Possible Participation of Endothelial Cell Apoptosis of Coronary Microvessels in the Genesis of Takotsubo Cardiomyopathy

Uchida, Yasumi; Egami, Haruko; Uchida, Yukiko; Sakurai, Takeshi; Kanai, Masahito; Shirai, Seiichiro; Nakagawa, Osamu; Oshima, Tadayuki

doi:10.1002/clc.20777

Cited by 64 publications

(30 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Irrespective of the ballooning variant, this abnormality in flow is frequently observed in all three epicardial vessels, suggesting a downstream microcirculatory disturbance that may be sympathetically mediated. This idea is supported by a study from Japan in which patients with SCM were found to have elevated plasma catecholamine levels and evidence from left ventricular endomyocardial biopsy of microvascular endothelial cell apoptosis (Uchida et al 2010).…”

Section: Possible Pathophysiologic Mechanisms Of Sympathetically Medimentioning

confidence: 95%

Stress Cardiomyopathy: A Syndrome of Catecholamine-Mediated Myocardial Stunning?

2012

View full text Add to dashboard Cite

During the past few years, a novel syndrome of heart failure and transient left ventricular systolic dysfunction precipitated by acute emotional or physical stress has been described. While patients with "stress cardiomyopathy"(SCM) typically present with signs and symptoms that resemble an acute coronary syndrome, it has become clear that this syndrome has unique clinical features that can readily be distinguished from acute infarction.In particular, in contrast to the irreversible myocardial injury seen with infarction, the myocardial dysfunction of SCM is completely reversible and occurs in the absence of plaque rupture and coronary thrombosis. There is increasing evidence that exaggerated sympathetic stimulation may play a pathogenic role in the development of SCM. Plasma catecholamine levels have been found to be markedly elevated in some patients with SCM, and the syndrome has been observed in other clinical states of catecholamine excess such as central neurologic injury and pheochromocytoma.Further, intravenous catecholamines can precipitate SCM in humans and can reproduce the syndrome in animal models. The precise mechanism in which excessive sympathetic stimulation may result in transient left ventricular dysfunction remains controversial. Abnormal myocardial blood flow due to sympathetically mediated microvascular dysfunction has been suggested and is supported by decreased coronary flow reserve during the acute phase of this syndrome. An alternative explanation is the direct effect of catecholamines on cardiac myocytes, possibly through cyclic AMP-mediated calcium overload. This manuscript will review the clinical and diagnostic features of SCM and will summarize the evidence supporting a sympathetically mediated pathogenesis. Clinical risk factors that appear to increase susceptibility to SCM, possibly by modulating myocyte and microvascular sensitivity to catecholamines, will also be highlighted.

show abstract

Section: Possible Pathophysiologic Mechanisms Of Sympathetically Medimentioning

confidence: 95%

Stress Cardiomyopathy: A Syndrome of Catecholamine-Mediated Myocardial Stunning?

2012

View full text Add to dashboard Cite

show abstract

“…Administration of catecholamines, such as epinephrine and dobutamine triggers TTC 44 6. Extensive LV microvascular endothelial cell apoptosis observed in myocardial biopsy 45 7. Increased sympathetic tone from mental stress can cause vasoconstriction in patients without coronary artery disease 46 8.…”

Section: Catecholamine-induced LV Dysfunction and Microvascular Dysfumentioning

confidence: 95%

Role of Coronary Microvascular Dysfunction in Takotsubo Cardiomyopathy

Vitale¹,

Rosano

Kaski

2016

Circ J

View full text Add to dashboard Cite

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp LV systolic function over a period of days or few weeks. The long-term prognosis of TTC is generally favorable, even though complications (ie, acute heart, cardiogenic shock, arrhythmias etc) may occur during the acute phase of TTC in some patients. The rate of cardiovascular death ranges from 0% to7%. 10, 11 The etiology of TTC has not been established as yet, and several and heterogeneous pathophysiologic mechanisms have been proposed to explain its occurrence, as summarized in Table 2. The notion that coronary microvascular dysfunction may have a pathogenic role in TTC is currently gaining acceptance and this review aims to critically assess the potential role of coronary microvascular abnormalities in the pathogenesis of this intriguing syndrome. Microvascular Dysfunction in TTCThe vast majority of patients presenting with TTC have angiographically normal coronary arteries or nonobstructive CAD (<75% stenosis). 12 Therefore, with obstructive coronary atherosclerotic disease ruled out as a cause of TTC, the coronary microcirculation has been identified as a suitable candidate that may play a central role in the pathophysiology of the syndrome. As is known, the coronary microcirculation, involving the coronary pre-arterioles and arterioles (<500 μm in diameter), modulates coronary blood flow in response to neural, mechanical and metabolic factors and its dysfunction compromises myocardial perfusion. With the use of invasive and noninvasive methods of assessing coronary artery microvascular abnormalities, several authors have reported data that akotsubo cardiomyopathy (TTC), also known as "transient left ventricular (LV) apical ballooning syndrome" or "stress-induced cardiomyopathy", is an acute clinical condition mimicking acute myocardial infarction. 1,2 Initially described in 1991 by Sato et al in Japan, 3 the condition has now become a relatively frequent occurrence worldwide. The typical presentation of TTC with chest pain, ischemic ECG changes and acute congestive heart failure leads to the initial diagnosis of anterior wall myocardial infarction. The typical angiographic (or echocardiographic) appearance with bulging of the LV apex ("apical ballooning") and hypercontractility of the basal segments of the LV has given TTC its name; that is, "takotsubo", the Japanese word for octopus pot. 4 The LV systolic dysfunction that characterizes TTC is often associated with diagnostic ST-segment elevation in the anterior ECG leads and increased cardiac troponin levels, albeit in the absence of obstructive epicardial coronary artery disease (CAD). In most cases, the clinical onset of TTC appears to be triggered by an acute emotional and/or physical stress, albeit in many cases the iatrogenic effect of certain pharmacological agents has been identified as a trigger (Table 1). 5,6 Recurrent episodes of TTC are not common, but cases have been described. 7, 8 The prevalence of TTC has been reported to be approximately 1-3% ...

show abstract

“…The plasma concentrations of catecholamines during the acute phase were 2-3-times higher than in patients with AMI and heart failure, and 20-times higher than in normal adults (Wittstein et al, 2005). Uchida et al also observed elevated levels of plasma epinephrine and norepinephrine in patients with stress-induced cardiomyopathy (Uchida et al, 2010). The plasma half-life of epinephrine is only 3 min (Zeb et al, 2011, as cited in Ferreira & Vane, 1967, so measurement of catecholamines should be conducted at the time of symptom onset.…”

Section: Laboratory Findingsmentioning

confidence: 95%

“…As mentioned above, contrast echocardiographic perfusion imaging, CMR and nuclear imaging provide evidences of coronary microvascular dysfunction. Uchida et al investigated the hypothesis that coronary microvessel apoptosis could be the missing link between stress and stress induced cardiomyopathy (Uchida et al, 2010). Plasma catecholamines, thrombolysis in myocardial infarction (TIMI) coronary flow grade and myocardial perfusion grade, and apoptosis of coronary microvessels in the biopsied myocardial specimens by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) were examined in 8 female patients with stress-induced cardiomyopathy.…”

Section: Catecholamine and Microvascular Spasmmentioning

confidence: 99%