Elsevier

Heart Rhythm

Volume 12, Issue 8, August 2015, Pages 1867-1877
Heart Rhythm

Creative Concepts
Myocardial edema as a substrate of electrocardiographic abnormalities and life-threatening arrhythmias in reversible ventricular dysfunction of takotsubo cardiomyopathy: Imaging evidence, presumed mechanisms, and implications for therapy

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Introduction

Takotsubo cardiomyopathy (TTC) is a cardiovascular condition that mimics acute coronary syndrome because of its acute clinical presentation with chest pain, ST-segment elevation followed by T-wave inversion, myocardial enzymatic release, and left ventricular (LV) wall motion abnormalities (so-called apical ballooning) in the absence of significant coronary artery lesions on angiography.1, 2 This syndrome usually affects postmenopausal women and is precipitated by physical stress, psychological triggers, or other states of adrenergic overstimulation such as administration of catecholamines, abrupt withdrawal of psychotropic drugs, and uncontrolled pain.3, 4, 5, 6 Affected patients usually survive, showing restoration of previous cardiovascular status with electrocardiographic (ECG) normalization and recovery of ventricular function within approximately 1 month.1

Based on the regional distribution of LV dysfunction, the following variants of TTC have been described: 1 “typical” (akinesia of the mid-apical LV segments) and 3 “atypical,” that is, “mid-ventricular” (akinesia of the mid-LV segments), “reverse” (wall motion abnormalities confined to the basal/mid LV segments), and “localized” to specific LV areas. Patients with atypical variants are younger and have a higher incidence of emotional or physical triggers than those with typical apical ballooning.7, 8 Nevertheless, both “typical” and “atypical” forms can occur in the same patient and the mechanism responsible for the involvement of specific LV segments is unknown.9

Although the pathophysiology of TTC remains to be completely elucidated, several mechanisms have been proposed that include catecholamine-induced myocardial stunning, ischemia-mediated stunning due to multivessel epicardial or microvascular spasm, coronary emboli with spontaneous fibrinolysis, or microvascular dysfunction.1 The epicardial coronary arteries are usually normal, and the association of TTC with myocardial bridging is controversial.10, 11, 12

TTC is usually characterized by prominent ECG changes consisting of mild ST-segment changes, followed by T-wave inversion and QT interval prolongation13, 14; life-threatening ventricular arrhythmias and sudden arrhythmic death may also occur at presentation or in the subacute stage of the disease course.15, 16, 17, 18, 19, 20, 21 Contrast-enhanced cardiac magnetic resonance (CMR) imaging has become the standard technique for tissue characterization and identification of myocardial lesions such as edema (T2 weighted sequences) and fibrosis (post-contrast late-gadolinium enhancement), which may represent the substrate for ventricular electrical disturbances in TTC.22, 23, 24

The present study addresses the evolving concepts in the pathogenesis of ECG changes and rhythm/conduction abnormalities in TTC. The emerging evidence in support of a link between myocardial edema, as evidenced by CMR, and T-wave inversion/QT interval prolongation and life-threatening arrhythmias leads to propose a unifying electrogenetic theory for explaining electrical abnormalities associated with reversible myocardial dysfunction of TTC. The implications of new pathophysiological insights for clinical therapy are also discussed.

Section snippets

Dynamics of ECG abnormalities in TTC

TTC is typically characterized by dynamic ECG repolarization changes similar to those seen in acute coronary syndrome, which consist of mild ST-segment elevation on presentation (acute phase) followed by T-wave inversion with QT interval prolongation within 24–48 hours after presentation (subacute phase).13, 14 The ECG pattern at admission depends on the time from symptom onset to ECG recording and inverted T waves may be already evident in the case of late presentation.13 Like wall motion

Acute ECG changes

On presentation, acute ECG changes consist of ST-segment elevation in anterior/anterolateral leads, often with a concomitant PR interval depression, which resemble those seen in acute coronary syndrome or acute pericarditis.14, 33 Transient ST-segment elevation reflects an acute transmural myocardial injury that is currently explained as the result of catecholamine-mediated myocardial toxicity.25 In contrast, the similarities of both atrial and ventricular ECG abnormalities of TTC with acute

Subacute ECG changes

The pathophysiological mechanism linking the Wellens’ ECG pattern (ie, transient T-wave inversion and QT interval prolongation) to the mechanical impairment of myocardial contractility common to TTC and other nonischemic conditions has recently been investigated using CMR imaging.32, 42, 43, 44

Vago et al42 reported transient deep T-wave inversion in the precordial leads of a 30-year-old professional soccer player who suffered a blunt chest trauma. ECG abnormalities were associated with

Life-threatening ventricular arrhythmias

Cardiac arrhythmias are not uncommon complication of TTC, and when they occur they are an important determinant of short-term clinical outcome. The estimated inhospital mortality rate during the TTC index episode ranges from 1% to 8% and is significantly greater for patients with arrhythmic complications than for those without arrhythmias.21 Inhospital ventricular arrhythmias, such as VF, torsades de pointes, or sustained ventricular tachycardia have been reported in 3.8%–8.6% of patients.

Atrioventricular block

New-onset atrioventricular (AV) block has been reported in 2.9% of the total TTC cases reported in the literature.20 AV block may occur at presentation or during the subacute phase of the disease and may be transient (with complete recover within few days), persistent with a late improvement after months or years or permanent.53, 54 Whether acute AV conduction disturbances are a cause or a consequence of TTC is unclear. Because TTC affects elderly women, AV conduction may be already damaged by

Unifying pathogenetic theory

Demonstration of an association between transient myocardial edema and dynamic T-wave inversion/QT interval prolongation suggests a unifying theory to explain both repolarization abnormalities and life-threatening ventricular arrhythmias observed in the subacute phase of TTC.18, 32, 43, 55 According to this pathogenetic theory, an acute inflammatory process, which may be the direct cause of TTC or a reactive phenomenon to sympathetic overdrive and/or microvascular ischemia, induces interstitial

Implications for therapy

Knowledge of the mechanisms underlying ECG abnormalities and ventricular arrhythmias in TTC may help in providing recommendations for clinical management. Unlike irreversible lesion of myocardial infarction, the isolated myocardial edema observed in patients with TTC with T-wave inversion/QTc interval prolongation predicts reversible LV dysfunction and benign long-term outcome. However, since TTC is a cause of acquired long QT syndrome, during hospitalization patients should undergo telemetry

Conclusion

The perspective that different pathophysiological mechanisms account for ECG changes and ventricular electrical instability occurring in the acute and subacute phases of TTC may help in establishing specific and appropriate management strategies for rhythm and conduction changes occurring at different times of the disease course.

CMR studies have provided new insights into our understanding of the pathogenesis of reversible mechanical and electrical alterations of TTC by demonstrating that

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      Citation Excerpt :

      Edema is a swelling due to the expansion of interstitial fluid volume in the myocardium and considered as a tissue response to acute myocardial injury [13]. Therefore, it is an important diagnostic target for assessing the acuity of tissue damage, including acute myocardial infarction, myocarditis, takotsubo cardiomyopathy, and heart transplantation graft rejection, and has been demonstrated to produce cardiac dysfunction and arrhythmia [14]. Infiltrations (iron, glycosphingolipids, amyloid) are important because although rare, expensive therapies are available.

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