Anastasios Athanasiadis

Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study.

OBJECTIVES This study was conducted to clarify the incidence of coronary spasm in emergency patients with suspected acute coronary syndrome (ACS) and acute chest pain at rest. BACKGROUND Chest pain at rest is a frequent symptom in the emergency room. Acute coronary syndrome is suspected in patients with elevation of cardiac markers, ischemic electrocardiographic changes, or simply typical clinical symptoms of unstable (usually resting) angina. However, of all patients with suspected ACS who undergo coronary angiography, up to 30% have nonobstructed coronary arteries. We sought to clarify how many of these patients suffer from coronary spasm as a possible cause of their chest pain. METHODS In a prospective study from June to December 2006, all patients with suspected ACS who underwent coronary angiography and had no culprit lesion underwent intracoronary provocation with acetylcholine. The ACH testing was considered positive at a vasoconstriction of >/=75% relative to the diameter after intracoronary nitroglycerine when the initially reported symptoms could be reproduced. RESULTS Of 488 consecutive patients, 138 had no culprit lesion (28%). Twenty-two were found to have another diagnosis. The ACH testing was performed in 86 of the remaining 116 patients. In 42 patients, coronary spasm was verified (49%). CONCLUSIONS Every fourth patient with ACS had no culprit lesion. Coronary spasm could be documented in nearly 50% of the patients tested by ACH. Coronary spasm is a frequent cause of ACS and should regularly be considered as a differential diagnosis.

Comparative Evaluation of Left and Right Ventricular Endomyocardial Biopsy Differences in Complication Rate and Diagnostic Performance

Background— Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin. Methods and Results— In this 2-center study, 755 patients with clinically suspected myocarditis (n=481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (n=274) underwent either selective LV-EMB (n=265; 35.1%), selective RV-EMB (n=133; 17.6%), or biventricular EMB (n=357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardial effusion that occurred after biventricular EMB, the minor complication rate for LV-EMB varied between 0.64% to 2.89% and for RV-EMB, between 2.24% and 5.10%. Diagnostic EMB results were achieved significantly more often in those patients who underwent biventricular EMBs (79.3%) compared to those who underwent either selective LV-EMB or selective RV-EMB (67.3%; P<0.001). In patients with biventricular EMB, myocarditis was diagnosed in LV-EMB samples in 18.7% and in RV-EMB samples in 7.9% (P=0.002), and it was diagnosed in both ventricles in 73.4%. There were no differences in the number of positive LV-EMB, RV-EMB, or LV- and RV-EMB findings when related to the site of cardiovascular magnetic resonance–based late gadolinium enhancement. Conclusions— Both LV-EMB and RV-EMB are safe procedures if performed by experienced interventionalists. The diagnostic yield of EMB may be optimized when samples from both ventricles are available. Preferential biopsy in regions showing late gadolinium enhancement on cardiovascular magnetic resonance does not increase the number of positive diagnoses of myocarditis.

Clinical Usefulness, Angiographic Characteristics, and Safety Evaluation of Intracoronary Acetylcholine Provocation Testing Among 921 Consecutive White Patients With Unobstructed Coronary Arteries

Background— Coronary spasm can cause myocardial ischemia and angina in patients with and those without obstructive coronary artery disease. However, provocation tests using intracoronary acetylcholine administration are rarely performed in clinical routine in the United States and Europe. Thus, we assessed the clinical usefulness, angiographic characteristics, and safety of intracoronary acetylcholine provocation testing in white patients with unobstructed coronary arteries. Methods and Results— From September 2007 to June 2010, a total of 921 consecutive patients (362 men, mean age 62±12years) who underwent diagnostic angiography for suspected myocardial ischemia and were found to have unobstructed coronary arteries (no stenosis ≥50%) were enrolled. The intracoronary acetylcholine provocation testing was performed directly after angiography according to a standardized protocol. Three hundred forty-six patients (35%) reported chest pain at rest, 222 (22%) reported chest pain on exertion, 238 (24%) reported a combination of effort and resting chest pain, and 41 (4%) presented with troponin-positive acute coronary syndrome. The overall frequency of epicardial spasm (>75% diameter reduction with angina and ischemic ECG shifts) was 33.4%, and the overall frequency of microvascular spasm (angina and ischemic ECG shifts without epicardial spasm) was 24.2%. Epicardial spasm was most often diffuse and located in the distal coronary segments (P<0.01). No fatal or irreversible nonfatal complications occurred. However, 9 patients (1%) had minor complications (nonsustained ventricular tachycardia [n=1], fast paroxysmal atrial fibrillation [n=1], symptomatic bradycardia [n=6], and catheter-induced spasm [n=1]). Conclusions— Epicardial and microvascular spasm are frequently found in white patients with unobstructed coronary arteries. Epicardial spasm is most often diffuse and located in the distal coronary segments. The intracoronary acetylcholine provocation test is a safe technique to assess coronary vasomotor function.

3-year follow-up of patients with coronary artery spasm as cause of acute coronary syndrome: the CASPAR (coronary artery spasm in patients with acute coronary syndrome) study follow-up.

OBJECTIVES We sought to determine the prognosis of patients with acute coronary syndrome without culprit lesion and proof of coronary spasm during 3 years of follow-up. BACKGROUND Coronary artery spasm has been identified as an alternative cause for acute coronary syndrome (ACS) in patients without culprit lesion. In the CASPAR (Coronary Artery Spasm as a Frequent Cause for Acute Coronary Syndrome) study, we recently showed that ∼50% of ACS patients without culprit lesion, in whom intracoronary acetylcholine provocation was performed, had coronary spasm. However, data on prognosis in these patients are sparse. METHODS After 3 years of follow-up, data regarding the following end points were obtained: death (cardiac and noncardiac), nonfatal myocardial infarction, and recurrent angina leading to repeated coronary angiography. The analysis focused on patients with a culprit lesion (n = 270) and patients without a culprit lesion (n = 76) but with acetylcholine provocation (total n = 346). RESULTS In patients without culprit lesion, there was no cardiac death or nonfatal myocardial infarction during follow-up; 1 patient died due to a noncardiac cause. However, 38 of 76 patients reported persistent angina requiring repeated angiography in 3 cases (3.9%). Thirty of 270 patients with culprit lesion died due to a cardiac cause (11.1%) and 13 due to a noncardiac cause (4.8%). Eleven patients had nonfatal myocardial infarction (4.1%) and 27 repeated angiography due to persistent or recurrent angina (10%). Patients with a culprit lesion had a higher mortality and more coronary events compared with those without (p < 0.0005, log-rank test). CONCLUSIONS ACS patients without culprit lesion and proof of coronary spasm have an excellent prognosis for survival and coronary events after 3 years compared with patients with obstructive ACS. However, persistent angina represents a challenging problem in these patients, leading in some cases to repeated coronary angiography.

Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis

Objective: To evaluate the incidence of coronary vasospasm as a possible pathophysiological mechanism causing chest pain symptoms in patients with clinically suspected myocarditis. Design and setting: Prospective study in a teaching hospital. Patients: 85 patients who presented at hospital with atypical chest pain and demonstrated clinical signs suggestive of myocarditis. Main outcome measures: Incidence of coronary vasospasm demonstrated by intracoronary acetylcholine (ACh) testing. Methods: The combined procedure of intracoronary ACh testing and endomyocardial biopsy (EMB) was performed after ruling out significant coronary artery disease (CAD). EMBs were analysed for myocardial inflammation by immunohistological methods and for virus genome persistence. Results: Pathological biopsy results, including myocardial inflammation or detection of viral genomes, or both, were found in 55 (64.7%) patients while 30 (35.3%) patients showed neither cardiac inflammation nor viral genomes and were defined as the control group. Coronary vasospasm was demonstrated in 39/55 (70.9%) patients with pathological results compared with only 12/30 (40.0%) with normal biopsy results (p = 0.01). Patients with isolated PVB19 infection (n = 22) demonstrated a significantly higher incidence of coronary vasospasm than both those with isolated HHV6 infection (86.4% vs 46.7%; p = 0.025) and those with normal biopsy results (86.4% vs 40.0%; p<0.001). Univariate and multivariate logistic regression analysis showed that only PVB19 infection was independently correlated with coronary vasospasm (OR = 4.9, 95% CI 1.56 to 15.28, p = 0.006). Conclusions: Coronary vasospasm is one of the main reasons for atypical chest pain in patients with clinical signs of myocarditis and biopsy-proven PVB19 myocarditis in the absence of significant CAD.

Gender differences in the manifestation of tako-tsubo cardiomyopathy

OBJECTIVE This study evaluated if there are gender differences in the manifestation of tako-tsubo cardiomyopathy (TTC). BACKGROUND TTC predominantly occurs in elderly females and mimics acute myocardial infarction (AMI) where men and women are known to have a different clinical profile. METHODS 324 patients from 37 hospitals were prospectively included in a TTC registry. Clinical, electrocardiographic, angiographic and outcome data from male and female patients were compared. RESULTS Of 324 patients 296 (91%) were female and 28 (9%) male. Mean age (68 ± 12 vs 66 ± 12 years) and prehospital delay were similar. A triggering event preceded TTC onset in 76% of women and 86% of men. Physical stress was more frequent in men (30% vs 57%, p=0.005) whereas more women experienced emotional or no stress. The prevalence of angina and dyspnea did not differ. Fewer females were admitted in cardiogenic shock and/or after out of hospital cardiac arrest (1% vs 14%, p=0.0006), and cardiac troponin was lower (median 7.2 vs 10.7 times the upper limit of normal, p=0.03). The QTc interval was longer in females than in males only on the day of admission (468 ± 52 vs 441 ± 51 ms, p=0.047). Overall, complications during the acute course (53% vs 40%) were comparable in both sexes. CONCLUSIONS In this large TTC registry, males and females showed a similar clinical profile. In males, physical stress as a trigger event and shock or cardiac arrest as presenting symptoms were more frequent. The QTc interval was longer in females only on admission but similar in males and females during the following days.

Complications in the clinical course of tako-tsubo cardiomyopathy

OBJECTIVE This study evaluated the frequency, severity and outcome of complications in the clinical course of tako-tsubo cardiomyopathy (TTC). BACKGROUND TTC is regarded as a benign disease since left ventricular (LV) function returns to normal within a short time. However, severe complications have been reported in selected patients. METHODS From 37 hospitals, 209 patients (189 female, age 69 ± 12 years) were prospectively included in a TTC registry. RESULTS Complications developed in 108/209 patients (52%); 23 (11%) had >2 complications. Complications occurred median 1 day after symptom onset, and 77% were seen within 3 days. Arrhythmias were documented in 45/209 patients (22%) including atrial fibrillation in 32 (15%) and ventricular tachycardia in 17 (8%). Of 8 patients resuscitated (4%), 6 survived. Additional complications were right ventricular involvement (24%), pulmonary edema (13%), cardiogenic shock (7%), transient intraventricular pressure gradients (5%), LV thrombi (3%) and stroke (1%). During hospitalization, 5/209 patients (2.5%) died. Patients with complications were older (70 ± 13 vs 67 ± 10 years, p=0.012), had a higher heart rate (91 ± 26 vs 83 ± 19/min, p=0.025), more frequently Q\ waves on the admission ECG (36% vs 21%, p=0.019) and a lower LV ejection fraction (47 ± 15 vs 54 ± 14%, p = 0.002). Multivariate regression analysis identified Q-waves on admission (OR 2.49, 95% CI 1.23-5.05, p=0.021) and ejection fraction ≤ 30% (OR 4.03, 95% CI 1.04-15.67, p=0.022) as independent predictors for complications. CONCLUSIONS TTC may be associated with severe complications in half of the patients. Since the majority of complications occur up to day 3, monitoring is advisable for this time period.

Transient left ventricular dysfunction with apical ballooning (tako-tsubo cardiomyopathy) in Germany.

SummaryAimsA peculiar type of an acute coronary syndrome is characterised by acute onset of chest pain, STsegment changes, elevated troponin I levels and a transient balloon–like apical left ventricular dysfunction, but without significant coronary artery disease. We sought to assess this syndrome in German patients.Methods and resultsA total of 22 females and 1 male with acute transient left ventricular dysfunction were identified during an interval of 2 years and were investigated clinically and angiographically. All patients presented without obstructive coronary artery disease. In 16 patients (70%) ST–segment elevations were observed mimicking acute myocardial infarction, whereas the remaining patients (30%) revealed only negative T waves. Deep negative Twaves were characteristically seen during the course of recovery in all patients. Elevated troponin I levels > 2.0 µg/l (upper level of normal) were measured in all patients (mean 18 ± 26.5 µg/l, range from 2.2–135.7 µg/l). Creatine kinase rose up to a mean of 282 ± 236 IU/l (upper level of normal 180 U/l). Emotional or physical stress situations associated with the onset of the symptoms were observed in 16 patients (70%). Other suspected trigger factors were gastrointestinal infection and in one case a surgical intervention. In four patients a trigger factor could not be identified. Left ventriculography showed an ejection fraction of 53 ± 15%. After an interval of 7 ± 2 days after the first angiogram, ejection fraction had increased from 48 ± 11% to 64 ± 11% in eight controlled patients by repeated ventriculography. Coronary spasm with a lumen reduction > 75% could be provoked using acetylcholine in 10 of 17 tested patients (59%) with reproduction of the symptoms. Within 14 days the LV dysfunction returned to normal in all patients. The ECG abnormalities disappeared completely as early as 3 months (74%) and were not seen in any patient after 6 months.ConclusionTako–tsubo cardiomyopathy is not exclusively a Japanese or Northern American phenomenon. Despite increased patient reports the exact underlying cause and pathophysiology of this syndrome remain unclear. However, despite the initial dramatic presentation of this disease the prognosis is good.

Diagnostic value of perfusion cardiovascular magnetic resonance in patients with angina pectoris but normal coronary angiograms assessed by intracoronary acetylcholine testing

Background Perfusion cardiovascular magnetic resonance (CMR) has a high sensitivity for the detection of significant coronary artery disease (CAD). However, the specificity of this method is lower than its sensitivity. The reason for this observation is hitherto unclear and has been either explained by ‘false-positive’ results or by microvascular dysfunction in patients without CAD. Objective To evaluate whether pathological myocardial perfusion-CMR imaging in symptomatic patients without significant CAD is associated with coronary epicardial or microvascular dysfunction. Methods In this retrospective study, 42 patients who presented with unstable angina pectoris underwent (a) an adenosine-stress perfusion-CMR study; (b) coronary angiography; (c) intracoronary acetylcholine (ACh) testing following coronary angiography with exclusion of significant CAD. The CMR protocol comprised cine imaging followed by adenosine first-pass perfusion imaging and late gadolinium enhancement-CMR. Diagnostic left ventriculography and multiplane coronary angiography were performed before intracoronary ACh testing. Results An adenosine-induced, reversible subendocardial perfusion defect was detected in 22/42 patients (52%) without significant CAD. Coronary epicardial vasospasm was detected in 10/42 patients (24%) while microvascular dysfunction was found in 20/42 patients (48%). Patients with a reversible stress-induced perfusion defect had significantly more often a pathological coronary epicardial or microvascular vasoreaction (20/22; 91%) during intracoronary ACh testing than those without a perfusion defect (10/20; 50%; p<0.01). Univariate correlation analyses revealed a substantial association between a pathological ACh-testing result and a perfusion defect in the antecedent CMR study (r= +0.45; p<0.01). Conclusions Reversible perfusion defects depicted by perfusion-CMR in patients without significant CAD are mostly due to coronary epicardial or microvascular dysfunction, and correct interpretation of such perfusion-CMR results may enable targeted treatment.

Gender-Related Differences in Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TTC) predominantly occurs in elderly women. Men comprise 10% of the patients, with a similar clinical profile. In contrast to myocardial infarction, age distribution; symptoms, such as angina; and prehospital delay in TTC are not different between genders. In men, physical stress as a triggering event and shock or cardiac arrest on presentation are more frequent. Gender-related differences in TTC need to be carefully investigated at the clinical and experimental levels to explain the evident gender discrepancy in the prevalence of TTC, to clarify the pathogenetic background, and to develop preventive and therapeutic means against this life-threatening disease.