The Broken Heart: It CAN Be Mended

Abstract & Commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips serves on the speakers bureaus for Cephalon, Resmed, and Respironics.

Synopsis: The authors advocate that cardiovascular magnetic resonance imaging using specific criteria may be useful as a diagnostic tool for patients with stress cardiomyopathy at the time of acute clinical presentation.

Source: Eitel I, et al. Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA 2011;306:277-286.

These investigators set out to learn more about the clinical presentation and outcomes of stress cardiomyopathy (also known as Takotsubo cardiomyopathy) in a multicenter study in Europe and North America. Potential patients for inclusion in the study were recruited at the time of initial hospitalization. The evaluation included electrocardiogram (ECG), transthoracic echocardiogram, blood sample analysis, coronary angiogram and ventriculogram, as well as cardiovascular magnetic resonance imaging. The diagnosis of stress cardiomyopathy was defined as: 1) an acute cardiac event typically presenting with chest pain and/or shortness of breath; 2) transient systolic dysfunction with marked left ventricular (LV) contraction abnormality extending beyond a single coronary perfusion bed; 3) absence of significant (> 50%) obstructive coronary artery disease or angiographic evidence of acute plaque rupture; 4) new ECG abnormalities (either ST elevation or T-wave inversion) or modest elevation in cardiac troponin level; 5) absence of pheochromocytoma; and 6) absence of myocarditis or typical ischemic transmural late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging.1 One to 6 months after the acute event, patients with suspected stress cardiomyopathy were readmitted for clinical evaluation and cardiovascular magnetic resonance imaging follow-up in order to confirm that diagnosis. Some participants chose not to undergo repeat imaging, and had echocardiography instead, but the cohort is remarkably well-studied.

Over a 5-year period, 256 patients were recruited, and most (93%) had cardiovascular resonance imaging performed shortly after admission. Patients who were ultimately diagnosed with stress cardiomypathy had a mean age of 69 years, and 89% were women. Most (207) of these women were postmenopausal. Men accounted for 11% of cases, and there were no age differences between men and women. Most (88%) of the patients reported symptoms consistent with acute coronary syndrome (ACS) at their initial presentation. Among those who did not, the acute event was most likely characterized as either syncope (n = 9 [4%]) or asystole (n = 3; [1%]). The rest were admitted for suspected ACS detected during monitoring of noncardiac conditions because of new ECG abnormalities, acute onset of chest pain, and/or positive troponin levels.

Most of the patients (71%) could identify a significant stressful event that happened within 48 hours of clinical symptoms. These events were emotional stress in 77 (30%) and physical stress in 105 (41%).

At initial presentation, ECGs showed abnormalities in 222 patients (87%). The initial troponin T level was typically only mildly increased in 231 patients (90%). No relation was evident between ballooning patterns seen on the imaging studies and troponin levels, age, sex, or reported stress trigger.

All 256 patients underwent cardiac catheterization at initial presentation. Left ventriculography revealed typical apical ballooning in 210 (82%), midventricular ballooning in 44 (17%), and an inverted, basal pattern in 2 (1%). Of note, most (75%) patients had healthy coronary arteries. Of the remainder, only 6% had coronary artery stenosis of 75% or more; and the areas of coronary artery stenosis did not correspond to the area of wall motion abnormality seen on magnetic resonance imaging. The remaining 47 patients (18%) had only mild coronary atherosclerosis. Two patients (1%) had spontaneous coronary spasm. No patient had cardiovascular plaque rupture.

Cardiovascular magnetic resonance imaging detected ballooning patterns with moderate to severe reduction of LV function in all patients (mean LV ejection fraction, 47.7%). Biventricular ballooning was observed in 81 patients (34%). Interestingly, LV ejection fraction was lower than in patients without RV involvement. Patients with biventricular ballooning were older (mean, 73.4 vs 66.5 years) and had significantly more frequent preceding stressful events. Myocardial edema was visible on cardiovascular resonance imaging in 162 of 199 patients (81%) with the regional distribution pattern matching the distribution of LV dysfunction. LGE (thought to be a marker of subtle fibrosis) was uncommon and did not correlate with clinical presentation. Pleural effusions were common (33%), as were pericardial effusions (43%).

Initially, most patients were treated using standard cardiovascular medications for ACS (aspirin, clopidogrel, heparin, beta-blockers, angiotensin-converting enzyme inhibitors, vasodilators, and diuretics). After exclusion of coronary artery stenosis, the patients received standard supportive care for congestive heart failure with beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, diuretics, and aldosterone antagonists. In seven patients (3%) with severe hemodynamic compromise, an intra-aortic balloon pump was implanted. Four patients had thrombi, and were treated with warfarin with no subsequent events. Four patients (3 women and 1 man) died in the hospital. Causes of death in these patients were ventricular fibrillation (n = 2), cardiogenic shock (n = 1), and hypoxic brain injury (n = 1). Of these, three patients had apical and one patient had midventricular ballooning. No relation was evident between in-hospital outcome and ECG pattern, troponin level, or clinical features. Another four patients died during the follow-up period.

Among the remaining 248 patients, a complete clinical follow-up including imaging and/or echocardiography for confirmation of LV function recovery was available.

Follow-up echocardiography and cardiovascular magnetic imaging showed normalization of LV ejection fraction in all patients, and end-diastolic and end-systolic volume decreased.

Commentary

This study was largely focused on cardiovascular magnetic resonance imaging in stress cardiomyopathy, but the authors helped us to expand our knowledge of this newly-described syndrome. Stress cardiomyopathy was first reported in Japan as takotsubo cardiomyopathy. It is characterized by acute, profound, but reversible left ventricular dysfunction in the absence of significant coronary artery disease, triggered by acute emotional or physical stress.1-4 This phenomenon is identified by a distinctive imaging pattern of "apical ballooning" and has previously been reported to primarily affect postmenopausal women. Most patients have a clinical presentation similar to that of ACS. Recent studies revealed a prevalence of approximately 2% of patients presenting with ACS in the United States and Europe.1,4 Enhanced sympathetic activity is believed to play a causal role in the transient myocardial dysfunction, and the prognosis is generally considered favorable.1,4

The current study is a large multicenter trial which used exquisite imaging techniques and careful follow-up. This carefully-described group of patients had a considerably broader clinical profile than previously reported, including men, some younger individuals, and some patients who could not identify a precipitating physical or emotional stress. The authors also advocate that cardiovascular magnetic resonance imaging using specific criteria may be useful as a diagnostic tool for patients with stress cardiomyopathy at the time of acute clinical presentation; they note that those with biventricular ballooning were more likely to have longer hospitalizations, markers of heart failure (as reflected by a lower LV ejection fraction and a high incidence of bilateral pleural effusions), and older age, and thus biventricular ballooning may be an important prognostic marker.

An important take home message from this study is that the absence of an identifiable stressful event does not rule out the diagnosis of stress cardiomyopathy. And, in this study, many more patients had a physical than an emotional stress as the precipitating event, contrary to the common notion that emotional stress is generally the trigger. The authors note, "...preceding stress is not evident in every case, and it would therefore seem inappropriate to assume a common trigger among all...patients." Clearly, we still have much to learn about the Broken Heart Syndrome.

References

1. Prasad A, et al. Apical ballooning syndrome (tako-tsubo or stress cardiomyopathy): A mimic of acute myocardial infarction. Am Heart J 2008;155:408-417.

2. Maron BJ, et al. Contemporary definitions and classification of the cardiomyopathies: An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113: 1807-1816.

3. Eitel I, et al. Differential diagnosis of suspected apical ballooning syndrome using contrast-enhanced magnetic resonance imaging. Eur Heart J 2008;29:2651-2659.

4. Sharkey SW, et al. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol 2010;55:333-341.