A Case of Ventricular Fibrillation in Masked Long-QT Syndrome Coexisting with Coronary Vasospasm.

Although long-QT syndrome (LQTS) with a normal range QT interval at rest leads to fatal ventricular arrhythmias, it is difficult to diagnose. In this article, we present a rare case of a patient who suffered a cardiac arrest and was recently diagnosed with LQTS and coronary vasospasm. A 62-year-old man with no syncopal episodes had a cardiopulmonary arrest while running. During coronary angiography, vasospasm was induced and we prescribed coronary vasodilators, including calcium channel blockers. An exercise stress test was performed to evaluate the effect of medications and accidentally unveiled exercise-induced QT prolongation. He was diagnosed with LQTS based on diagnostic criteria. Pharmacotherapy and an implantable cardioverter defibrillator were used for his medical management. It is extremely rare for LQTS and coronary vasospasm to coexist. In cases of exercise-induced arrhythmic events, the exercise stress test might be helpful to diagnose underlying disease.

Recurrent syncope due to ischemia with non-obstructive coronary artery disease: a case report.

BACKGROUND: Ischemia with non-obstructive coronary artery disease is a prevalent form of ischemic heart disease. The majority of ischemia with non-obstructive coronary artery disease cases are attributed to underlying factors such as coronary microvascular dysfunction (CMD) and/or coronary artery spasm. Ischemia with non-obstructive coronary artery disease can present with various clinical manifestations. Recurrent syncope is an atypical complaint in patients with ischemia with non-obstructive coronary artery disease. CASE PRESENTATION: This case report describes the presentation of a 58-year-old Chinese male patient who experienced repeated episodes of syncope. The syncope was found to be caused by concomitant coronary artery spasm and presumptive coronary microvascular dysfunctionc suggested by "slow flow" on coronary angiography. The patient was prescribed diltiazem sustained-release capsules, nicorandil, and atorvastatin. During the three-month follow-up conducted on our outpatient basis, the patient did not experience a recurrence of syncope. CONCLUSION: This study highlights the importance of considering ischemia with non-obstructive coronary artery disease as a potential cause of syncope in the differential diagnosis. It emphasizes the need for early diagnosis of ischemia with non-obstructive coronary artery disease to facilitate more effective management strategies.

Comparison of the Diagnostic Yield of Intracoronary Acetylcholine Infusion and Acetylcholine Bolus Injection Protocols During Invasive Coronary Function Testing.

Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina with no obstructive coronary arteries in patients. Both can be diagnosed by invasive coronary function testing (ICFT) using acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared with a 1-minute ACh bolus injection protocol in testing CED and CAS. We evaluated 220 consecutive patients with angina and no obstructive coronary arteries who underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion, and thereafter 110 patients using 1-minute bolus injections, because of a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low-dose ACh and CAS according to the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%, p = 0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3 vs 1-minute protocol (24% vs 44%, p = 0.004). Including T-wave abnormalities in the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as a diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as a diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

Vasospastic angina: a review on diagnostic approach and management.

Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.

Diagnosis and treatment of epicardial coronary artery spasmVasospastic angina (VSA) refers to chest pain experienced as a consequence of a sudden narrowing of the epicardial coronary arteries. VSA can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction. Reduced blood and oxygen supply in patients with non-obstructive coronary arteries is not a benign condition, as patients are at elevated risk of adverse cardiovascular events. These patients also experience impaired quality of life and associated increased healthcare costs. This review aims to summarise current data relating to the diagnosis of VSA and provides details on treatment strategies.

Association of the interleukine-6 polymorphism with catheter-induced coronary artery spasm in Egyptians.

BACKGROUND: The role of coronary artery spasm (CAS) was extended beyond variant angina to ischemic heart disease in general, including effort angina, unstable angina, acute myocardial infarction (MI) and sudden death. It is difficult and cumbersome to examine CAS during coronary angiography. Risk factors for CAS include smoking and genetic polymorphisms. AIM: We aimed to investigate the association of the interleukin-6 (IL-6) polymorphism with catheter-induced CAS in Egyptian patients who undergo coronary angiography. METHODS: This is a case-control study. Two hundred patients with chronic coronary artery disease who underwent elective coronary angiography were included in the study. Patients were divided into two groups: the non-CAS group (100 patients) and the CAS group (100 patients). The subjects were genotyped to the -572 C>G (rs 1800796) polymorphism of the IL-6 gene by PCR-restriction fragment length polymorphism. RESULTS: We found that patients with CAS have more risk factors for atherosclerosis compared to those without CAS. Smoking, the IL-6 GG genotype, and the G allele were independent risk factors for CAS. CONCLUSION: We concluded that the GG genotype and G allele of the IL-6 gene are associated with CAS. Smoking, the GG genotype, and the G allele of the IL-6 gene are independent predictors of catheter-induced CAS.

Safety and potential usefulness of sequential intracoronary acetylcholine and ergonovine administration for spasm provocation testing.

BACKGROUND: Although guidelines recommend intracoronary acetylcholine (ACh) and ergonovine (ER) provocation testing for diagnosis of vasospastic angina, the feasibility and safety of sequential (combined) use of both pharmacological agents during the same catheterization session remain unclear. OBJECTIVES: In this study, we investigated the feasibility and safety of sequential intracoronary ACh and ER administration for coronary spasm provocation testing. METHODS: The study included 235 patients who showed positive results on ACh and ER provocation testing. Initial intracoronary ACh administration was followed by ER administration for left coronary artery (LCA) spasm provocation testing. Subsequently, the right coronary artery (RCA) was subjected to sequential ACh and ER administration for provocation testing. The primary outcome of the study was the safety of sequential intracoronary ACh and ER provocation testing, which was assessed based on a composite of all-cause death, sustained ventricular tachycardia and fibrillation, and cardiogenic shock. RESULTS: Even in patients with negative results on sequential intracoronary ACh and ER provocation testing in the LCA and only ACh administration into the RCA, additional administration of ER into the RCA showed a positive provocation test result in 33 of 235 (14.0%) patients; three (1.3%) patients developed adverse effects (cardiogenic shock occurred in all cases) during LCA provocation testing. We observed no deaths attributable to spasm provocation testing. CONCLUSION: Sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of vasospastic angina.

Safety and potential usefulness of novel coronary spasm provocation testing protocolCoronary spasm represents a subtype of ischemic heart disease, potentially leading to heart attack. Although guidelines recommend intracoronary administration of different pharmacological agents, acetylcholine (ACh) and ergonovine (ER), for coronary spasm provocation testing, the feasibility and safety of sequential (combined) use of both drugs are unclear. In the present study, we showed that sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of coronary vasospasm.

Sudden diffuse spasm of multiple coronary arteries: A case report.

RATIONALE: Diffuse multivessel coronary artery spasm (DMV-CAS) was defined as a severe and reversible diffuse spasm occurring in more than 2 major coronary arteries, which is rare in clinical practice. Due to a wide lesion scope, DMV-CAS often occurs in the form of complications. It is not easy to be clinically diagnosed because it is too brief to be caught. Here, we report a rare case of spontaneous subtotal occlusion of 3 major coronary arteries induced by Vasalva action, which was confirmed in real-time by CAG. PATIENT CONCERNS: A 68-year-old man had sudden chest pain after forced defecation during hospitalization. The electrocardiogram showed transient ST segment elevation of the inferior wall lead, inversion of the anterior wall, and lateral wall leads T waves. Emergency CAG revealed elongated vessel beds in 3 coronary arteries and multiple diffuse stenosis, but none of the coronary arteries were completely occlusive. DIAGNOSES: Diagnoses of DMV-CAS were made based on CAG findings and postmedication response. INTERVENTIONS: Nitroglycerin was administered in the coronary arteries. The anti-vasospasm, antiplatelet aggregation and lipid-regulating drugs were administered orally. OUTCOMES: The patient was discharged on the 7th day with complete resolution of symptoms and normalization of the electrocardiography findings. No ischemic events occurred during a follow-up for 5 months. LESSONS: This case highlights the identification of multivessel diffuse coronary spasm and acute myocardial infarction, and the prevention of CAS triggers, which requires the attention of clinicians.

Atherosclerosis Vindicated: A Case of Chest Pain Due to Capecitabine-Induced Coronary Artery Spasm.

BACKGROUND Capecitabine and other 5-fluorouracil prodrugs are medications widely employed in treating solid tumors, including breast and colorectal cancer. However, they carry a notable risk for cardiotoxicity, including coronary vasospasm, possibly related to their impact on vascular endothelium and smooth muscle. CASE REPORT We present a case of a 45-year-old male with a pancreatic neuroendocrine tumor who developed exertional chest pain after starting capecitabine. Initial evaluations in the emergency department, including a 12-lead electrocardiogram and cardiac enzymes, were normal, but suspicion for coronary vasospasm persisted due to the temporal relationship with drug initiation and symptom characteristics. A graded exercise test reproduced his symptoms, accompanied by hyperacute peaked T waves and subsequent ST segment elevations in the inferior leads. Coronary angiography revealed patent coronary arteries, rendering provocative testing unnecessary due to a high clinical suspicion of capecitabine-induced vasospasm. Discontinuing the patient's medication was a more efficient approach than continuing additional cardiac workup while the drug was still administered. After multidisciplinary discussion, capecitabine was discontinued, leading to symptom resolution and a negative repeat graded exercise test. CONCLUSIONS This case underscores the potential for capecitabine to induce coronary artery vasospasm, emphasizing the importance of prompt medication cessation. Patients receiving capecitabine therapy and experiencing chest pain should undergo an evaluation with consideration of capecitabine-induced vasospasm in the differential diagnosis. Prompt recognition and medication cessation are critical to prevent serious cardiovascular complications including death. In our patient, discontinuing capecitabine resolved his symptoms, emphasizing the significance of discontinuing the causative drug and seeking alternative chemotherapy regimens.

Omitting 50 µg of intracoronary acetylcholine injection in the left coronary artery during spasm provocation test.

BACKGROUND: Although guidelines recommend intracoronary administration of acetylcholine (ACh) with incremental doses of 20, 50, and 100 µg into the left coronary artery (LCA) during spasm provocation test for diagnosing vasospastic angina, 50 µg of ACh rarely induced significant coronary vasospasm when no vasoconstriction was observed with 20 µg of ACh in a previous report. The aim of this study was to evaluate the safety and feasibility of omitting 50 µg according to the vasoreactivity by 20 µg of ACh in the LCA. METHODS: A total of 556 patients undergoing ACh provocation test with 20 µg followed by 50 and/or 100 µg were retrospectively included. Injection of 50 µg of ACh was primarily omitted when vasoconstriction <25 % was observed with 20 µg, which was left to operator's discretion. Adverse events were defined as a composite of ventricular fibrillation, sustained ventricular tachycardia, and cardiogenic shock during ACh test in the LCA. RESULTS: Positive ACh test in the LCA was observed in 245 (44.1 %) patients. Overall, patients with LCA constriction <25 % by 20 µg of ACh had a lower rate of positive ACh test than their counterpart (24.0 % vs. 88.4 %, p < 0.001). In patients with LCA constriction ≥25 % by 20 µg, the incidence of adverse events was significantly higher than in those with LCA constriction <25 % during the provocation test at doses of 50 and 100 µg (2.3 % vs. 0 %, p = 0.009). CONCLUSIONS: Omitting 50 µg of ACh in the LCA may be safe and feasible when little vasoconstriction was observed with preceding injection of 20 µg of ACh during spasm provocation test for diagnosing vasospastic angina. However, we believe that 50 µg of ACh should not be omitted when 20 µg of ACh induced LCA constriction ≥25 %.

Insights into the invasive diagnostic challenges of coronary artery vasospasm - A systematic review.

Coronary provocation testing is an essential diagnostic procedure when evaluating vasospastic angina. Invasive methods using acetylcholine or ergonovine are considered the current gold standard. Despite efforts from global cardiovascular institutions, current protocols vary in dosage, administration time, and procedural approach. In addition, concerns over the specificity of findings and potential complications have limited routine uptake of this procedure in clinical practice. This systematic review evaluates current diagnostic protocols, focusing on invasive provocation testing. We included studies using intracoronary provocation testing with acetylcholine or ergonovine for the assessment of coronary artery vasospasm that detailed specific elements of the procedure (dosage, administration time, etc.) and included ≥50 patients. A total of 28 articles met strict inclusion criteria. Our review highlights the heterogeneity between current diagnostic protocols for invasive provocation testing. We believe standardization of a diagnostic protocol will encourage both current and future cardiologists to incorporate such procedures in the evaluation of variant angina.

Familial risk of vasospastic angina: a nationwide family study in Sweden.

OBJECTIVES: Vasospastic angina (VSA) is a complex coronary vasomotor disorder associated with an increased risk of myocardial infarction and sudden death. Despite considerable advances in understanding VSA pathophysiology, the interplay between genetic and environmental factors remains elusive. Accordingly, we aimed to determine the familial VSA risk among first-degree relatives of affected individuals. METHODS: A population-based multigenerational cohort study was conducted, including full-sibling pairs born to Swedish parents between 1932 and 2018. Register-based diagnoses were ascertained through linkage to the Swedish Multigeneration Register and National Patient Register. Incidence rate ratios (IRRs) and adjusted HRs were calculated for relatives of individuals with VSA compared with relatives of individuals without VSA. RESULTS: The total study population included 5 764 770 individuals. Overall, 3461 (0.06%) individuals (median age at disease onset 59 years, IQR: 63-76) were diagnosed with VSA. Of these, 2236 (64.61%) were women. The incidence rate of VSA for individuals with an affected sibling was 0.31 (95% CI: 0.24 to 0.42) per 1000 person-years compared with 0.04 (95% CI: 0.04 to 0.04) per 1000 person-years for those without an affected sibling, yielding an IRR of 7.58 (95% CI: 5.71 to 10.07). The risk of VSA for siblings with an affected sibling was significantly increased in the fully adjusted model (HR: 2.56; 95% CI: 1.73 to 3.79). No increased risk of VSA was observed in spouses of affected individuals (HR: 0.63; 95% CI: 0.19 to 2.09). CONCLUSIONS: In this nationwide family study, we identified high familial risk for VSA independent of shared environmental risk factors. Our findings indicate that VSA tends to cluster in families, emphasising the need to explore genetic and non-genetic factors that may contribute.

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

BACKGROUND Although coronary artery disease and coronary artery spasm (CAS) can lead to acute myocardial infarction, there are clear differences in treatment between coronary heart disease and CAS, and the therapeutic schedule should not be confused. Furthermore, electrocardiogram (ECG) "6+2" phenomenon is recommend as a specific ECG indicator for lesions in the left main coronary artery or multiple vessels. Currently, no reports of this phenomenon in CAS exist. CASE REPORT A 72-year-old man had history of recurrent chest pain for over 6 years, with episodes lasting about 10 min and resolving with rest. He experienced symptom recurrence and exacerbation due to substance abuse. He was admitted to our Emergency Department for chest pain at rest. His emergency ECG revealed a 6+2 phenomenon, accompanied by troponin levels exceeding 18 times the reference value. Promptly, we conducted coronary angiography, with unexpected normal findings. Following thorough assessment, we postulated the patient could have CAS. Subsequent to medical team intervention, the patient's ECG normalized, leading to his discharge upon condition stabilization. CONCLUSIONS We report a case of CAS in a patient with ECG 6+2 phenomenon, without significant coronary artery stenosis. This differs from transient ST-segment elevation on ECG, a well-recognized hallmark of CAS; however, such a presentation has not been documented before. Additionally, treatment strategies for myocardial ischemic conditions stemming from coronary atherosclerosis diverge from those employed for CAS. Therefore, clinicians should advocate for coronary angiography whenever feasible. This approach serves to elucidate the underlying disease etiology and facilitates the administration of precision-targeted interventions for patients.

Pharmacological coronary spasm provocative testing in clinical practice: A French Coronary Atheroma and Interventional Cardiology Group (GACI) position paper.

Vasospastic angina, also described as Prinzmetal angina, was first described as a variant form of angina at rest with transient ST-segment elevation; it is common and present in many clinical scenarios, including chronic and acute coronary syndromes, sudden cardiac death, arrhythmia and syncope. However, vasospastic angina remains underdiagnosed, and provocative tests are rarely performed. The gold-standard diagnostic approach uses invasive coronary angiography to induce coronary spasm using ergonovine, methylergonovine or acetylcholine as provocative stimuli. The lack of uniform protocol decreases the use and performance of these tests, accounting for vasospastic angina underestimation. This position paper from the French Coronary Atheroma and Interventional Cardiology Group (GACI) aims to review the indications for provocative tests, the testing conditions, drug protocols and positivity criteria.

Acute coronary syndrome due to multi-vessel coronary artery spasm in an Afghan refugee adolescent mimicking recurrent myocarditis.

Vasospastic angina is extremely uncommon for adolescents to experience chest discomfort, which is defined by transitory ST segment elevation or depression and angina symptoms that occur while at rest. It may result in potentially fatal conditions like myocardial infarction, ventricular fibrillation, or even sudden cardiac arrest. To aim of this article is to report a very rare case of a 17-year-old male Afghan refugee who was diagnosed with vasospastic angina after presenting with chest pain, and after receiving calcium channel blocker and nitrates for medical therapy, there were no angina attacks. Our case underlines the value of a thorough evaluation of adolescent's chest pain, the need to diagnose based on the symptoms, and the necessity of performing coronary angiography to rule out coronary causes when there is a high suspicion to a cardiac cause.

Vasospastic angina: Past, present, and future.

Vasospastic angina (VSA) is characterized by episodes of rest angina that are responsive to short-acting nitrates and are attributable to coronary artery vasospasm. The condition is underdiagnosed as the provocation test is rarely performed. VSA, the most important component of non-obstructive coronary artery disease, can present with angina, be asymptomatic, or can even present with fatal arrhythmias and cardiac arrest. Although most patients with VSA respond well to vasodilating medications, prognosis does not improve as expected in most patients, suggesting the existence elusive prognostic factors and pathogenesis that warrant further exploration. Moreover, patients with either severe or refractory VSA barely respond to conventional treatment and may develop life-threatening arrhythmias or suffer sudden cardiac death during ischemic attacks, which are associated with immune-inflammatory responses and have been shown to achieve remission following glucocorticoid and immunoglobulin treatments. Our recent work revealed that inflammation plays a key role in the initiation and development of coronary spasms, and that inflammatory cytokines have predictive value for diagnosis. In contrast to the existing literature, this review both summarizes the theoretical and clinical aspects of VSA, and also discusses the relationship between inflammation, especially myocarditis and VSA, in order to provide novel insights into the etiology, diagnosis, and treatment of VSA.

Effect of Statins on Major Adverse Cardiovascular Events in Patients with Coronary Artery Spasm: A Meta-Analysis of the Asia Region.

Background: Whether statins can reduce major cardiovascular adverse events (MACE) in patients with coronary artery spasm (CAS) is controversial. And most of the relevant research to date has been conducted in Asia. Methods: We systematically searched electronic databases for studies on the effect of statins on MACE in patients with CAS in Asia and published up to September 2022. We included data on MACE in a statin therapy patient group and a no-statin therapy control group. We then evaluated the effect of statin therapy on MACE in patients with CAS in Asia by meta-analysis and trial sequential analysis (TSA). All statistical analyses were performed using Stata 16.0 software and TSA software. Results: A total of 10 studies (n = 9333 patients) were included in the final analysis. Meta-analysis showed that the use of statins had a significant effect on MACE in CAS patients (with RR, 0.70; 95% CI, 0.49-0.99), and the sensitivity analysis further confirmed this finding. Subgroup analysis suggested that the correlation between statin therapy and reduced MACE endpoint was stronger in Japanese patients and patients followed up for more than 4 years. But our TSA results indicated that the available samples were insufficient and further research is needed. Conclusions: Our meta-analysis suggests that statin therapy can reduce MACE in patients with CAS in Asia, and the correlation between the two was stronger in Japanese patients and patients followed up for more than 4 years.