Acute cardiac sympathetic disruption in the pathogenesis of the takotsubo syndrome: A systematic review of the literature to date

Takotsubo syndrome (TS), also known as broken heart syndrome and neurogenic stunned myocardium, is an acute cardiac disease entity characterized by a clinical picture mimicking that of an acute coronary syndrome. The pathogenesis of TS has not been established yet. Among the most often debated pathologic mechanisms of TS are as follows: first, multi-vessel coronary spasm; second, myocardial microvascular dysfunction; third, aborted myocardial infarction caused by transient thrombotic occlusion of a long wrap-around left anterior descending artery; fourth, left ventricular outflow tract obstruction; fifth, blood-borne catecholamine cardiac toxicity; and sixth, cardiac sympathetic disruption and norepinephrine seethe and spillover. The aim of this review is to provide a thorough analysis of the literature data coming mainly from the neurological literature and dealing with the pathogenesis of TS. Substantial evidence challenging the first five hypotheses and arguing in favor of the hypothesis that acute cardiac sympathetic eruption and norepinephrine seethe and spillover is causing TS in predisposed patients is presented.     

Plasma catecholamine levels in the acute and subacute stages of takotsubo syndrome: Results from the Stockholm myocardial infarction with normal coronaries 2 study

AimsIt is well‐accepted that takotsubo syndrome (TS) is characterized by a massive surge of plasma catecholamines despite lack of solid evidence. The objective of this study was to examine the hypothesis of a massive catecholamine elevation in TS by studying plasma‐free catecholamine metabolites in patients participating in the Stockholm myocardial infarction (MI) with normal coronaries 2 (SMINC‐2) study where TS constituted more than one third of the patients.Methods and resultsThe patients included in the SMINC‐2 study were classified, according to cardiac magnetic resonance (CMR) imaging findings (148 patients), which was performed at a median of 3 days after hospital admission. Plasma‐free catecholamine metabolites; metanephrine, normetanephrine, and methoxy‐tyramine were measured on day 2–4 after admission. Catecholamine metabolite levels were available in 125 patients. One hundred and ten (88%) of the 125 patients included in SMINC‐2 study, and 38 (86.4%) of the 44 patients with TS had completely normal plasma metanephrine and normetanephrine levels. All patients had normal plasma methoxy‐tyramine levels. Fourteen (11.2%) of the 125 patients included in SMINC‐2 study, and 5 (11.6%) of the 43 patients with TS had mild elevations (approximately 1.2 times the upper normal limits) of either plasma metanephrine or normetanephrine. One patient with pheochromocytoma‐triggered TS had marked elevation of plasma metanephrine and mild elevation of plasma normetanephrine. There were no significant differences between the number or degree of catecholamine metabolite elevations between the different groups of patients with CMR imaging diagnosis included in SMINC‐2 study.ConclusionThere was no evidence of massive catecholamine elevations in the acute and subacute stages of TS apart from one patient with pheochromocytoma‐induced TS. Most of the TS patients had normal catecholamine metabolites indicating that blood‐borne catecholamines do not play a direct role in the pathogenesis of TS.     

Provocation of microvessel spasm by low-dose acetylcholine in patients with suspected coronary artery disease--two case reports

Endothelial dysfunction plays an important role in the pathogenesis of cardiac syndrome X, and intracoronary low-dose acetylcholine infusion is a widely used diagnostic modality for studying the coronary artery endothelial function. The authors herein report 2 cases of cardiac syndrome X with coronary artery endothelial dysfunction and microvessel spasm. The findings of non-invasive testing were positive for ischemia. Coronary angiograms appeared entirely normal in both cases. However, the intracoronary infusion of low-dose (1.5-15 microg/minute) acetylcholine demonstrated an impairment of the coronary blood flow response and consequently provoked an ST-segment elevation in an electrocardiogram. The coronary angiograms showed no spasm in the epicardial arteries. These patients are thus suggested to have cardiac syndrome X with microvessel spasms associated with coronary artery endothelial dysfunction.     

Takotsubo Syndrome (Stress Cardiomyopathy): An Intriguing Clinical Condition in Search of Its Identity

Takotsubo syndrome is a relatively frequent clinical entity presenting typically as an acute coronary syndrome in the absence of obstructive coronary artery disease and characterized angiographically by transient left ventricular systolic dysfunction, sparing the basal segments of the left ventricle (“apical ballooning”). Takotsubo syndrome characteristically affects peri- or postmenopausal women, albeit recent series show that men also are at risk. Takotsubo syndrome is characteristically triggered by severe emotional or physical stress, which suggests a pathogenic role for increased sympathetic activity leading to myocardial perfusion abnormalities and ventricular dysfunction. The reasons why severe emotional and physical stress result in the development of takotsubo syndrome in certain individuals but not others is still a matter of speculation, but strongly suggests the existence of predisposing factors/mechanisms in certain subjects. The present article reviews the different factors that can play a role in the development of takotsubo syndrome in different patients. We propose that triggers (ie, emotional stressors, physical stressors, iatrogenic stressors, and neurologic triggers), pathogenic mechanisms (ie, increased catecholamine levels, coronary vasomotor abnormalities leading to myocardial ischemia), and predisposing factors (ie, cardiovascular risk factors, endothelial dysfunction, comorbidities) all interact in a complex fashion and possibly differently in different patients to cause takotsubo syndrome. Identifying these factors may help in preventing and managing the condition more effectively.     

The role of vascular failure in coronary artery spasm

Coronary artery spasm plays an important role in the pathogenesis of angina pectoris as well as acute coronary syndrome and sudden death. The prevalence of coronary spasm is greater in East Asian populations than in other parts of the world. Although the mechanism of coronary spasm is still unclear, both endothelial and smooth muscle dysfunction have been reported to play a role. We recently proposed a new concept termed 'vascular failure' that represents an integration of endothelial and smooth muscle abnormalities. Thus, vascular failure is the primary cause of coronary artery spasm.     

Pathogenesis of the Takotsubo syndrome: a unifying hypothesis

The takotsubo syndrome (TS) is defined by a constellation of clinical observations in a subgroup of patients with acute coronary syndromes. Separating patients with TS from the general population with acute ischemic events are 2 important findings: obstructive coronary artery disease is missing, but the sine qua non is a distinctive pattern of abnormal left ventricular contraction. As with many newly recognized clinical syndromes, TS seems not to conform to accepted pathogenetic mechanisms. Thus, physicians are challenged to identify previously unrecognized mechanisms of disease. Two schools of thought have emerged in this regard. Most consider its pathogenesis to be a stress-induced neurohormonal phenomenon, while a smaller but substantial group believe that the transient occlusion of an epicardial coronary artery is responsible and that the syndrome is simply an unusual manifestation of coronary atherosclerosis. This editorial outlines briefly the evidence for each of these positions and presents a novel construct that may encompass the 2 views. Central to this unifying hypothesis is the belief that a neurohormonal surge triggers the hallmark left ventricular contraction abnormality, the sine qua non of the TS. In conclusion, the authors postulate that this pattern will result regardless of the state of the epicardial coronary arteries and can be observed in patients with angiographically normal coronary arteries, as well as those with obstructed or occluded arteries.     

Thrombo‐embolic complications in takotsubo syndrome: Review and demonstration of an illustrative case

Thrombo‐embolism is one of the serious complications of takotsubo syndrome (TS) in addition to heart failure, pulmonary edema, cardiogenic shock, cardiac arrest, life‐threatening arrhythmias, left ventricular outlet tract obstruction, mitral regurgitation, cardiac rupture, and death. The most common cardio‐embolic events in TS are cerebral, renal, and peripheral embolism. Approximately, one‐third of patients with left ventricular thrombus (LVT) in TS develop embolic complications. Cardio‐embolism in TS may occur with or without the presence of detectable LVT. In the present report, the thrombo‐embolic complications in TS with the emphasis on the association of TS to both acute coronary syndrome (ACS) including coronary embolism and ischemic stroke including cerebral embolism are reviewed. This serious complication is elucidated by demonstration of the case of a 67‐year‐woman with mid‐apical TS complicated by LVT, left anterior descending artery (LAD) and left middle cerebral artery (segment M2) thrombo‐embolic occlusions. The cerebral artery thrombotic occlusion was treated successfully with endovascular thrombectomy with complete resolution of the neurological deficits. There was spontaneous recanalization of the apical LAD occlusion verified by cardiac computed tomography angiography.     

Pathophysiology of the Syndrome: Biventricular Takotsubo Cardiomyopathy: Case Report and General Discussion

In recent years, our understanding of the physiologic mechanisms of transient takotsubo cardiomyopathy has improved because of the growing use of emergent heart catheterization in patients who present with severe ischemic syndromes. However, even this procedure has revealed only that, in most patients with takotsubo syndrome, the sudden onset of ventricular dysfunction is not due to fixed coronary artery occlusions. We present a case of transient takotsubo cardiomyopathy with an exceptional feature—uneven impairment of both right and left ventricular function, or biventricular takotsubo—and we discuss a novel, comprehensive theory that we have devised to explain the pathophysiology of this syndrome''s many manifestations.Key words: Acetylcholine/diagnostic use, angina pectoris, variant, coronary endothelial dysfunction, coronary vasospasm/physiopathology, takotsubo cardiomyopathy/classification/diagnosis/physiopathology, ventricular dysfunction, left/etiology/diagnosis, ventricular dysfunction, right/etiology/diagnosisOnly during the last 2 decades have Japanese authors^1,2 specifically categorized transient takotsubo cardiomyopathy (TTC) as an entity in itself. Before that time, TTC was often called “acute myocardial infarction with normal coronary arteries.”³ Its prevalence is probably as low today as in the remote past. However, acute coronary artery syndromes are now studied aggressively with emergent heart catheterization, which documents better than any previous means the transience of the myopathy and the presence of apparently normal coronary arteries. These circumstances have stimulated the quest to generate a pathophysiologic concept broad enough to encompass the full clinical spectrum of TCC.Apical ballooning (resulting in a systolic takotsubo or “octopus trap”) is the most frequent and emblematic feature of TTC. The use of this term has successfully promoted awareness of the disease in the cardiology community at large, but it has also impeded clinicians'' understanding of the breadth of this entity''s clinical manifestations. Our persistently inadequate knowledge of the nature and spectrum of TTC seems to warrant an update on the subject.Here, we present a case of right ventricular (in union with left ventricular) TTC. In addition, we discuss a pathophysiologic theory that our group has recently proposed, which might explain the newly discovered and broad spectrum of TTC clinical manifestations.     

The "broken heart syndrome": State of the art

Takotsubo cardiomyopathy is a reversible condition, characterized by transient left ventricular systolic dysfunction, that mimics an acute coronary syndrome. It usually occurs after physical or emotional stress, predominantly in postmenopausal women, although it also can affect younger age groups and males. It often presents as chest pain or dyspnea with electrocardiographic changes and mild elevation of cardiac enzymes suggesting acute myocardial infarction. Coronary angiography excludes obstructive coronary disease, and imaging reveals ventricular apical akinesia and compensatory hypercontractility of the basal segments. Various pathophysiological mechanisms have been proposed for the syndrome, such as occult atherosclerotic disease, multivessel spasm and/or microvascular dysfunction. However, the most widely accepted hypothesis at present is an excess of catecholamines causing calcium overload in cardiac myocytes, leading to disruption of contraction and ventricular function. Treatment is essentially supportive, with spontaneous and complete reversal of the changes within days or weeks. However, the presence of complications and comorbidities may predict a more adverse prognosis. As much is still unknown about takotsubo cardiomyopathy and the number of reported cases is growing, we present a literature review.     

Plasma Epinephrine Level and its Causal Link to Takotsubo Syndrome Revisited: Critical Review with a Diverse Conclusion

Takotsubo syndrome (TS) is a recognized acute cardiac syndrome with a clinical presentation resembling that of an acute coronary syndrome (ACS). The defining feature of TS is the reversible left ventricular wall motion abnormality (LVWMA), which has a unique circumferential pattern resulting in a conspicuous ballooning of the left ventricle during systole, and extending beyond the coronary artery supply territory. The pathogenesis of TS is still elusive and several pathophysiological mechanisms have been proposed. A common portrayal of the syndrome in the literature is that the disease is characterized by massive surge of plasma catecholamines including epinephrine. Based on the assumption of massive plasma epinephrine elevation, some investigators hypothesized that the circulatory plasma epinephrine plays a pivotal role in the pathogenesis of TS. One typical such hypothesis is epinephrine induced switch in signal trafficking causing apical or mid-apical ballooning in TS. In-depth analysis of the literature reveals that no study with certainty has shown “massive” plasma epinephrine elevations in TS. Furthermore, the literature evidences challenging the epinephrine-induced switch in signal trafficking are substantial. In this review, sufficient data, indicating that the plasma epinephrine in TS is either normal or moderately elevated in all studies, are provided. Noteworthy, epinephrine may act as a trigger factor for TS-induction but there is no evidence for a direct causal link between epinephrine and TS.     

Spontaneous coronary artery dissection triggered post-ischemic myocardial stunning and takotsubo syndrome: two different names for the same condition

An acute coronary ischemic insult may “cause” prolonged post-ischemic myocardial stunning. In spite of being a major stress factor, acute coronary syndrome is regarded as an exclusion criterion for takotsubo syndrome. We describe the case of a 39-year-old female patient presented with anterior ST-elevation myocardial infarction. Emergency coronary angiography revealed spontaneous coronary artery dissection confirmed with intravascular ultrasound examination. The patient developed clinical, angiographic and cardiac image features consistent with both post-ischemic myocardial stunning and takotsubo syndrome. Complete healing of the coronary dissection occurred with conservative treatment. There was also resolution of the greatest part of the left ventricular dysfunction. The findings in the present case indicate that the post-ischemic myocardial stunning and takotsubo syndrome are two different names for the same clinical condition and that the acute coronary syndrome triggers rather than excludes takotsubo syndrome.     

Spontaneous coronary artery dissection and takotsubo syndrome: An often overlooked association; review

Spontaneous coronary artery dissection (SCAD) and takotsubo syndrome (TS) are two cardiovascular syndromes with predilection for women. Both conditions may be preceded by an emotional stress or, for the affected individual, an unusual severe physical exercise. “Restitution ad integrum” occurs in most cases suffering from SCAD or TS with complete angiographic resolution of the dissected vessel and left ventricular dysfunction respectively. Recently, many cases, which were initially diagnosed as TS because of typical left ventricular ballooning pattern showed to have SCAD, have been reported; these cases were deemed to be “SCAD misdiagnosed as TS”. The left ventricular wall motion abnormality has been attributed to the ischemia caused by SCAD-affected coronary vessel especially in the left anterior descending artery (LAD) with “wrap-around course”. However, the left ventricular ballooning pattern have occurred in patients with SCAD in non-long-wrap-around LAD and SCAD in other coronary branches where coronary ischemia on its own cannot explain the left ventricular ballooning. In this review, sufficient data supporting the evidence for the possibility of coexistence of SCAD and TS is provided. Misdiagnosis of the association of the two conditions may result in mismanagement of the patient with undesirable consequences. Furthermore, the causal links between SCAD and TS is discussed.     

Impact of delta-sarcoglycan gene polymorphism on the occurrence of coronary spastic angina in Japanese patients with hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) frequently complain of angina-like symptoms in the absence of organic coronary stenoses. Coronary spasm might cause myocardial ischemia in HCM patients. Delta-sarcoglycan plays a crucial role in the pathogenesis of HCM and coronary spasm in a mouse model. METHODS AND RESULTS: This is a retrospective, single-center study with a small sample size. Seventy patients with HCM underwent coronary angiography and received acetylcholine provocation test. Coronary risk factors and 5'-untranslated region (UTR) G to C polymorphism on delta-sarcoglycan gene (n=64) were evaluated in the HCM patients. In 31 (44.3%) of 70 HCM patients, coronary spasm was induced by the provocation. None of the coronary risk factors was significantly different between the coronary spasm group and the non-coronary spasm group. The 5'-UTR gene polymorphism was associated with the occurrence of coronary spasm with an additive effect on the coexistence (p=0.025). Multiple logistic regression analysis showed that the C allele of 5'-UTR polymorphism was a significant risk factor for coronary spasm in patients with HCM (odds ratio, 3.1; 95% confidence interval, 1.0 to 9.5; p=0.045) that was independent of traditional coronary risk factors. CONCLUSIONS: The 5'-UTR polymorphism on delta-sarcoglycan gene was associated with coronary spasm in Japanese patients with HCM.     

Recurrent takotsubo with prolonged QT and torsade de pointes and left ventricular thrombus

Takotsubo cardiomyopathy, also known as “takotsubo syndrome,” refers to transient apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome and is a recently recognized syndrome typically characterized by transient and reversible left ventricular dysfunction that develops in the setting of acute severe emotional or physical stress. Increased catecholamine levels have been proposed to play a central role in the pathogenesis of the disease, although the specific pathophysiology of this condition remains to be fully determined. At present, there have been very few reports of recurrent takotsubo cardiomyopathy. In this case report, we present a patient with multiple recurrences of takotsubo syndrome triggered by severe emotional stress that presented with recurrent loss of consciousness, QT prolongation, and polymorphic ventricular tachycardia (torsade de pointes) and left ventricular apical thrombus.     

Thrombo-embolic renal infarction in a case of mid-ventricular takotsubo syndrome

Thrombo-embolism is one of the serious complications of takotsubo syndrome (TS). It typically occurs in the classical mid-apical left ventricular ballooning form of TS. This complication has not been reported in cases of left mid-ventricular ballooning type of TS. We describe a 67-year-old woman who presented with 2-3 days of increasing signs and symptoms of heart failure. Echocardiography showed marked hypokinesia/akinesia in the mid-anterior, mid-anterolateral, and mid-inferior wall of the left ventricle and mild hypokinesia in the apical region. There was also hypokinesia of the mid and apical parts of the right ventricle. One day after admission, she developed acute left-sided renal infarction. Left ventriculography and coronary angiography 3 days after admission showed typical left mid-ventricular ballooning with no identifiable coronary lesion. Follow-up echocardiography showed complete resolution of left and right ventricular dysfunction. Takotsubo syndrome with right ventricular involvement complicated with heart failure and left renal embolic infarction was diagnosed. The mechanism of left renal embolic infarction is discussed.     

Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis

Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient''s left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy.     

Exercise-induced coronary arterial spasm: Angiographic demonstration,documentation of ischemia by myocardial scintigraphy and results of pharmacologic intervention

Exercise-induced coronary arterial spasm is an infrequently recognized phenomenon whose mechanism and management are not well established. In two patients with reproducible exercise-induced S-T segment elevation and angina pectoris thallium-201 scintigraphy showed areas of reversible anteroapical hypoperfusion, and gated radionuclide ventriculography revealed anteroapical hypokinesia with a decrease in left ventricular ejection fraction at peak exercise. During coronary arteriography, supine exercise provoked occlusive spasm of the left anterior descending coronary artery, which at rest had only minimal plaques'. Consequently, treadmill testing was performed with five different pharmacologically provoked interventions: direct vasodilatation (nitrates), alpha adrenergic blockade (phenoxybenzamine), beta adrenergic blockade (propranolol), calcium flux blockade (verapamil), and prostaglandin inhibition (indomethacin). Exercise-induced coronary arterial spasm, manifested as S-T segment elevation and angina, was prevented by nitrates, but was not eliminated by short-term oral administration of an alpha or beta blocking agent, a calcium antagonist or a prostaglandin inhibitor. Further, beta adrenergic blockade appeared to be detrimental. Thus, this study demonstrates (1) that coronary arterial spasm may be the underlying mechanism of at least some cases of exertional angina associated with transient perfusion deficits and left ventricular dysfunction, and (2) that it may be prevented by oral nitrates.     

Pathophysiology of the Syndrome: Biventricular Takotsubo Cardiomyopathy: Case Study and Review of Literature

Biventricular takotsubo cardiomyopathy is associated with more hemodynamic instability than is isolated left ventricular takotsubo cardiomyopathy; medical management is more invasive and the course of hospitalization is longer.In March 2011, a 62-year-old woman presented at our emergency department with abdominal pain, nausea, and vomiting. On hospital day 2, she experienced chest pain. An electrocardiogram and cardiac enzyme levels suggested an acute myocardial infarction. She underwent cardiac angiography and was found to have severe left ventricular systolic dysfunction involving the mid and apical segments, which resulted in a left ventricular ejection fraction of 0.10 to 0.15 in the absence of obstructive coronary artery disease. Her hospital course was complicated by cardiogenic shock that required hemodynamic support with an intra-aortic balloon pump and dobutamine. A transthoracic echocardiogram revealed akinesis of the mid-to-distal segments of the left ventricle and mid-to-apical dyskinesis of the right ventricular free wall characteristic of biventricular takotsubo cardiomyopathy. After several days of medical management, the patient was discharged from the hospital in stable condition.To the best of our knowledge, this is the first review of the literature on biventricular takotsubo cardiomyopathy that compares its hemodynamic instability and medical management requirements with those of isolated left ventricular takotsubo cardiomyopathy. Herein, we discuss the case of our patient, review the pertinent medical literature, and convey the prevalence and importance of right ventricular involvement in patients with takotsubo cardiomyopathy.Key words: Cardiomyopathies/radiography, hemodynamic instability/takotsubo, magnetic resonance angiography, takotsubo cardiomyopathy, biventricular/diagnosis, transient apical ballooning syndrome, ventricular dysfunction, left, ventricular dysfunction, rightTransient left ventricular apical ballooning syndrome (TLVABS) is an acute cardiac syndrome that typically is characterized by transient left ventricular (LV) wall-motion abnormalities, electrocardiographic (ECG) findings of ST-T segment changes, and minimal release of cardiac enzymes in the absence of significant stenosis of the coronary arteries (<50% luminal stenosis).^1–8 This syndrome was first described in Japan in 1991 and named takotsubo-like LV dysfunction in reference to the asynergy, which consists of hypokinesis or akinesis of the mid-to-apical LV and hyperkinesis of the basal LV extending over more than one coronary artery region.^8–11 Since then, this asynergy has been called takotsubo cardiomyopathy (TC), stress cardiomyopathy, ampulla syndrome, broken-heart syndrome, and neurogenic stunned myocardium.^12–14 Takotsubo cardiomyopathy presents clinically with chest pain and dyspnea associated with ECG changes, thereby mimicking ST-segment elevation myocardial infarction that is often preceded by emotional or physical stress.^1-7,9,10 Indeed ST-segment elevation is the most common ECG abnormality, reported in approximately 82% of patients with TC, followed by T-wave inversion in 64%.^8,15 This peculiar cardiac syndrome results in severe impairment of systolic function.There are several variants of TC. Isolated LV involvement is the most common variant, but right ventricular (RV) involvement is gaining increased recognition. Although there is only one documented case of isolated RV stress cardiomyopathy,¹⁶ the recognition of biventricular TC is increasing. It has been reported that RV involvement affects approximately 25% to 42% of patients diagnosed with TC.^12,13,17,18 In addition to isolated LV, isolated RV, and biventricular involvement, a variety of ballooning patterns has been observed. The typical apical-ballooning shape, with akinesis of the apical and mid-ventricular LV segments, is the most common; however, a mid-ventricular variant with apical sparing and a variant with isolated basal ballooning have been recognized.¹⁸ Left ventricular systolic dysfunction and heart failure—with simultaneous RV dysfunction—identifies a patient population with an extremely poor prognosis.¹⁹ Therefore, it is not surprising that TC with RV involvement appears to be associated with more severe LV dysfunction that results in significantly longer hospitalization and hemodynamic instability that is associated with a worse prognosis.^1-4,13,18 Clinicians need to be aware of the prevalence and complications of RV involvement and dysfunction, because it can affect patient management, morbidity, and, ultimately, mortality rates in substantial ways.The data concerning RV involvement in TC are sparse, because they are derived from several case reports and case series studies. This review of the literature documents the prevalence, pathophysiology, diagnostic imaging characteristics, clinical findings, management, and prognosis of patients with biventricular TC. Throughout this article, TC with RV involvement will be referred to as biventricular TC, whereas classic left ventricular TC (with apical ballooning) will be referred to as TLVABS. All of the documented cases of biventricular TC have been evaluated and analyzed in regard to how the patient presented, how the TC was diagnosed and managed, and how we can improve in managing the even more hemodynamically unstable biventricular TC, in comparison with TLVABS.     

Spontaneous coronary artery dissection and takotsubo syndrome: The chicken or the egg causality dilemma

Acute coronary syndrome (ACS) including spontaneous coronary artery dissection (SCAD) has been reported to trigger its own clinical twin takotsubo syndrome (TS). The pathogenetic association between SCAD and TS remains to be elucidated. The two diseases afflict predominantly women and both conditions may be triggered by an emotional stress factor and an unusual extreme physical exercise. Herein, we describe a case of 54‐year‐old woman presenting with ACS caused by an obtuso‐marginal SCAD. Concurrently, the patient had typical clinical features and course of mid‐apical pattern of TS. The causal link between the two conditions is discussed. © 2017 Wiley Periodicals, Inc.