Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner

Redfors, Björn; Ali, Anwar; Shao, Yangzhen; Lundgren, Joel; Gan, Li‐Ming; Ömerovic, Elmir

doi:10.1016/j.ijcard.2014.04.103

Cited by 99 publications

(79 citation statements)

References 16 publications

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“…This is usually measured hours after the initial stressful trigger and catecholamine surge, and so whether it is present immediately during the acute stress remains to be clarified. It is clear that there are abnormalities of peripheral sympathetic nerve function and arterial vasomotor regulation in the aftermath of the acute catecholamine storm 33, [80][81][82] . These vasodilating catecholamines may also activate myocardial β2ARs in addition to vascular β2ARs, and therefore this may reflect a mixed effect.…”

Section: Excessive Transient Ventricular Afterload and Takotsubo Varimentioning

confidence: 99%

Epidemiology and pathophysiology of Takotsubo syndrome

2015

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Takotsubo syndrome is an acute cardiac syndrome first described in 1990 and characterized by transient left ventricular dysfunction affecting more than one coronary artery territory, and often in a circumferential apical, mid-ventricular or basal distribution. A number of pathophysiological explanations for this syndrome with its intriguing appearance have been proposed, and there is a growing awareness that these are not mutually exclusive, and that the reversible apical myocardial dysfunction observed could result from more than one pathophysiological phenomenon. The pathophysiology of takotsubo syndrome is complex, with integration of both neuroendocrine physiology involving the cognitive centres of the brain and hypothalamic-pituitary-adrenal axis, and the cardiovascular responses to the sudden sympathetic activation and surge in circulating catecholamines. The latter have been explored in detail, starting with the histological findings at biopsy, with the multiple morphological changes seen in the myocardium matching those seen after established catecholamine cardiotoxic effects. Clinically, both the acute prognosis and recurrence rate are unfortunately worse than previously reported. It is clear that the modern cardiology community has much still to learn regarding the epidemiology and the underlying pathophysiology of this fascinating condition in order to improve diagnostic and treatment pathways. 3 Key points Approximately 2% of all patients presenting to the hospitals with suspected acute coronary syndrome are usually identified with takotsubo syndrome. There is a predominance in post-menopausal women compared to men or younger women. Both the acute and long-term mortality are higher than previously recognized.The cumulative incidence of recurrence increased from 1.2% at first 6 months to nearly 5% at 6 years, and there is no current evidence to support treatment with any specific to prevent recurrence. Systemic surges in catecholamines may cause vascular effects including acute coronary vasospasm and severe acute hypertension due to acute peripheral vasospasm followed by later peripheral vasodilation and hypotension. In the clinical setting, profound hypotension and cardiogenic shock is a common complication, however, it is not solely related to the extent of impairment of left ventricular (LV) systolic function, and thus probably relates in part to inappropriate peripheral vasodilation. Biopsies during acute takotsubo syndrome are characterized by multiple morphological changes that are similar to those after catecholamine cardiotoxic effects supporting a direct effect in addition to the vascular influences. The apical myocardium of the left ventricle has the highest density of β-adrenergic receptors (βAR), and is therefore most sensitive to circulating catecholamines.

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Section: Excessive Transient Ventricular Afterload and Takotsubo Varimentioning

confidence: 99%

Epidemiology and pathophysiology of Takotsubo syndrome

2015

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“…This hypertensive surge activates an initial reflex bradycardia, demonstrating the importance of observing all elements of the cardio-circulatory response, as proposed by Redfors et al 24 They recently reported that multiple catecholamines (epinephrine, norepinephrine, dopamine and phenylalanine) with αAR activity/efficacy, injected intraperitoneally, are able to induce TTS-like dysfunction in rats (albeit of the inverted type) and show initial elevations in central blood pressure. 25 This is an intriguing finding, because isoproterenol, which robustly induces classical apical ballooning when administered to rats or mice intraperitoneally, 9,26 initially causes acute hypotension. This suggests that acute changes in systemic vascular resistance and aortic pressure may have some effect on which myocardial region is dysfunctional, and show the importance of ventriculo-arterial coupling in understanding the responses to catecholamine surges.…”

Section: -60 Secondsmentioning

confidence: 99%

“…8 When injected intraperitoneally, epinephrine, norepinephrine and dopamine induce their maximal effects on pressure at diastole and systole at approximately 5 min. 25 There is a disconnect between models, because when injected intravenously, epinephrine induces its effects on pressure almost instantly and this is achieved with a dose many orders of magnitude lower than that supplied intraperitoneally. The data from the respective …”

Section: -10 Minutesmentioning

confidence: 99%

Pathophysiology of Takotsubo Syndrome

Wright

Tranter

Morley-Smith

et al. 2014

Circ J

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Takotsubo syndrome (TTS), also known as takotsubo cardiomyopathy, stress cardiomyopathy and apical ballooning syndrome, is an acute, reversible heart failure (HF) syndrome that has increasingly come to medical attention over the past 24 years with wider access to early diagnostic coronary angiography for patients with acute chest pain and ECG abnormalities. 1 The typical case is a postmenopausal woman with an extremely stressful emotional or physical trigger, who presents with chest pain and breathlessness, ECG changes and acute hypokinesia of the apical and middle segments of the left ventricle (LV) in a circumferential pattern extending beyond a single coronary territory, and in the absence of culprit obstructive coronary artery disease (CAD). 2,3 Providing the patient survives the acute event, the dysfunctional segments recover, at least macroscopically, within days to weeks. 4 Many other variations on this "typical case" exist, including different demographics (men, younger women), different anatomical variants (basal/inverted, mid-LV, biventricular), spontaneous cases without a triggering stressor, cases triggered by other medical, surgical or psychiatric emergencies and permanent cardiac abnormalities (permanent "new" left bundle branch block, apical transmural necrosis).One common feature appears to be an extreme surge in catecholamines in response to the triggering stress or coexisting medical condition (eg, subarachnoid hemorrhage, pheochromocytoma, and thyrotoxicosis). 5-7 Animal models can replicate the features of this HF syndrome in order to dissect its mechanisms. 8-11 In contrast to the reductionist approach in most modern pathophysiological research, the more that is understood about TTS, the more it is apparent that a number of processes may result in the final common pathway of acute apical dysfunction. There are a number of mediators that may modify the severity and course of a particular episode. Defining the precise pathophysiology is challenging, and we suggest that an integrated approach to studying the cardiovascular responses to extreme surges in catecholamines is appropriate.Here we use a novel approach to reviewing the pathophysiology of TTS. Animal and clinical studies have reported findings at different phases through the development of this condition, and it is intuitive that the observed integrated cardiovascular responses to surges in serum catecholamines and sympathetic neural outflow would change over time. We discuss the pathophysiology in a sequential fashion describing effects as they occur at different time-points, integrating the observations and explaining the negative inotropic response and potential activation of cardioprotective mechanisms.Before discussing the temporal sequence of events, it is important to note a growing body of evidence that TTS is not a form of acute myocardial infarction (MI). Firstly, the epide- Takotsubo syndrome (TTS), also known as takotsubo cardiomyopathy, is an acute heart failure syndrome that typically occurs after a period of great emotion...

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“…21 Direct evidence for the role of stress hormones in disease pathogenesis was obtained from animal studies after iatrogenic administration of catecholamines. 21,25,26 Catecholamine-induced takotsubo cardiac dysfunction appears to be afterload dependent rather than dependent on stimulation of a specific adrenergic receptor subtype in rat models. 25 The sympathetic nervous system is a central regulator of the activities of organs in response to stressful events.…”

Section: General Aspects Of Takotsubo Cardiomyopathymentioning

confidence: 99%

“…21,25,26 Catecholamine-induced takotsubo cardiac dysfunction appears to be afterload dependent rather than dependent on stimulation of a specific adrenergic receptor subtype in rat models. 25 The sympathetic nervous system is a central regulator of the activities of organs in response to stressful events. There is evidence of the role of the sympathetic nervous system in the pathophysiology of TCM via the increased levels of endogenous catecholamines after emotional or physical stress.…”

Section: General Aspects Of Takotsubo Cardiomyopathymentioning

confidence: 99%

Untitled

2017

Exp Clin Transplant

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Objectives: Takotsubo cardiomyopathy, also known as "broken heart syndrome," "apical ballooning syndrome," and "stress-induced cardiomyopathy," was first des cribed in Japanese patients in 1990 by Sato and colleagues. Takotsubo cardiomyopathy is an increasingly recognized syndrome characterized by transient and reversible systolic dysfunction of the apical and middle segments of the left ventricle. This syndrome resembles acute myocardial infarction in the absence of evident coronary artery occlusion. Although the precise pathophysiology of takotsubo cardiomyopathy is still unknown, it seems that it is associated with excessive sympathetic stimulation, microvascular dysfunction, coronary artery vasospasm, and abnormal myocardial tissue metabolism. Materials and Methods: Herein, we sought to recognize and summarize the available literature data on Takotsubo cardiomyopathy regarding solid-organ transplant, in an attempt to provide the demographic and morphologic functional characteristics of patients with Takotsubo cardiomyopathy and related clinical implications. Results and Conclusions: Transplant surgeons should maintain a high index of clinical suspicion and never underestimate takotsubo cardiomyopathy as a potential cause of heart failure following solid-organ transplant.

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Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner

Cited by 99 publications

References 16 publications

Epidemiology and pathophysiology of Takotsubo syndrome

Epidemiology and pathophysiology of Takotsubo syndrome

Pathophysiology of Takotsubo Syndrome

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