A case of early repolarization syndrome in which hyponatremia and coronary vasospasms induced ventricular fibrillation.

A 60-year-old man was referred to our hospital presenting with unconsciousness due to severe hyponatremia. The twelve­lead ECG on admission exhibited prominent J waves in the inferolateral leads. During the treatment for hyponatremia, ventricular fibrillation (VF) occurred and the electrogram (ECG) after the VF incident exhibited marked ST elevation in the inferolateral leads. An Ach provocation test induced vasospasms in the right and left coronary arteries and J wave augmentation, suggesting a high risk for vasospastic angina. Finally, a subcutaneous implantable cardioverter defibrillator was implanted in the patient. We hereby discuss the possible contribution of hyponatremia to VF episodes in early repolarization syndrome based on the present case.

Multivessel Coronary Function Testing Increases Diagnostic Yield in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.

The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal.

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

Long-acting cilostazol versus isosorbide mononitrate for patients with vasospastic angina: a randomized controlled trial.

BACKGROUND: Cilostazol has a vasodilatory function that may be beneficial for patients with vasospastic angina (VSA). We conducted a randomized, open-label, controlled trial to compare the efficacy and safety of long-acting cilostazol and isosorbide mononitrate (ISMN) for VSA. METHODS: The study included patients with confirmed VSA between September 2019 and May 2021. Participants were randomly assigned to receive long-acting cilostazol (test group, 200 mg once daily) or conventional ISMN therapy (control group, 20 mg twice daily) for 4 weeks. The clinical efficacy and safety were evaluated using weekly questionnaires. RESULTS: Forty patients were enrolled in the study (long-acting cilostazol, n  = 20; ISMN, n  = 20). Baseline characteristics were balanced between the two groups. Long acting cilostazol showed better angina symptom control within the first week compared to ISMN [reduction of pain intensity score, 6.0 (4.0-8.0) vs. 4.0 (1.0-5.0), P  = 0.005; frequency of angina symptom, 0 (0-2.0) vs. 2.0 (0-3.0), P  = 0.027, respectively]. The rate of neurological adverse reactions was lower in the cilostazol group than in the ISMN group (headache or dizziness, 40 vs. 85%, P  = 0.009; headache, 30 vs. 70%, P  = 0.027). CONCLUSION: Long-acting cilostazol provided comparable control of angina and fewer adverse neurologic reactions within 4 weeks compared to ISMN. Long-acting cilostazol provides more intensive control of angina within 1 week, suggesting that it may be an initial choice for the treatment of VSA.

Relation of Vasoreactivity in the Left and Right Coronary Arteries During Acetylcholine Spasm Provocation Testing.

The diagnosis of vasospastic angina (VSA) according to Japanese guidelines involves an initial intracoronary acetylcholine (ACh) provocation test in the left coronary artery (LCA) followed by testing in the right coronary artery (RCA). However, global variations in test protocols often lead to the omission of ACh provocation in the RCA, potentially resulting in the underdiagnosis of VSA. This study assessed the validity of the LCA-only ACh provocation approach for the VSA diagnosis and whether vasoreactivity in the LCA aids in determining further provocation in the RCA. A total of 273 patients who underwent sequential intracoronary ACh provocation testing in the LCA and RCA were included. Patients with a positive ACh provocation test in the LCA were excluded. Relations between vasoreactivity in the LCA and ACh test outcomes (positivity and adverse events) in the RCA were evaluated. In patients with negative ACh test results in the LCA, subsequent ACh testing was positive in the RCA in 23 of 273 (8.4%) patients. In patients with minimal LCA vasoconstriction (<25%), only 3.0% had a positive ACh test in the RCA, whereas the ACh test in the RCA was positive in 13.5% of those with LCA constriction of 25% to 90% (p = 0.002). No major adverse events occurred during ACh testing in the RCA. In conclusion, for the VSA diagnosis, the omission of ACh provocation in the RCA may be clinically acceptable, particularly when vasoconstriction induced by ACh injection was minimal in the LCA. Further studies are needed to define ACh provocation protocols worldwide.

Elevated white blood cell count and long-term clinical outcomes of patients with vasospastic angina.

OBJECTIVES: Inflammation is known as one of key pathophysiologic mechanisms of coronary artery disease. We aimed to investigate the relationship between white blood cell (WBC) count and long-term clinical outcomes of patients with vasospastic angina (VA). METHODS: A total of 823 patients who were diagnosed as VA without significant coronary lesion by coronary angiography with ergonovine provocation test were enrolled for analysis. Patients were divided according to WBC count tertile at the time of diagnosis: group I, tertile 1 and 2 (n = 546, <7490/ml); group II, tertile 3 (n = 277, ≥7490/ml). Primary outcome was defined as major adverse cardiovascular events (MACE), a composite outcome of all-cause death, cardiac death, myocardial infarction (MI), readmission due to cardiac symptoms, and revascularization. RESULTS: Median follow-up duration was 4.3 years. No significant difference of primary outcome was observed between group I and group II (14.7% vs. 20.2%, hazard ratio (HR) 1.29, confidence interval (CI) 0.90-1.83, P  = 0.162), while incidence of cardiac death and MI was significantly higher in group II (1.5% vs. 4.3%, HR 2.86, CI 1.14-7.17), P  = 0.025). In multivariate Cox regression model, elevated WBC count at the time of diagnosis of VA was an independent predictor of MI (HR 3.43, CI 1.02-11.59, P  = 0.047). CONCLUSION: Elevated WBC count at the time of diagnosis was associated with a significantly increased risk of cardiac death and MI during long-term follow-up in VA patients.

Spontaneous multivessel coronary artery spasm: a case report.

A 60-year-old male presented to the emergency department of our hospital with persistent dull pain in the lower and middle sternum with generalized sweating after a heated argument with another person, and his symptoms did not resolve after 3 hours of onset.

Hyperventilation testing in the diagnosis of vasospastic angina: A clinical review and meta-analysis.

BACKGROUND: Given the limited access to invasive vasospastic reactivity testing in Western Countries, there is a need to further develop alternative non-invasive diagnostic methods for vasospastic angina (VSA). Hyperventilation testing (HVT) is defined as a class IIa recommendation to diagnose VSA by the Japanese Society of Cardiology. METHODS: In this systematic review and meta-analysis reported according to the PRISMA statement, we review the mechanisms, methods, modalities and diagnostic accuracy of non-invasive HVT for the diagnostic of VSA. RESULTS: A total of 106 articles published between 1980 and 2022 about VSA and HVT were included in the systematic review, among which 16 were included in the meta-analysis for diagnostic accuracy. Twelve electrocardiogram-HVT studies including 804 patients showed a pooled sensitivity of 54% (95% confidence intervals [CI]; 30%-76%) and a pooled specificity of 99% (95% CI; 88%-100%). Four transthoracic echocardiography-HVT studies including 197 patients revealed a pooled sensitivity of 90% (95% CI; 82%-94%) and a pooled specificity of 98% (95% CI; 86%-100%). Six myocardial perfusion imaging-HVT studies including 112 patients yielded a pooled sensitivity of 95% (95% CI; 63%-100%) and a pooled specificity of 78% (95% CI; 19%-98%). Non-invasive HVT resulted in a low rate of adverse events, ventricular arrhythmias being the most frequently reported, and were resolved with the administration of nitroglycerin. CONCLUSIONS: Non-invasive HVT offers a safe alternative with high diagnostic accuracy to diagnose VSA in patients with otherwise undiagnosed causes of chest pain.

Comparison of clinical outcomes in patients with mixed angina and pure vasospastic angina.

OBJECTIVE: This study investigated differences in clinical outcomes between mixed angina (MA) and pure vasospastic angina (PVA). METHODS: A total of 524 vasospastic angina patients who did or did not have >50% coronary artery stenosis from January 2005 to January 2021 were divided into two groups (Group 1: PVA, N  = 399; Group 2: MA, N  = 125) and then three groups [Group 1: PVA, N  = 399; Group 2: MA without percutaneous coronary intervention (PCI), N  = 67; Group 3: MA with PCI, N  = 58] for assessment. We recorded the incidence of major adverse cardiac and cerebrovascular events (MACCE: the composite of death, myocardial infarction, nonfatal stroke or rehospitalization) during 3-year clinical follow-up. RESULTS: Compared to the PVA group, there were significant differences in MACCE (20.8% vs. 11.8%, P  = 0.011) and rehospitalization (20.0% vs. 9.8%, P  = 0.002) in the MA group. Kaplan-Meier analysis showed that patients in the MA with PCI group had the highest cumulative incidence rate of MACCE during the 3-year follow-up (log-rank P  < 0.001). CONCLUSION: Compared with the PVA patients, MA patients had significantly worse clinical outcomes during long-term follow-up.

Severe coronary artery spasm during left atrial appendage closure plus catheter ablation for atrial fibrillation: case presentation.

BACKGROUND: Left atrial appendage closure (LAAC) combined with radiofrequency catheter ablation (RFCA) as a hybrid procedure is commonly performed to treat atrial fibrillation (AF). Although this treatment carries a low risk of coronary artery spasm (CAS), and has never been observed in LAAC procedure, caution still needed to be taken. We presented a case of CAS that occurred in an AF patient during the hybrid procedure. CASE PRESENTATION: The patient was a 65-year-old man with paroxysmal AF who developed CAS during RFCA and LAAC. In this case, LAAC was performed ahead of RFCA. After atrial septal puncture, the occluder was advanced into left atrium through delivery sheath, and successfully deployed in the LAA. After verifying the assessment of "PASS" criteria, we decided to release the device. However, before releasing the occluder in LAAC, the patient's blood pressure (BP) fell to 70/45 mmHg with heart rate (HR) drop and ST-segment elevation in II, III, and aVF and reciprocal ST-segment depression in I and aVL. Isotonic sodium chloride load was administered. After 3 min, the BP and HR raised, and ST-segment returned to normal. The occluder was successfully released after the stable condition of the patient. Then, RFCA was sequentially performed. When isolating the right pulmonary veins, the patient's BP and HR fell again with ST-segment elevation in inferior leads. Spontaneous ventricular tachycardia and fibrillation developed rapidly and defibrillation was performed immediately with success. Coronary angiography revealed the obstruction of the right coronary artery which disappeared completely after intracoronary nitroglycerin injection (1 mg). Under systemic diltiazem infusion, the RFCA procedure was accomplished. After the procedure, the patient recovered without any neurologic deficit, and CAS has never recurred with isosorbide mononitrate treatment during follow-up. CONCLUSIONS: CAS is a rare complication associated with AF hybrid procedure. Attention should be paid to this rare but potentially life-threatening complication.

Recurrent idiopathic carotid and coronary artery vasospasm treated by stent implantations.

Arterial vasospasm is a well known cause of ischemia and, if prolonged, of parenchymal infarction. The clinical presentation varies according to the involved arterial district. We describe a rare case, which occurred in a young lady, of recurrent and multisystem vasospasm, resulting in multiple cerebral and myocardial infarctions. Our patient was resistant to medical therapy, requiring stent implantation of the involved vessels.

Pathophysiology of Takotsubo Cardiomyopathy: Reopened Debate.

Takotsubo cardiomyopathy (TTC), a persistently obscure dysfunctional condition of the left ventricle, is uniquely transient but nevertheless dangerous. It features variable ventricular patterns and is predominant in women. For 30 years, pathophysiologic investigations have progressed only slowly and with inadequate focus. It was initially proposed that sudden-onset spastic obliteration of coronary flow induced myocardial ischemia with residual stunning and thus TTC. Later, it was generally accepted without proof that, in the presence of pain or emotional stress, the dominant mechanism for TTC onset was a catecholamine surge that had a direct, toxic myocardial effect. We think that the manifestations of TTC are more dynamic and complex than can be assumed from catecholamine effects alone. In addition, after reviewing the recent medical literature and considering our own clinical observations, especially on spasm, we theorize that atherosclerotic coronary artery disease modulates and physically opposes obstruction during spasm. This phenomenon may explain the midventricular variant of TTC and the lower incidence of TTC in men. We continue to recommend and perform acetylcholine testing to reproduce TTC and to confirm our theory that coronary spasm is its initial pathophysiologic factor. An improved understanding of TTC is especially important because of the condition's markedly increased incidence during the ongoing COVID-19 pandemic.

Interplay Between Myocardial Bridging and Coronary Spasm in Patients With Myocardial Ischemia and Non-Obstructive Coronary Arteries: Pathogenic and Prognostic Implications.

Background Myocardial bridging (MB) may represent a cause of myocardial ischemia in patients with non-obstructive coronary artery disease (NOCAD). Herein, we assessed the interplay between MB and coronary vasomotor disorders, also evaluating their prognostic relevance in patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) or stable NOCAD. Methods and Results We prospectively enrolled patients with NOCAD undergoing intracoronary acetylcholine provocative test. The incidence of major adverse cardiac events, defined as the composite of cardiac death, non-fatal myocardial infarction, and rehospitalization for unstable angina, was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires summary score. We enrolled 310 patients (mean age, 60.6±11.9; 136 [43.9%] men; 169 [54.5%] stable NOCAD and 141 [45.5%] MINOCA). MB was found in 53 (17.1%) patients. MB and a positive acetylcholine test coexisted more frequently in patients with MINOCA versus stable NOCAD. MB was an independent predictor of positive acetylcholine test and MINOCA. At follow-up (median, 22 months; interquartile range, 13-32), patients with MB had a higher rate of major adverse cardiac events, mainly driven by a higher rate of hospitalization attributable to angina, and a lower Seattle Angina Questionnaires summary score (all P<0.001) compared with patients without MB. In particular, the group of patients with MB and a positive acetylcholine test had the worst prognosis. Conclusions Among patients with NOCAD, coronary spasm associated with MB may predict a worse clinical presentation with MINOCA and a higher rate of hospitalization attributable to angina at long-term follow-up with a low rate of hard events.

Case report of an acute myocardial infarction complicated by coronary spasm in a patient with chronic systemic lupus erythematosus.

Acute myocardial infarction (AMI) is a major cause of death in a patient with systemic lupus erythematosus (SLE). Due to their chronic inflammatory state, patient with SLE has an increased risk of developing coronary artery disease. We report a case of a middle-aged woman with an acute myocardial infarction (AMI) caused by a right coronary artery (RCA) stenosis complicated with severe coronary artery spasm. Our patient has a history of long-standing SLE. Clinical expression of coronary artery disease (CAD) in SLE is the result of different pathophysiologic mechanism. From this case, we raise the importance of the clinician to be aware of the diverse pathophysiologic pathways involving a coronary artery in a patient with SLE.

Peripheral Administration of Nitroglycerin in Pulseless Ventricular Tachycardia due to Cocaine-Induced Coronary Vasospasm.

Cocaine use accounts for 40% of the annual drug use related emergency department visits in the United States. Cocaine use is hence recognized as a major health problem. Cocaine blocks the presynaptic reuptake of norepinephrine and dopamine. The resulting increased adrenergic activity leads to vasoconstriction. Additionally, via various mechanisms, cocaine leads to a prothrombotic state and increases myocardial demand. Cocaine can cause coronary vasospasm and is therefore, associated with acute myocardial injury even in the absence of pre-existing atherosclerotic coronary artery disease. Nitroglycerin has a class 1C indication by the ACCF/AHA guidelines for patients with ST-segment elevation or depression that accompanies ischemic chest discomfort in the setting of cocaine use. It has been shown to reverse cocaine-induced coronary vasospasm and chest pain. In this case report, for the first time, we discuss how intravenous administration of high dose nitroglycerin to a patient in pulseless ventricular tachycardia with angiographically confirmed vasospasm induced by cocaine resulted in return of spontaneous circulation.

Absolute Coronary Blood Flow Measured by Continuous Thermodilution in Patients With Ischemia and Nonobstructive Disease.

BACKGROUND: Intracoronary continuous thermodilution is a novel technique to quantify absolute coronary flow (Q) and resistance (R) and has potential advantages over current methods such as coronary flow reserve (CFR) and index of microvascular resistance (IMR). However, no data are available in patients with ischemia and nonobstructive coronary artery disease (INOCA). OBJECTIVES: This study aimed to assess the relationship of Q and R with the established CFR/IMR in INOCA patients, to explore the potential of absolute Q, and to predict self-reported angina. METHODS: Consecutive INOCA patients (n = 84; 87% women; mean age 56 ± 8 years) underwent coronary function testing, including acetylcholine (ACH) provocation testing, adenosine (ADE) testing (CFR/IMR), and continuous thermodilution (absolute Q and R) with saline-induced hyperemia. RESULTS: ACH testing was abnormal (ACH+) in 87%, and ADE testing (ADE+) in 38%. The median absolute Q was 198 ml/min, and the median absolute R was 416 WU. The absolute R was higher in patients with ADE+ versus ADE- (495 WU vs. 375 WU; p = 0.04) but did not differ between patients with ACH+ versus ACH- (421 WU vs. 409 WU; p = 0.74). Low Q and high R were associated with severe angina (odds ratio: 3.09; 95% confidence interval: 1.16 to 8.28; p = 0.03; and odds ratio: 2.60; 95% confidence interval: 0.99 to 6.81; p = 0.05), respectively. CONCLUSIONS: In this study, absolute R was higher in patients with abnormal CFR/IMR, whereas both Q and R were unrelated to coronary vasospasm. Q and R were associated with angina, although their exact predictive value should be determined in larger studies.

Structural Thickening of Medial Layer in Coronary Artery With Spasm in Patients With Myocardial Infarction.

Background The underlying pathophysiology of coronary artery spasm (CAS) remains unclear. We aim to determine whether coronary artery medial layer thickness is associated with CAS using optical coherence tomography. Methods and Results A total of 50 patients with previous myocardial infarction underwent optical coherence tomography of the left anterior descending artery: 20 with CAS and 30 without CAS. Intimal and medial layer areas were measured by planimetric analysis of optical coherence tomography images. The medial area/external elastic membrane (EEM) area was significantly greater in patients with than without CAS (0.13±0.01 versus 0.09±0.01, respectively, P<0.01), whereas the intimal area/EEM area was similar in the 2 groups. In patients without CAS, the relationship of intimal area/EEM area with medial area/EEM area and coronary diameter response to intracoronary injection of acetylcholine was characterized by an inverted U-shaped curve (y=-1.85x2+0.81x+0.01, R2=0.43, P<0.001) and a U-shaped curve (y=2993.2x2-1359.6x+117.1, R2=0.53, P<0.001), respectively. Thus, the medial layer became thin and the contractile response became weak in coronary arteries with greater intimal area in the non-CAS patients. In contrast, in patients with CAS, the intimal area/EEM area had no significant relationship with the medial area/EEM area in either linear correlation analysis or quadratic regression analysis. Thus, even when the intimal layer thickened, the medial layer did not thin in patients with CAS. Conclusions The structural thickness of the coronary medial layer was increased in patients with CAS, which may provide mechanistic insight into the pathogenesis of CAS. Registration URL: https://www.upload.umin.ac.jp; Unique identifier: UMIN000018432.

Coincidence between spontaneous and inducible coronary spasm: acetylcholine test is clinically valued for diagnosing coronary spasm.

There is no report regarding the correlation between spontaneous documented coronary spasm and acetylcholine (ACh)-inducible spasm. We retrospectively analyzed the coincidence between angiographical spontaneous coronary spasm and ACh-inducible spasm in the same patients. We recruited 28 patients with 30 angiographical spontaneous coronary spasm in 6009 patients with diagnostic and follow-up coronary arteriography from Jan 1991 and Mar 2019 in the cardiac catheterization laboratory. We could perform intracoronary ACh testing in 19 patients with 20 vessels. ACh was injected in incremental dose of 20/50/100 µg into the left coronary artery and 20/50/80 µg into the right coronary artery. Positive spasm was defined as > 90% stenosis and ischemic ECG changes. Angiographical documented spontaneous coronary spasm was observed in 0.47% (28/6009) of patients with diagnostic and follow-up coronary angiography. Intracoronary administration of ACh reproduced 15 spontaneous coronary spasm and no provoked spasm was observed in the remaining 5 vessels due to the administration of nitroglycerine or under medications. Spasm-provoked sites by ACh tests and ACh-inducible spasm configurations were almost similar to spontaneous spasm. Coincidence of provoked spasm site (93.3% vs. 6.7%, p < 0.001) and spasm configuration (93.3% vs. 6.7%, p < 0.001) was markedly higher than discordance. Intracoronary ACh testing can reproduce spontaneous coronary artery spasm in 75% of vessels with almost similar sites and same morphological characteristics irrespective of the administration of nitroglycerine or vasodilators. ACh test is a reliable method to document coronary artery spasm in the clinic.

Coronary artery lumen complexity as a new marker for refractory symptoms in patients with vasospastic angina.

Refractory angina is an independent predictor of adverse events in patients with vasospastic angina (VSA). The aim of this study was to investigate the relationship between coronary lumen complexity and refractory symptoms in patients with VSA. Seventeen patients with VSA underwent optical coherence tomography. The patients were divided into the refractory VSA group (n = 9) and the stable VSA group (n = 8). A shoreline development index was used to assess the coronary artery lumen complexity. Shear stress was estimated using a computational fluid dynamics model. No difference was observed in the baseline characteristics between the two groups. The refractory VSA group showed the higher shoreline development index (refractory VSA 1.042 [1.017-1.188] vs stable VSA 1.003 [1.006-1.025], p = 0.036), and higher maximum medial thickness (refractory VSA 184 ± 17 µm vs stable VSA 148 ± 31 µm, p = 0.017), and higher maximum shear stress (refractory VSA 14.5 [12.1-18.8] Pa vs stable VSA 5.6 [3.0-10.5] Pa, p = 0.003). The shoreline development index positively correlates with shear stress (R2 = 0.46, P = 0.004). Increased medial thickness of the coronary arteries provokes lumen complexity and high shear stress, which might cause refractory symptoms in patients with VSA. The shoreline index could serve as a marker for irritability of the medial layer of coronary arteries and symptoms.