Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why, How, and When

Thomas J Ford, Peter Ong, Udo Sechtem, John Beltrame, Paolo G Camici, Filippo Crea, Juan-Carlos Kaski, C Noel Bairey Merz, Carl J Pepine, Hiroaki Shimokawa, Colin Berry, COVADIS Study Group, Thomas J Ford, Peter Ong, Udo Sechtem, John Beltrame, Paolo G Camici, Filippo Crea, Juan-Carlos Kaski, C Noel Bairey Merz, Carl J Pepine, Hiroaki Shimokawa, Colin Berry, COVADIS Study Group

Abstract

Ischemic heart disease secondary to coronary vascular dysfunction causes angina and impairs quality of life and prognosis. About one-half of patients with symptoms and signs of ischemia turn out not to have obstructive coronary artery disease, and coronary vascular dysfunction may be relevant. Adjunctive tests of coronary vasomotion include guidewire-based techniques with adenosine and reactivity testing, typically by intracoronary infusion of acetylcholine. The CorMicA (Coronary Microvascular Angina) trial provided evidence that routine management guided by an interventional diagnostic procedure and stratified therapy improves angina and quality of life in patients with angina but no obstructive coronary artery disease. In this paper, the COVADIS study group provide a comprehensive review of why, how, and when coronary vascular dysfunction should be assessed invasively. They discuss the rationale through a shared understanding of vascular pathophysiology and clinical evidence. They propose a consensus approach to how an interventional diagnostic procedure is performed with focus on practical aspects. Finally, the authors discuss the clinical scenarios in patients with stable and acute coronary syndromes in which measurement of coronary vascular function may be helpful for patient care.

Keywords: MINOCA; angina; ischemic heart disease; microvascular angina; stratified medicine; vasospastic angina.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Clinical Utility of an IDP in Patients With Symptoms and/or Signs of Ischemia But No Obstructive CAD Two patients with similar baseline angiograms and clinical presentations without obstructive epicardial coronary artery disease (CAD). Each patient undergoes the an interventional diagnostic procedure (IDP), which reveals a distinct diagnosis. Therapies for microvascular and vasospastic angina are distinct and should be guided by the IDP results. The yellow figure shows a typical case of vasospastic angina with preserved microvascular function. The patient was previously on a beta-blocker, and this was substituted for by a calcium-channel blocker with smoking cessation counseling. The blue figure depicts a patient with proven microvascular dysfunction but no severe vasospasm. There were abnormalities in both microcirculatory resistance (index of microcirculatory resistance [IMR]) and coronary vasodilator reserve (coronary flow reserve [CFR]). The patient had a diagnosis of microvascular angina and cessation of long-acting nitrate medication with up-titration of a beta-blocker. The patient underwent cardiac rehabilitation classes to assist in weight loss and identify relevant life-style factors implicated in the condition. Note that some operators may prefer to perform vasoreactivity testing before instrumenting the artery for guidewire based invasive CFR and microvascular resistance measurement. ACEi = angiotensin-converting enzyme inhibitor; angio = angiography; DS = diameter stenosis; ECG = electrocardiography; FFR = fractional flow reserve; GTN = glyceryl trinitrate; rehab = rehabilitation.
Central Illustration
Central Illustration
Limited Visualization of the Coronary Microvasculature With Invasive Coronary Angiography (A) This figure illustrates a typical normal coronary angiogram (left) with a smooth and well-opacified left anterior descending coronary artery. The right image is a bismuth stereo angiogram from a cadaveric heart in work performed more than 50 years ago by the late Prof. S. Fulton (reproduced with permission from Fulton [30]). This image offers an unsurpassed illustration of the coronary microcirculation, contrasting starkly with the lack of microcirculatory information on the invasive coronary angiogram (30). (B) This schematic illustrates compartmentalized physiological assessment according to the probes acetylcholine and adenosine. The metrics fractional flow reserve and nonhyperemic pressure ratios are predominantly tests of epicardial coronary obstruction to blood flow, whereas index of microcirculatory resistance and hyperemic microcirculatory resistance are more specific to the microcirculatory function. Finally, coronary flow reserve is a metric that can be influenced by any combination of epicardial or microvascular disease or changes in resting flow.
Figure 2
Figure 2
Cardiac Catheterization Laboratory Interventional Diagnostic Procedure Protocol Proposed step-by-step approach to guidewire-based assessment of coronary vascular function using thermodilution or Doppler and then vasoreactivity testing using acetylcholine (Ach). This simple approach focuses on thermodilution, which is straightforward to include during daily practice. Note that some operators may prefer to perform vasoreactivity testing first without the guidewire, allowing Ach challenge prior to any short-acting nitrate administration. HMR = hyperemia microvascular resistance; IC = intracardiac; LVEDP = left ventricular end-diastolic pressure; LV gram = left ventriculogram; NHPR = nonhyperemic pressure ratio; seg = segment; TT = transit time (for bolus of normal saline); other abbreviations as in Figure 1.
Figure 3
Figure 3
Rising Trend in Citations in Human Coronary Vascular Physiology A stacked area chart depicting the magnitude of change in citations between 1988 and 2018 and total values across this time period. Citations of “coronary vascular dysfunction and human” (https://www.ncbi.nlm.nih.gov/pubmed/?term=coronary+vascular+dysfunction+human; search date February 2, 2020).

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