Exploring the ECG “6+2” Phenomenon in Coronary Artery Disease and Coronary Artery Spasm: A Case Report Analysis and Treatment Implications

Background

Coronary artery spasm (CAS) represents a distinctive variant of coronary artery disease. In a clinical context, it frequently presents as angina pectoris during periods of rest, devoid of precipitants such as physical exertion or emotional arousal. In certain instances, a subset of patients can encounter acute myocardial infarction, and in rare cases, sudden cardiac demise can transpire due to relentless, pronounced constriction of the coronary arteries. Notably, the clinical presentation of CAS is typified by episodes of angina at rest and transient elevation of the ST segment, discernible on surface electrocardiogram (ECG). In ECG standardization recommendations (2009) and acute myocardial infarction guidelines (2017) of the American Heart Association, ECG “6+2” phenomenon is recommend as a specific ECG indicator for lesions in the left main coronary artery or multiple vessels [1,2]. In this particular case, despite the manifestation of a 6+2 phenomenon on the patient’s ECG and the troponin level being elevated by over 18 times the reference value, the outcomes of the invasive coronary angiography revealed no noteworthy anomalies. To date, there is no report of this phenomenon in CAS.

Case Report

A 72-year-old man presented to Emergency Department with recurrent chest pain for more than 6 years. He had hypertension and had taken medicine regularly for more than 10 years. In 2016, 2017, and 2020, he was admitted to our hospital owing to repeated chest pain, without obvious inducement. Each episode of pain lasted for about 10 min and was relieved after rest. He was administered aspirin, clopidogrel, isosorbide mononitrate sustained-release tablets, and β-receptor blockers for a long time. Despite our team’s persistent recommendations for the patient to undergo either invasive coronary angiography or coronary computed tomography (CT) imaging, the patient and his family explicitly declined, resulting in our inability to achieve clarity regarding the patient’s coronary artery condition. At this admission, he was referred to our hospital owing to chest pain at rest. As shown in Figure 1A, an ECG 6+2 phenomenon appeared in the Emergency Department: ST segments in more than 6 leads, including I, aVL, II, III, aVF, and V3–V6, were obviously decreased, and ST segments in leads aVR and V1 were elevated. Troponin level were increased from 0.038 to 10.882 μg/L (reference range: 0–0.060 μg/L), and the brain natriuretic peptide level was 47.730 pg/mL (reference range: 0–100 pg/mL). Therefore, emergency invasive coronary angiography was performed immediately. Surprisingly, the result of coronary angiography was normal. No obvious abnormality was found after completing other examinations.

After comprehensive judgment, it was considered that the patient might have had CAS. Thus, our team stopped the use of aspirin, clopidogrel, and β-receptor blockers, and prescribed diltiazem hydrochloride sustained-release capsules 90 mg twice daily and trimetazidine hydrochloride tablets 20 mg 3 times daily to prevent CAS and improve cardiac muscle metabolism. The patient’s chest pain was gradually relieved, and the ST segment of all leads almost completely recovered to normal, as shown in Figure 1B. Two days later, he had chest pain again at rest. The ECG showed that the changes were similar to that in Figure 1A. Therefore, he temporarily received isosorbide dinitrate injection to expand the coronary artery and relieve the spasm. His chest pain disappeared again. The changes in the re-examined ECG were similar to those in Figure 1B. After the patient’s condition had stabilized, he was discharged from the hospital. Our team followed this case for 3 months, and the patient took regular anti-coronary spasm medication, without recurrence of similar symptoms.

Discussion

Patients suspected of having acute occlusion of the left main coronary artery or CAS should undergo coronary angiography in time to determine the cause and perform accurate treatment. Although both can give rise to acute myocardial infarction, there are many clear differences in treatment between them. Patients with coronary heart disease (CHD) were treated mainly with antiplatelet, lipid-lowering, and plaque-stabilizing drugs, while patients with CAS were treated mainly with suppression of the spasm and coronary expansion, when necessary. This patient had refused coronary angiography, and therefore we could not identify the pathogenesis. More seriously, substance abuse (including long-term misuse of β-receptor antagonists, isosorbide mononitrate sustained-release tablets, and aspirin) caused the symptoms to recur and worsen, and even drug-induced gastrointestinal bleeding had occurred. In this case, the patient had chest pain repeatedly at rest, although the coronary angiography was normal. After correct drug treatments, the chest pain was relieved, and the ECG changed correspondingly with his symptoms and treatment. Therefore, CAS could be basically diagnosed by the patient’s history, symptoms, ECG changes, laboratory examination results, and coronary angiography results. Confirming the diagnosis of CAS frequently necessitates acetylcholine or ergometrine provocation tests; however, both of these tests entail the potential hazard of exacerbating myocardial ischemic injury. Regrettably, after being apprised of this risk, the patient and his family declined the tests. This is a deficient aspect of this case. Moreover, CAS guidelines emphasize the importance of improving lifestyle, avoiding overwork, reducing mental stress, and controlling CHD risk factors. Calcium antagonists are recommended as the priority drugs (class I) to prevent the onset of CAS [3]. Although short-acting nitrates are the most effective drugs for rapidly alleviating CAS, long-acting nitrates are not recommended to be used for a long time, because their drug resistance cannot be overcome [4]. Especially, β-receptor blockers should not be used alone for CAS patients without significant stenosis of the coronary artery, because they could cause α receptor excitation and induce CAS. For those patients with both CHD and CAS, guidelines recommend that β-receptor blockers should be used in combination with calcium antagonists and nitrates (class IIa). A study indicates that aspirin might not effectively diminish subsequent adverse cardiovascular events in patients with CAS lacking significant atherosclerotic stenosis [5]. Furthermore, Mori et al reported that statin drugs failed to reduce the main clinical events of patients with CAS [6]. Therefore, there are clear differences in treatment for CHD and CAS, and the therapeutic schedule should not be confused. This patient took aspirin, isosorbide mononitrate sustained-release tablets, β-receptor antagonists, and other drugs for a long time, so that his condition failed to be uncontrollable. More seriously, substance abuse further caused repeated attacks of chest pain and even serious complications, such as gastrointestinal bleeding.

Coronary artery spasmodic angina, once also known as Prinzmetal angina, occurs most often at rest and during regular activity, usually without an obvious trigger. An ECG shows transient ST-segment elevation during the attack, which is different from other manifestations of myocardial ischemia and angina pectoris due to coronary atherosclerosis [7]. In 1993, Gorgels et al found that the positive predictive value of ST-segment elevation in lead aVR with the depression of ST-segment leads I, II, and V4–V6 was 62% for the lesions in left main trunk or 3 branches [8]. Since then, researches of this phenomenon have been emerging, and the concept of ECG 6+2 has been proposed [9,10]. In ECG standardization recommendations (2009) and acute myocardial infarction guidelines (2017) of the American Heart Association, the ECG 6+2 phenomenon is recommend as a specific ECG indicator for lesions in the left main coronary artery or multiple vessels [1,2]. Obviously, ECG changes in the present case completely conformed to the 6+2 phenomenon, but coronary angiography revealed no stenosis in the coronary artery, indicating that in cases of such ECG changes, we cannot make an arbitrary conclusion and give treatment. Coincidentally, Sclarovsky et al believe that ST-segment elevation in the lead aVR was a mirror image change of ST-segment depression in leads V5 and V6 [11]. This ECG phenomenon has also been observed in many other clinical diseases, such as myocardial hypertrophy and acute aortic dissection. In the present case, CAS might have affected multiple coronary vessels, and the combined effect caused the occurrence of ECG 6+2 phenomenon. To date, there is no report of this phenomenon in CAS.

Conclusions

We report a case with the primary symptom of recurrent, long-term chest pain. It is noteworthy that the patient’s surface electrocardiogram presented the 6+2 phenomenon, but coronary angiography indicated the absence of significant plaque or narrowing. Although the patient did not undergo acetylcho-line or ergonovine provocation tests, a reasonable determination of CAS could still be made based on his medical history, symptomatology, negative coronary angiography results, and positive response to anti-CAS treatment. The ECG manifestation of the 6+2 phenomenon, currently used to diagnose left main or multivessel coronary artery disease, is clearly different from the classic transient ST-segment elevation seen in coronary vasospastic angina. This case serves as a reminder to clinicians that the 6+2 phenomenon is not a specific marker for left main coronary artery or coronary artery multivessel disease; a comprehensive analysis is necessary to establish an accurate diagnosis. Furthermore, despite the patient and family’s right to decline clinical examinations and treatment plans, we emphasize the role of coronary angiography as the criterion standard for clinicians to precisely determine a patient’s coronary artery vascular health. Through this approach, clinicians can implement treatment in a more scientific and targeted manner, thereby avoiding medication misuse.