Feature Story | Takotsubo Syndrome: Key Points to Remember to Improve Practice
An International Expert Consensus Document on Takotsubo Syndrome (TTS) was published last month. Part I of the document focuses on the clinical characteristics, diagnostic criteria and pathophysiology, and reviews controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease and etiology. New diagnostic criteria are proposed based on current knowledge to improve diagnostic accuracy.
Part II focuses on the diagnostic workup to improve correct and timely diagnosis, outcomes and management of TTS. In addition, the document reviews areas where controversies still exist in risk stratification and management of TTS. Recommendations for optimal care of TTS patients, based on available data, are provided.
Ten Key Points to Remember for Part I of the International Expert Consensus Document on Takotsubo Syndrome.
TTS is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications, including death, and that its prevalence is probably underestimated.
TTS derived its name from the Japanese word for octopus trap, because of the shape of the left ventricle at the end of systole. It has been described under a remarkable number of different names in the literature including “broken heart syndrome,” “stress cardiomyopathy” and “apical ballooning syndrome.”
The most common symptoms of TTS are acute chest pain, dyspnea or syncope. Thus it is indistinguishable from acute myocardial infarction (AMI) at first glance.
TTS is estimated to represent approximately 1-3 percent of all patients and 5-6 percent of female patients presenting with suspected STEMI.
The diagnosis of TTS is often challenging because its clinical phenotype may closely resemble AMI regarding electrocardiographic abnormalities and biomarkers. While a widely established noninvasive tool allowing a rapid and reliable diagnosis of TTS is currently lacking, coronary angiography with left ventriculography is considered the “gold standard” diagnostic tool to exclude or confirm TTS.
The precise pathophysiological mechanisms of TTS are incompletely understood, but there is considerable evidence that sympathetic stimulation is central to its pathogenesis. An identifiable emotionally or physically triggering event precipitates the syndrome in most cases. TTS has been associated with conditions of catecholamine excess (e.g., pheochromocytoma, central nervous system disorders) and activated specific cerebral regions.
Physical triggers are more common than emotional stress factors. Of note, male patients are more often affected from a physical stressful event, while in women, an emotional trigger can be observed more frequently.
Current evidence suggests that TTS is caused by an acute release of catecholamines from either sympathetic nerves, the adrenal medulla or as drug therapy, and occurs primarily in patients with increased susceptibility of the coronary microcirculation and of cardiac myocytes to the stress hormones leading to prolonged but transient left ventricular dysfunction with secondary myocardial inflammation.
Although several anatomical TTS variants have been described, four major types can be differentiated based on the distribution of regional wall motion abnormalities. The most common TTS type and widely recognized form is the apical ballooning type, also known as the typical TTS form, which occurs in the majority of cases. Over the past years, atypical TTS types have been increasingly recognized. These include the midventricular, basal and focal wall motion patterns.
A growing body of evidence reveals that acute cardiovascular events are not distributed randomly over time, but instead depend on the time of day, day of the week and months/season of the year. Most conducted studies reported a summer preference for TTS, while one study reported a winter peak.
Ten Key Points to Remember for Part II of the International Expert Consensus Document on Takotsubo Syndrome.
Patients presenting with ST-segment elevation should undergo urgent coronary angiography with left ventriculography to exclude AMI. In patients with non–ST-segment elevation, the InterTAK Diagnostic Score can be considered. Patients with a low probability (InterTAK Score ≤70 points) should undergo coronary angiography with left ventriculography, while in patients with a high score (score ≥70), transthoracic echocardiography should be considered.
The InterTAK Diagnostic Score comprises seven parameters (female sex; emotional trigger; physical trigger; absence of ST-segment depression [except in lead aVR]; psychiatric disorders; neurologic disorders; and QT prolongation) ranked by their diagnostic importance with a maximum attainable score of 100 points.
Recently, specific cardiac magnetic resonance criteria for TTS diagnosis at the time of acute presentation were established, which include the combination of typical regional wall motion abnormalities, edema, and the absence of evidence of irreversible tissue injury (late gadolinium enhancement).
Although TTS has generally been considered a benign disease, contemporary observations show that rates of cardiogenic shock and death are comparable to acute coronary syndrome (ACS) patients treated according to current guidelines.
Guidelines regarding TTS management are lacking, as no prospective randomized clinical trials have been performed in this patient population. Therapeutic strategies are therefore based on clinical experience and expert consensus.
As TTS is clinically difficult to distinguish from ACS, upon first presentation, patients should be transferred to a cardiology unit with imaging capabilities and a cardiac catheterization laboratory. And they should receive guideline-based treatment of ACS, in particular aspirin, heparin, and if required, morphine and oxygen. Patients with cardiogenic shock or post-cardiac arrest require intensive care.
As catecholamine levels are elevated in TTS, beta-blockers seem to be reasonable until full recovery of left ventricular ejection fraction, but trials supporting this hypothesis are lacking. Furthermore, due to the potential risk of pause-dependent torsades de pointes, beta-blockers should be used cautiously, especially in patients with bradycardia and QTc >500 ms.
The use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers was associated with improved survival at one-year follow-up even after propensity matching. In contrast, there was no evidence of any survival benefit for the use of beta-blockers.
Psychiatric disorders (e.g., depression, anxiety) are common in TTS patients, and those patients might benefit from a combined psychocardiologic rehabilitation.
TTS is more than a cardiac disease, and it requires a new and interdisciplinary approach to increase awareness among not only cardiologists but physicians at large. To establish evidence-based strategies for effective TTS treatment, randomized prospective trials will be necessary, utilizing a large number of patients from multicenter international consortia.
This article was authored for ACC.org by Debabrata Mukherjee, MD, FACC, chair of the department of internal medicine and chief of cardiovascular medicine at Texas Tech University of Health Sciences Center, in El Paso, TX.
- Ghadri JR, Wittstein IS, Prasad A, et al. Eur Heart J 2018;May 29:[Epub ahead of print].
Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging, Stress
Keywords: ACC Publications, Cardiology Interventions, Acute Coronary Syndrome, Adrenal Medulla, Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Anxiety, Arrhythmias, Cardiac, Aspirin, Biological Markers, Bradycardia, Cardiac Catheterization, Catecholamines, Central Nervous System Diseases, Chest Pain, Consensus, Coronary Angiography, Coronary Artery Disease, Critical Care, Depression, Dyspnea, Echocardiography, Edema, Follow-Up Studies, Gadolinium, Heart Arrest, Heart Ventricles, Heparin, Inflammation, Magnetic Resonance Spectroscopy, Mental Disorders, Microcirculation, Morphine, Myocardial Infarction, Myocytes, Cardiac, Nervous System Diseases, Octopodiformes, Oxygen, Phenotype, Pheochromocytoma, Prevalence, Probability, Prospective Studies, Shock, Cardiogenic, Stress, Psychological, Stroke Volume, Syncope, Systole, Takotsubo Cardiomyopathy, Torsades de Pointes
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