scholarly journals Targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced sustained ventricular tachycardia in conscious rats

2010 ◽  
Vol 298 (5) ◽  
pp. H1330-H1339 ◽  
Author(s):  
Heidi L. Lujan ◽  
Gurunanthan Palani ◽  
Lijie Zhang ◽  
Stephen E. DiCarlo

The Cardiac Arrhythmia Suppression Trial demonstrated that antiarrhythmic drugs not only fail to prevent sudden cardiac death, but actually increase overall mortality. These findings have been confirmed in additional trials. The “proarrhythmic” effects of most currently available antiarrhythmic drugs makes it essential that we investigate novel strategies for the prevention of sudden cardiac death. Targeted ablation of cardiac sympathetic neurons may become a therapeutic option by reducing sympathetic activity. Thus cholera toxin B subunit (CTB) conjugated to saporin (a ribosomal inactivating protein that binds to and inactivates ribosomes; CTB-SAP) was injected into both stellate ganglia to test the hypothesis that targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced, sustained ventricular tachycardia in conscious rats. Rats were randomly divided into three groups: 1) control (no injection); 2) bilateral stellate ganglia injection of CTB; and 3) bilateral stellate ganglia injection of CTB-SAP. CTB-SAP rats had a reduced susceptibility to ischemia-induced, sustained ventricular tachycardia. Associated with the reduced susceptibility to ventricular arrhythmias were a reduced number of stained neurons in the stellate ganglia and spinal cord (segments T1-T4), as well as a reduced left ventricular norepinephrine content and sympathetic innervation density. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing the susceptibility to ventricular arrhythmias.

ESC CardioMed ◽  
2018 ◽  
pp. 941-944
Author(s):  
Heikki Huikuri ◽  
Lars Rydén

Cardiac arrhythmias are more common in subjects with diabetes mellitus (DM) than in their counterparts without diabetes. Atrial fibrillation (AF) is present in 10–20% of the DM patients, but the association between DM and AF is mostly due to co-morbidities of DM patients increasing the vulnerability to AF. When type 2 DM and AF coexist, there is a substantially higher risk of cardiovascular mortality, stroke, and heart failure, which indicates screening of AF in selected patients with DM. Anticoagulant therapy either with vitamin K antagonists or non-vitamin K antagonist oral anticoagulants is recommended for DM patients with either paroxysmal or permanent AF, if not contraindicated. Palpitations, premature ventricular beats, and non-sustained ventricular tachycardia are common in patients with DM. The diagnostic work-up and treatment of these arrhythmias does not differ between the patients with or without DM. The diagnosis and treatment of sustained ventricular tachycardia, either monomorphic or polymorphic ventricular tachycardia, or resuscitated ventricular fibrillation is also similar between the patients with or without DM. The risk of sudden cardiac death is higher in DM patients with or without a diagnosed structural heart disease. Patients with diabetes and a left ventricular ejection fraction less than 30–35% should be treated with a prophylactic implantable cardioverter defibrillator according to current guidelines. Beta-blocking therapy is recommended for DM patients with left ventricular dysfunction or heart failure to prevent sudden cardiac death due to arrhythmia.


EP Europace ◽  
2019 ◽  
Vol 21 (10) ◽  
pp. 1559-1565 ◽  
Author(s):  
Gabrielle Norrish ◽  
Tao Ding ◽  
Ella Field ◽  
Karen McLeod ◽  
Maria Ilina ◽  
...  

Abstract Aims Sudden cardiac death (SCD) is the most common cause of death in children with hypertrophic cardiomyopathy (HCM). The European Society of Cardiology (ESC) recommends consideration of an implantable cardioverter-defibrillator (ICD) if two or more clinical risk factors (RFs) are present, but this approach to risk stratification has not been formally validated. Methods and results Four hundred and eleven paediatric HCM patients were assessed for four clinical RFs in accordance with current ESC recommendations: severe left ventricular hypertrophy, unexplained syncope, non-sustained ventricular tachycardia, and family history of SCD. The primary endpoint was a composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate ICD therapy, or sustained ventricular tachycardia), defined as a major arrhythmic cardiac event (MACE). Over a follow-up period of 2890 patient years (median 5.5 years), MACE occurred in 21 patients (7.5%) with 0 RFs, 19 (16.8%) with 1 RFs, and 3 (18.8%) with 2 or more RFs. Corresponding incidence rates were 1.13 [95% confidence interval (CI) 0.7–1.73], 2.07 (95% CI 1.25–3.23), and 2.52 (95% CI 0.53–7.35) per 100 patient years at risk. Patients with two or more RFs did not have a higher incidence of MACE (log-rank test P = 0.34), with a positive and negative predictive value of 19% and 90%, respectively. The C-statistic was 0.62 (95% CI 0.52–0.72) at 5 years. Conclusions The incidence of MACE is higher for patients with increasing numbers of clinical RFs. However, the current ESC guidelines have a low ability to discriminate between high- and low-risk individuals.


Author(s):  

Dilated cardiomyopathy (DCM) is a disease characterised as left ventricular (LV) or biventricular dilatation with impaired systolic function. Regardless of underlying cause patients with DCM have a propensity to ventricular arrhythmias and sudden cardiac death. Implantable Cardioverter Defibrillator (ICD) implantation for these patients results in significant reduction of sudden cardiac death [1-3]. ICD devices may be limited by right ventricle (RV) sensing dysfunction with low RV sensing amplitude. We present a clinical case of patient with DCM, implanted ICD and low R wave sensing on RV lead.


Circulation ◽  
2020 ◽  
Vol 141 (18) ◽  
pp. 1477-1493 ◽  
Author(s):  
Yihui Wang ◽  
Chunyan Li ◽  
Ling Shi ◽  
Xiuyu Chen ◽  
Chen Cui ◽  
...  

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary heart disease characterized by fatty infiltration, life-threatening arrhythmias, and increased risk of sudden cardiac death. The guideline for management of ARVC in patients is to improve quality of life by reducing arrhythmic symptoms and to prevent sudden cardiac death. However, the mechanism underlying ARVC-associated cardiac arrhythmias remains poorly understood. Methods: Using protein mass spectrometry analyses, we identified that integrin β1 is downregulated in ARVC hearts without changes to Ca 2+ -handling proteins. As adult cardiomyocytes express only the β1D isoform, we generated a cardiac specific β1D knockout mouse model and performed functional imaging and biochemical analyses to determine the consequences of integrin β1D loss on function in the heart in vivo and in vitro. Results: Integrin β1D deficiency and RyR2 Ser-2030 hyperphosphorylation were detected by Western blotting in left ventricular tissues from patients with ARVC but not in patients with ischemic or hypertrophic cardiomyopathy. Using lipid bilayer patch clamp single channel recordings, we found that purified integrin β1D protein could stabilize RyR2 function by decreasing RyR2 open probability, mean open time, and increasing mean close time. Also, β1D knockout mice exhibited normal cardiac function and morphology but presented with catecholamine-sensitive polymorphic ventricular tachycardia, consistent with increased RyR2 Ser-2030 phosphorylation and aberrant Ca 2+ handling in β1D knockout cardiomyocytes. Mechanistically, we revealed that loss of DSP (desmoplakin) induces integrin β1D deficiency in ARVC mediated through an ERK1/2 (extracellular signal–regulated kinase 1 and 2)–fibronectin–ubiquitin/lysosome pathway. Conclusions: Our data suggest that integrin β1D deficiency represents a novel mechanism underlying the increased risk of ventricular arrhythmias in patients with ARVC.


2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Mohammad Ali Zakeri ◽  
Vahid Mohammadi ◽  
Gholamreza Bazmandegan ◽  
Maryam Zakeri

Medicinal herbs and some derivatives have been used in the treatment of heart disease which is rarely responsible for ventricular arrhythmias and cardiac arrest. Ventricular tachycardia (VT) increases the risk of sudden cardiac death (SCD). However, only a few reports are available about the cardiac ventricular arrhythmia followed by taking herbal medicines. We present two patients (a couple) without a history of heart disease who referred to the hospital with ventricular arrhythmia.


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