Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death 1 1Funded in part by an American Heart Association grant-in-aid to SSC.

John, Benjamin T.; Tamarappoo, Balaji; Titus, Jack L.; Edwards, William D.; Shen, Win Kuang; Chugh, Sumeet S.

doi:10.1016/j.hrthm.2004.02.021

Cited by 48 publications

(36 citation statements)

References 41 publications

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“…In our model, untreated dTGR with terminal cardiac damage commonly develop microinfarctions, with variable areas of damaged cells, fibrosis, and inflammation. Such areas also contribute to an arrhythmogenic substrate (15).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II-induced sudden arrhythmic death and electrical remodeling

Fischer

Dechend²,

Gapelyuk³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Rats harboring the human renin and angiotensinogen genes (dTGR) feature angiotensin (ANG) II/ hypertension-induced cardiac damage and die suddenly between wk 7 and 8. We observed by electrocardiogram (ECG) telemetry that ventricular tachycardia (VT) is a common terminal event in these animals. Our aim was to investigate electrical remodeling. We used ECG telemetry, noninvasive cardiac magnetic field mapping (CMFM) at wk 5 and 7, and performed in vivo programmed electrical stimulation at wk 7. We also investigated whether or not losartan (Los; 30 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) would prevent electrical remodeling. Cardiac hypertrophy and systolic blood pressure progressively increased in dTGR compared with Sprague-Dawley (SD) controls. Already by wk 5, untreated dTGR showed increased perivascular and interstitial fibrosis, connective tissue growth factor expression, and monocyte infiltration compared with SD rats, differences that progressed through time. Left-ventricular mRNA expression of potassium channel subunit Kv4.3 and gap-junction protein connexin 43 were significantly reduced in dTGR compared with Los-treated dTGR and SD. CMFM showed that depolarization and repolarization were prolonged and inhomogeneous. Los ameliorated all disturbances. VT could be induced in 88% of dTGR but only in 33% of Los-treated dTGR and could not be induced in SD. Untreated dTGR show electrical remodeling and probably die from VT. Los treatment reduces myocardial remodeling and predisposition to arrhythmias. ANG II target organ damage induces VT. magnetocardiography; noninvasive mapping; double-transgenic rat model; in vivo electrophysiological study ELECTRICAL REMODELING INVOLVES acquired changes in cardiac structure or function that promote the occurrence of atrial or ventricular cardiac arrhythmias (22). On the molecular level, electrical remodeling involves changes in function and expression of membrane ion channels, gap-junction proteins, Ca 2ϩ -cycling proteins, and extracellular matrix composition. All these factors predispose to arrhythmogenic mechanisms such as early and delayed afterdepolarizations and reentry (13). The multifactorial origin of electrical remodeling has been extensively studied in cardiac ischemia and heart failure. However, electrical remodeling in hypertension is less well defined. Patients with hypertension-induced left-ventricular hypertrophy are at increased risk for arrhythmias, which contribute to a twofold increase in cardiovascular mortality (7). Monitoring electrical remodeling is challenging. The standard 12-lead electrocardiogram (ECG), ECG-based body surface potential mapping, and signal-averaged ECG are correlated with an increased risk to develop malignant arrhythmias. However, the positive predictive accuracy is unacceptably low or not sufficiently tested in randomized trials (14).Multichannel cardiac magnetic field mapping (CMFM) reflects the magnetic fields generated by the myocardial electrical currents occurring during the cardiac cycle. CMFM signals have several advantages: 1) they are littl...

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Section: Discussionmentioning

confidence: 99%

Angiotensin II-induced sudden arrhythmic death and electrical remodeling

Fischer

Dechend²,

Gapelyuk³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…The reason was that fibroblasts coupling reduced the Ca 2+ concentration and caused a reduction in T a . Due to the strong correlation between fibroblast proliferation and heart failure (John et al, 2004;Assomull et al, 2006;Pellman et al, 2010), it can be expected that once the number of fibroblasts increases, a significant reduction would occur in T a .…”

Section: Effects Of Fibroblast Coupling On Human Ventricular Myocyte mentioning

confidence: 99%

“…Once the percentage of fibroblasts in the heart increases up to 10%-35%, a remodeling of the cardiac structure occurs, increasing muscle stiffness and reducing the coupling between adjacent muscle fiber bundles (Rossi, 2001;ten Tusscher and Panfilov, 2007). This process is strongly correlated with atrial and ventricular tachyarrhythmias and sudden cardiac death (John et al, 2004;Assomull et al, 2006;Pellman et al, 2010). The elastic modulus rises from (18±2) kPa in the normal heart muscle of non-infarcted animals to (55±15) kPa in significant fibroblast proliferous muscle of infarcted animals, an almost three-fold increase (Berry et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study

Zhan

Xia

Shou

et al. 2014

J. Zhejiang Univ. Sci. B

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Abstract:In this study, the effects of cardiac fibroblast proliferation on cardiac electric excitation conduction and mechanical contraction were investigated using a proposed integrated myocardial-fibroblastic electromechanical model. At the cellular level, models of the human ventricular myocyte and fibroblast were modified to incorporate a model of cardiac mechanical contraction and cooperativity mechanisms. Cellular electromechanical coupling was realized with a calcium buffer. At the tissue level, electrical excitation conduction was coupled to an elastic mechanics model in which the finite difference method (FDM) was used to solve electrical excitation equations, and the finite element method (FEM) was used to solve mechanics equations. The electromechanical properties of the proposed integrated model were investigated in one or two dimensions under normal and ischemic pathological conditions. Fibroblast proliferation slowed wave propagation, induced a conduction block, decreased strains in the fibroblast proliferous tissue, and increased dispersions in depolarization, repolarization, and action potential duration (APD). It also distorted the wave-front, leading to the initiation and maintenance of re-entry, and resulted in a sustained contraction in the proliferous areas. This study demonstrated the important role that fibroblast proliferation plays in modulating cardiac electromechanical behaviour and which should be considered in planning future heart-modeling studies.

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“…[6][7][8][9][10] A differential diagnosis includes the entity known as idiopathic myocardial fibrosis (IMF), which accounts for 1-3% of cases of SCD. [11][12][13] IMF is characterised by heterogeneous interstitial fibrosis with a predilection for the inferior LV wall. 13 Replacement fibrosis is also observed and fatty infiltration is usually absent.…”

Section: Case Reportmentioning

confidence: 99%

“…[11][12][13] IMF is characterised by heterogeneous interstitial fibrosis with a predilection for the inferior LV wall. 13 Replacement fibrosis is also observed and fatty infiltration is usually absent. 17 Coronary artery disease and other structural abnormalities are by definition absent, indicating myocardial structural damage, for which the primary insult is unknown.…”

Section: Case Reportmentioning

confidence: 99%

Left Dominant Arrhythmogenic Cardiomyopathy Causing Sustained Ventricular Tachycardia – A Case Report

Guglielmi¹,

Cannas²,

Arancio³

et al. 2016

European Journal of Arrhythmia &Amp; Electrophysiology

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A 56-year-old white man was admitted to hospital because of palpitations and dyspnoea. He had no family history of cardiomyopathy or sudden death, and the electrocardiograms (ECG) of his son and parents were normal. He had an history of palpitations, and in the emergency department ECG showed sustained ventricular tachycardia-flutter with inferior axis right bundle branch block (RBBB) in V1 and heart rate 250 beats per minute. His standard ECG showed a complete RBBB pattern with minor ST-T segment changes. 2D echo and coronary angiography were normal, while magnetic resonance imaging (MRI) revealed a reduction in left mid-lateral wall thickening with hypokinetic movement and mild reduction of ejection fraction. An Extensive sub-epicardial area of conspicuous left ventricular intra-myocardial fat and sub-epicardial left ventricular late enhancement in lateral wall, was also seen at MRI. Case reportA 56-year-old white man was admitted to hospital because of palpitations and dyspnoea. He had no family history of cardiomyopathy or sudden death. He complained of palpitations starting in 2002, but had not been to see a doctor. In the emergency department, the ECG showed sustained ventricular tachycardia-flutter with apparently inferior axis right bundle branch block (RBBB) in V1 and heart rate 250 beats per minute (Figure 1). The ventricular tachycardia was associated with initial signs and symptoms of left heart failure and the patient was referred to the Coronary Care Unit where sinus rhythm was restored by direct current electric shock. Symptoms promptly restored after the procedure. The results of the investigation performed are listed in Table 1. LimitationsGenetic studies have not yet been performed because of high cost/ effectiveness ratio. DiscussionAfter the description of Markus and Fontaine, 1 the arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has crossed the borders of the right ventricle. LDAC has been recognised as an associated or isolated entity also characterised pathologically by fibro-adipose replacement of the LV, often occurring as a circumferential band in the outer third of the myocardium and the right side of the inter-ventricular septum.2-5 First described at post-mortem examination in sudden cardiac death (SCD) victims,

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Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death 1 1Funded in part by an American Heart Association grant-in-aid to SSC.

Cited by 48 publications

References 41 publications

Angiotensin II-induced sudden arrhythmic death and electrical remodeling

Angiotensin II-induced sudden arrhythmic death and electrical remodeling

Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study

Left Dominant Arrhythmogenic Cardiomyopathy Causing Sustained Ventricular Tachycardia – A Case Report

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