A 65-year-old woman with medical history of smoking, myocardial infarction, hypertension, chronic obstructive pulmonary disease, and migraine is evaluated in the clinic for anginal chest pain. The patient reports episodic chest pain that is retrosternal and radiates to the jaw for the last 4 months. The pain is mostly exertional but sometime occurs without clear triggers. Each episode usually lasts up to 20 minutes before spontaneous resolution. She had an anterior ST-segment elevation myocardial infarction 2 years before, and the coronary angiogram then showed subtotal occlusion of the mid left anterior descending artery (LAD), which was revascularized with a drug-eluting stent. A subsequent echocardiogram showed normal left ventricular ejection fraction with no wall motion abnormalities. Her current medications include aspirin 81 mg daily, carvedilol 6.25 mg twice daily, lisinopril 10 mg daily, isosorbide mononitrate 30 mg daily, and rosuvastatin 20 mg daily.
On examination, her body mass index is 31 kg/m2, heart rate is 72 bpm, and blood pressure is 135/85 mmHg. Cardiovascular examination discloses normal first and second heart sounds with no rubs, gallops, or murmurs. The rest of examination is unremarkable. An electrocardiogram (ECG) in the office shows normal sinus rhythm and no ST-T wave abnormalities. An ECG done during an emergency department visit for chest pain showed a normal sinus rhythm with T-wave inversions in leads V4-V6. The patient was then referred for invasive coronary angiogram, which showed a patent stent in the mid LAD with no evidence of obstructive coronary artery disease (CAD) in the other coronary arteries. Given the nature of her symptoms, as well as risk factors, provocation testing with intracoronary acetylcholine was done, during which the patient experienced similar anginal chest pain but without any significant epicardial coronary spasm on angiography.
Which, if any, of the following tests is most likely to be abnormal in this patient and provide additional prognostic information?
Show Answer
The correct answer is: C. Assessment of coronary flow reserve (CFR)
This patient has angina with nonobstructive coronary arteries (ANOCA), a disease entity that is increasingly recognized. It is estimated that almost half of all patients with stable angina will have nonobstructive CAD on coronary angiography and thus fall under this entity, with a higher prevalence in women compared with men.1,2 The pathophysiologic mechanism seems to be related to abnormal coronary vasomotor tone, whether due to transient pathological constriction (coronary spasm) or impaired microvascular vasodilation (impaired CFR). Prior research had established that the presence of epicardial CAD is associated with the presence of coronary microvascular dysfunction (CMD).3 According to the Coronary Vasomotor Disorders International Study Group, the criteria to diagnose ANOCA are
symptoms of myocardial ischemia,
absence of obstructive CAD,
objective evidence of myocardial ischemia, and
evidence of microvascular dysfunction.4
In this patient, provocation testing with intracoronary acetylcholine showed no epicardial coronary spasm but reproduced her symptoms, making it most likely that she has an element of CMD. And ECG at the time of symptoms demonstrated ischemic changes.
Evaluation for CMD can be done invasively during coronary angiography or noninvasively using different imaging modalities (positron emission tomography, magnetic resonance imaging, CT angiography, and transthoracic Doppler of the LAD artery). Invasive evaluation remains the gold standard to evaluate for microvascular dysfunction. This evaluation could be done by injection of a provocative agent into a coronary artery and by evaluation of CFR. Thus, answer C is correct. Identification of abnormal CFR (<2.0-2.5 based on modality used for assessment) can aid in risk stratifying the patient for future cardiovascular events.
CT coronary angiography will likely be abnormal in this patient with known CAD and a prior percutaneous coronary intervention. However, invasive angiography, which provides a more accurate anatomical assessment of the coronary arteries, was already performed. Therefore, findings of CT coronary angiography will not provide additional prognostic information than what is already known, and so answer A is incorrect.
Echocardiogram performed after the acute myocardial infarction and revascularization showed normal left ventricular ejection fraction with no wall motion abnormalities. Despite the patient's current anginal symptoms, there were no significant epicardial coronary arterial lesions. Also, she does not have any symptoms of heart failure. It is unlikely that the echocardiogram would be abnormal, and so answer B is incorrect.
Answer D is incorrect because studies have shown substantial morbidity and mortality in patients with coronary vasomotor disorders.5-8
Lastly, iFR uses pressure wire passed down an epicardial coronary artery to measure the pressure ratio across intermediate lesions and helps guide the decision to intervene. In this patient, however, the LAD was clearly patent on coronary angiogram without suspicious or intermediate lesions. Therefore, answer E is incorrect.
References
Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med 2010;362:886-95.
Murthy VL, Naya M, Taqueti VR, et al. Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation 2014;129:2518-27.
Rubinshtein R, Yang EH, Rihal CS, et al. Coronary microcirculatory vasodilator function in relation to risk factors among patients without obstructive coronary disease and low to intermediate Framingham score. Eur Heart J 2010;31:936-42.
Ong P, Camici PG, Beltrame JF, et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol 2018;250:16-20.
Bairey Merz CN, Handberg EM, Shufelt CL, et al. A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve. Eur Heart J 2016;37:1504-13.
AlBadri A, Bairey Merz CN, Johnson BD, et al. Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women. J Am Coll Cardiol 2019;73:684-93.
Bajaj NS, Osborne MT, Gupta A, et al. Coronary Microvascular Dysfunction and Cardiovascular Risk in Obese Patients. J Am Coll Cardiol 2018;72:707-17.
Taqueti VR, Shaw LJ, Cook NR, et al. Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease. Circulation 2017;135:566-77.
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