Painless Coronary Spastic Angina First Diagnosed Perioperatively: Importance of Spasm Provocation Testing Under Medication to Confirm Optimal Therapy

Abstract

A 67-year-old man underwent surgery and, postoperatively, suddenly collapsed and developed ventricular fibrillation. Emergent coronary angiography revealed diffuse narrowing of the coronary arteries, which was reversed with isosorbide dinitrate. We attributed his aborted sudden cardiac death to coronary artery spasm. A transvenous implantable cardioverter defibrillator was implanted following the administration of vasodilators. Two years after implantation, the patient developed ventricular tachycardia, which was terminated by anti-tachycardia pacing. We then performed a spasm provocation test under medication. Intracoronary injection of acetylcholine induced spasm in the coronary artery, although no chest symptoms were observed. We diagnosed the patient with painless coronary spastic angina.

Introduction

Patients with coronary spastic angina can present with various manifestations, such as acute coronary syndrome, life-threatening ventricular arrhythmias, and hypotension (1). While optimal medical therapy, including calcium-channel antagonists or nitrates, is effective in many cases, there are no reliable objective methods for evaluating their effectiveness other than monitoring the frequency of chest pain or nitroglycerin use (2). However, this evaluation is even more challenging in patients with painless coronary spastic angina. We present a case of a patient diagnosed with painless coronary spastic angina during the perioperative period.

Case Report

A 67-year-old man underwent surgery for a pelvic fracture. He was a current smoker and had a history of untreated hypertension with no other risk factors for coronary artery disease. He had no chest pain or discomfort in his daily life. During recovery from general anesthesia, sudden hypotension (systolic arterial pressure: 40 mmHg) and ST-segment elevation on the monitor electrocardiogram (ECG) lead II were observed (Fig. 1A, B). Subsequently, the patient showed no pulse pressure and progressed to cardiopulmonary arrest. Cardiopulmonary resuscitation was initiated with a bolus injection of adrenaline and the patient was revived after 8 min of resuscitation. A 12-lead ECG taken after recovery showed a wide QRS complex without ST-segment elevation (Fig. 1C); however, the ECG quickly returned to normal (Fig. 1D). Echocardiography did not reveal any abnormalities in the ventricular wall motion. A laboratory analysis revealed the following values: sodium, 137 mmol/L (reference: 138-146 mmol/L); potassium, 5.5 mmol/L (reference: 3.6-4.9 mmol/L); chloride, 109 mmol/L (reference: 99-109 mmol/L); creatine kinase (CK), 382 IU/L (reference: 62-287 IU/L); creatine kinase-MB (CK-MB), 21 U/L (reference: ＜25); troponin I, ＜10.0 μg/L (reference: ＜26.2); and D-dimer, 45.96 mg/L (reference: ＜1.00). One and a half hours after admission to the intensive care unit, the ST-segment on the monitor ECG gradually elevated again, and ventricular fibrillation occurred (Fig. 2A-D). Immediate electrical shock terminated the arrhythmia, and emergent coronary angiography (CAG) revealed diffuse narrowing of the coronary arteries (Fig. 3A, B). Intracoronary injection of isosorbide dinitrate (0.5 mg) completely dilated the arteries (Fig. 3C). We attributed his aborted sudden cardiac death to coronary artery spasm. A transvenous implantable cardioverter defibrillator (TV-ICD) was implanted after the administration of benidipine hydrochloride (8 mg/day) and nicorandil (15 mg/day). After discharge, the patient quit smoking and exhibited no chest symptoms.

Figure 1.

Electrocardiogram. (A) Monitor lead II electrocardiogram showing slight ST-segment elevation before collapse. (B) Monitor lead II electrocardiogram showing ST-segment elevation coinciding with sudden hypotension. (C) Twelve-lead electrocardiogram recorded after return of spontaneous circulation showing wide QRS morphology without obvious ST-segment elevation. (D) Twelve-lead electrocardiogram recorded before leaving the operating room.

Figure 2.

Six-lead monitor electrocardiogram. Six-lead monitor electrocardiogram revealing progressive ST-segment elevation (A-C) followed by ventricular fibrillation (D).

Figure 3.

Coronary angiography. Right (A) and left (B) coronary angiography at baseline. Left (C) coronary angiography after intracoronary injection of isosorbide dinitrate.

Two years after implantation, the patient developed ventricular tachycardia, which was terminated by anti-tachycardia pacing (Fig. 4A-C). During this episode, the patient did not experience any chest pain. A CAG with a spasm provocation test was performed while the patient was on his usual medication. The CAG before the provocation test showed slight narrowing (Fig. 5A). Intracoronary injection of 50 μg acetylcholine provoked coronary spasm in the left anterior descending artery and left circumflex artery, but no chest symptoms were observed (Fig. 5B). For safety reasons, spasm provocation test was not performed in the right coronary artery. Magnetic resonance imaging (MRI) revealed no abnormalities, such as delayed enhancement, which could explain the sudden cardiac death. We finally diagnosed him with painless coronary spastic angina and increased the dose of vasodilators [nifedipine (80 mg/day), isosorbide mononitrate (40 mg/day), and nicorandil (15 mg/day)]. In the subsequent 2 years of follow-up, TV-ICD interrogation revealed no significant events.

Figure 4.

Ventricular tachycardia episode in implantable cardioverter defibrillator interrogation record. (A) Device interrogation revealing an episode of ventricular tachycardia and termination of the arrhythmia through second anti-tachycardia pacing. (B, C) Intracardiac electrocardiogram of ventricular tachycardia (B) and termination of the arrhythmia via anti-tachycardia pacing (C).

Figure 5.

Coronary angiography of spasm provocation test under medication. (A) Left coronary angiography at baseline. (B) Left coronary angiography after intracoronary injection of 50 μg acetylcholine.

Discussion

We report a fatal case of painless coronary spastic angina that was first diagnosed in the perioperative period. Evaluating the effects of medical therapy in patients with painless coronary spasm is challenging. Sueda et al. advocated the use of a pharmacological spasm provocation test under medication (2). If coronary spasm is provoked, they recommend increasing the dose of vasodilators (3). Therefore, a spasm provocation test under medical therapy should be performed in patients with painless coronary spasm.

Patients who experience aborted sudden cardiac death due to coronary artery spasm are at higher risk of cardiac death (4). Sueda et al. recommended administering least two calcium channel blockers with different mechanisms, such as dihydropyridine and diltiazem, along with nitrates or nicorandil, for high-risk patients (5). They also highlighted that insufficient doses of medication were often prescribed to patients with aborted sudden cardiac death due to coronary spasm after implantation of an implantable cardioverter defibrillator (ICD) (6). It should be recognized from the initial episode that multiple pharmacologic therapies may be essential for patients who experience aborted sudden cardiac death.

In clinical practice, physicians often encounter patients with refractory coronary spastic angina and ventricular arrhythmias including ventricular tachycardia, despite the use of multiple vasodilators (4,7,8). Fatal events are not necessarily caused by coronary spasm itself. In this case, the second event could have been due to myocardial scarring or irritable myocardium resulting from recurrent ischemic attacks (4). As MRI revealed no abnormalities, such as delayed enhancement, which could explain the sudden cardiac death, we ultimately diagnosed the ventricular arrhythmia as being caused by coronary spasm. The frequency of appropriate ICD shocks during the follow-up period has been reported to be approximately one in four patients with aborted cardiac death due to coronary spasm (5). Several factors increase the risk of recurrent ventricular fibrillation, such as younger age, hypertension, hyperlipidemia, family history of sudden cardiac death, multivessel spasm, left anterior descending artery spasm, and early repolarization pattern. The precise prediction of sudden cardiac death remains difficult (4,9). Therefore, ICD implantation is recommended for secondary prevention in patients with coronary spastic angina and aborted sudden cardiac death (4). According to the Japanese Circulation Society/Japanese Association of Cardiovascular Intervention and Therapeutics/Japanese College of Cardiology 2023 Guideline Focused Update on Diagnosis and Treatment of Vasospastic Angina (Coronary Spastic Angina) and Coronary Microvascular Dysfunction, ICD implantation is considered class IIb, regardless of whether the patient has received appropriate medical therapy (10). Although ICD implantation was performed in accordance with current guidelines and the patient's request, it may not be necessary in all cases. There are no well-established indications for ICD implantation in patients with aborted sudden cardiac death caused by coronary spasm. Sueda et al. advocated sequential spasm provocation testing for patients with aborted sudden cardiac death due to coronary spasm, conducted under sufficient medication 1-3 months after the diagnosis of coronary spastic angina, to evaluate the need for ICD implantation (6). A report from Japan found that only 47.4% of institutions recognized the importance of spasm provocation tests under medication (11), highlighting the need for renewed awareness of its clinical significance. Furthermore, previous studies have suggested that the coexistence of vasospastic angina and coronary microvascular dysfunction is associated with a poor prognosis (12). However, coronary microvascular dysfunction was not investigated in this patient.

Coronary spasm is relatively rare in the perioperative period. A study found that more than half of the patients who experienced vasospastic events during this period had no prior history of chest pain (13). Therefore, patients who are first diagnosed with coronary spastic angina during the perioperative period may suffering from painless coronary spastic angina. Yasue et al. reported that two-thirds of variant angina attacks were asymptomatic or silent myocardial ischemia (14). However, diagnosing painless coronary spastic angina in patients under general anesthesia is particularly challenging. Even in the absence of chest symptoms, careful follow-up is necessary. Further studies, including studies with larger sample sizes, are needed to evaluate the treatment of patients first diagnosed with coronary spastic angina in the perioperative period.

Conclusions

We herein described a case of painless coronary spastic angina that was first diagnosed in the perioperative period. Patients diagnosed with coronary spastic angina in this setting may suffering from painless coronary spastic angina. It is difficult to evaluate the effectiveness of medical therapy in these patients. Spasm provocation testing under adequate medical therapy is useful for evaluating the treatment response in patients with aborted sudden cardiac death due to coronary artery spasm.

The authors state that they have no Conflict of Interest (COI).