Stereotactic Radioablation for Ventricular Tachycardia in the Setting of Electrical Storm.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been reported as a safe and efficient therapy for treating refractory ventricular tachycardia (VT) despite optimal medical treatment and catheter ablation. However, data on the use of SBRT in patients with electrical storm (ES) is lacking. The aim of this study was to assess the clinical outcomes associated with SBRT in the context of ES. METHODS: This retrospective study included patients who underwent SBRT in the context of ES from March 2020 to March 2021 in one tertiary center (CHU Lille). The target volume was delineated according to a predefined workflow. The efficacy was assessed with the following end points: sustained VT recurrence, VT reduced with antitachycardia pacing, and implantable cardioverter defibrillator shock. RESULTS: Seventeen patients underwent SBRT to treat refractory VT in the context of ES (mean 67±12.8 age, 59% presenting ischemic heart disease, mean left ventricular ejection fraction: 33.7± 9.7%). Five patients presented with ES related to incessant VT. Among these 5 patients, the time to effectiveness ranged from 1 to 7 weeks after SBRT. In the 12 remaining patients, VT recurrences occurred in 7 patients during the first 6 weeks following SBRT. After a median 12.5 (10.5-17.8) months follow-up, a significant reduction of the VT burden was observed beyond 6 weeks (-91% [95% CI, 78-103]), P<0.0001). The incidence of implantable cardioverter defibrillator shock and antitachycardia pacing was 36% at 1 year. CONCLUSIONS: SBRT is associated with a significant reduction of the VT burden in the event of an ES; however, prospective randomized control trials are needed. In patients without incessant VT, recurrences are observed in half of patients during the first 6 weeks. VT tolerance and implantable cardioverter defibrillator programming adjustments should be integrated as part of an action plan defined before SBRT for each patient.

Incidence and predictors of mortality after an electrical storm in the ICU.

AIMS: For assessing predictors of early mortality following hospitalization for electrical storm (ES), only limited data are available. The purpose of this study was to assess the incidence and predictors of early mortality following hospitalization in the intensive care unit (ICU) for ES in a large retrospective study. METHODS AND RESULTS: In this retrospective study, we included all patients who were hospitalized for ES from July 2015 to May 2020 in our tertiary centre. A total of 253 patients were included. The median age was 66 [56; 73], and 64% had ischemic cardiomyopathy. A total of 37% of patients presented hemodynamic instability requiring catecholamine at admission. A total of 17% of patients presented an acute reversible cause for ES. The one-year mortality was 34% (95% CI, 30-43%), mostly driven by heart failure (HF). The multivariable Cox's regression model identified age, left ventricular ejection fraction, right ventricle dysfunction, haemoglobin level as independent predictors of one-year mortality. The use of catecholamine at admission was identified as the only variable related to the initial management of ES associated with an increased 30-day mortality risk (HR: 7.95 (95%CI, 3.18-19.85). CONCLUSION: In patients admitted for ES in ICU, the one-year mortality remains high and mostly driven by HF. The use of catecholamine at admission is associated with a seven-fold risk for mortality within 30 days. In such patients, the potential use of VT ablation can be questioned and a careful action plan regarding invasive HF-related therapy could be considered.

Usefulness of remote monitoring for the early detection of back-up mode in implantable cardioverter defibrillators.

BACKGROUND: Reversion of an implantable cardioverter defibrillator (ICD) to back-up mode degrades the operating capabilities of the device, puts patients at risk and requires rapid intervention by a manufacturer's technician. AIM: To illustrate the usefulness of remote monitoring of ICDs for the early detection of reversion to back-up mode. METHODS: In our centre, all patients implanted with an ICD, with or without resynchronisation, were offered remote monitoring as soon as the technology became available. Alerts triggered by the remote monitoring system were included prospectively in a register. During a mean follow-up of 5.7±1.3 years, a total of 1594 patients with an ICD (441 with resynchronisation function) followed with remote monitoring were included in the register. RESULTS: Among 15,874 alerts, only 10 were related to a reversion to back-up mode. Among those, seven reversions were caused by radiotherapy, two were fake events and one was caused by magnetic resonance imaging. Except for the two fake events, the eight other patients had an emergency admission for the resetting and reprogramming of their ICD. None of the reversion to back-up mode alerts was followed by a clinical alert (i.e. a shock alert) before the ICD problem was resolved. CONCLUSIONS: Reversion to back-up mode is a very rare event, accounting for 0.06% of total alerts; remote monitoring facilitates the early detection of this critical event to resolve the problem faster than the next scheduled follow-up. Remote monitoring can prevent serious damage to the patient and avoids systematic ambulatory control of the ICD after each radiotherapy session.

Predictors of Subcutaneous Implantable Cardioverter-Defibrillator Shocks and Prognostic Impact in Patients With Structural Heart Disease.

BACKGROUND: In this study we aimed to assess long-term outcomes in subcutaneous implantable cardioverter-defibrillator (S-ICD) recipients with structural heart disease by focussing especially on shock incidence, predictors, and associated prognoses. METHODS: In this multicenter registry‒based study, we retrospectively included all patients who underwent S-ICD implantation at 3 tertiary centers. The prognostic impact of S-ICD shock was assessed with a composite outcome that included all-cause death and hospitalisation for heart failure. RESULTS: A total of 351 patients with underlying cardiomyopathy were included in the investigation. Using multivariable Fine and Gray regression models, secondary prevention, left ventricular ejection fraction (LVEF), conditional shock threshold, and QRS duration appeared to be independent predictors of appropriate S-ICD shock occurrence. In the multivariate Cox regression model adjusted for age, baseline LVEF, underlying cardiomyopathy subtype, New York Heart Association class, and appropriate shocks were significantly associated with increased composite prognostic outcome risk (hazard ratio [HR], 2.61; 95% confidence interval [CI], 1.21-5.65; P = 0.014), whereas inappropriate shocks were not (HR, 1.35; 95% CI, 0.75-4.48; P = 0.18). The analysis of each component of the composite prognostic outcome highlighted that the occurrence of appropriate shocks was associated with an increased risk of hospitalisation for heart failure (HR, 3.10; 95% CI, 1.26-7.58; P = 0.013) and a trend for mortality (HR, 2.19; 95% CI, 0.78-6.16; P = 0.14). CONCLUSIONS: Appropriate S-ICD shocks were associated with a 3-fold increase in acute heart failure admission, whereas inappropriate shocks were not. Conditional shock threshold programming is an independent predictor of S-ICD shock, and its prognostic impact should be investigated further in patients with structural heart disease.

A report on the impact of remote monitoring in patients with S-ICD: Insights from a prospective registry.

INTRODUCTION: Several clinical studies have demonstrated that remote monitoring (RM) offers potential benefits in transvenous implantable cardioverter defibrillator (ICD). The potential interest of RM in subcutaneous-ICD (S-ICD) recipients has never been evaluated. The aim of this study was to evaluate the alert burden and its clinical relevance in a prospective cohort of S-ICD recipients. METHODS: We prospectively and consecutively enrolled all patients undergoing S-ICD implantation at Lille University Hospital from September 2015 to January 2017 and gave them a LATITUDE™ NXT RM system. The relevance of transmissions was assessed by the following ratio: number of transmissions leading to reaction or intervention per patient/number of transmissions per patient. RESULTS: From September 2015 to January 2017, 69 patients were enrolled with a mean follow-up of 415 ± 96.3 days. The mean age was 44.6 ± 15.6 years old, and 25% (n = 17) had ischemic cardiomyopathy. At the end of follow-up, 12% of the patients had events recorded by RM. These events were related to nine ICD shocks and eight untreated events. A total of 1,423 transmissions were collected. Most of these transmissions were patient-initiated without any event (77%, n = 1,096) or scheduled without any event (19%, n = 272). Only 3.2% ± 1.1 of the transmissions per patient led to reactions or interventions. CONCLUSION: On the basis of the current method of transmitting, S-ICD RM allowed detection of relevant events in 12% of patients but generated a high unactionable transmission burden. As a result of these findings, efforts should be made to optimize transmissions considering automatic transmissions and to focus on patient education.

Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.

BACKGROUND: On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. METHODS: We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia-reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia-reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901. FINDINGS: In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32-0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68-0·93; p=0·0045]). Ex-vivo analysis of human myocardium revealed an intrinsic morning-afternoon variation in hypoxia-reoxygenation tolerance, concomitant with transcriptional alterations in circadian gene expression with the nuclear receptor Rev-Erbα being highest in the morning. In a mouse Langendorff model of hypoxia-reoxygenation myocardial injury, Rev-Erbα gene deletion or antagonist treatment reduced injury at the time of sleep-to-wake transition, through an increase in the expression of the ischaemia-reperfusion injury modulator CDKN1a/p21. INTERPRETATION: Perioperative myocardial injury is transcriptionally orchestrated by the circadian clock in patients undergoing aortic valve replacement, and Rev-Erbα antagonism seems to be a pharmacological strategy for cardioprotection. Afternoon surgery might provide perioperative myocardial protection and lead to improved patient outcomes compared with morning surgery. FUNDING: Fondation de France, Fédération Française de Cardiologie, EU-FP7-Eurhythdia, Agence Nationale pour la Recherche ANR-10-LABX-46, and CPER-Centre Transdisciplinaire de Recherche sur la Longévité.

Long-term outcome of implantable cardioverter-defibrillator implantation in secondary prevention of sudden cardiac death.

BACKGROUND: Little is known about the long-term outcomes of patients who receive an implantable cardioverter-defibrillator (ICD) for purely secondary prevention indications. AIMS: To assess the rates and predictors of appropriate therapies over a very long-term follow-up period in this population. METHODS: Between June 2003 and August 2006, 239 consecutive patients with structural left ventricular disease and a secondary prophylaxis indication for ICD therapy (survivors of life-threatening ventricular tachyarrhythmias) were prospectively enrolled. An extended follow-up of these patients was carried out. The primary endpoint was the occurrence of appropriate device therapy. Secondary endpoints were all-cause death, electrical storm and inappropriate therapy. RESULTS: The study population consisted of 239 patients (90% men; mean age 64±12 years; 72% ischaemic cardiomyopathy; left ventricular ejection fraction 37±12%). During a median follow-up of 7.8 (3.5-9.3) years, appropriate device therapy occurred in 139 (58.2%) patients. Death occurred in 141 patients (59%), electrical storm in 73 (30.5%) and inappropriate therapy in 42 (17.6%). Multivariable analysis identified patients whose presenting arrhythmia was ventricular fibrillation as being less likely to require appropriate device therapy than those whose presenting arrhythmia was ventricular tachycardia (sub-hazard ratio 0.62, 95% confidence interval 0.40-0.97; P=0.04). Independent predictors of all-cause death were age at implantation (P<0.0001), wide QRS complexes (P=0.024), creatinine concentration (P=0.0002) and B-type natriuretic peptide at implantation (P=0.0001). CONCLUSION: Secondary prevention ICD recipients exhibit a high risk of appropriate device therapy and death over prolonged follow-up. Patients who presented initially with ventricular fibrillation were less likely to require the delivery of appropriate device therapy.

Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients.

BACKGROUND: Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy. METHODS AND RESULTS: Right atrial myocardium was obtained from 141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex vivo isometric contraction, mitochondrial respiration and calcium retention capacity, and respiratory chain complex activities and oxidative stress status. Diabetes mellitus was associated with a pronounced impairment of intrinsic contraction, mitochondrial dysfunction, and increased myocardial oxidative stress, regardless of weight status. In contrast, obesity was associated with less pronounced contractile dysfunction without any significant perturbation of mitochondrial function or oxidative stress status. Tested as continuous variables, glycated hemoglobin A1C, but neither body mass index nor the insulin resistance index (homeostasis model assessment-insulin resistance), was independently associated with cardiac mitochondrial function. Furthermore, diabetes mellitus was associated with cardiac mitochondrial network fragmentation and significantly decreased expression of the mitochondrial fusion related protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin A1C. CONCLUSION: Worsening of intrinsic myocardial contraction in the transition from obesity to diabetes mellitus is likely related to worsening of cardiac mitochondrial function because impaired mitochondrial function and dynamics and contractile dysfunction are observed in diabetic patients but not in "metabolically healthy" obese patients at early stage in insulin resistance.