left chest and left arm – induced from walking flat or walking uphill, resulting in the person slowing down or stopping, with the pain subsiding within 10 minutes.

Meanwhile, criteria for typical angina were met in 66% of people. Typical angina is defined by chest discomfort induced by physical exertion that can be relieved by rest or nitroglycerin within minutes.

"In clinical practice, we frequently work backwards from the anatomical finding of coronary artery disease to a re-interpretation of the patient's symptoms through the lens of the stenosis. In this context any symptom, including shortness of breath, can be labelled as some variant of 'angina' or 'angina-equivalent' to make the case for revascularization," Simader's group wrote.

"However, the present study shows that if the nature of the symptoms does not fit Rose angina, and therefore may not be cardiac in origin, relief of a stenosis is unlikely to relieve symptoms beyond placebo," the group wrote.

The main report from ORBITA-2 had shown PCI's effectiveness reducing angina in stable CAD in the absence of antianginal medications. However, 59% of patients still had residual symptoms at 12 weeks despite complete revascularization with near resolution of ischemia, motivating investigators to search for responder subgroups.

"I think the case is closed. PCI does ameliorate ischemia and does improve symptoms ... Angina is not a trivial matter. It's disruptive and affects the psychology as well as the physical wellness of our patients," said session panelist Samir Alam, MD, of American University of Beirut, Lebanon.

However, citing the 80% of ORBITA-2 participants having single-vessel driven ischemia that was ameliorated by PCI but nearly 60% still having symptoms, Alam urged that the relationship between ischemia and symptoms be reconsidered.

Simader's group reported that shortness of breath and other symptoms were poor predictors of PCI's effectiveness for angina relief. Symptom severity and nature both did not correspond with anatomical disease severity or physiological severity of ischemia -- assessed with quantitative coronary angiography (QCA), stress echocardiography, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR).

Christina Lalani, MD, and Robert Yeh, MD, MSc, both of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, called this "another reminder of the limitations of our diagnostic tools."

"[G]reater focus on ascertaining the quality of patients' presenting symptoms, rather than on anatomical or physiological measures, could improve shared decision-making for patients with symptomatic CAD. Against a background of rapidly changing technology, an important solution may be found simply in taking more careful histories from our patients," they wrote in an .

Simader told the audience that her team remains unsure what was the driver of lingering symptoms in people without typical symptoms. "Perhaps it was because their symptoms weren't cardiac in the first place," she suggested.

ORBITA-2 was a double-blind trial with 301 people from 14 U.K. centers. Participants were people with evidence of ischemia in single and multivessel disease.

The cohort averaged 64, and 79% were men. Approximately 28% had diabetes. Nearly 60% were in Canadian Cardiovascular Society (CCS) class II, and nearly 40% in CCS class III.

Following 2 weeks of symptom assessment, patients then underwent stress echocardiography and treadmill exercise testing before reaching the randomization phase. Patients were randomized to PCI or a placebo procedure under conscious sedation. For the rest of the study, patients were asked to report their symptoms weekly on a dedicated smartphone app.

Participants started with a median 0.8 angina episodes per day. Median QCA diameter stenosis 61, stress echocardiography score 1.0, FFR 0.63, and iFR 0.78.

Chief among the study's limitations was its short follow-up.