Coronary Artery Spasm-Related Heart Failure Syndrome: Literature Review

Abstract

Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden's angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF.

Keywords: coronary artery spasm; heart failure with preserved ejection fraction; heart failure with reduced ejection fraction.

Figure 1

The 12-lead electrocardiograms and coronary angiography of variant angina. Angina attack (A) and post-sublingual nitroglycerin 0.6 mg (B) 12-lead electrocardiograms of a 47-year-old male revealed brief ST-segment elevation in II, III, and aVF leads. Ten months later because of recurrent chest pain, he underwent coronary angiography. The coronary angiography revealed intracoronary methylergonovine-induced CAS in the middle portion of the right coronary artery (C, arrow), which was alleviated after intracoronary nitroglycerin 200 μg (D). (Reproduced from [33], with permission of the publisher.).

Figure 2

Epicardial CAS-induced ventricular ectopics: 24 h Holter monitor, electrocardiograms, pressure tracing, and right coronary arteriogram in a 53-year-old female presenting with frequent palpitation and unstable rest angina. (A) A 24 h Holter monitor showed sinus rhythm with runs of ventricular ectopics in singles and couplets without preceding ST segment changes; (B) simultaneous lead I, II, III electrocardiogram and systemic arterial pressure tracing during intracoronary ergonovine testing; (C) baseline angiographically normal right coronary artery with minimal plaquing; (D) middle spasm (arrow) immediately after intracoronary administration of 45 μg ergonovine. Ventricular ectopics in singles and one couplet occurred at the same time; (E) the CAS and ventricular ectopics were relieved after intracoronary administration of 200 μg nitroglycerin. The patient’s consciousness remained clear throughout the examination.

Figure 3

Epicardial CAS-induced VF: electrocardiograms, pressure tracing, and right coronary arteriogram in a 50-year-old male with unstable angina, presenting after wakening with rest angina at night. (A) Simultaneous lead I, II, aVR electrocardiogram, and systemic arterial pressure tracing during intracoronary ergonovine testing; (B) baseline angiographically normal right coronary artery with minimal plaquing; (C) ostial spasm (arrow) immediately after intracoronary administration of 15 μg ergonovine; (D) in 10 s, the ostial spasm recovered spontaneously, multi-focal spasms appeared in the proximal and middle portion, and ventricular fibrillation occurred at the same time for 10 s and recovered spontaneously without intervention; (E) multi-focal spasms were relieved after intracoronary administration of 100 μg nitroglycerin. The patient’s consciousness remained clear throughout the examination. (Reproduced from [63], with permission of the publisher).

Figure 4

Microvascular CAS-induced VF: electrocardiograms (green line), pressure tracing (purple line), and right coronary arteriogram in a 75-year-old male with unstable rest angina. (A) Simultaneous lead I, II, III electrocardiogram and systemic arterial pressure tracing during intracoronary ergonovine testing; (B,C) baseline angiographically normal right coronary artery with minimal plaquing (white and red arrows); (D,E) microvascular spasm (white and red arrows) immediately after intracoronary administration of 45 μg ergonovine. Ventricular fibrillation occurred at the same time for 17 s and recovered spontaneously without intervention; (F,G) microvascular spasms were relieved after intracoronary administration of 200 μg nitroglycerin (white and red arrows). The patient’s consciousness remained clear throughout the examination.

Figure 5

Risk factors and precipitating factors are represented by rectangles and circles, respectively, for CAS. (Adapted from [33], with permission of the publisher).

Figure 6

Graphical abstract depicting the multifactorial molecular and cellular mechanisms involved in the initiation and progression of CAS and CAS-related preclinical HF to clinical overt HF. The development of CAS can be contributed to by smoking, CRP, and Lp(a). Fasudil, Tocilizumab, Garcinol, and Riociguat are potential disease-modifying therapies of CAS [196,197,201,252]. The reversible nature of CASHF is suggested and represented by a reciprocal relationship and a positive feedback loop between epicardial and microvascular CAS. Solid arrows: direct activating interactions; Dashed arrow: indirect activating interactions; Blunt arrows: inhibition. Ach: acetylcholine; α7-nAChR: α7-nicotinic acetylcholine receptor; CHRNA7: α7-nAChR protein coding gene; CamKII: calmodulin-dependent kinase II; CAS: coronary artery spasm; CRP: C-reactive protein; HFpEF: heart failure with reduced ejection fraction; HFrEF: heart failure with reduced ejection fraction; ICAM-1: intercellular adhesion molecule 1; IL-6: Interleukin-6; INOCA: ischemia with non-obstructive coronary artery disease; Lp(a): lipoprotein(a); MINOCA: myocardial infarction with non-obstructive coronary artery disease; p38MAPK: p38 mitogen-activated protein kinase; VCAM-1: vascular cell adhesion molecule 1.