Natural history of ischemia with no obstructive coronary disease ‘ebbs and flows’
Ischemia with no obstructive coronary artery disease (INOCA) is common, comprising approximately 20% of participants with moderate or severe ischemia screened in the recent International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial. A new analysis of people who were screened for ISCHEMIA but did not qualify for inclusion because they had less than 50% stenosis on coronary angiography finds that their symptoms and stress test results change over time in the absence of any intervention.
The ancillary study to ISCHEMIA, known as Changes in Ischemia and Angina over One year among ISCHEMIA trial screen failures with non-obstructive coronary artery disease on CT angiography (CIAO-ISCHEMIA), demonstrated that the change in symptoms and the change in ischemia on their stress tests did not necessarily correlate, according to lead investigator Harmony R. Reynolds, MD, from the Sarah Ross Soter Center for Women’s Cardiovascular Disease at NYU Langone Health, New York City.
CIAO-ISCHEMIA enrolled 208 people who were screened for the ISCHEMIA trial but were found to have INOCA.
Angina frequency, as assessed by the Seattle Angina Questionnaire (SAQ AF), and ischemia were quantified at baseline and after 1 year, and were compared with those from the 865 patients enrolled in ISCHEMIA who had a stress echocardiogram and obstructive coronary artery disease (CAD) on coronary computed tomographic angiography. At baseline, the two groups of patients had similar amounts of ischemia on their stress tests.
INOCA patients in CIAO were far more likely than patients in ISCHEMIA to be female (66% vs 26%), consistent with findings from previous studies (P < .001). They were also less likely to have diabetes (19% vs 33%; P < .001), a prior myocardial infarction (2% vs 15%; P < .001), less likely to be current or former smokers (41% vs 56%; P = .001), and more likely to have a history of depression (19% vs 9%; P < .001).
Indications for stress testing in the INOCA patients were typical angina in 50%, atypical chest pain in 32%, and shortness of breath in 49%, with some overlap between indications. On stress echocardiography at enrollment, participants had a median of 4 ischemic segments. Some 44% of CIAO participants with INOCA and 58% of those enrolled in ISCHEMIA had anterior ischemia (P < .001).
The median SAQ AF score was 90 in patients with INOCA at enrollment compared with 100 in those with CAD at enrollment. CIAO participants with INOCA had more frequent angina; 14% of these patients had weekly angina weekly and 2.5% had daily angina, compared with 3.6% and 0.6%, respectively, among those in ISCHEMIA. CIAO patients were also more likely to have angina in the previous month; 41% of CIAO patients with INOCA reported no angina in the previous month compared with 62% of ISCHEMIA patients with CAD.
At 1 year, in patients in CIAO, stress echocardiograms normalized in 50% of patients, and in 45% they were unchanged from baseline or worse. Angina symptoms improved in 42% and worsened in 14% and angina frequency improved by a clinically meaningful amount, defined as at least a 10-point improvement on the SAQ AF, in 39% of patients with INOCA, said Dr. Reynolds. Weekly angina was present in 7.6% at 1 year (compared with 14% at enrollment) and daily angina was present in 0.5% (compared with 2.5% at 1 year). The median number of antianginal medications was one at enrollment and at 1 year.
No correlation was found between 1-year changes in ischemia and angina, the primary endpoint of the study.
“There’s always the hypothesis that maybe plaque is diffuse and that is explaining the appearance of no obstructive disease [in patients with INOCA], but here we have CT so we are not just seeing the lumen but we’re seeing the wall,” said Dr. Reynolds.
The take-home message is that “there’s a lot of variability in symptoms and ischemia in these patients over time,” she said. “I believe that they probably came to medical attention and therefore got enrolled in ISCHEMIA because they were at a time when they were most symptomatic. We know that coronary flow reserve can change over time, and that spasm is inherently variable. I think there’s just an ebb and flow in the symptoms for these patients and in the stress test findings, and that is one of the challenges of taking care of them.”
CIAO-ISCHEMIA was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Reynolds disclosed, Research/Research Grants: Abbott Vascular, BioTelemetry Inc.