Masked inherited primary arrhythmia syndromes in sudden cardiac death patients accompanied by coronary vasospasm.

BACKGROUND/AIMS: Coronary vasospasms are one of the important causes of sudden cardiac death (SCD). Provocation of coronary vasospasms can be useful, though some results may lead to false positives, with patients potentially experiencing recurrent SCD despite appropriate medical treatments. We hypothesized that it is not coronary vasospasms but inherited primary arrhythmia syndromes (IPAS) that underlie the development of SCD. METHODS: We analyzed 74 consecutive patients (3.8%) who survived out-of-hospital cardiac arrest among 1,986 patients who had angiographically proven coronary vasospasms. Electrical abnormalities were evaluated in serial follow-up electrocardiograms (ECGs) during and after the index event for a 3.9 years median follow-up. Major clinical events were defined as the composite of death and recurrent SCD events. RESULTS: Forty five patients (60.8%) displayed electrocardiographic abnormalities suggesting IPAS: Brugada type patterns in six (8.2%), arrhythmogenic right ventricular dysplasia patterns in three (4.1%), long QT syndrome pattern in one (2.2%), and early repolarization in 38 (51.4%). Patients having major clinical events showed more frequent Brugada type patterns, early repolarization, and more diffuse multivessel coronary vasospasms. Brugada type pattern ECGs (adjusted hazard ratio [HR], 4.22; 95% confidence interval [CI], 1.16 to 15.99; p = 0.034), and early repolarization (HR, 2.97; 95% CI, 1.09 to 8.10; p = 0.034) were ultimately associated with an increased risk of mortality. CONCLUSIONS: Even though a number of aborted SCD survivors have coronary vasospasms, some also have IPAS, which has the potential to cause SCD. Therefore, meticulous evaluations and follow-ups for IPAS are required in those patients.

The 24-Month Prognosis of Patients With Positive or Intermediate Results in the Intracoronary Ergonovine Provocation Test.

OBJECTIVES: This study was an observational, multicenter registry to determine clinical characteristics and 24-month prognosis of patients who underwent intracoronary ergonovine provocation tests. BACKGROUND: The clinical characteristics and prognosis of patients who underwent the ergonovine provocation for vasospastic angina were not fully elucidated. METHODS: A total of 2,129 patients in the VA-KOREA (Vasospastic Angina in Korea) registry were classified into positive (n = 454), intermediate (n = 982), and negative (n = 693) groups by intracoronary ergonovine provocation tests. The 24-month incidences of cardiac death, new-onset arrhythmia, and acute coronary syndrome were determined (mean 26.7 ± 8.8 months). RESULTS: The number of smokers, frequency of angina before angiography, high-sensitivity C-reactive protein, and triglyceride were higher in the positive group than in other groups. The clinical characteristics of the intermediate and the negative groups were very similar. In the positive group, the incidences of diffuse, focal, and mixed spasm were 65.9%, 23.6%, and 10.6%. Coronary spasm was more frequently provoked on atherosclerotic segments. The 24-month incidences of cardiac death, arrhythmia, and acute coronary syndrome were low (0.9%, 1.6%, and 1.9%, respectively) in the positive group, and there was no cardiac death in the intermediate group (p = 0.02). In the positive group, frequent angina, current smoking, and multivessel spasm were independent predictors for adverse events. CONCLUSIONS: The 24-month prognosis of the positive group in the intracoronary ergonovine provocation test was relatively worse than that of the intermediate group. More intensive clinical attention should be paid to vasospastic angina patients with high-risk factors including frequent angina before angiography, current smoking, and multivessel spasm.

Should an implanted defibrillator be considered in patients with vasospastic angina?

UNLABELLED: Vasospastic angina is a frequent and well-recognized pathology with a high risk of life-threatening ventricular arrhythmias and sudden cardiac death. The diagnosis of vasospastic angina requires the combination of clinical and electrocardiographic variables and the results of provocation tests, such as ergonovine administration. Smoking cessation is the first step in the management of vasospastic angina. Optimal medical treatment using calcium-channel blockers and/or nitrate derivatives can provide protection, but life-threatening ventricular arrhythmias may occur despite optimal medical treatment and several years after the start of treatment. In this review, we evaluate the role of implantable defibrillators as a complement to optimal medical management in patients with life-threatening ventricular arrhythmias due to vasospastic angina; this role is not well characterized in the literature or guidelines. We discuss the role of implantable defibrillators in secondary prevention in light of three recent cases managed in our departments and a review of the literature. An implantable defibrillator was implanted in two of the three cases of vasospastic angina with ventricular arrhythmias that we managed. We considered secondary prevention by implantable defibrillator to be justified even in the absence of any obvious risk factor. Ventricular arrhythmias recurred during implantable defibrillator follow-up in the two patients implanted. CONCLUSION: In patients with life-threatening ventricular arrhythmias due to vasospastic angina, an implantable defibrillator should be considered because of the risk of recurrence despite optimal medical management.

Typical angina without significant coronary stenosis: comparison of clinical profile, circadian presentation, and long-term follow-up between patients with and patients without vasospastic angina.

OBJECTIVES: The spectrum of patients with 'angina and normal coronary arteries' ranges from severe vasospasm to atypical chest pain. Among those with typical angina, however, little is known about similarities in the clinical profile and circadian presentation between typical nonvasospastic angina and normal coronary arteries (tANCA) and vasospastic angina (VA). MATERIALS AND METHODS: Clinical, ECG, and angiographic features as well as the circadian characteristics of angina were compared between 384 tANCA and 273 VA patients. Follow-up events were also analyzed. RESULTS: tANCA patients had greater female predominance (61 vs. 18%), higher incidence of dyspnea to moderate exertion (49 vs. 12%), lower incidence of tobacco smoking (25 vs. 67%), but a similar low rate of diabetes (8.9 vs. 4.4%). In both groups, however, dyspnea and smoking were associated with female and male sex, respectively. tANCA patients showed lower but non-negligible frequency of early morning (25 vs. 67%) and evening angina (37 vs. 54%), similar rate of nocturnal angina (47 vs. 50%), and higher rate of emotional angina (49 vs. 31%). Moreover, a high proportion of patients gained pain relief with nitroglycerin (97% in VA, 246/253, and 76% in tANCA, 231/306). At 140 months, frequent angina (>10 episodes/year) was rare (VA: 7.1% vs. tANCA: 6.3%) as was the rate of cardiac death/myocardial infarction (7.3 vs. 6.0%, P=0.524). CONCLUSION: Despite differences in the clinical profile between VA and tANCA patients, there is notable sharing of circadian presentation of rest angina, response to nitroglycerin, and long-term presence and frequency of angina that suggests more similarities in underlying mechanisms than heretofore suspected.

Gender differences in the clinical characteristics and outcomes of patients with vasospastic angina--a report from the Japanese Coronary Spasm Association.

BACKGROUND: Accumulating evidence has demonstrated the gender differences in the clinical characteristics and outcomes of patients with ischemic heart disease. However, it remains to be elucidated whether it is also the case for vasospastic angina (VSA). METHODS AND RESULTS: We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median age 66 years) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. As compared with male patients, female patients were characterized by older age (median 69 vs. 66 years), lower incidence of smoking (20% vs. 72%) and less significant organic stenosis (9% vs. 16%) (all P=0.001). Multivariate analysis demonstrated that the predictors of major adverse cardiac events (MACE) were considerably different by genders; women were more associated with age and electrical abnormalities, whereas men with structural abnormalities. Overall 5-year MACE-free survival was comparable between both genders. However, when the patients were divided into 3 groups by age [young (<50 years), middle-aged (50-64 years) and elderly (≥65 years)], the survival was significantly lower in the young female group (young 82%, middle-aged 92%, elderly 96%, P<0.01), where a significant interaction was noted between age and smoking. In contrast, the survival was comparable among the 3 age groups of male patients. CONCLUSIONS: These results indicate that there are gender differences in the characteristics and outcomes of VSA patients, suggesting the importance of gender-specific management of the disorder.

Rates of coronary intervention due to de novo significant atherosclerosis and cardiac death are very low in Korean patients with vasospastic angina: 36-month follow-up results of the Vasospastic Angina in the Catholic Medical Center (VA-CMC) registry.

BACKGROUND: The rate of percutaneous coronary intervention (PCI) due to the development of significant atherosclerosis and the cardiac mortality rate in Korean patients with vasospastic angina (VSA) was estimated. METHODS AND RESULTS: A total of 831 patients with VSA from 8 centers were registered in the Vasospastic Angina in the Catholic Medical Center (VA-CMC) registry. Their provocation tests for VSA showed positive results. The patients with significant atherosclerosis (>50% luminal narrowing) on the baseline angiography were excluded. Subjects were VSA patients without significant atherosclerosis. A total of 745 patients were included in the final analysis. The mean follow-up duration was 36.1±9.8 months. The PCI rate was 2.01% (15/745). Current smoking (odds ratio: 2.31, P<0.05) and high levels of baseline high-sensitivity C-reactive protein (hsCRP) (odds ratio: 1.57, P<0.05) were independent risk factors for PCI. The mortality rate was 2.55% (19/745). Eleven patients died of cardiac causes (1.48%). Cessation of medication was an independent risk factor for cardiac mortality (odds ratio: 1.47, P<0.05). The mean duration from the diagnosis to the cardiac deaths was 10.6±4.3 months. CONCLUSIONS: Korean patients with VSA demonstrated low rates of development of significant atherosclerosis leading to PCI and cardiac mortality. However, cessation of medication, smoking, and high baseline hsCRP were the independent risk factors for unfavorable outcomes.

Takotsubo cardiomyopathy as an underlying mediator of myocardial infarction with normal coronary arteries.

OBJECTIVE: The purpose of the present study was to describe our experience with myocardial infarction with normal coronary arteries (MINCA) with regards to the prevalence, clinical characteristics, possible underlying etiologies (including Takotsubo cardiomyopathy, TCM) and the short- and long-term outcomes associated with this condition. METHODS: We retrospectively analyzed the records of 596 consecutive patients presenting with acute myocardial infarction over a 4-year period and identified 24 patients (14 female, 10 male) with angiographically normal coronary arteries. Demographic and clinical variables and outcomes were reviewed. RESULTS: Mean patient age was 59 +/- 20 years. The presumed MINCA mechanism was TCM in 10 patients (41.7%), probable myocarditis in 5 (20.8%), coronary spasm in 4 (16.7%), coronary thrombus in 3 (12.5%) and aortic dissection in 2 patients (8.3%). After a mean follow-up of 19 +/- 14 months, 2 patients with probable myocarditis had died of cardiovascular causes, 1 patient with aortic dissection had died due to sepsis after surgery and 1 patient with TCM had died of noncardiovascular causes 2 years after discharge. CONCLUSION: In this study, we found that MINCA occurred in 4% of patients with acute myocardial infarction undergoing emergent coronary angiography, with the most frequent underlying mechanism being TCM.

[Long-term prognosis of coronary artery spasm]. / Pronostic à long terme du spasme artériel coronaire.

This study analyses the long-term prognosis of 210 patients with coronary spasm documented at coronary angiography. All patients with a previous history of myocardial infarction or who had undergone coronary angioplasty were excluded. The average follow-up was 55 months and only 11 patients were lost to follow-up. The actuarial survival figures showed the 1 year, 2 year and 5 year survival rates to be 95, 92 and 89 per cent respectively. Extracardiac mortality was mainly related to smoking (lung cancer, laryngeal cancer, etc.) and was higher than cardiac mortality. More than half of the cardiovascular events (sudden death, myocardial infarcts) occurred during the first year of follow-up. Ten patients (4.7%) died suddenly. The predictive factors of this event were: previous syncopal episodes or syncopal angina due to coronary spasm, percritical arrhythmias and the documentation of multiple spasms at coronary angiography. Myocardial infarction was observed in 10.6 per cent of patients. Only those with significant coronary arterial lesions developed this complication. At the end of the follow-up period, 75 per cent of patients were asymptomatic or had only atypical chest pain. No significant differences were observed between the two groups treated medically, by aortocoronary bypass or by the association of coronary bypass and plexectomy with the exception of non-lethal myocardial infarcts being significantly less common in patients treated medically. Therefore, the long-term prognosis of patients with coronary spams is relatively satisfactory.

Factors influencing the long-term prognosis of treated patients with variant angina.

To determine the prognosis of variant angina and the factors influencing it, 169 consecutive patients hospitalized in our coronary unit were followed for a mean of 15.3 months (range 1 to 68). Survival at 1, 2, and 3 years was 95%, 90%, and 87%, respectively; survival without myocardial infarction was 80%, 78%, and 75%. Twenty of the 22 myocardial infarctions and eight of the 14 deaths occurred within the first 3 months. Mantel-Haenszel log-rank analysis demonstrated that coronary disease, ventricular function, and the degree of disease activity were significant interdependent variables that influenced both survival and survival without infarction. At 1, 2, and 3 years, survival for patients with multivessel disease was 81%, 76%, and 66%; for patients with one-vessel disease, 97%, 92%, and 92%; and for patients without stenoses greater than or equal to 70%, 98% at each year (p = .0003). Survival without infarction at 1 year was 88% in patients with no stenoses greater than or equal to 70% and 82% in patients with single-vessel disease; it did not change thereafter in either group, but was 62%, 58%, and 50% at 1, 2, and 3 years in patients with multivessel disease (p = .001). Treatment did not influence survival in any subgroup (only 14 patients died overall) or survival without infarction in patients with multivessel disease. However, in patients without multivessel disease, treatment with nifedipine, diltiazem, and verapamil improved survival without infarction compared to treatment with perhexiline maleate or long-acting nitrates alone (92% vs 67% at 1, 2, and 3 years; p less than .005). Thus in addition to preventing angina, nifedipine, diltiazem, and verapamil appear to reduce complications in patients with variant angina without multivessel disease.