SAN DIEGO – Don’t be satisfied with a diagnosis of angina with no obstructive coronary artery disease; push for acetylcholine testing, the findings from a trial in Scotland suggest.

Going a little further with an acetylcholine challenge in the cath lab will usually uncover microvascular or vasospastic heart problems, and this can lead to appropriate treatment. Patients will have less angina and a better quality of life at 6 months, according to investigators from the University of Glasgow (Scotland).

Invasive angiography usually ends on both sides of the Atlantic when no occlusions are found. There are concerns about the safety of going further with acetylcholine challenges, and until now, there had been no grade A evidence from a randomized trial that it improves outcomes. The Glasgow team filled the evidence gap with their presentation of the Coronary Microvascular Angina (CorMicA) trial at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, and there wasn’t a single serious adverse event (J Am Coll Cardiol. 2018 Sep 25. doi: 10.1016/j.jacc.2018.09.006).

“This was a proof-of-concept study, which we believe [should] substantiate a large, multicenter trial,” said senior investigator Colin Berry, PhD, a professor of cardiology and imaging at the university.

Acetylcholine was infused down the pressure wire in 151 subjects diagnosed with angina with no obstructive coronary artery diseases before they left the catheter lab. Of these patients, 76 were randomized to have their results shared with their treating cardiologist, and 75 were randomized to not have their results shared. Coronary functional testing is hardly ever done, so the no-share group was considered the standard-of-care control arm. The idea was to see whether it made a difference when treating physicians knew what was causing chest pain when their patients didn’t have occlusive disease.

It turned out to make a huge difference. The diagnosis of “chest pain of noncardiac origin” almost fell off the map. Once cardiologists knew what was going on, they switched up treatment according to European Society of Cardiology guidelines for functional heart pain. Patients with microvascular angina were given beta-blockers and switched off nitrates because these drugs make angina worse in microvascular disease. Subjects with vasospasms were shifted to calcium channel blockers and long-acting nitrates and away from beta-blockers because beta-blockers make vasospasms worse.

Cardiologists who didn’t know the results kept muddling along with what patients came in on at baseline – beta-blockers in two-thirds, long-acting nitrates in half, and calcium channel blockers in a third.

Subjects who got the right treatment because of acetylcholine testing outpaced the standard care group by almost 12 points on the Seattle Angina Questionnaire at 6 months; they could walk farther and didn’t have crushing angina almost every day (P = .001). They reported a statistically significant improvement in quality of life, and they were much happier with their doctors.

“This is the first randomized, sham-controlled trial in this space”; functional testing “was routinely safe and feasible. Therapy guided by the results of physiologic testing improved outcomes” and “treatment satisfaction,” said University of Glasgow interventional cardiologist Tom Ford, MD.

Acetylcholine was infused down the pressure wire into the radial artery, with the left anterior descending coronary artery as the target vessel. A final bolus of less than 100 mcg checked for coronary artery spasms; a symptomatic constriction of greater than 90% was considered positive. Glyceryl trinitrate was used to reverse the effects.

Three-quarters of the subjects were women, which Dr. Ford noted is unusual in an angina study. The mean age was 61 years, and subjects had about a 20% chance of a heart attack within 10 years. The whole procedure, including the angiogram, randomization, and functional testing, took a median of about 60 minutes.

There were no differences in major adverse cardiac events at 6 months, at 2.6% in both groups.

One patient developed persistent atrial fibrillation with acetylcholine testing that was converted to sinus rhythm with intravenous amiodarone, without a night in the hospital.

The work was funded by the British Heart Foundation. No companies were involved. The investigators didn’t have any relevant disclosures. The TCT meeting is sponsored by the Cardiovascular Research Foundation.