Silenced SOX2‐OT alleviates ventricular arrhythmia associated with heart failure by inhibiting NLRP3 expression via regulating miR‐2355‐3p

Background: Mitral valve prolapse (MVP) is a frequent disease that can be complicated by mitral regurgitation (MR), heart failure, arterial embolism, rhythm disorders and death. Left ventricular (LV) replacement myocardial fibrosis, a marker of maladaptive remodeling, has been described in patients with MVP, but the implications of this finding remain scarcely explored. We aimed at assessing the prevalence, pathophysiological and prognostic significance of LV replacement myocardial fibrosis through late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) in patients with MVP. Methods: Four hundred patients (53±15 years, 55% male) with MVP (trace to severe MR by echocardiography) from 2 centers, who underwent a comprehensive echocardiography and LGE CMR, were included. Correlates of replacement myocardial fibrosis (LGE+), influence of MR degree, and ventricular arrhythmia were assessed. The primary outcome was a composite of cardiovascular events (cardiac death, heart failure, new-onset atrial fibrillation, arterial embolism, and life-threatening ventricular arrhythmia). Results: Replacement myocardial fibrosis (LGE+) was observed in 110 patients (28%; 91 myocardial wall including 71 basal inferolateral wall, 29 papillary muscle). LGE+ prevalence was 13% in trace-mild MR, 28% in moderate and 37% in severe MR, and was associated with specific features of mitral valve apparatus, more dilated LV and more frequent ventricular arrhythmias (45 vs 26%, P<0.0001). In trace-mild MR, despite the absence of significant volume overload, abnormal LV dilatation was observed in 16% of patients and ventricular arrhythmia in 25%. Correlates of LGE+ in multivariable analysis were LV mass (OR 1.01, 95% CI [1.002-1.017], P=0.009) and moderate-severe MR (OR: 2.28, 95% CI [1.21-4.31], P=0.011). LGE+ was associated with worse 4-year cardiovascular event-free survival (49.6±11.7 in LGE+ vs 73.3±6.5% in LGE-, P<0.0001). In a stepwise multivariable Cox model, MR volume and LGE+ (HR: 2.6 [1.4-4.9], P=0.002) were associated with poor outcome. Conclusions: LV replacement myocardial fibrosis is frequent in patients with MVP, is associated with mitral valve apparatus alteration, more dilated LV, MR grade, ventricular arrhythmia, and is independently associated with cardiovascular events. These findings suggest a MVP-related myocardial disease. Finally, CMR provides additional information to echocardiography in MVP.

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Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia

The Korean Journal of Thoracic and Cardiovascular Surgery ◽

10.5090/kjtcs.2016.49.4.292 ◽

2016 ◽

Vol 49 (4) ◽

pp. 292-294

Author(s):

Hak Ju Kim ◽

Sungkyu Cho ◽

Woong-Han Kim

Keyword(s):

Heart Failure ◽

Ventricular Arrhythmia ◽

Cardiac Resynchronization Therapy ◽

Cardiac Resynchronization ◽

Resynchronization Therapy

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Abstract 372: MicroRNA-9 Inhibits Hyperglycemia-induced Cardiac Pyroptosis by Targeting ELAVL1

Circulation Research ◽

10.1161/res.119.suppl_1.372 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Prince Jeyabal ◽

Rajarajan A Thandavarayan ◽

Darukeshwara Joladarashi ◽

Sahana Suresh Babu ◽

Shashirekha Krishnamurthy ◽

...

Keyword(s):

Heart Failure ◽

High Glucose ◽

Cardiac Tissue ◽

Critical Role ◽

Left Ventricular ◽

Diabetic Patients ◽

Therapeutic Implications ◽

Caspase 1 ◽

Ventricular Cardiomyocytes ◽

Nlrp3 Expression

Diabetic cardiomyopathy is a common complication in patients with diabetes and is associated with underlying chronic inflammation and cardiac cell death, subsequently leading to left ventricular dysfunction and heart failure. ELAV-like protein 1 (ELAVL1, mRNA stabilizing protein) and NLRP3 activation (inflammasome complex protein)-mediated IL-1beta synthesis play a critical role in the progression of heart failure. However, ELAVL1 regulation of pyroptosis (caspase-1-mediated programmed apoptosis) and associated IL-1beta release in cardiomyocytes, especially under diabetic condition, remains elusive. Human diabetic, non-diabetic heart tissues, human ventricular cardiomyocytes and rat cardiomyoblasts exposed to high glucose (HG) were used for our studies. Our data demonstrates that human ventricular cardiomyocytes exposed to high glucose condition showed significant increase in ELAVL1 and NLRP3 expression with a concomitant increase in caspase-1 and IL-1 beta expression. Furthermore, human cardiac tissue from diabetic patients showed increased ELAVL1, caspase-1 and NLRP3 expression as compared to non-diabetic hearts. Intriguingly, ELAVL1 knockdown abrogates TNF-α induced canonical pyroptosis via NLRP3, caspase-1 and IL-1beta suppression. Interestingly, miRNA-9 expression significantly reduces in high glucose treated cardiomyocytes and in human diabetic hearts. Bioinformatics analysis and target validation assays showed that miR-9 directly targets ELAVL1. Inhibition of miR-9 up regulates ELAVL1 expression and activates caspase-1. Alternatively, miR-9 mimics attenuate hyperglycemia-induced ELAVL1 and inhibit cardiomyocyte pyroptosis. To our knowledge, this is the first report to demonstrate the role of miR-9/ELAVL1 in hyperglycemia-induced cardiac pyroptosis. Taken together our study highlights the potential therapeutic implications in preventing cardiomyocyte cell loss in human diabetic failing heart.

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Mechanisms linking electrical alternans and clinical ventricular arrhythmia in human heart failure

Heart Rhythm ◽

10.1016/j.hrthm.2016.05.017 ◽

2016 ◽

Vol 13 (9) ◽

pp. 1922-1931 ◽

Cited By ~ 12

Author(s):

J.D. Bayer ◽

G.G. Lalani ◽

E.J. Vigmond ◽

S.M. Narayan ◽

N.A. Trayanova

Keyword(s):

Heart Failure ◽

Ventricular Arrhythmia ◽

Human Heart ◽

Human Heart Failure ◽

Electrical Alternans

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Exendin-4 Reduces Ventricular Arrhythmia Activity and Calcium Sparks-Mediated Sarcoplasmic Reticulum Ca Leak in Rats with Heart Failure

International Heart Journal ◽

10.1536/ihj.19-327 ◽

2020 ◽

Vol 61 (1) ◽

pp. 145-152 ◽

Cited By ~ 2

Author(s):

Jingjing Chen ◽

Shunen Xu ◽

Wei Zhou ◽

Lirong Wu ◽

Long Wang ◽

...

Keyword(s):

Heart Failure ◽

Sarcoplasmic Reticulum ◽

Ventricular Arrhythmia ◽

Calcium Sparks

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Cardiovascular magnetic resonance T2* mapping for the assessment of cardiovascular events in hypertrophic cardiomyopathy

Open Heart ◽

10.1136/openhrt-2019-001152 ◽

2020 ◽

Vol 7 (1) ◽

pp. e001152 ◽

Cited By ~ 1

Author(s):

Mareike Gastl ◽

Christiane Gruner ◽

Karin Labucay ◽

Alexander Gotschy ◽

Jochen Von Spiczak ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Magnetic Resonance ◽

Hypertrophic Cardiomyopathy ◽

Magnetic Resonance ◽

Ventricular Arrhythmia ◽

Cardiovascular Events ◽

Imaging System ◽

T2 Mapping ◽

Univariate Analysis ◽

Increased Risk

BackgroundHypertrophic cardiomyopathy (HCM) is associated with an increased risk of adverse cardiac events. Beyond classic risk factors, relative myocardial ischaemia and succeeding myocardial alterations, which can be detected using either contrast agents or parametric mapping in cardiovascular magnetic resonance (CMR) imaging, have shown an impact on outcome in HCM. CMR may help to risk stratify using parametric T2* mapping. Therefore, the aim of the present study was to evaluate the association of T2* values or fibrosis with cardiovascular events in HCM.MethodsThe relationship between T2* with supraventricular, ventricular arrhythmia or heart failure was retrospectively assessed in 91 patients with HCM referred for CMR on a 1.5T MR imaging system. Fibrosis as a reference was added to the model. Patients were subdivided into groups according to T2* value quartiles.Results47 patients experienced an event of ventricular arrhythmia, 25 of atrial fibrillation/flutter and 17 of heart failure. T2*≤28.7 ms yielded no association with ventricular events in the whole HCM cohort. T2* of non-obstructive HCM showed a significant association with ventricular events in univariate analysis, but not in multivariate analysis. For the combined endpoint of arrhythmic events, there was already an association for the whole HCM cohort, but again only in univariate analyses. Fibrosis stayed the strongest predictor in all analyses. There was no association for T2* and fibrosis with heart failure.ConclusionsDecreased T2* values by CMR only provide a small association with arrhythmic events in HCM, especially in non-obstructive HCM. No information is added for heart failure.

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Monomorphic Ventricular Tachycardia as a Presentation of Giant Cell Myocarditis

Case Reports in Cardiology ◽

10.1155/2019/7276516 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Michael H. Chiu ◽

Cvetan Trpkov ◽

Saman Rezazedeh ◽

Derek S. Chew

Keyword(s):

Heart Failure ◽

Ventricular Arrhythmia ◽

Giant Cell ◽

Complex Disease ◽

Acute Myocarditis ◽

Left Ventricular ◽

Myocardial Inflammation ◽

Icd Implantation ◽

Severe Left Ventricular Dysfunction ◽

Giant Cell Myocarditis

Background. Idiopathic giant cell myocarditis (GCM) has a fulminant course and typically presents in middle-aged adults with acute heart failure or ventricular arrhythmia. It is a rare disorder which involves T lymphocyte-mediated myocardial inflammation. Diagnosis is challenging and requires a high index of suspicion since therapy may improve an otherwise uniformly fatal prognosis. Case Summary. A previously healthy 54-year-old female presented with hemodynamically significant ventricular arrhythmia (VA) and was found to have severe left ventricular dysfunction. Cardiac MRI demonstrated acute myocarditis, and endomyocardial biopsy showed giant cell myocarditis. She was treated with combined immunosuppressive therapy as well as guideline-directed medical therapy. A secondary prevention implantable cardioverter defibrillator (ICD) was implanted. Discussion. GCM is a rare, lethal myocarditis subtype but is potentially treatable. Combined immunosuppression may achieve partial clinical remission in two-thirds of patients. VA is common, and patients should undergo ICD implantation. More research is needed to better understand this complex disease. Learning Objectives. Giant cell myocarditis is an incompletely understood, rare cause of myocarditis. Patients present predominately with heart failure and dysrhythmia. Diagnosis is confirmed by histopathology, and immunosuppression may improve outcomes. ICD implantation should be considered. In the absence of treatment, prognosis is poor with a median survival of three months.

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Ablation of Ventricular Arrhythmia in Patients with Heart Failure

Heart Failure Clinics ◽

10.1016/j.hfc.2014.12.009 ◽

2015 ◽

Vol 11 (2) ◽

pp. 319-336 ◽

Cited By ~ 3

Author(s):

William W.B. Chik ◽

Francis E. Marchlinski

Keyword(s):

Heart Failure ◽

Ventricular Arrhythmia ◽

Patients With Heart Failure

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