Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: An Analysis of All Appropriate Therapy in the PRAETORIAN trial

Background: The PRAETORIAN trial showed non-inferiority of the subcutaneous implantable cardioverter-defibrillator (S-ICD) compared to the transvenous ICD (TV-ICD) with regard to inappropriate shocks and complications. In contrast to the TV-ICD, the S-ICD cannot provide antitachycardia pacing (ATP) for monomorphic ventricular tachycardia (VT). This pre-specified secondary analysis evaluates appropriate therapy and whether ATP reduces the number of appropriate shocks. Methods: The PRAETORIAN trial was an international, investigator-initiated randomized trial, which included patients with an indication for ICD therapy. Patients with prior VTs below 170 bpm or refractory recurrent monomorphic VTs were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (N=426) or TV-ICD (N=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. Results: In the S-ICD group, 86/426 patients received appropriate therapy, versus 78/423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%, P=0.45). In the S-ICD group, 83 patients received at least one shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%, P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared to 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first ATP attempt successfully terminated 46% of all monomorphic VTs, but accelerated the arrhythmia in 9.4%. Ten S-ICD patients experienced 13 electrical storms, versus 18 TV-ICD patients with 19 electrical storms. Patients with appropriate therapy had an almost two-fold increased relative risk of electrical storms in the TV-ICD group compared to the S-ICD group (P=0.05). Conclusions: In this trial, no difference was observed in shock efficacy of the S-ICD compared with the TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the two groups.

Single center experience of ICD implantation in pediatric age

Funding Acknowledgements Type of funding sources: None. Background Despite sudden cardiac death (SCD) is a rare phenomenon in pediatric age, the use of the implantable defibrillator (ICD) is progressively increasing in consideration of its life-saving role both in primary and in secondary prevention. Our work aims at evaluating our pediatric population from the point of view of distribution according to heart disease, indication and implantation technique. We also want to verify the protective role of the device in terms of SCD prevention, acute and chronic complications and to evaluate the role played by the device as a bridge to transplantation. METHODS The retrospective study includes patients under the age of 18 underwent ICD implantation, following the guidelines and recommendations currently in force, in the time period between March 2000 and July 2020. Each device has been programmed in a personalized way based on age and cardiac pathology. The subjects were divided into three groups depending on the cardiac pathology. All patients were then followed-up by evaluating the appropriate shocks, the acute and chronic complications, especially the inappropriate shocks. RESULTS The study group includes 55 subjects (41 males and 12 females) with a mean age of 14 ± 4 years and a mean follow-up time of 6.2 years. Thirty subjects had cardiomyopathy (CM), 15 electrical disease (ED) and 10 congenital heart disease (CHD) respectively. We used three different implantation technique (endocavitary, subcutaneus and hybrid technique) depending on the size of the patient and the cardiac anatomy. There is no gender difference as regards the indication to the implant in primary/secondary prevention (67% in secondary prevention vs 33% in primary prevention). CHD and CM are mostly implanted in primary prevention. The rate of appropriate shocks in secondary prevention is higher than that in the primary one regardless of the disease. Thirty-eight percent of patients received appropriate shock, of which 66.7% were patients who had received defibrillator as a bridge to heart transplant. Two patients (3.6%) received inappropriate shocks on supraventricular tachycardia. There were no acute post-implantation complications. None dysfunctions or ruptures of the shock catheter or episodes of T wave oversensing took place. Peri-procedural and post-transplant mortality is zero, except for a deceased subject awaiting transplantation due to congestive heart failure. CONCLUSIONS The study confirmed the protective role of the device, in terms of prevention of sudden cardiac death, and its relevance as bridge to heart transplantation in pediatric age. An implant technique adequate to the size, age and heart disease of the patient associated with an adequate programming of the device significantly reduced inappropriate shocks in our patients.

Safety of omitting defibrillation efficacy testing with subcutaneous defibrillators: a propensity matched case-control study

Funding Acknowledgements Type of funding sources: None. Background Defibrillation efficacy testing (DT) is recommended at implantation of subcutaneous implantable cardioverter–defibrillators (S-ICD). However, prior works found that adherence to this recommendation is declining in clinical practice. Purpose To compare survival from all-cause death and first ineffective shock (primary endpoint) and the composite of all-cause death, ineffective shock, inappropriate shock and device-related complication (secondary endpoint) between patients who underwent DT and those with omitted DT. Methods We analyzed 1652 consecutive patients who underwent S-ICD implantation in 60 Italian centers from 2013 to 2019. Results DT was not performed in 325 (20%) patients (no-DT patients). As compared with the DT group, these patients were older (51 ± 16 vs. 48 ± 15 years; p < 0.01) and had lower ejection fraction (37 ± 16% vs. 46 ± 16%; p < 0.01). The 325 no-DT patients were propensity matched with 325 patients of the DT group. During a median follow up of 19 months, 27 (4.2%) patients died for any-cause. During follow-up, 34 (5.2%) patients received appropriate shocks to treat discrete episodes of VT/VF. The first shock was effective in 30 out of 34 patients (88%), whereas a second shock was required to terminate VT/VF in 3 patients and a third shock in the last one. The primary endpoint occurred in 31 (4.8%) patients, and the risk was not significantly increased in the no-DT cohort (HR = 1.26, 95%CI:0.62-2.55, p = 0.522). Inappropriate shocks were reported in 36 (5.5%) patients and device-related complications in 25 (3.8%) patients during follow-up. Survival from the composite secondary endpoint was comparable between groups (HR = 0.86, 95%CI:0.57-1.32, p = 0.500). Conclusions Our data confirmed that DT is frequently omitted in current clinical practice, especially in older patients with worse systolic function. A strategy that omits DT did not appear to compromise the effectiveness of the S-ICD and no additional risk seems associated with DT omission at a mid-term follow-up. These data suggest that routine DT at S-ICD implant might not be necessary. Randomized trials are needed to confirm this finding.

Genotype-phenotype association in patients with arrhythmic variant of non-compaction cardiomyopathy

Funding Acknowledgements Type of funding sources: None. Purpose. To evaluate the genotype-phenotype association in Belarusian patients with non-compaction cardiomyopathy (NCCM) and clinically significant ventricular arrhythmias. Methods. The study included 170 unrelated pts with NCCM prospectively observed in the RSPC "Cardiology", who underwent 24-hour Holter ECG monitoring for 12 months after entering the study. The median follow-up was 36 months [6; 152,0]. The median age of pts was 42 [18; 69] years, men – 63,2%. The arrhythmic phenotype of NCСM was diagnosed by the presence of unexplained syncope; nonsustained ventricular tachycardia, defined as ≥3 consecutive ventricular contractions lasting <30 seconds with a frequency of ≥120 bpm; the presence of ≥ 500 ventricular premature beats (VPB) per day. The diagnosis of NCCM was established on the basis of the following criteria: 1) Echocardiography of the R. Jenni criteria; 2) CMR of the S. Petersen and A. Jaquier criteria. The mutations search in the coding sequences of 174 genes was performed in 30 unrelated pts with NCCM using next generation sequencing (NGS). Results. In 76 out of 170 (44,7%) pts, clinically significant arrhythmias were the leading manifestation of the disease. Nonsustained VT was recorded in 54 (71,1%) pts, sustained VT – in 15 (19,7%) pts, VPB more than 500 per day – in 50 (65,8%), chronic AF with episodes of nonsustained VT was noted in 34 (44,7%) pts. During the follow-up period (median follow-up of 36 months), devices (ICD/CRT-D) were implanted in 15 (19,7%) pts, appropriate shocks were observed in two of them; three pts died, among which SCD occurred in one patient with CRT-D therapy, which was ineffective in stopping sustained VT. NGS sequencing revealed 40 changes in the nucleotide sequence (5 pathogenic mutations, 30 variants with uncertain significance (VUS), 5 new substitutions) in 27 genes in 26 (86,7%) probands. The proportion of mutations in sarcomeric proteins genes was 26,9%, and in ion channel proteins genes was 23,1%. Nucleotide changes in genes encoding structural proteins accounted for 11,5%. In 38,5% of cases, not one, but two or more rare mutations were detected, and in 30,8% – amino acid replacements were found in proteins of different functional classes. Conclusions. The frequency of multiple mutations was higher (38,5%) in the group of pts with the arrhythmic NCCM phenotype. In the group of pts with implantable devices (ICD/CRT-D), mutations in the genes of sarcomeric proteins were observed more often. The genetic characteristics of pts, along with their clinical characteristics, are markers of a high risk of developing life-threatening arrhythmias and can be additionally used for predicting adverse events in pts with NCCM, as well as for early diagnosis of the disease in their relatives.

Outcomes of Pediatric Patients with Defibrillators Following Initial Presentation with Sudden Cardiac Arrest

Background - Implantable cardioverter defibrillators (ICD) are recommended for secondary prevention after sudden cardiac arrest (SCA). The outcomes of pediatric patients receiving an ICD after SCA remain unclear. The objective of this study is to evaluateoutcomes, future risk for appropriate shocks, and identify characteristics associated with appropriate ICD therapy during follow-up. Methods - Multi-center retrospective analysis of patients (≤21 yrs) without prior cardiac disease who received an ICD following SCA. Patient/device characteristics, cardiac function, and underlying diagnoses were collected, along with SCA event characteristics. Patient outcomes including complications and device therapies were analyzed. Results - In total, 106 patients were included, median age 14.7 yrs. Twenty (19%) received appropriate shocks and 16 (15%) received inappropriate shocks (median follow up 3 yrs). First-degree relative with SCA was associated with appropriate shocks (p<0.05). In total, 40% patients were considered idiopathic. Channelopathy was the most frequent late diagnosis not made at time of presentation. Neither underlying diagnosis nor idiopathic status was associated with increased incidence of appropriate shock. Monomorphic ventricular tachycardia (HR 4.6 [1.2; 17.3]) and family history of sudden death (HR 6.5 [1.4;29.8]) were associated with freedom from appropriate shock in a multivariable model (AUC=0.8). Time from diagnoses to evaluation demonstrated a non-linear association with freedom from appropriate shock (p=0.015). In patients >2 yrs from implantation, younger age (p=0.02) and positive exercise test (p=0.04) were associated with appropriate shock. Conclusions - The risk of future device therapy is high in pediatric patients receiving an ICD after SCA, irrelevant of underlying disease. Lack of a definitive diagnosis after SCA was not associated with lower risk of subsequent events and does not obviate the need for secondary prophylaxis.

Combination of Arrhythmogenic Right Ventricular Dysplasia with Left Ventricular Non-Compaction as a Special Form of Cardiomyopathy: Clinic, Diagnostics, Genetic, Natural Course

Background. A few cases of combination of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) with left ventricular noncompaction (LVNC) have been described. Aims to study the genetics, diagnostical features and clinical course of the combination of ARVC with LVNC. Methods. 58 patients with ARVC diagnosis (26 men; mean age 39.1 14.2 years; mean follow-up period 21.5 [6; 60] months) and 125 patients with LVNC (74 men; mean age 46.4 15.1 years; mean follow-up period 14 [3; 40] months). All patients underwent electrocardiogram (ECG), echocardiography, 24-h ECG monitoring. Heart MRI was performed in 53 (91.4%) patients with ARVC and 60 (48%) with LVNC, heart CT in 18 (31%) patients with ARVC and 89 (71.2%) with LVNC. For all patients with combination of ARVC and LVNC DNA-diagnostic was performed using both ARVC (PKP2, DSG2, DSP, DSC2, JUP, TMEM43, TGFB3, PLN, LMNA, DES, CTTNA3, EMD, SCN5A, LDB3, CRYAB, FLNC) and LVNC (MYH7, MYBPC3, TAZ, TPM1, LDB3, MYL2, MYL3, ACTC1, TNNT2, TNI3) gene panels. Results. Combination of ARVC and LVNC was found in 9 patients (15.5% of patients form ARVC cohort and 7.2% from LVNC cohort). These patients were distinguished from patients with isolated ARVC or LVNC by aggressive ventricular arrhythmias (frequent premature ventricular beats, sustained ventricular tachycardia, significantly worse antiarrhythmic therapy effect, appropriate shocks of implanted cardioverter-defibrillators (ICD) in all patients with ICD). Patients with combination of ARVC + LVNC were also distinguished from patients with isolated LVNC by the dilatation of RV, low QRS voltage on ECG, presence of AV block, absence of signs of LV hypertrophy on ECG. LV dilatation with reduction of its ejection fraction distinguished patients with mixed cardiomyopathy from patients with isolated ARVC. Potentially pathogenic variants (IVV classes of pathogenicity) and variants of unclear clinical significance (III class of pathogenicity) were found in both desmosomal and non-desmosomal genes in 78% of patients, including 3 (33%) in DSP gene. Conclusions. The combination of ARVC and LVNC can be caused by mutations in both desmosomal and non-desmosomal genes and has typical features: aggressive, resistant ventricular rhythm abnormalities leading to appropriate ICD shocks and a high risk of sudden cardiac death.

Ventricular tachycardia: beginning and ending fate of a benign invasive cardiac lipoma

Cardiac lipomas are rare benign heart tumors. Their clinical manifestations primarily depend on their dimension and location. We describe a case of a 14-year-old boy complaining of palpitations. ECG showed non-sustained ventricular tachycardia (NSVT). Echocardiography and cardiac MRI showed a large apical mass suggestive of a cardiac lipoma. The patient underwent open-heart surgery which detected a pericardial mass, partially attached to the myocardium, and crossed by the distal segment of LAD. This critical anatomical relationship prevents its complete resection. The biopsy confirmed mature fat tissue. Postoperatively, Propranolol was started for NSVT episodes. After 8 months, he presented with VT recurrence. A subcutaneous ICD (S-ICD) was implanted. Two months later, he was admitted for an electrical storm with six appropriate shocks. Since then, amiodarone was added. Lipomas are not always benign and their surgery might be very difficult and unhelpful. A multidisciplinary team is crucial for their diagnosis and management.

Effectiveness, efficacy, and safety of wearable cardioverter-defibrillators in the treatment of sudden cardiac arrest – Results from a health technology assessment

ObjectivesTo assess the effectiveness, efficacy, and safety of a wearable cardioverter-defibrillator (WCD) in adult persons with high risk for sudden cardiac arrest and for which an implantable cardioverter is currently not applicable.MethodsWe performed a systematic literature search in Medline, Embase, Cochrane Library, and CRD-databases. Study selection was performed by two reviewers independently. Data were presented quantitatively; due to heterogeneity of studies no meta-analysis was performed.ResultsOne randomized-controlled trial (RCT), one non-randomized comparative trial, and forty-four non-comparative trials were included. The RCT reported an overall mortality of 3.1 percent in the WCD group versus 4.9 percent in controls (relative risk [RR]: .64; 95 percent confidence interval [CI], .43–.98, p = .04), but no significant effect on arrhythmia-related mortality. The RR for arrhythmia-related mortality amounted to .67 (95 percent CI, .37–1.21, p = .18) as assessed in the RCT. Appropriate shocks were observed in 1.3 percent of patients in both comparative studies, and inappropriate shocks in .6 percent of patients in the RCT. Termination of ventricular tachycardia (VT) or ventricular fibrillation (VF) was successful in 75 to 100 percent of appropriate shocks in all studies. Adverse events assessed in the RCT showed a lower incidence of shortness of breath (38.8 percent vs. 45.3 percent; p = .004), higher incidence of rash at any location (15.3 percent vs. 7.1 percent; p < .001), and higher incidence of itching at any location (17.2 percent vs. 6.4 percent; p < .001) for WCD.ConclusionsAvailable evidence demonstrates that the WCD detects and terminates VT/VF events reliably and shows a high rate of appropriate shocks in mixed patient populations. Data of large registries confirm that the WCD is a safe intervention.

P521Conversion test during Subcutaneous Implantable Cardioverter-Defibrillator Implantation in clinical practice: in-hospital and mid-term outcome

Funding Acknowledgements No funding OnBehalf RHYTHM DETECT Registry Background With subcutaneous implantable cardioverter–defibrillators (S-ICD), conversion test (CT) is still recommended at implantation. However, prior works found that adherence to this recommendation is declining in clinical practice. Purpose To describe current practice regarding CT at S-ICD implantation, and also measure in-hospital outcome of patients who underwent CT and mid-term outcome of patients without CT. Methods We analyzed 1652 consecutive patients (49 ± 15 years old, 80% male, 51% with ischemic or non-ischemic dilated cardiomyopathy, 45% with ejection fraction ≤35%) who underwent S-ICD implantation in 60 Italian centers from 2013 to 2019. Results CT data were missing in 27 patients. CT was performed in 1300 patients. Successful conversion with ≤65J was obtained in 97.4% of patients. Shock at 80J was not effective in 12 (0.9%) patients. In 10 of these patients the CT was successful after device repositioning, while in 2 patients it was decided to implant a transvenous ICD. Two (0.15%) episodes of electromechanical dissociation (1 fatal) were reported as consequence of CT. CT was not performed in 325 patients (for clinical reasons in 182 patients, for facility preference in 71, ventricular fibrillation not inducible in 72 patients). As compared to the CT group, these patients were older (51 ± 16 vs. 48 ± 15 years; p &lt; 0.01) and had lower ejection fraction (37 ± 16% vs. 46 ± 16%; p &lt; 0.01). 243 non-CT patients had at least 6 months follow-up (median 15 months). In this group, 12 (4.9%) patients had appropriate shocks to treat VT/VF (all successfully terminated with the first shock), and 9 (3.7%) patients had inappropriate shocks. Conclusions This analysis showed that CT is frequently omitted in current clinical practice, especially in older patients with worse systolic function. Shocks at CT are very frequently effective and system revision after CT is rarely required. CT is also safe, although serious adverse events cannot be excluded. A strategy that omits CT did not appear to compromise the effectiveness of the S-ICD, but larger populations and longer follow-up are needed to confirm this finding.