Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction.

This review discusses the rapidly progressing field of cardiomyocyte signal transduction and the regulation of the hypertrophic response. When stimulated by a wide array of neurohumoral factors or when faced with an increase in ventricular-wall tension, individual cardiomyocytes undergo hypertrophic growth as an adaptive response. However, sustained cardiac hypertrophy is a leading predictor of future heart failure. A growing number of intracellular signaling pathways have been characterized as important transducers of the hypertrophic response, including specific G protein isoforms, low-molecular-weight GTPases (Ras, RhoA, and Rac), mitogen-activated protein kinase cascades, protein kinase C, calcineurin, gp130-signal transducer and activator of transcription, insulin-like growth factor I receptor pathway, fibroblast growth factor and transforming growth factor beta receptor pathways, and many others. Each of these signaling pathways has been implicated as a hypertrophic transducer, which collectively suggests an emerging paradigm whereby multiple pathways operate in concert to orchestrate a hypertrophic response

Cytoplasmic Signaling Pathways That Regulate Cardiac Hypertrophy

The relationship between the heart and the brain is complex and integral in the maintenance of normal cardiovascular function. Certain pathological conditions can interfere with the normal brain-heart regulatory mechanisms and result in impaired cardiovascular function. The mechanisms through which the central and autonomic nervous systems regulate the heart and the manner in which their impairment adversely affects cardiovascular function have recently been reviewed by Samuels.1 The purpose of this article is to provide an up-to-date review of the clinical presentation of the stress-related cardiomyopathy syndromes, discuss possible causal mechanisms, and highlight the similarities and differences between them.2–16

The stress-related cardiomyopathies appear similar in that they seemingly occur during times of enhanced sympathetic tone and may be precipitated in part or entirely by excessive endogenous or exogenous catecholamine stimulation of the myocardium. Although significant clinical overlap exists in those presenting with stress-associated cardiomyopathy, it is unclear whether myocardial adrenergic hyperstimulation is the only pathophysiological mechanism responsible for these syndromes (Tables 1 and 2⇓). 

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Table 1. Precipitants of Stress Cardiomyopathy 



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Table 2. Morphological LV Variants of Stress Cardiomyopathy 



In the early 1990s, Japanese authors began reporting a unique, reversible cardiomyopathy that appeared to be precipitated by acute emotional stress.2,13,16 They found that these patients were usually postmenopausal women and often developed signs and symptoms of an acute coronary syndrome (ACS) proximate to a strong emotional stressor associated with a transient apical and midventricular wall motion abnormality despite the lack of obstructive coronary artery disease (CAD) at the time of emergent coronary angiography. This syndrome was initially given the name Takotsubo cardiomyopathy (TC) and has subsequently been referred to as the apical ballooning syndrome and broken heart syndrome. It is now recognized that TC can also occur in the setting of acute medical illness and after surgery. TC …

Stress-Related Cardiomyopathy Syndromes

Background—Transgenic cardiac β2-adrenergic receptor (AR) overexpression has resulted in enhanced signaling and cardiac function in mice, whereas relatively low levels of transgenically expressed Gαs or β1AR have resulted in phenotypes of ventricular failure. Potential relationships between the levels of βAR overexpression and biochemical, molecular, and physiological consequences have not been reported. Methods and Results—We generated transgenic mice expressing β2AR at 3690, 7120, 9670, and 23 300 fmol/mg in the heart, representing 60, 100, 150, and 350 times background βAR expression. All lines showed enhanced basal adenylyl cyclase activation but a decrease in forskolin- and NaF-stimulated adenylyl cyclase activities. Mice of the highest-expressing line developed a rapidly progressive fibrotic dilated cardiomyopathy and died of heart failure at 25±1 weeks of age. The 60-fold line exhibited enhanced basal cardiac function without increased mortality when followed for 1 year, whereas 100-fold overexpres...

Early and Delayed Consequences of β2-Adrenergic Receptor Overexpression in Mouse Hearts Critical Role for Expression Level

Clinical expression of phaeochromocytoma may involve numerous cardiovascular manifestations, but usually presents as sustained or paroxysmal hypertension associated with other signs and symptoms of catecholamine excess. Most of the life-threatening cardiovascular manifestations of phaeochromocytoma, such as hypertensive emergencies, result from a rapid and massive release of catecholamines from the tumour. More rarely, patients with phaeochromocytoma present with low blood pressure or even shock that may then precede multisystem crisis. Sinus tachycardia, with palpitations as the presenting symptom, is the most prevalent abnormality of cardiac rhythm in phaeochromocytoma, but tumours can also be associated with more serious ventricular arrhythmias or conduction disturbances. Reversible dilated or hypertrophic cardiomyopathy are well established cardiac manifestations of phaeochromocytoma, with more recent attention to an increasing number of cases with Takotsubo cardiomyopathy. This review provides an update on the cause, clinical presentation and treatment of the cardiovascular manifestations of phaeochromocytoma. As the cardiovascular complications of phaeochromocytoma can be life-threatening, all patients who present with manifestations that even remotely suggest excessive catecholamine secretion should be screened for the disease.

Cardiovascular manifestations of phaeochromocytoma

Phaeochromocytoma is rare and usually presents as paroxysmal or sustained hypertension; none the less, it can also cause severe acute pulmonary oedema in normotensive individuals. Six patients with phaeochromocytoma presenting in Cornwall and West Devon between 1982 and 1986 are described. Five of them died of pulmonary oedema within 24 hours of the onset of symptoms. At necropsy all five had normal sized hearts and in the four hearts examined by histology there was evidence of catecholamine induced heart disease in the form of focal myocardial necrosis. The sixth patient presented with arterial spasms and pulmonary oedema. Surgical removal of the causative tumour was successful in this patient.

https://heart.bmj.com/content/heartjnl/63/4/234.full.pdf

Y Sivathandon

Papers

Phaeochromocytoma and catecholamine induced cardiomyopathy presenting as heart failure.