RNF213 Variants, Vasospastic Angina, and Risk of Fatal Myocardial Infarction.

Importance: Vasospastic angina (VSA) is vasospasm of the coronary artery and is particularly prevalent in East Asian populations. However, the specific genetic architecture for VSA at genome-wide levels is not fully understood. Objective: To identify genetic factors associated with VSA. Design, Setting, and Participants: This was a case-control genome-wide association study of VSA. Data from Biobank Japan (BBJ; enrolled patients from 2002-2008 and 2013-2018) were used, and controls without coronary artery disease (CAD) were enrolled. Patients from the BBJ were genotyped using arrays or a set of arrays. Patients recruited between 2002 and 2005 were classified within the first dataset, and those recruited between 2006 and 2008 were classified within the second dataset. To replicate the genome-wide association study in the first and second datasets, VSA cases and control samples from the latest patients in the BBJ recruited between 2013 and 2018 were analyzed in a third dataset. Exposures: Single-nucleotide variants associated with VSA. Main Outcomes and Measures: Cases with VSA and controls without CAD. Results: A total of 5720 cases (mean [SD] age, 67 [10] years; 3672 male [64.2%]) and 153 864 controls (mean [SD] age, 62 [15] years; 77 362 male [50.3%]) in 3 datasets were included in this study. The variants at the RNF213 locus showed the strongest association with VSA across the 3 datasets (odds ratio [OR], 2.34; 95% CI, 1.99-2.74; P = 4.4 × 10-25). Additionally, rs112735431, an Asian-specific rare deleterious variant (p.Arg4810Lys) experimentally shown to be associated with reduced angiogenesis and a well-known causal risk for Moyamoya disease was the most promising candidate for a causal variant explaining the association. The effect size of rs112735431 on VSA was distinct from that of other CADs. Furthermore, homozygous carriers of rs112735431 showed an association with VSA characterized by a large effect estimate (OR, 18.34; 95% CI, 5.15-65.22; P = 7.0 × 10-6), deviating from the additive model (OR, 4.35; 95% CI, 1.18-16.05; P = .03). Stratified analyses revealed that rs112735431 exhibited a stronger association in males (χ21 = 7.24; P = .007) and a younger age group (OR, 3.06; 95% CI, 2.24-4.19), corresponding to the epidemiologic features of VSA. In the registry, carriers without CAD of the risk allele rs112735431 had a strikingly high mortality rate due to acute myocardial infarction during the follow-up period (hazard ratio, 2.71; 95% CI, 1.57-4.65; P = 3.3 × 10-4). As previously reported, a possible overlap between VSA and Moyamoya disease was not found. Conclusions and Relevance: Results of this study suggest that vascular cell dysfunction mediated by variants in the RNF213 locus may promote coronary vasospasm, and the presence of the risk allele could serve as a predictive factor for the prognosis.

Severe ST-segment elevation and AV block during pulsed-field ablation due to vasospastic angina - a novel observation.

Catheter ablation of atrial fibrillation using non-thermal electroporation represents a promising ablation modality due to its believed superior safety profile. Still, if electroporation is delivered in proximity to a coronary artery, vasospasms can occur. We report the first case of severe right coronary artery vasospasm resulting in ST-segment elevation and AV block despite a remote distance from the ablation site to the right coronary artery, indicating a different mechanism. In this case, electroporation most likely triggered a previously unknown Prinzmetal vasospastic angina in the patient, resulting in the coronary vasospasm. Thus, meticulous monitoring of ST-segment changes following PFA delivery even from regions remote to coronary arteries is required.

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.

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.

Dietary inflammation index association with serum levels of nitric oxide, prostacyclin, and thromboxane B2 among prinzmetal angina patients and healthy persons.

BACKGROUND AND AIM: This study aimed to assess the association between dietary inflammation index with serum Nitric oxide, Prostacyclin, and Thromboxane B2 among Prinzmetal angina patients and healthy persons. METHODS AND RESULTS: This case-control study was conducted among 120 Prinzmetal angina patients and 120 healthy persons referred to the Ardabil Imam Khomeini Hospital between 2021 and 2022. Blood samples were gained from all study participants for measurement of serum Nitric oxide, Prostacyclin, and Thromboxane B2. The serum Nitric oxide in patients who had higher DII was less than in patients with less dietary inflammation index (ß = -0.75 p = 0.02). The serum Prostacyclin level in patients with greater dietary inflammation index was 0.68 ng/ml less than in patients with less dietary inflammation index (ß = -0.68 p = 0.04). The level of serum Thromboxane B2 had a positive association with dietary inflammation index (ß = 0.81 p = 0.04). CONCLUSION: In Prinzmetal angina patients, more dietary inflammation index can increase the serum Thromboxane B2 and decrease the serum Nitric oxide and Prostacyclin. More clinical trial study is needed to confirm these results.

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.

Prinzmetal angina in a child with actin gene ACTC1 mutation.

Prinzmetal angina is a rare cause of intermittent chest pain in paediatrics. Here, we report the case of a 2-year-old female who presented with episodic chest pain, malaise, diaphoresis, fatigue, and poor perfusion on exam. During her hospitalisation, these episodes were associated with significant low cardiac output as evidenced by lactic acidosis and low mixed venous oxygen saturations. Her workup revealed an actin alpha cardiac muscle 1 (ACTC1) gene mutation and associated left ventricular non-compaction with decreased systolic function. She was started on oral heart failure medications as well as a calcium channel blocker but continued to have episodes which were found to promptly resolve with nitroglycerine. She was ultimately listed for cardiac transplant given her perceived risk of sudden death.

Vasospastic Angina With ST-Segment Elevation Seen During Mobile Cardiac Outpatient Telemetry (MCOT) Monitoring.

A 54-year-old man presented with significant ST-segment elevations noted on both channels displayed on the mobile cardiac outpatient telemetry (MCOT). Pertinent cardiac history was remarkable for syncope and episodes of atypical chest pain. The latter were described as infrequent and not associated with exercise intolerance. His syncopal episodes were described as occurring mostly in the mornings after the use of the restroom. Episodes happen 1 or 2 times a year since 2015. Patient had undergone thorough investigation with no significant findings. An MCOT was prescribed since frequency of symptoms has recently increased. Significant ST-segment elevations were noted. The patient described atypical chest pain and a sensation of presyncope during these recordings. He was urgently admitted, and a coronary angiogram revealed no epicardial luminal stenosis. However, the presence of sluggish coronary flow was suggestive of possible vasospastic angina. No ST-segment changes were noted during his coronary angiogram. The remarkable element portrayed by this case hinges in showing the unique utility of MCOT, as the most uncharacteristic diagnostic tool, in identifying transient ST-segment elevations that finally led to the diagnosis.

Adherence to the Mediterranean Diet Association with Serum Levels of Nitric Oxide, Prostacyclin, and Thromboxane B2 among Prinzmetal Angina Patients and Healthy Persons.

This study aimed to assess the association between adherence to the Mediterranean diet with serum Nitric oxide, Prostacyclin, and Thromboxane B2 among Prinzmetal angina patients and healthy persons. This case-control study was conducted among 100 Prinzmetal angina patients and 100 healthy persons referred to the Ardabil Imam Khomeini hospital between 2021 and 2022. Blood samples were obtained from all study participants for measurement of serum Nitric oxide, Prostacyclin, and Thromboxane B2. To calculate adherence to the Mediterranean diet, the ten-item screener was used. The serum Nitric oxide in patients who adhered more to the Mediterranean diet was higher than patients with less adherence (coeff. = 0.41 p = 0.04). The serum Prostacyclin level in patients with greater adherence to the Mediterranean diet was 0.34 units higher than patients with less adherence (coeff. = 0.34 p = 0.02). The level of serum Thromboxane B2 had a negative association with adherence to the Mediterranean diet (coeff. = -0.48 p = 0.04). The amount of consumption of olive oil, fruits, vegetables, and legumes in healthy people was more than Prinzmetal angina patients. In Prinzmetal angina patients, more adherence to the Mediterranean diet can decrease the serum Thromboxane B2 and increase the serum Nitric oxide and Prostacyclin.

Life-threatening Vasospastic Angina Induced by Carteolol Eye Drops.

Vasospastic angina (VSA) can be worsened by oral nonselective beta-blockers. Ophthalmic carteolol eye drops are nonselective beta-blockers and effective against glaucoma and ocular hypertension. Systemic effects of ophthalmic beta-blockers on VSA have not yet been reported. We herein report a case of VSA that developed after a patient started carteolol eye drops for ocular hypertension. Even though benidipine, a calcium channel blocker, was started, a VSA attack with incessant non-sustained ventricular tachycardia occurred. Once the carteolol eyedrops were discontinued, the VSA resolved. This case demonstrates that carteolol eye drops can induce life-threatening VSA.

Successful Use of Continuous Erector Spinae Plane Blocks in a Patient With Variant Angina After Large Ventral Hernia Repair.

Coronary artery spasm constitutes the primary underlying pathology of variant angina. Because provocation of coronary artery spasm may occur with both excess sympathetic and excess parasympathetic stimulation, patients with this disorder have extremely limited options for perioperative pain control. This is especially true for procedures involving extensive abdominal incision/manipulation. Whereas neuraxial analgesia might otherwise be appropriate in these cases, several studies have demonstrated that coronary artery spasm can occur as a result of epidural placement, and therefore, that this may not be an optimal choice for patients with variant angina. This report discusses the case of a patient with a preexisting diagnosis of variant angina who underwent an exploratory laparotomy with large ventral hernia repair and for whom continuous erector spinae plane blocks were successfully used as analgesic adjuncts without triggering coronary artery spasm.

Spontaneous Multivessel Coronary Spasm During Diagnostic Coronary Angiography.

Acute vasospastic angina, formerly known as Prinzmetal angina, is characterized by transient electrocardiographic changes that are not related to exertion. Its atypical presentation makes it difficult to establish the diagnosis, so it is probably underrecognized and therefore mismanaged. We treated a 49-year-old woman who presented with a 2-day history of chest pain associated with palpitations. Abnormal radionuclide stress test results prompted diagnostic coronary angiography, during which the patient reported chest pain and became hemodynamically unstable. Active coronary vasospasm at multiple sites was treated with intracoronary nitroglycerin and nicardipine, leading to immediate recovery. Our case highlights the importance of accurate, timely diagnosis of vasospastic angina, and of early recognition and management of spontaneous coronary spasm during angiography.