Off Script: Phantom Hearts and the Elusive Nature of Angina

SAN DIEGO, CA—Many of us in interventional cardiology are drawn to the definitive black-and-white logic of our specialty. See significant, appropriate lesion; stent significant, appropriate lesion with the full belief that in doing so, we save lives and prevent suffering. Oftentimes, though, our simplistic frameworks fail us, and we sometimes face patients who simply do not fit in this world view. In a small but not insignificant proportion of the patients we care for, our angiograms fail to show lesions in patients with chest pain and our stents fail to take the chest pain away. In spite of the large body of literature describing clinical entities of chest pain without epicardial coronary disease, patients are frequently told “It’s not your heart, it’s in your head,” leaving both parties upset and dissatisfied.

Pain is very real on a personal level, but so far we have failed to establish an objective meter for it, having to rely primarily on self-reported pain intensity. The foundations of modern empiric medicine are heavily grounded in the Virchowian world-view of disease as visible, measurable pathology, and unmeasurable pain is anathema to this objective, grounded approach. Pain syndromes such as fibromyalgia, irritable bowel syndrome. and anginal syndrome X continue to be a source of frustration, disappointment, and nihilism for many of us who practice clinical medicine and a phantom menace for those who suffer the pain itself. Two trials presented as late breakers on the last day of TCT 2018 will hopefully help us to shed light into this shadowy corner of clinical practice.

Chasing Angina in ABSORB IV

The results of ABSORB IV, designed to further the cause of the struggling first-generation Absorb bioresorbable vascular scaffold (BVS; Abbott), offered us something potentially more meaningful, namely, some interesting insights into angina. In order to conclusively test the hypothesis that a BVS would result in less angina compared to a rigid, metallic stent (an observation from ABSORB II, but not ABSORB III), investigators went to exquisite lengths to ensure suppression of any psychological placebo effect of the perception that they had “special treatment” with the new “special stent.”  More than 2,600 patients were randomized, and comprehensive measures undertaken to guarantee patients were truly blinded to their treatment allocation, including the use of headphones playing music during the procedure and follow-up by a physician without knowledge of the original procedure. Extensive, standardized angina questionnaires were issued after the fact and testing of the effectiveness of masking was performed in both groups, proving that the masking was effective.

Despite what would be presumed to be full revascularization, and accounting for repeat revascularization, 20% of all patients in both arms still had angina, a common finding in PCI trials. One other finding also struck me as interesting: at the end of a year, in the 17% of patients who felt they knew what type of stent they had received, 85% felt they had received the “special” device—the BVS—whether or not they were treated with a regular drug-eluting stent or the BVS.  

CorMicA: Hope for Syndrome X?

ABSORB IV was followed by a fascinating, first of its kind randomized trial, CorMicA, in which patients with angina, most of whom had positive stress tests, were enrolled if they had no significant epicardial coronary artery disease on coronary angiography or fractional flow reserve testing. In the study, sponsored by the British Heart Foundation, all patients underwent objective, standardized coronary microvascular and vasoreactivity testing, but only half were randomized to have the results shared with their treating teams. Strikingly, only 12% of patients were free of objective abnormalities and almost 90% had objective evidence of either microvascular, vasospastic, or mixed angina.

Using knowledge of the objective findings, the patient’s cardiologist and primary care physician applied the European Society of Cardiology guidelines on the treatment of angina without epicardial coronary artery disease, which notably recommends against the use of beta-blockers in vasospastic disease. In contrast, there is an absence of specific guidelines for therapy of similar patients in the American College of Cardiology guidelines and many of these patients may have simply been classified as “syndrome X patients.” This strategy resulted in significant improvements in anginal scores at 6 months, patient (and undoubtedly physician) satisfaction, and quality of life.

The study lays the groundwork for much to come in what will likely be a field that will grow with renewed interest. Should index of microcirculatory resistance (IMR) testing be more widespread? Should we resume pharmacological provocative vasospastic testing on a regular basis? How important will it be to subcategorize patients with “angina without epicardial coronary disease,” and what implications will this have on choice of therapeutic protocols in their anticipated efficacy and avoidance of specific agents? Should we consider testing in patients treated with PCI who have persistent angina—can patients have both?

Many questions remain, but it appears we may be starting to exorcise some demons.