Arrhythmia-induced cardiomyopathies: the riddle of the chicken and the egg still unanswered?

Simantirakis, Emmanuel N.; Koutalas, Emmanuel; Vardas, Panos

doi:10.1093/europace/eur348

Cited by 49 publications

(38 citation statements)

References 73 publications

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“…Here, we show that older ST3Gal4 −/− animals present with a mild late-onset DCM. Potential cellular mechanisms responsible for human congenital arrhythmic DCM as described by others (for e.g., see [5, 25, 26, 48, 54, 59]) include: (1) disruption or weakening of cytoskeletal components or of interacting voltage-gated ion channel auxiliary proteins [25, 59], and (2) altered Ca 2+ homeostasis secondary to aberrant electrical signaling [5, 26, 48]. While we cannot definitively rule out involvement of cytoskeletal components, we see no evidence to support a mechanism that involves disruption of proteins interacting with voltage-gated ion channel alpha subunits, as no change in current densities of any cardiomyocyte voltage-gated ionic current was observed [18, 19].…”

Section: Discussionmentioning

confidence: 99%

Aberrant sialylation causes dilated cardiomyopathy and stress-induced heart failure

Deng

Ednie

et al. 2016

Basic Res Cardiol

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Dilated cardiomyopathy (DCM), the third most common cause of heart failure, is often associated with arrhythmias and sudden cardiac death if not controlled. The majority of DCM is of unknown etiology. Protein sialylation is altered in human DCM, with responsible mechanisms not yet described. Here we sought to investigate the impact of clinically relevant changes in sialylation on cardiac function using a novel model for altered glycoprotein sialylation that leads to DCM and to chronic stress-induced heart failure (HF), deletion of the sialyltransferase, ST3Gal4. We previously reported that 12- to 20-week-old ST3Gal4−/− mice showed aberrant cardiac voltage-gated ion channel sialylation and gating that contribute to a pro-arrhythmogenic phenotype. Here, echocardiography supported by histology revealed modest dilated and thinner-walled left ventricles without increased fibrosis in ST3Gal4−/− mice starting at 1 year of age. Cardiac calcineurin expression in younger (16–20 weeks old) ST3Gal4−/− hearts was significantly reduced compared to WT. Transverse aortic constriction (TAC) was used as a chronic stressor on the younger mice to determine whether the ability to compensate against a pathologic insult is compromised in the ST3Gal4−/− heart, as suggested by previous reports describing the functional implications of reduced cardiac calcineurin levels. TAC’d ST3Gal4−/− mice presented with significantly reduced systolic function and ventricular dilation that deteriorated into congestive HF within 6 weeks post-surgery, while constricted WT hearts remained well-adapted throughout (ejection fraction, ST3Gal4−/− = 34 ± 5.2 %; WT = 53.8 ± 7.4 %; p < 0.05). Thus, a novel, sialo-dependent model for DCM/HF is described in which clinically relevant reduced sialylation results in increased arrhythmogenicity and reduced cardiac calcineurin levels that precede cardiomyopathy and TAC-induced HF, suggesting a causal link among aberrant sialylation, chronic arrhythmia, reduced calcineurin levels, DCM in the absence of a pathologic stimulus, and stress-induced HF.

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Section: Discussionmentioning

confidence: 99%

Aberrant sialylation causes dilated cardiomyopathy and stress-induced heart failure

Deng

Ednie

et al. 2016

Basic Res Cardiol

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“…Interestingly in recent research subclinical Doppler pathophysiologic changes were identified in nearly 20% of Long QT syndrome patients [120]. These findings prompt speculation that electrical dysfunction (abnormal cardiac repolarization and rhythm) may precipitate macroscopic structural and functional changes visible on focused echocardiograms [120,121].…”

Section: Channelopathiesmentioning

confidence: 95%

Part 2 - Sudden Cardiac Death in Athletes Focused Cause-and-Effect Screening

Paterick¹,

Choudhary²,

Chandrasekaran³

et al. 2015

JESO

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Echo/Doppler screening should be looked upon as a strategy used in a select population of healthy, asymptomatic individuals to identify pre-emergent disease. Using focused echo/Doppler screening the incidence of a cardiovascular finding in athletes has been reported to be roughly one case in every 170 athletes screened with a "false positive" finding in only 8 of 508 athletes [2,10,[13][14][15]. We describe how to provide a highest quality, exceptionally low cost pathophysiologic athletic screening test, which is validated to differentiate the status of a normal state from an abnormal life-threatening pathophysiologic state.Matching pre-emergent disease (without phenotypic expression) "associated" with sudden death through diastolic parameters is the key to differentiating normal from abnormal pathophysiology [5,9,[16][17][18][19][20][21][22][23][24]. These data are focused on two principal objectives: detect an imminent life-threatening state at a time when the opportunity for prevention is optimal [25,26], and define the magnitude of imminent risk that enlightens physician decision making and management [23,[26][27][28]. Rule-Out vs. Rule-in ScreeningA sensitive screening approach must be distinguished from a specific screening methodology [5,6]. The current trend in athletic screening is searching for an "abnormal" disease feature in a low risk population. This fact alone (searching for a specific rare event) is a major contributor to the controversies and shortfalls surrounding athletic screening [5,6].The most optimal screening test for a large, asymptomatic athletic population prioritizes testing to confirm wellness and rule out disease. An abnormality in screening would be referred for comprehensive evaluation. The rule out principle is important because the penalty for missing a disease has the potential for athletic death. This principle reduces the number of specific diseases to be considered during screening. All cardiomyopathies are grouped as having abnormal diastolic tissue Doppler examination. Conversely, ruling in a disease is more applicable when confirming a high frequency disease. Confirming wellness AbstractSudden death in an athlete is a tragic event. There is a strong social imperative to implement effective means of predicting and preventing sudden death in athletes. However, the design and implementation of a solution seems unobtainable [2]. Part Two discusses how novel attributes of systems biology and digital technology are capable of delivering high quality, low cost athletic screening. The merit of a transformative idea does not necessarily predict its adoption. The greatest barrier to change lies in the acquiescence to familiar practices even in light of new ideas and technology. The current thought in athletic screening is more centered on specific disease associations (rule-in principle), [3][4][5] and much less about the sensitivity of pathophysiologic causality (ruleout principle) [5][6][7][8].A solution will languish until the expert community takes direct action to embrace 21 s...

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“…40,41 Thus, a more current definition of TIC is the following: Atrial and/or ventricular dysfunction secondary to rapid and/or asynchronous/irregular myocardial contraction, partially or completely reversed after treatment of the causative arrhythmia. 42 An important element in the definition of true TIC is the exclusion of underlying structural heart disease, since LV dysfunction is totally reversible in TIC as opposed to structural heart disease. To date, the rate of persistent SVT likely to cause LV impairment remains unclear.…”

Section: Tachycardia-induced Cardiomyopathymentioning

confidence: 99%

Reversible Dilated Cardiomyopathy: Into the Thaumaturgy of the Heart—Part 1

et al. 2016

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Dilated cardiomyopathy (DCM) is a genetic or acquired heart muscle disorder characterized by dilation and impaired contraction of one or both ventricles. In the acquired forms of the disease, if the pathogenic agent is persistent, undiagnosed or untreated, permanent ultrastructural and morphological changes may lead to irreversible dysfunction. Conversely, when DCM is promptly recognized and treated, the heart may show an extraordinary ability to recover from left ventricular (LV) systolic dysfunction. While much research in heart failure has focused on morbidity and mortality associated with persistent LV systolic dysfunction, relatively little attention has been devoted to this remarkable potential for recovery. In this two-part review we will focus on the most common types of reversible DCM. The first part will deal with Tako-Tsubo cardiomyopathy, tachycardiainduced cardiomyopathy, metabolic DCM and recovery after Left ventricular assist device implantation. Although diverse in etiopathogenesis, genetic background, therapeutic options and outcome, the forms of DCM characterized by reversible LV dysfunction share similar challenges in diagnosis and clinical management. The identification of pathways to recovery may show the way for novel therapeutic targets ultimately benefitting all cardiac patients.

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Arrhythmia-induced cardiomyopathies: the riddle of the chicken and the egg still unanswered?

Cited by 49 publications

References 73 publications

Aberrant sialylation causes dilated cardiomyopathy and stress-induced heart failure

Aberrant sialylation causes dilated cardiomyopathy and stress-induced heart failure

Part 2 - Sudden Cardiac Death in Athletes Focused Cause-and-Effect Screening

Reversible Dilated Cardiomyopathy: Into the Thaumaturgy of the Heart—Part 1

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