Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNFα (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities in a murine model of KD vasculitis. METHODS: Lactobacillus casei cell wall extract-induced KD vasculitis model was used to investigate the therapeutic efficacy of clinically relevant IL-1Ra (IL-1 receptor antagonist) and TNFα neutralization. Echocardiography, in vivo electrophysiology, whole-heart optical mapping, and imaging were performed. RESULTS: KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity. Since our transcriptomic analysis of human patients showed elevated levels of both IL-1ß and TNFα, we asked whether either cytokine was linked to the development of myocardial dysfunction. Remarkably, only inhibition of IL-1 signaling by IL-1Ra but not TNFα neutralization was able to prevent changes in ejection fraction and arrhythmias, whereas both IL-1Ra and TNFα neutralization significantly improved vasculitis and heart vessel inflammation. The treatment of L casei cell wall extract-injected mice with IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk. In contrast, in mice with gain of function of the IL-1 signaling pathway, L casei cell wall extract induced spontaneous ventricular tachycardia and premature deaths. CONCLUSIONS: Our results characterize the electrophysiological abnormalities associated with L casei cell wall extract-induced KD and show that IL-1Ra is more effective in preventing KD-induced myocardial dysfunction and arrhythmias than anti-TNFα therapy. These findings support the advancement of clinical trials using IL-1Ra in patients with KD.

Right ventricular function is a predictor for sustained ventricular tachycardia requiring anti-tachycardic pacing in arrhythmogenic ventricular cardiomyopathy: insight into transvenous vs. subcutaneous implantable cardioverter defibrillator insertion.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients develop ventricular arrhythmias (VAs) responsive to anti-tachycardia pacing (ATP). However, VA episodes have not been characterized in accordance with the device therapy, and with the emergence of the subcutaneous implantable cardioverter defibrillator (S-ICD), the appropriate device prescription in ARVC remains unclear. Study aim was to characterize VA events in ARVC patients during follow-up in accordance with device therapy and elicit if certain parameters are predictive of specific VA events. METHODS AND RESULTS: This was a retrospective single-centre study utilizing prospectively collated registry data of ARVC patients with ICDs. Forty-six patients were included [54.0 ± 12.1 years old and 20 (43.5%) secondary prevention devices]. During a follow-up of 12.1 ± 6.9 years, 31 (67.4%) patients had VA events [n = 2, 6.5% ventricular fibrillation (VF), n = 14], 45.2% VT falling in VF zone resulting in ICD shock(s), n = 10, 32.3% VT resulting in ATP, and n = 5, 16.1% patients had both VT resulting in ATP and ICD shock(s). Lead failure rates were high (11/46, 23.9%). ATP was successful in 34.5% of patients. Severely impaired right ventricular (RV) function was an independent predictor of VT resulting in ATP (hazard ratio 16.80, 95% confidence interval 3.74-75.2; P < 0.001) with a high predictive accuracy (area under the curve 0.88, 95%CI 0.76-1.00; P < 0.001). CONCLUSION: VA event rates are high in ARVC patients with a majority having VT falling in the VF zone resulting in ICD shock(s). S-ICDs could be of benefit in most patients with ARVC with the absence of severely impaired RV function which has the potential to avoid consequences of the high burden of lead failure.

[Implantable cardioverter-defibrillator explosion after gunshot: when the device protects not only from arrhythmic death]. / Esplosione di defibrillatore impiantabile in seguito a colpo d'arma da fuoco: quando il defibrillatore non previene soltanto la morte aritmica.

A 70-year-old man presented to the emergency department with accidental gunshot wound at left hemithorax and left shoulder/arm. Initial clinical assessment showed stable vital signs and an implantable cardioverter-defibrillator (ICD) protruding outside from large wound in the infraclavicular region. The ICD, previously implanted for secondary prevention of ventricular tachycardia, appeared burned and the battery was exploded. Urgent chest computed tomography scan was performed with evidence of left humeral fracture without significant arterial injury. The ICD generator was disconnected from passive fixation leads and removed. The patient was stabilized and the humeral fracture was fixed. Then lead extraction was successfully performed in a hybrid operating room with cardiac surgery standby. The patient was discharged in good clinical conditions after reimplantation of a novel ICD in the right infraclavicular region.Emerging technologies are promising in making lead extraction safer and more accessible for patients worldwide. This case report provides the most up-to-date indications and procedural approaches for lead extraction and insights on the future trends in this field.

Impact of synchronized left ventricular pacing rate on risk for ventricular tachyarrhythmias after cardiac resynchronization therapy in patients with heart failure.

BACKGROUND: The adaptive cardiac resynchronization therapy (aCRT) algorithm automatically produces synchronized left ventricular pacing (sLVP) with intrinsic atrioventricular conduction to improve clinical outcomes. However, relationship between sLVP percentage and risk for ventricular tachyarrhythmia (VT/VF) remains unclear. This study aimed to evaluate the clinical impact of sLVP rate on VT/VF occurrence. METHODS: In total, 1,419 device interrogation data from 42 consecutive patients who underwent new aCRT device implantation were retrospectively analyzed. The primary endpoint was the first time VT/VF episode after aCRT device implantation. RESULTS: During a median follow-up of 34 months, 15 patients had VT/VF episodes. Patients were divided into a high sLVP (the average sLVP percentage of ≥ 51.5%, n = 27) or low sLVP group (< 51.5%, n = 15). The high sLVP group had a significantly lower VT/VF incidence (22% vs. 60%; p = 0.014) and an independent predictor for VT/VF occurrence on multivariate analysis (hazard ratio 0.21; p = 0.007). LV ejection fraction improvements after 6 months (12.3 ± 8.7% vs. 2.8 ± 10.3%; p = 0.004) and 12 months (13.8 ± 9.3% vs. 6.2 ± 11.1%; p = 0.030) were significantly greater in the high sLVP group than in the low sLVP group. Age, PR interval, and left atrial diameter were significantly associated with the sLVP rate after aCRT. CONCLUSIONS: Patients with high sLVP percentage after aCRT had lower long-term risk of VT/VF incidence with a favorable response to CRT. A synchronized pacing algorithm using intrinsic conduction may prevent malignant arrhythmias, as well as recover cardiac functions.

Implantable defibrillators in primary prevention of genetic arrhythmias. A shocking choice?

Many previously unexplained life-threatening ventricular arrhythmias and sudden cardiac deaths (SCDs) in young individuals are now recognized to be genetic in nature and are ascribed to a growing number of distinct inherited arrhythmogenic diseases. These include hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (VT), and short QT syndrome. Because of their lower frequency compared to coronary disease, risk factors for SCD are not very precise in patients with inherited arrhythmogenic diseases. As randomized studies are generally non-feasible and may even be ethically unjustifiable, especially in the presence of effective therapies, the risk assessment of malignant arrhythmic events such as SCD, cardiac arrest due to ventricular fibrillation (VF), appropriate implantable cardioverter defibrillator (ICD) interventions, or ICD therapy on fast VT/VF to guide ICD implantation is based on observational data and expert consensus. In this document, we review risk factors for SCD and indications for ICD implantation and additional therapies. What emerges is that, allowing for some important differences between cardiomyopathies and channelopathies, there is a growing and disquieting trend to create, and then use, semi-automated systems (risk scores, risk calculators, and, to some extent, even guidelines) which then dictate therapeutic choices. Their common denominator is a tendency to favour ICD implantation, sometime with reason, sometime without it. This contrasts with the time-honoured approach of selecting, among the available therapies, the best option (ICDs included) based on the clinical judgement for the specific patient and after having assessed the protection provided by optimal medical treatment.

Limited Left Thoracoscopic Sympathectomy Effectively Silences Refractory Electrical Storm.

BACKGROUND: An electrical storm (ES) is a life-threatening condition that affects up to 20% of patients with implantable cardioverter defibrillators. In this small retrospective study, we report our results with left video-assisted thoracoscopic sympathectomy/ganglionectomy (VATSG) to treat refractory ES in low-ejection fraction patients who were not candidates for catheter ablation. METHODS: We identified 12 patients who presented with ES and underwent a total of 14 video-assisted thoracoscopic sympathectomy/ganglionectomy, including 3 patients on venoarterial extracorporeal membrane oxygenation. We reviewed demographic data, survival to discharge, number of cardioversions (before and after VATSG), need for readmissions, and need for right-sided procedures. RESULTS: In the 30 days before a left VATSG, mean number of shocks was 22.67 for all patients. For the patients who survived to discharge, the mean was 3.55 since surgery and the median was zero shocks after a median follow-up of 358 days. Six patients did not experience further cardioversions since the last VATSG and 5 were not readmitted for ventricular tachycardia. Two patients had staged bilateral procedures owing to recurrences; of those, 1 did not require further cardioversions. CONCLUSIONS: Limited left VATSG is an appropriate and effective initial treatment for ES patients who are not candidates for catheter ablation, including those on venoarterial extracorporeal membrane oxygenation for hemodynamic support.

Bruton's tyrosine kinase Inhibitors and Cardiotoxicity: More Than Just Atrial Fibrillation.

PURPOSE OF REVIEW: The purpose of this review is to summarize the epidemiology, mechanisms, and management of cardiovascular complications of Bruton's Tyrosine Kinase inhibitors (BTKIs). RECENT FINDINGS: Ibrutinib increases the risk of atrial fibrillation, bleeding, and hypertension compared with non-BTKI therapies. The evidence to support an association between ibrutinib and other cardiovascular complications including ventricular tachyarrhythmias or cardiomyopathy is limited. Ibrutinib metabolism can be inhibited by some medications used to treat cardiovascular complications. The cardiovascular effects of more selective BTKIs, such as acalabrutinib, remain to be determined. Future research should address the mechanisms underlying the cardiovascular complications of BTKIs and how best to manage them. The risks and benefits of more selective BTKIs as compared with ibrutinib require further evaluation.

Resveratrol Confers Protection Against Ischemia/Reperfusion Injury by Increase of Angiotensin (1-7) Expression in a Rat Model of Myocardial Hypertrophy.

ABSTRACT: Left ventricular hypertrophy (LVH) makes the heart vulnerable to ischemia/reperfusion (IR) injury. Angiotensin (Ang) (1-7) is recognized as a cardioprotective peptide. We investigated the effect of polyphenol resveratrol on myocardial IR injury after hypertrophy and examined cardiac content of Ang (1-7) and transcription of its receptor (MasR). Rats were divided into sham-operated, LVH, IR, LVH + IR, and resveratrol + LVH + IR groups. Myocardial hypertrophy and IR models were created by abdominal aortic banding and left coronary artery occlusion, respectively. To evaluate the electrocardiogram parameters and incidence of arrhythmias, electrocardiogram was recorded by subcutaneous leads (lead II). Blood pressure was measured through the left carotid artery. Infarct size was determined by the triphenyl tetrazolium chloride staining. The Ang (1-7) level was evaluated by immunohistochemistry. The Mas receptor mRNA level was assessed by the real-time real time reverse transcription polymerase chain reaction technique. QT-interval duration, infarct size, and incidence of ischemia-induced arrhythmia were significantly higher in the LVH + IR group. However, in the resveratrol-treated group, these parameters were decreased significantly. The cardiac level of Ang (1-7) was decreased in untreated hypertrophied hearts (LVH and LVH + IR groups). Pretreatment with resveratrol normalized the cardiac level of Ang (1-7). The mRNA level of Mas receptor was increased in all of hypertrophied hearts in the presence or absence of resveratrol. Resveratrol can decrease IR injury in rats with LVH. The anti-ischemic effect of resveratrol may be related to the enhancement of Ang (1-7)/MasR axis.

Electrical storm after correction of an uncomplicated congenital atrial septal defect in an adult: a case report.

BACKGROUND: There is a paucity of published literature describing electrical storm after the correction of uncomplicated atrial septal defect (ASD) in an adult. CASE PRESENTATION: We present a 49-year-old woman with a congenital ASD combined with mild tricuspid regurgitation who denied any history of arrhythmia or other medical history. She suffered from electrical storm (≥ 3 episodes of ventricular tachycardias or ventricular fibrillations) in the early stage after ASD repair with combined tricuspid valvuloplasty. During electrical storm, her electrolytes were within normal ranges and no ischemic electrocardiographic changes were detected, which suggested that retained air embolism or acute coronary thrombosis were unlikely. Additionally, echocardiographic findings and her central venous pressure (5-8 mmHg during the interval between attacks) failed to support the diagnosis of pericardial tamponade. After a thorough discussion, the surgeons conducted an emergent re-exploration and repeated closure of the ASD with combined DeVega's annuloplasty. Eventually, the patient recovered uneventfully, without reoccurring arrhythmias during follow-up. Although we fail to determine the definite cause, we speculate that the causes probably are iatrogenic injury of the conduction system due to a rare anatomic variation, poor intraoperative protection, latent coronary distortion during tricuspid valvuloplasty, or idiopathic or secondary abnormalities of the conduction system. CONCLUSIONS: For most surgeons, performing re-exploration without a known etiology is a difficult decision to make. This case illustrates that re-exploration could be an option when electrical storm occurs in the early stage postoperatively. Nevertheless, surgeons should assess the benefit-risk ratio when taking this unconventional measure.

Advanced heart failure patients supported with ambulatory inotropic therapy: What defines success of therapy?

OBJECTIVE: The objective of this study was to describe the profiles and outcomes of a cohort of advanced heart failure patients on ambulatory inotropic therapy (AIT). BACKGROUND: With the growing burden of patients with end-stage heart failure, AIT is an increasingly common short or long-term option, for use as bridge to heart transplant (BTT), bridge to ventricular assist device (BTVAD), bridge to decision regarding advanced therapies (BTD) or as palliative care. AIT may be preferred by some patients and physicians to facilitate hospital discharge. However, counseling patients on risks and benefits is critically important in the modern era of defibrillators, durable mechanical support and palliative care. METHODS: We retrospectively studied a cohort of 241 patients on AIT. End points included transplant, VAD implantation, weaning of inotropes, or death. The primary outcomes were survival on AIT and ability to reach intended goal if planned as BTT or BTVAD. We also evaluated recurrent heart failure hospitalizations, incidence of ventricular arrhythmias (VT/VF) and indwelling line infections. Unintended consequences of AIT, such reaching unintended end point (e.g. VAD implantation in BTT patient) or worse than expected outcome after LVAD or HT, were recorded. RESULTS: Mean age of the cohort was 60.7 ± 13.2 years, 71% male, with Class III-IV heart failure (56% non-ischemic). Average ejection fraction was 19.4 ± 10.2%, pre-AIT cardiac index was 1.5 ± 0.4 L/min/m2 and 24% had prior ventricular arrhythmias. Overall on-AIT 1-year survival was 83%. Hospitalizations occurred in 51.9% (125) of patients a total of 174 times for worsening heart failure, line complication or ventricular arrhythmia. In the BTT cohort, only 42% were transplanted by the end of follow-up, with a 14.8% risk of death or delisting for clinical deterioration. For the patients who were transplanted, 1-year post HT survival was 96.7%. In the BTVAD cohort, 1-year survival after LVAD was 90%, but with 61.7% of patients undergoing LVAD as INTERMACS 1-2. In the palliative care cohort, only 24.5% of patients had a formal palliative care consult prior to AIT. CONCLUSIONS: AIT is a strategy to discharge advanced heart failure patients from the hospital. It may be useful as bridge to transplant or ventricular assist device, but may be limited by complications such as hospitalizations, infections, and ventricular arrhythmias. Of particular note, it appears more challenging to bridge to transplant on AIT in the new allocation system. It is important to clarify the goals of AIT therapy upfront and continue to counsel patients on risks and benefits of the therapy itself and potential unintended consequences. Formalized, multi-disciplinary care planning is essential to clearly define individualized patient, as well as programmatic goals of AIT.

Macrophage depletion in stellate ganglia alleviates cardiac sympathetic overactivation and ventricular arrhythmogenesis by attenuating neuroinflammation in heart failure.

Cardiac sympathetic overactivation is involved in arrhythmogenesis in patients with chronic heart failure (CHF). Inflammatory infiltration in the stellate ganglion (SG) is a critical factor for cardiac sympathoexcitation in patients with ventricular arrhythmias. This study aims to investigate if macrophage depletion in SGs decreases cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Surgical ligation of the coronary artery was used for induction of CHF. Clodronate liposomes were microinjected into bilateral SGs of CHF rats for macrophage depletion. Using cytokine array, immunofluorescence staining, and Western blot analysis, we found that macrophage expansion and expression of TNFα and IL-1ß in SGs were markedly increased in CHF rats. Flow cytometry data confirmed that the percentage of macrophages in SGs was higher in CHF rats than that in sham rats. Clodronate liposomes significantly reduced CHF-elevated proinflammatory cytokine levels and macrophage expansion in SGs. Clodronate liposomes also reduced CHF-increased N-type Ca2+ currents and excitability of cardiac sympathetic postganglionic neurons and inhibited CHF-enhanced cardiac sympathetic nerve activity. ECG data from 24-h, continuous telemetry recording in conscious rats demonstrated that clodronate liposomes not only restored CHF-induced heterogeneity of ventricular electrical activities, but also decreased the incidence and duration of ventricular tachycardia/fibrillation in CHF. Macrophage depletion with clodronate liposomes attenuated CHF-induced cardiac sympathetic overactivation and ventricular arrhythmias through reduction of macrophage expansion and neuroinflammation in SGs.

Integrin-Linked Kinase Activation Prevents Ventricular Arrhythmias Induced by Ischemia/Reperfusion Via Inhibition of Connexin 43 Remodeling.

Ischemia reperfusion (I/R)-induced arrhythmia is a serious complication in patients with cardiac infarction. Remodeling of connexin (Cx) 43, manifested as phosphorylation, contributes significantly to arrhythmogenesis. Integrin-linked kinase (ILK) attenuated ventricular remodeling and improved cardiac function in rats after myocardial infarction. We hypothesized that ILK, through Cx43 phosphorylation, would be protective against I/R-induced ventricular arrhythmias. Our study showed that I/R-induced ventricular arrhythmias were attenuated by an ILK agonist LPTP and worsened by the ILK inhibitor Cpd22. I/R disrupted Cx43 distribution, but it was partially normalized in the presence of LPTP. Compared with I/R, the phosphorylation of Akt was increased significantly after pretreatment with LPTP. The increase in phosphorylated Akt was physiologically significant because, in the presence of the Akt inhibitor MK2206, the protective effects of LPTP were blocked. This indicated that ILK activation prevented I/R-induced-ventricular arrhythmia, an effect potentially related to inhibition of Cx43 remodeling via Akt activation.

Interpretation of arrhythmogenic effects of COVID-19 disease through ECG.

OBJECTIVE: We aimed to detect the malignant arrhythmic potential of COVID-19 with surface electrocardiographic (ECG) markers. MATERIAL AND METHOD: Of the ECG parameters PR, QT, QTc, QTd, TPe, and Tpe/QTc were measured in 51 COVID-19 patients and 40 in control subjects. RESULTS: Compared to control group mean QTc (410.8 ± 24.3 msec vs. 394.6 ± 20.3 msec, p < .001) and Tpe/QTc (0.19 ± 0.02 vs. 0.18 ± 0.04, p = .036) and median QTd (47.52 vs. 46.5) values were significantly higher in COVID-19 patients. Troponin levels were significantly correlated with heart rate (r = 0.387, p = .006) but not with ECG parameters. CONCLUSION: Several ventricular arrhythmia surface ECG predictors including QTc, QTd, and Tpe/QTc are increased in COVID-19 patients. Since medications used in COVID-19 patients have the potential to affect these parameters, giving importance to these ECG markers may have a significant contribution in decreasing disease-related arrhythmias.

Intraoperative cryoablation in late pulmonary valve replacement for tetralogy of Fallot.

Ventricular tachyarrhythmia (VT) is a major cause of late morbidity and mortality in patients who underwent surgical repair of tetralogy of Fallot. The majority of VTs are monomorphic macro-reentrant VT (MVT) and depend on slow conducting areas of diseased myocardium bordered by unexcitable tissue (anatomical isthmuses). Myocardial fibrosis due to surgical incisions, patch material and valve annuli are typical boundaries of anatomical isthmuses (AI). The conducting myocardium between the pulmonary valve and ventricular septum defect patch is called isthmus 3, and the majority of MVTs originate from this area. During pulmonary valve replacement, there is excellent exposure of isthmus 3. Importantly, after pulmonary valve replacement, the homograft may cover important parts of isthmus 3, which makes percutaneous catheter ablation at a later stage impossible. In all patients who need pulmonary valve replacement late after tetralogy of Fallot repair, preoperative electrophysiology study and electroanatomical mapping can identify patients with inducible MVT or slow conduction carrying high risk of MVT. In these patients, intraoperative cryoablation of isthmus 3 should be performed and bidirectional conduction block across the cryoablation line should be demonstrated by intraoperative differential pacing.

Low-Intensity Ultrasound Modulation May Prevent Myocardial Infarction-induced Sympathetic Neural Activation and Ventricular Arrhythmia.

BACKGROUND: Low-intensity focused ultrasound (LIFU) has been shown to be a beneficial tool for autonomic nervous system modulation, but its effect on the left stellate ganglion (LSG) remains unknown. OBJECTIVE: To seek the effect of LIFU on myocardial infarction (MI)-induced LSG activation and ventricular arrhythmias (VAs). METHODS: In this study, 20 dogs were included and randomly divided into the LIFU (LIFU & MI, n = 8), Sham (sham LIFU & MI, n = 8), and Control group (sham LIFU & sham MI, n = 4). For each LIFU intervention (1.0-2.0 W, 10 minutes) of the LSG, the LSG function, ventricular effective refractory period (ERP), and temperature were tested pre-intervention and postintervention. Thereafter, MI was induced by left anterior artery ligation and VAs were recorded for 1 hour. At the end, both the LSG and the heart were extracted for biomedical and histological analysis. RESULTS: In the Sham group, no significant change was shown in ventricular ERP or LSG function for any intensity settings of sham LIFU intervention when compared with the group baseline. In the LIFU group, however, both 1.5 and 2.0 W LIFU modulation of LSG resulted in significant prolongation of ERP and attenuation of LSG function. Furthermore, the incidence of VAs was significantly attenuated in the LIFU group compared with the Sham group. Moreover, histological analysis showed that no damage or apoptosis was observed in LSG although a statistically significant increase was shown in temperature (maximal increase <1°C) with 1.5 and 2.0 W LIFU intervention. CONCLUSION: LIFU stimulation may be a safe and beneficial tool for LSG attenuation and VA prevention in the MI canine model.

Noninvasive light emitting diode therapy: A novel approach for postinfarction ventricular arrhythmias and neuroimmune modulation.

BACKGROUND: Sympathetic neural activation plays a key role in the incidence and maintenance of acute myocardial infarction (AMI) induced ventricular arrhythmia (VA). Furthermore, previous studies showed that AMI might induce microglia and sympathetic activation and that microglial activation might contribute to sympathetic activation. Recently, studies showed that light emitting diode (LED) therapy might attenuate microglial activation. Therefore, we hypothesized that LED therapy might reduce AMI-induced VA by attenuating microglia and sympathetic activation. METHODS: Thirty anesthetized rats were randomly divided into three groups: the Control group (n = 6), AMI group (n = 12), and AMI + LED group (n = 12). Electrocardiogram (ECG) and left stellate ganglion (LSG) neural activity were continuously recorded. The incidence of VAs was recorded during the first hour after AMI. Furthermore, we sampled the brain and myocardium tissue of the different groups to examine the microglial activation and expression of nerve growth factor (NGF), interleukin-18 (IL-18), and IL-1ß, respectively. RESULTS: Compared to the AMI group, LED therapy significantly reduced the incidence of AMI-induced VAs (ventricular premature beats [VPB] number: 85.08 ± 13.91 vs 27.5 ± 9.168, P < .01; nonsustained ventricular tachycardia (nSVT) duration: 34.39 ± 8.562 vs 9.005 ± 3.442, P < .05; nSVT number: 18.92 ± 4.52 vs 7.583 ± 3.019, P < .05; incidence rate of SVT/VF: 58.33% vs. 8.33%, P < .05) and reduced the LSG neural activity (P < .01) in the AMI + LED group. Furthermore, LED significantly attenuated microglial activation and reduced IL-18, IL-1ß, and NGF expression in the peri-infarct myocardium. CONCLUSION: LED therapy may protect against AMI-induced VAs by suppressing sympathetic neural activity and the inflammatory response.

Ventricular arrhythmias and myocardial inflammation: Long-term follow-up of patients with suspected myocarditis.

BACKGROUND: Inflammatory heart disease is known to be associated with ventricular arrhythmias (VA) and impaired ventricular function at presentation or during follow-up. We aimed to investigate the need for implanted cardioverter defibrillator (ICD) due to ventricular dysfunction and occurrence of VA during long-term follow-up in patients admitted with suspected myocarditis. METHODS: Between 2000 and 2016, 191 patients (age 43 ±â€¯13 years, 71% male, mean left ventricular ejection fraction (LVEF) 33 ±â€¯15%) with clinically suspected myocarditis, who underwent endomyocardial biopsies (EMB), were prospectively enrolled and followed up in 6-months-intervals (median follow-up was 83 (49-156) months). The primary endpoint was deterioration of cardiac function (LVEF ≤ 35%) or occurrence of VA leading to ICD implantation. RESULTS: According to EMB results, patients were stratified in three diagnostic groups: acute myocarditis (5%), chronic myocarditis (50%) and dilated cardiomyopathy (DCM) (45%). An ICD implantation was performed in 58 patients (30%, n = 38 for primary prevention). Besides LVEF at baseline, chronic myocardial inflammation was the only independent predictor of ICD implantation for primary prevention (hazard ratio 2.48 (95% confidence interval 1.02-5.5); p = 0.045). VA requiring ICD therapy occurred in 29 of 58 patients (50%) after a median of 14 (2-37) months without a significant difference between presence and absence of myocardial inflammation. CONCLUSIONS: Nearly one third of patients with suspected myocarditis require an ICD due to impaired LVEF or occurrence of VA. Half of these patients experienced VA with adequate ICD therapy.

Hybrid thoracoscopic epicardial ablation of right ventricular outflow tract in patients with Brugada syndrome.

BACKGROUND: Abnormal delayed electrograms (EGMs) from the anterior wall of the right ventricular outflow tract (RVOT) epicardium have become the ablation target in Brugada syndrome (BrS). OBJECTIVE: The aim of this study was to analyze the safety, feasibility, and efficacy of a novel hybrid thoracoscopic approach to perform epicardial RVOT radiofrequency ablation in BrS. METHODS: Thirty-six patients with BrS (26 men (72.2%); mean age 36.6±15.8 years; range 3-63 years) who underwent hybrid thoracoscopic epicardial ablation of RVOT from January 2016 to April 2018 were included in this study. Two expert electrophysiologists analyzed the EGMs during ajmaline challenge and guided the surgeon to perform ablation. Ajmaline challenge was repeated after 1 month to assess the absence of the BrS electrocardiographic pattern. Patients were followed by remote monitoring and outpatient visits every 6 months. RESULTS: The elimination of all abnormal EGMs was achieved in 94.4% of patients. After a mean follow-up of 16 ± 8 months (range 6-30 months), freedom from ventricular arrhythmias was obtained in 7 (77.8%) patients in secondary prevention 9/36 (25%) and in 24 (100%) patients in primary prevention 24/36 (75%). Major complications were observed in 1 patient (2.8%), who experienced late cardiac tamponade. CONCLUSION: Hybrid thoracoscopic epicardial RVOT ablation in BrS is a safe and feasible approach, allowing direct visualization of ablation during radiofrequency delivery. Because of ventricular arrhythmia recurrences, implantable cardioverter-defibrillator implantation is still mandatory in patients treated in secondary prevention and with high risk.