Ischemia but no obstructive coronary artery disease: more than meets the eye

Figures & data

Table 1. Cardiac stress testing modalities and INOCA.

Method	Factors
Exercise stress test	Electrocardiographic changes (ST-segment and T-wave changes) Stress-induced arrhythmias Symptoms Provides functional capacity
Exercise echocardiography	Wall motion abnormalities Left and right ventricular systolic function Diastolic function Assesses left ventricular hypertrophy, valvular disease, structural heart disease and pulmonary pressures May be normal in INOCA
Cardiac SPECT	Regional ischemic defect(s) Transient ischemic left ventricular dilation May be normal in INOCA
Cardiac PET	Regional ischemic defect(s) Quantifies myocardial blood flow at rest and stress Low myocardial flow reserve = CMD Normal PET result does not exclude coronary vasospasm
Cardiac MRI	Regional ischemic defect(s) Myocardial structure and function Detects edema, fibrosis, inflammation, myocarditis, scar Impaired myocardial perfusion reserve index = CMD Normal MRI does not exclude coronary vasospasm

CMD, coronary microvascular dysfunction; INOCA, ischemia with no obstructive coronary arteries; MRI, magnetic resonance imaging; PET, positron emission tomography; SPECT, single-photon emission computed tomography.

Figure 1. Risk factors for ischemia with no obstructive coronary arteries (INOCA). HPA, hypothalamic–pituitary–adrenal axis; PCOS, polycystic ovary syndrome; PTSD, post-traumatic stress disorder. Image © Emory University, CC-by-SA.

Figure 2. Endothelium-independent and endothelium-dependent angina mechanisms. IMR, Index of Microcirculatory Resistance. *Coronary flow reserve (CFR), an integrated measure of flow through both epicardial and microvascular vessels, but in the absence of epicardial disease it serves as a measure of microvascular function. Figure made using biorender.com. Image © Emory University, CC-by-SA.

Table 2. Therapy target and management strategies.

Target	Strategy
Risk factors and lifestyle	Smoking cessation
	Optimize blood pressure control
	Optimize glycemic control
	Control cholesterol levels
	Sleep hygiene/treat sleep apnea
	Weight management
	Exercise/cardiac rehabilitation
Endothelial dysfunction	Statins
	ACE-I/ARB
	Aldosterone antagonists
	l-Arginine
Limited coronary flow reserve	Beta-blockers and alpha–beta-blockers
	Ranolazine
	Phosphodiesterase-5 inhibitors
Coronary vasospasm	Calcium channel blockers (non-dihydropyridine or dihydropyridine)
	Nitrates (long-acting or short-acting)
	Nicorandil
Abnormal cardiac nociception	Tricyclic anti-depressants
	Xanthine derivatives
Non-pharmacologic options	Neuromodulation, spinal cord stimulator
	Coronary sinus reducer
	Cognitive behavioral therapy
	Enhanced external counter pulsation

ACE-I, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker.

Figure 3. Key points of ischemia with no obstructive coronary arteries (INOCA). CAD, coronary artery disease; CHF, congestive heart failure; CV, cardiovascular; MI, myocardial infarction; QoL, quality of life; SCD, sudden cardiac death. Image ^©Emory University, CC-by-SA.