Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis.

After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.

Massive Air Embolism During Atrial Fibrillation Ablation: Averting Disaster in a Time of Crisis.

A 62-year-old male with symptomatic persistent atrial fibrillation underwent radiofrequency catheter ablation. During exchange of the saline irrigation bag, the patient developed sudden hypotension and bradycardia and was found to have a massive air embolism. Air was successfully aspirated with catheters, and the patient did not suffer any permanent sequelae. (Level of Difficulty: Intermediate.).

Arrhythmic Risk Profile and Outcomes of Patients Undergoing Cardiac Sympathetic Denervation for Recurrent Monomorphic Ventricular Tachycardia After Ablation.

Background Cardiac sympathetic denervation (CSD) has been used as a bailout strategy for refractory ventricular tachycardia (VT). Risk of VT recurrence in patients with scar-related monomorphic VT referred for CSD and the extent to which CSD can modify this risk is unknown. We aimed to quantify arrhythmia recurrence risk and impact of CSD in this population. Methods and Results Adjusted competing risk time to event models were developed to adjust for risk of VT recurrence and sustained VT/implantable cardioverter-defibrillator shocks after VT ablation based on patient comorbidities at the time of VT ablation. Adjusted VT and implantable cardioverter-defibrillator shock recurrence rates were estimated for the subgroup who subsequently required CSD after ablation. The expected adjusted recurrence rates were then compared with the observed rates after CSD. Data from 381 patients with scar-mediated monomorphic VT who underwent VT ablation were analyzed, excluding patients with polymorphic VT. Sixty eight patients underwent CSD for recurrent VT. CSD reduced the expected adjusted VT recurrence rate by 36% (expected rate of 5.61 versus observed rate of 3.58 per 100 person-months, P=0.01) and the sustained VT/implantable cardioverter-defibrillator shock rates by 34% (expected rate of 4.34 versus observed 2.85 per 100 person-months, P=0.03). The median number of sustained VT/implantable cardioverter-defibrillator shocks in the year before versus the year after CSD was reduced by 90% (10 versus 1, P<0.0001). Conclusions Patients referred for CSD for refractory scar-mediated monomorphic VT are at a higher risk of VT recurrence after ablation as compared with those not requiring CSD, mostly because of their cardiac comorbidities. CSD significantly reduced both the expected risk of recurrences and VT burden.

Non-invasive stereotactic body radiation therapy for refractory ventricular arrhythmias: an institutional experience.

BACKGROUND: Initial studies have reported excellent safety and efficacy for stereotactic body radiation therapy (SBRT) in patients with refractory ventricular tachycardia (VT). METHODS: This is a single-center retrospective analysis of eight consecutive patients who underwent SBRT for refractory, scar-related VT. The anatomic target for radioablation was defined based on surface 12-lead ECG VT morphology, cardiac magnetic resonance imaging, and electroanatomic mapping data when available. The target volume treated and the prescribed radiation dose (15-25 Gy) was based on the combined clinical assessment of the cardiac electrophysiologist and radiation oncologist. Ventricular arrhythmias, radiation-related outcomes, and adverse events were monitored at follow-up. RESULTS: Eight patients underwent nine SBRT sessions. All patients were male with an average age of 75 ± 7.3 years and mean ejection fraction of 21 ± 7%. SBRT was performed with delivery of an average of 22.2 ± 3.6 Gy in a single session with a procedure time of 18.2 ± 6.0 min. All but one session was performed on an inpatient basis. No acute complications occurred. During a median follow-up of 7.8 months (IQR 4.8, 9.9), ICD therapies decreased from median 69.5 (43.5, 115.8) pre-SBRT to 13.3 (IQR 7.7, 35.8) post-SBRT (p = 0.036). There were three patient deaths in the follow-up period, unrelated to SBRT. Apparent clinical benefit occurred 33% of the time after SBRT. CONCLUSIONS: The patients experienced overall reduction in VT burden following SBRT, though not with the immediate effect seen in other patient series. Further studies (basic, translational, and clinical) are essential to determine the benefit of SBRT and if so, the optimal protocols and patient selection.

Recurrent ventricular tachycardia after cardiac sympathetic denervation: Prolonged cycle length with improved hemodynamic tolerance and ablation outcomes.

INTRODUCTION: Cardiac sympathetic denervation (CSD) is utilized for the management of ventricular tachycardia (VT) in structural heart disease when refractory to radiofrequency ablation (RFA) or when patient/VT characteristics are not conducive to RFA. METHODS: We studied consecutive patients who underwent CSD at our institution from 2009 to 2018 with VT requiring repeat RFA post-CSD. Patient demographics, VT/procedural characteristics, and outcomes were assessed. RESULTS: Ninety-six patients had CSD, 16 patients underwent RFA for VT post-CSD. There were 15 male and 1 female patients with mean age of 54.2 ± 13.2 years. Fourteen patients had nonischemic cardiomyopathy. A mean of 2.0 ± 0.8 RFAs for VT was unsuccessful before the patient undergoing CSD. The median time between CSD and RFA was 104 days (interquartile range [IQR] = 15-241). The clinical VT cycle length was significantly increased after CSD both spontaneously on ECG and/or ICD interrogation (355 ± 73 ms pre-CSD vs. 422 ± 94 ms post-CSD, p = .001) and intraprocedurally (406 ± 86 ms pre-CSD vs. 457 ± 88 ms post-CSD, p = .03). Two patients had polymorphic and 14 had monomorphic VT (MMVT) pre-CSD, and all patients had MMVT post-CSD. The proportion of mappable, hemodynamically stable VTs increased from 35% during pre-CSD RFA to 58% during post-CSD RFA (p = .038). At median follow-up of 413 days (IQR = 43-1840) after RFA, eight patients had no further VT. CONCLUSION: RFA for recurrent MMVT post-CSD is a reasonable treatment option with intermediate-term clinical success in 50% of patients. Clinical VT cycle length was significantly increased after CSD with associated improvement in mappable, hemodynamically tolerated VT during RFA.

Renal denervation as adjunctive therapy to cardiac sympathetic denervation for ablation refractory ventricular tachycardia.

BACKGROUND: Autonomic modulation is finding an increasing role in the treatment of ventricular arrhythmias. Renal denervation (RDN) has been described as a treatment modality for refractory ventricular tachycardia (VT) in case series. OBJECTIVE: The purpose of this study was to evaluate RDN as an adjunctive therapy to cardiac sympathetic denervation (CSD) for ablation refractory VT. METHODS: Patients who underwent RDN after radiofrequency ablation and CSD procedures at our center from 2012 to 2019 were evaluated. RESULTS: Ten patients underwent RDN after CSD (9 bilateral and 1 left-sided only) with a median follow-up of 23 months. The mean age was 59.9 ± 10.4 years, and 9/10 (90%) were men. All had cardiomyopathy with a mean ejection fraction of 33% ± 11% (20% ischemic). Four (40%) underwent CSD during the same hospitalization as that for RDN. Patients who underwent RDN as adjunctive therapy to CSD had a decrease in all implantable cardioverter-defibrillator therapies (shocks + antitachycardia pacing [ATP]) from 29.5 ± 25.2 to 7.1 ± 10.1 comparing 6 months pre-RDN to 6 months post-RDN (P = .028). Implantable cardioverter-defibrillator shocks were significantly decreased from 7.0 ± 6.1 to 1.7 ± 2.5 comparing 6 months pre-RDN to 6 months post-RDN (P = .026). This benefit was driven by a decrease in therapies for 6 patients who had a staged procedure, not performed during the same hospitalization (28.5 ± 24.3 to 1.0 ± 1.2; P = .043). CONCLUSION: RDN demonstrates the potential benefit when VT recurs after radiofrequency ablation and CSD. The benefit is seen in patients who undergo a staged procedure. The need for acute RDN after CSD portends a poor prognosis.

Update on prevention and treatment of sudden cardiac arrest.

Sudden cardiac arrest is the leading cause of cardiovascular mortality, posing a substantial public health burden. The incidence and epidemiology of sudden death are a function of age, with primary arrhythmia syndromes and inherited cardiomyopathies representing the predominant causes in younger patients, while coronary artery disease being the leading etiology in those who are 35 years of age and older. Internal cardioverter defibrillators remain the mainstay of primary and secondary prevention of sudden cardiac arrest. In the acute phase, cardiac chain of survival, early reperfusion, and therapeutic hypothermia are the key steps in improving outcomes. In the chronic settings, ventricular tachycardia ablation has been shown to improve patients' quality of life by reducing frequency of defibrillator shocks. Moreover, recent studies have suggested that it may increase survival. Neuromodulation represents a novel therapeutic modality that has a great potential for improving treatment of ventricular arrhythmias.

Hybrid surgical vs percutaneous access epicardial ventricular tachycardia ablation.

BACKGROUND: There is limited experience of surgical epicardial access in the contemporary era of ventricular tachycardia ablation after cardiac surgery. OBJECTIVES: The purpose of this study was to describe our institutional experience with surgical epicardial access and the influence of surgical approach and compare outcomes with those of a propensity-matched percutaneous epicardial access control group. METHODS: We performed a retrospective study of consecutive surgical epicardial ventricular tachycardia (VT) ablation cases from a single center. Surgical cases were propensity-matched to percutaneous epicardial ablation controls and short-term and long-term outcomes were compared. RESULTS: Between 2004 and 2016, 38 patients underwent 40 surgical epicardial access procedures (subxiphoid, n = 22; thoracotomy, n = 18). The commonest indication was prior coronary artery bypass grafting (45%), valve surgery (22%), or ventricular assist device (VAD) (10%). The mean procedure time was 444 minutes (standard deviation, 107 minutes). Mapped epicardial geometry area was 149 cm2 (interquartile range 182 cm2), which comprised 36% of the mapped epicardial geometric area of a percutaneous control group. Subxiphoid access gave preferential access to the inferior and inferolateral left ventricular segments and was less frequently able to access the anterior, anterolateral, and apical segments compared with a thoracotomy approach. When compared with results from a propensity-matched percutaneous-access group, short-term outcomes, complication rates, and 1-year survival free from a combined end point of VT recurrence, death, or transplantation were not statistically different. CONCLUSIONS: Surgical epicardial access after cardiac surgery for ablation of VT in patients with careful preprocedure evaluation can be performed with acceptable safety with no statistical difference in long-term outcomes compared with a propensity-matched percutaneous epicardial cohort. The region of left ventricular epicardium that can be mapped is limited compared with that of percutaneous cases and is determined by the surgical approach.

Increased Nonalternans Repolarization Variability Precedes Ventricular Tachycardia Onset in Patients with Implantable Defibrillators.

BACKROUND: T-wave alternans (TWA) is associated with ventricular tachycardia (VT). Nonalternans repolarization variability (NARV) precedes VT in certain experimental models, but its link to clinical arrhythmia is unproven. This study was conducted to determine if NARV increases prior to VT in patients with implantable cardioverter defibrillators (ICDs). METHODS: TWA and NARV were calculated from shock-channel electrograms preceding onset of VT or non-VT events in patients with an ICD. In each patient, presence of both a VT and a non-VT event with the same QRS morphology before the event was required. Mixed linear model was used for data analysis, using heart rate (HR) and the number of analyzed beats as covariates. RESULTS: Five hundred and sixty-eight events from 64 patients (males/females 51/13, 67 ± 13 years) were analyzed. HR preceding non-VT events was higher than before VT events (RR interval 595 ± 159 vs 706 ± 111 ms; P < 0.0001). Both TWA and NARV increased with increasing HR (P < 0.001). TWA decreased with increasing number of analyzed beats. When controlled for number of analyzed beats and HR, both TWA and NARV were higher before VT than before non-VT events (P < 0.002 and P < 0.0005, respectively). CONCLUSIONS: NARV is elevated prior to spontaneous VT onset. Both NARV and TWA increase with HR. The decrease of TWA with increasing number of analyzed beats may indicate contamination with NARV or noise when only a small number of beats is available for analysis. NARV might be useful for VT prediction in the future.