Nonarrhythmic Causes Research Articles

Long-term prognosis of idiopathic ventricular fibrillation: An eighteen-year experience from a tertiary center

Introduction and objectivesIdiopathic ventricular fibrillation (IVF) is diagnosed in patients who survive sudden cardiac arrest (SCA), preferably with documented ventricular fibrillation (VF), without any identifiable structural or electrical abnormality. Current evidence provides limited guidance on the diagnosis and follow-up of these patients. Our aim was to assess the clinical outcomes of survivors of an aborted SCA attributed to IVF. MethodsWe retrospectively collected clinical data from all patients who survived SCA and implanted a cardiac defibrillator (ICD) between 2005 and 2023. ResultsA total of 38 patients, 36.8% female, with a mean age of 44±14 years old were included. Median follow-up time was 8.7 years (interquartile range (IQR) 4.7–14.7 years). All patients underwent a comprehensive diagnostic evaluation that excluded structural and coronary disease. During follow-up, underlying diagnoses were established in 34.2% of the whole cohort. Genetic testing, performed in 37.2%, revealed underlying diagnoses in 57.1% of those tested, compared to only 26.3% of patients who did not undergo genetic testing [p=0.035, OR=5.1 (95% confidence interval (CI) 1.2–21.5)]. Mortality was 10.5% (due to non-arrhythmic causes) and 36.8% patients received appropriate therapies with a median time to first ICD therapy of 39 [5.4–47.3] months. Conclusion(s)Etiological diagnosis and recurrence prediction in patients with IVF remains challenging, even with extensive diagnostic evaluation and long-term follow-up. In our study, genetic testing enhanced diagnostic yield. Consistent with previous findings, our cohort experienced a notable arrhythmic recurrence, with no cardiac deaths, underlining the pivotal role of ICD implantation in these patients.

Abstract 19166: Activity Level and Causes of Sudden Death: From the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) Study

Introduction: Level of activity has a reported association with sudden death, but cardiac causes are presumed by convention. We investigated association between activity level and causes of presumed SCD (pSCD) in the San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study. Methods: POST SCD is a prospective cohort study using autopsy, clinical records, and toxicology to adjudicate arrhythmic (potentially rescuable with implantable defibrillator) or non-arrhythmic (e.g., tamponade, overdose) causes among pSCDs (WHO defined) 18-90 years in San Francisco. We included all incident cases from 2/1/11-3/1/14 (n=525) and incident cases approximately every 3rd day from 3/1/14-12/31/21 (n=358). Activity level at time of pSCD was determined by forensic investigator reports. For unwitnessed deaths, activity level was inferred based on time of arrest and location found. Activity level was classified as: sleep, recently awoke (&lt10 min before death), awake with no activity (e.g., sitting), mild/moderate (e.g., bathing, feeding, walking), and rigorous (e.g., strenuous activity, sexual activity). Results: Of the total 883 pSCDs (mean 60 years, 73% male), 247 (28%) were sleeping, and 516 (58%) were awake at time of event. Cases with unclear circumstances (n=120, 14%) were excluded from analysis. Sleep was associated with non-cardiac cause of death (p=.01), specifically SUDEP (p=.02) and occult overdose (p&lt.001). Wakefulness was associated with SAD (p=0.005), pulmonary embolism (p=.007), and vascular damage (p=.004) (Table). Nearly all cases engaging in rigorous activity at time of death (n=32) were SADs (31/32, 97%) and male (29/32, 91%). Conclusions: Most sudden deaths in this 11-year countywide postmortem study occurred during wakefulness. Sleep was associated with non-arrhythmic cause (specifically SUDEP and occult overdose), while wakefulness and rigorous activity were associated with arrhythmic cause of sudden death.

Defibrillator exchange in the elderly.

Implantable cardioverter-defibrillator (ICD) therapy in elderly patients is controversial because survival benefits might be attenuated by nonarrhythmic causes of death. The purpose of this study was to investigate the outcome of septuagenarians and octogenarians after ICD generator exchange (GE). A total of 506 patients undergoing elective GE were analyzed to determine the incidence of ICD shocks and/or survival after GE. Patients were divided into a septuagenarian group (age70-79 years) and an octogenarian group (age ≥80 years). The primary endpoint was death from any cause. Secondary endpoints were survival after appropriate ICD shock and death without experiencing ICD shocks after GE ("prior death"). The association of the ICD with all-cause mortality and arrhythmic death was determined for septuagenarians and octogenarians. Comparing both groups, similar left ventricular ejection fraction (35.6% ± 11.2% vs 32.4% ± 8.9%) and baseline prevalence of New York Heart Association functional class III or IV heart failure (17.1% vs 14.7%) were found. During the entire follow-up period of the study, 42.5% of patients in the septuagenarian group died compared to 79% in the octogenarian group (P<.01). Prior death was significantly more frequent in both age groups than were appropriate ICD shocks. Predictors of mortality were common in both groups and included advanced heart failure, peripheral arterial disease, and renal failure. In clinical practice, decision-making for ICD GE among the elderly should be considered carefully for individual patients.

PO-04-202 RESUSCITATED OUT OF HOSPITAL CARDIAC ARREST AS THE INITIAL PRESENTATION OF HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, and it is associated with ventricular arrhythmias and sudden death. Out-of-hospital cardiac arrest (OHCA) may be the first presentation of HCM in some patients. To determine the frequency of resuscitated OHCA as the initial presentation of HCM, as well as the characteristics, initial management, and outcomes of these patients. Patients with HCM were identified with a comprehensive phenotyping approach, including natural language processing of electronic medical records, cardiac imaging reports, and diagnosis codes. HCM diagnoses were validated by trained reviewers. Among these, we focused on patients who had resuscitated OHCA as the initial presentation leading to the HCM diagnosis. Baseline characteristics, HCM treatments and outcomes were obtained from the electronic medical record. Of 6,276 patients diagnosed with HCM at our institution between 2001-2019, we identified 29 (0.5%) patients with resuscitated OHCA as their initial HCM presentation (17% female; mean age at the time of OHCA 34 ± 17 years). Ventricular tachyarrhythmia was the confirmed cause of OHCA in 24 patients. No patients had a primary acute coronary event as the etiology of OHCA. The median of the thickest wall segment was 30.5 mm and 8 (28%) patients had obstructive HCM. An apical pouch was present in 5 (17%) patients. All patients underwent ICD implantation following OHCA and survived hospital discharge. The mean follow-up post-OHCA was 9 ± 6.6 years. During follow-up, 13 (45%) patients underwent septal reduction therapy. 8 (28%) patients had at least one appropriate ICD shock or antitachycardia pacing event for VT/VF. Two (7%) patients died during follow-up, one from a cardiac non-arrhythmic cause and one from an unknown cause. Resuscitated OHCA is an infrequent initial presentation of HCM. These patients remain at risk for recurrent VT/VF, but overall long-term survival is favorable with secondary prevention ICDs and other HCM-directed therapies.

HeartFailure Burden by Autopsy, Guideline-Directed Medical Therapy, and ICD Utilization Among Sudden Deaths.

Studies of heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) report high sudden cardiac death (SCD) rates but presume cardiac cause. Underlying causes, guideline-directed medical therapy (GDMT), and implantable cardioverter-defibrillator (ICD) use in community sudden deaths with heart failure (HF) are unknown. This study aims to assess the burden of HF, GDMT, and ICD use among autopsied sudden deaths in the POST SCD (Postmortem Systematic Investigation of Sudden Cardiac Death) study, a countywide postmortem study of all presumed SCDs. Incident WHO-defined (presumed) SCDs for individuals of ages 18 to 90 years were autopsied via prospective surveillance of consecutive out-of-hospital deaths in San Francisco County from February 1, 2011, to March 1, 2014. Sudden arrhythmic deaths (SADs) had no identifiable nonarrhythmic cause (eg, pulmonary embolism), and are thus considered potentially rescuable with ICD. Of 525 presumed SCDs, 100 (19%) had HF. There were 85 patients with known HF (31 HFpEF, 54 HFrEF) and 15 with subclinical HF (postmortem evidence of cardiomyopathy and pulmonary edema without HF diagnosis). SADs comprised 56% (293 of 525) of all presumed SCDs, and 69% (69 of 100) of HF SCDs. The rates were similar in HFrEF (40 of 54 [74%]) and HFpEF (19 of 31 [61%], P=0.45). Four SAD patients (4%) had ICDs, 3 of which experienced device failure. Twenty-eight SCDs had ejection fraction≤35%: 22 (79%) with arrhythmic and 6 (21%) with noncardiac causes. Of the 22 SAD patients, 8 (36%) had no identifiable barrier to ICD referral. Complete use of GDMT in HFrEF was 6%. One in 5 community sudden deaths had HF; two-thirds had autopsy-confirmed arrhythmic causes. ICD prevention criteria captured only 8% (22 of 293) of all SAD cases countywide; GDMT and ICD use remain important targets for HF sudden death prevention.

Long-term prognosis of out-of-hospital cardiac arrest due to idiopathic ventricular arrhythmias.

Life-threatening ventricular arrhythmias (VA) may occur in patients with unknown cardiac disease. A sizable part of them remains labeled as Idiopathic VA and limited data is available regarding their natural history. Our aim was to evaluate the long-term clinical outcomes of survivors of an idiopathic life-threatening VA. Patients who survived an idiopathic life-threatening VA referred to an ICD were included and followed for a median follow-up of 7 years. Clinical and device data were collected and a comparison between genders was made. A total of 29 patients, 41% female, mean age of 50 (19) years were studied; all were implanted with an ICD at index hospitalization. At follow-up, an etiological diagnosis was established in 38% of patients. Genetic testing improved the diagnosis and allowed the identification of a distinct clinical entity in 60% of patients (p=0.04, OR=7.0), especially in women. Regarding ICD data, 31% received appropriate therapies with a median time to first appropriate shock of 39 months (IQR 12-46 months). Men had a significantly higher prevalence of appropriated shocks (50% vs 8%, p=0.04), with a similar time to the first arrhythmic event between genders. Two of the patients died, both from non-arrhythmic causes. Etiologic diagnosis and recurrence prediction in patients with idiopathic VA is challenging, even with long-term follow-up and sophisticated diagnostic evaluation. Genetic testing significantly improved the diagnostic yield, especially in women. Arrhythmia recurrence occurred in about one-third of patients and is significantly higher in men, underscoring the importance of ICD implantation.

Catecholaminergic polymorphic ventricular tachycardia: risk modulators in patients treated with beta-blockers

Abstract Background Due to the catecholaminergic nature of arrhythmias that define the Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), beta-blockers (BBs) represent the first line therapy for this severe arrhythmogenic syndrome. Despite optimal BB therapy, a proportion of patients continue to suffer breakthrough life-threatening arrhythmias (LAE). Purpose To evaluate the role different classes of BBs (β1-selective vs. non-selective) in LAE reduction and to identify risk factors for breakthrough LAE while on BB monotherapy. Methods We studied 238 consecutive patients with CPVT and treated with BB monotherapy followed-up prospectively. CPVT was diagnosed according to the 2015 European Society of Cardiology Guidelines. The endpoint was the occurrence of the first LAE (sudden cardiac death, aborted cardiac arrest, or hemodynamically non-tolerated ventricular tachycardia) in BB monotherapy. The follow-up for each patient was calculated from BB therapy start to the occurrence of the endpoint, death from non-arrhythmic cause, the date of last visit, or the initiation of other treatments (i.e.: other antiarrhythmics or left cardiac sympathetic denervation [LCSD]), whichever occurred first. Multivariable Cox proportional hazards model was used to evaluate the effects of history of LAE before diagnosis of CPVT, occurrence of unexplained syncope before diagnosis of CPVT, genotype, and type of BB therapy, as a time-dependent variable, on the risk of experiencing an LAE during BB monotherapy. Results We enrolled 238 CPVT patients (135 probands, 135 females): 226 with typical CPVT (n=216 RYR2; n=10 CASQ2) and 12 with atypical CPVT (n=5 RYR2-Loss-of-Function, n=4 TRDN and n=3 TECRL). Prior to BB monotherapy, 48/238 (20%) patients had survived an LAE, and 110/238 (46%) patients had experienced an unexplained syncope. During 1,629 person-years of follow-up during BB monotherapy, 35 patients experienced an LAE (annual LAE rate 2.1%, 95% CI: 1.5%–3.0%; Figure A). Five-year cumulative probability of experiencing an LAE during BB monotherapy was 11.9% (95% CI: 7.0%-16.6%). In this population, multivariable analysis showed that history of LAE before diagnosis (HR 3.6; 95% CI: 1.6–8.1; p=0.002) and syncope before diagnosis (HR 6.1; 95% CI: 2.5–14.9; p&amp;lt;0.001) were clinical risk factors for LAE occurrence. Patients with TRDN mutations were significantly more likely to suffer LAE (HR 20.9; 95% CI: 2.2–196.3; p=0.008). Using nadolol as the gold standard, the use of β1-selective BBs (HR 3.4; 95% CI: 1.4–8.6; p=0.009), but not propranolol (HR: 0.9; 95% CI: 0.2–3.8; p=0.887), was associated with poorer outcome during BB monotherapy (Figure B). Conclusions In patients with CPVT, selective BBs are associated with a higher risk of LAE as compared to nadolol. Patients who have survived an LAE and/or experienced an unexplained syncope prior to diagnosis, as well as carriers of TRDN mutations are at high risk of BB failure. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ricerca Corrente Funding scheme of the Italian Ministry of Health and Italian Ministry of Research and University Dipartimenti di Eccellenza 2018–2022 grant to the Molecular Medicine Department (University of Pavia).

Psychological Aspects of Syncopes and Possible Association with Recurrency-The Role of Implantable Loop Recorders.

Syncopes are a very common phenomenon and have a high recurrence rate. The differentiation between the psychogenic and physical, especially of arrhythmic origin, remains difficult. In many cases, an implantable loop recorder is used for the detection of possible arrhythmias, leading to syncopes. Yet, the existing literature suggests that psychological factors may play a significant role in recurrent syncopes. We aimed at analyzing the potential role of several psychological factors on the recurrence of arrhythmic or non-arrhythmic syncopes. Methods and results: A total of 119 patients, who had received an implantable loop recorder for recurrent syncopes at our center between 01/2018 and 12/2021, participated in this retrospective cohort study. Anxiety, depression and quality of life were assessed using extensively validated questionnaires (GAD-7, PHQ-9 and SF-12). The mean follow-up after loop recorder implantation was 710 ± 430 days and 50% of patients were female. The mean patient age was 54.8 ± 18.6 years. Most patients had no evidence of structural heart disease (84%), and normal LV function (92%). A statistical analysis revealed that the presence of structural heart disease was the strongest predictor for arrhythmic syncope during follow-up. In patients with non-arrhythmic syncopes, we found significantly higher levels of anxiety (GAD-7 score: 2.5 ± 2.6 vs. 4.8 ± 4.3) and depression (PHQ-9 score: 3.9 ± 3.6 vs. 6.8 ± 5.1), and a lower quality of life (SF-12 score: 33.7 ± 6.4 vs. 29.6 ± 7.8). Discussion: We identified factors as contributors to a better identification of patients at risk for arrhythmic as well as non-arrhythmic syncopes. Especially anxious or depressive symptoms may hinted at non-arrhythmic causes of syncope. However, the study was limited by its retrospective design and low patient number. Further trials should likewise combine the diagnostic yield of loop recorders with psychometric evaluations before implantation and combine it with additional diagnostic measures, such as video monitoring, to further examine the role of psychological factors in the pathomechanism and treatment of syncope.

Determinants of mortality after stereotactic radio-ablation for ventricular tachycardia. Results from the international MUSIC consortium

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council Background SBRT is currently restrained to the most severe patients with drug- and catheter ablation-refractory VT, often associated with advanced heart failure. Purpose To analyze the determinants of mortality after SBRT for VT. Methods Patients with drug- and catheter ablation-refractory VT underwent imaging prior to SBRT. The inHEART technology was used to create image-based 3D models of substrate, cardiac anatomy, and organs at risk (coronaries, phrenic nerve, GI tract, AV node). In MUSIC software (IHU Liryc-Inria), 3D models were fused with prior EP maps, and SBRT targets were interactively drawn in 3D by the referring EP cardiologist. Transmural target volumes and organs at risk were fused with a 4D planning CT and used to plan SBRT in Eclipse (Varian). SBRT was delivered with either Truebeam or Edge systems (Varian), at a total dose of 25 Gy in a single session. The determinants of adverse outcomes after SBRT were analyzed. Results 30 pts from 7 centers were included (age 70±10, 90% men). Mean LVEF was 26±9%. The VT etiology was ischemic in 67%, and non-ischemic or mixed in 47%. Patients had undergone a mean of 1.7±1.2 prior failed catheter ablation procedures. SBRT was delivered on median planning treatment volumes (PTVs) of 96[63-149] mL. Complications attributed to SBRT were observed in 2/30 (7%), none of which were fatal (heart failure and pneumonitis, both managed with steroids). Over a median FU of 4[2-8] months, death or heart transplant occurred in 11(37%) pts, attributed to VT recurrence in 4(13%), and heart failure in 7(23%). On univariate analysis, patients experiencing death or transplant after SBRT were older (77±6 vs. 66±9 years, P=0.001) and showed lower LVEF (22±6 vs. 29±10%, P=0.03). In contrast, mortality or transplant did not relate to the underlying VT etiology (P=0.30), the number of prior catheter ablations (P=0.20), the pre-SBRT VT burden (P=0.20) and the SBRT treatment volume (P=0.18). Conclusion In patients with severe drug- and catheter ablation-refractory VT undergoing cardiac SBRT, mortality is most often due to non-arrhythmic causes, and is more driven by age and LV dysfunction than by the VT substrate, pre-SBRT arrhythmia burden, and SBRT treatment volume.

Prediction Efficiency of MADIT-ICD Benefit Score for Outcome in Asian Patients with Implantable Cardioverter-Defibrillator.

BackgroundNot all patients with heart failure derive consistent benefit from prophylactic implantable cardioverter-defibrillator (ICD). We aimed to evaluate the role of MADIT-ICD benefit score in risk-stratifying in Asian patients with left ventricular ejection fraction (LVEF) ≤35%.MethodsIn this two-center, retrospective study, a total of 136 patients with LVEF ≤35% who received an ICD for primary prevention were enrolled. The endpoints were defined as the ventricular tachycardia ≥200bpm (VT) or ventricular fibrillation (VF) and non-arrhythmic death. Based on the MADIT-ICD benefit score system, all patients were categorized into three groups: highest benefit group (n = 41), intermediate benefit group (n = 80), and lowest benefit group (n = 15).ResultsForty patients experienced VT/VF and seven died of non-arrhythmic causes during a median follow-up of 44.8 ± 28.9 months. Kaplan–Meier curves showed that patients in highest benefit group had a worse VT/VF occurrence compared to those in other groups. In the highest benefit group, the predicted risk of VT/VF was 17-fold higher than the risk of non-arrhythmic mortality (41.5% vs 2.4%, P < 0.001). In the intermediate benefit group, the predicted risk of VT/VF was 4.2-fold higher than the risk of non-arrhythmic mortality (26.3% vs 6.3%, P = 0.001). In the lowest benefit group, however, the difference in the corresponding predicted risks was attenuated without statistically significant (13.3% vs 5.1%, P = 0.56).ConclusionWe demonstrate that MADIT-ICD benefit score can be used for the assessment of ICD primary prevention benefits in Asian patients with LVEF ≤35%.

Abstract 11967: Benefit of Implantable Cardioverter Defibrillator Therapy in Patients With Advanced Renal Impairment: A Competing Risk Analysis From the MADIT Trials

Introduction: The life-saving benefit of the implantable cardioverter defibrillator (ICD) in patients with advanced chronic kidney disease (A-CKD) is still controversial. This is possibly due to a higher risk of dying from non-arrhythmic causes in A-CKD patients, and thereby die prior to receiving therapy from the ICD. We aimed to evaluate the competing risk for ventricular tachycardia/fibrillation (VT/VF) vs. death without prior VT/VF in ICD recipients by renal function. Methods: The study population comprised 3953 patients with an ICD enrolled in the landmark MADIT trials, categorized by renal function into: A-CKD (estimated Glomerular Filtration Rate [eGFR] ≤40 ml/min/1.73 m 2 [N=403]; Moderate CKD (eGFR 41-60 ml/min/1.73 m 2 [N=995]); and No-CKD (eGFR &gt;60 ml/min/1.73 m 2 [N=2555)). Cumulative incidence function curves were used to display the rate of fast VT/VF (&gt;200 bpm) and the competing risk of death without experiencing prior fast VT/VF using the Fine and Gray method. Results: At 4-years of follow-up, patients in the A-CKD group had a significantly lower cumulative incidence of VT/VF compared to patients with Moderate-CKD and No-CKD (13%, 17%, and 20%, respectively; p=0.006 for the overall difference [Figure: left panel]). In contrast, the corresponding 4-year rates of death without experiencing prior fast VT/VF were significantly highest among patients with A-CKD and attenuated among those with Moderate- and No-CKD (28%, 17%, and 9%, respectively; p&lt;0.001 for the overall difference [Figure: right panel]). Conclusion: Our data from 4 landmark primary prevention ICD trials show significant differences in the risk of VT/VF vs the competing risk of death without experiencing prior VT/VF by renal function. This suggests an attenuated benefit of ICD therapy with declining renal function.

Abstract 10914: Refining Genotype-Phenotype Correlations for Post-Mortem Genetic Testing of Sudden Cardiac Death: From the POST SCD Study

Introduction: The POST SCD (POstmortem Systematic InvesTigation of Sudden Cardiac Death) Study is the only prospective unbiased sudden cardiac death (SCD) cohort to use comprehensive postmortem investigation to refine the SCD phenotype to true cardiac and arrhythmic causes. Most postmortem genetic testing focuses on genotypes while tolerating a SCD phenotype that is presumed cardiac. Hypothesis: We hypothesize that a comprehensive postmortem evaluation following presumed SCD will refine genotype-phenotype associations and interpretation of postmortem genetic testing. Methods: The POST SCD study prospectively identified all deaths attributed to out-of-hospital cardiac arrest between 18-90 years of age in San Francisco County between February 2011-March 2014 (20,440 deaths reviewed). Medical record review identified 525 presumed SCDs that met World Health Organization criteria. Comprehensive autopsy, toxicology, and histology ruled out non-arrhythmic causes (overdose, hemorrhage, PE) to arrive at 293 sudden arrhythmic deaths (SADs). In the first 30 SADs with high suspicion for heritable cause, a comprehensive 300-gene cardiac/arrhythmia panel was performed, then whole exome testing in cases with negative or non-contributory panel. Results: By pathologic criteria, the 30 autopsy-defined SADs (21 males [70%], median age 53 years) for genetic testing included dilated cardiomyopathy (37%), hypertrophic cardiomyopathy (HCM; 10%), hypertrophy without pathologic features of HCM (33%), primary electrical disease (10%), arrhythmogenic cardiomyopathy (3%), mitral valve prolapse (3%), or non-compaction (3%). In 3 SADs, we identified 4 pathogenic/likely pathogenic (P/LP) variants in APOB , MYBPC3 , GAA , and TTN , but 3 of 4 ( APOB, GAA , TTN ) were non-contributory to SCD. There were 61 variants of uncertain significance in 24 patients (80%). Further exome testing in 7 SADs identified no compelling variants. Conclusions: Postmortem genetic testing identified P/LP variants in 10% of autopsy-proven SADs with high suspicion for heritable cause, but detailed postmortem phenotyping excluded 75% as non-contributory to SCD. These results highlight the importance of comprehensive autopsy evaluation to refine genotype-phenotype correlations.

ICD exchange in the elderly

Abstract Background ICD therapy in elderly patients is controversially discussed, since survival benefits might be attenuated by non-arrhythmic causes of death. Purpose This study aimed to investigate the outcome of septua- and octogenarians after ICD generator exchange (GE). Methods 506 patients undergoing elective GE were analysed to determine the incidence of ICD shocks and survival after GE. For further analysis, patients were divided according to age (70 – 79 or ≥80 years) and previous ICD therapy: patients that did not experience a shock and patients that received at least one shock from prior ICDs. Results The effect of the ICD on all-cause mortality and arrhythmic death was determined for two groups (patients with 70 – 79 and ≥80 years). Comparing septua- with octogenarians, similar left ventricular ejection fraction (35.6±11.2% vs. 32.4±8.9%) and baseline prevalence of NYHA class 3 or 4 heart failure (17.1% vs. 14.7%) was found. Older patients were more likely to die of non-arrhythmic death (22% per year vs. 8% per year, p&amp;lt;0.001). We also investigated the necessity of ICD therapy dependent on whether ICD therapy occurred during the previous battery live. Septuagenarians and octogenarians with previous shocks had a higher incidence of further ICD therapy in the following battery life period (41% vs. 19%, p&amp;lt;0.001, and 22% vs. 17%, p&amp;lt;0.001). Conclusion Decision making for ICD generator exchange among elderly patients should be considered carefully for an individual patient during clinical practice. Funding Acknowledgement Type of funding sources: None.

Long term prognosis of out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation - a tertiary center experience

Abstract Funding Acknowledgements Type of funding sources: None. Background Sudden cardiac death (SCD) is an uncommon event in the absence of structural heart disease. However, ventricular fibrillation (VF) may occur in patients with unknown cardiac disease and a comprehensive work-up is needed to further improve diagnostic. Still, a significant and heterogenous group of patients remains labelled of Idiopathic VF and limited data is available regarding their natural history. Purpose The aim of this study was to evaluate the clinical outcomes of survivors of an aborted sudden cardiac death due to idiopathic VF or pulseless ventricular tachycardia (VT) and to assess possible predictors of recurrence. Methods Patients who survived an idiopathic VF or pulseless VT between 2005 and 2019 referred to a cardiac defibrillator (ICD) implantation were included. Patients were followed for 1 to 15 years (median follow-up of 7 years). Clinical and device data were collected. Results A population of 29 patients, 59% male, with a median age of 50 years (age ranging from 18 to 76) at the time of the aborted SCD was studied. All patients implanted an ICD (69% single chamber, 24% dual chamber and 3% subcutaneous) at the index hospitalization. The initial rhythm was VF in 76% and pulseless VT in 24%. In relation to the context of the arrhythmic event, 48.3% occurred during daily life activities, 13.8% after an emotional stress, 6.9% during efforts and a similar percentage occurred either in rest or asleep. Of note, 12.5% of patients had previous history of syncope. Normal ECG was present in 83% of patients. Family history of SCD was present in 12% of the cases. As for the cardiovascular risk factors, 61.5% had hypertension, 19% dyslipidemia, 17% diabetes, 31% were smokers or previous smokers. Paroxysmal atrial fibrillation was present in 15% of patients. To exclude possible causes of VF, all patients were submitted to coronary angiogram and echocardiogram, 64% to genetic testing, 68% to cardiac magnetic resonance, 20% to electrophysiologic study, 12% to pharmacological provocative test and 4% were submitted to endomyocardial biopsy. At follow-up, an etiological diagnosis was established in 31% of patients: 3 events were attributed to coronary vasospasm, 3 to short coupled polymorphic VT, 1 patient had long QT syndrome, 1 had Brugada syndrome and in 1 patient an ANK2 mutation was identified. As for the clinical outcomes, 8% patients died (from non-arrhythmic causes), 31% patients received appropriate therapies and 19% had unappropriated shocks (of those 60% for sinus tachycardia and 40% for supraventricular tachycardia). Conclusion Etiologic diagnosis and prediction of recurrence of arrhythmic events in patients with idiopathic VF is challenging, even with a long-term follow-up and more sophisticated diagnostic evaluation. Idiopathic VF is a rare but serious condition with recurrence in about one third of patients. Although not free of complications, ICD remains the gold standard of treatment.

Factors Predisposing to Survival After Resuscitation for Sudden Cardiac Arrest

BackgroundIn the POST SCD study, the authors autopsied all World Health Organization (WHO)–defined sudden cardiac deaths (SCDs) and found that only 56% had an arrhythmic cause; resuscitated sudden cardiac arrests (SCAs) were excluded because they did not die suddenly. They hypothesized that causes underlying resuscitated SCAs would be similarly heterogeneous. ObjectivesThe aim of this study was to determine the causes and outcomes of resuscitated SCAs. MethodsThe authors identified all out-of-hospital cardiac arrests (OHCAs) from February 1, 2011, to January 1, 2015, of patients aged 18 to 90 years in San Francisco County. Resuscitated SCAs were OHCAs surviving to hospitalization and meeting WHO criteria for suddenness. Underlying cause was determined by comprehensive record review. ResultsThe authors identified 734 OHCAs over 48 months; 239 met SCA criteria, 133 (55.6%) were resuscitated to hospitalization, and 47 (19.7%) survived to discharge. Arrhythmic causes accounted for significantly more resuscitated SCAs overall (92 of 133, 69.1%), particularly among survivors (43 of 47, 91.5%), than WHO-defined SCDs in POST SCD (293 of 525, 55.8%; p < 0.004 for both). Among resuscitated SCAs, arrhythmic cause, ventricular tachycardia/fibrillation initial rhythm, and white race were independent predictors of survival. None of the resuscitated SCAs due to neurologic causes survived. ConclusionsIn this 4-year countywide study of OHCAs, only one-third were sudden, of which one-half were resuscitated to hospitalization and 1 in 5 survived to discharge. Arrhythmic cause predicted survival and nearly one-half of nonsurvivors had nonarrhythmic causes, suggesting that SCA survivors are not equivalent to SCDs. Early identification of nonarrhythmic SCAs, such as neurologic emergencies, may be a target to improve OHCA survival.

Antemortem and Post-Mortem Characteristics of Lethal Mitral Valve Prolapse Among All Countywide SuddenDeaths.

The goal of this study was to investigate the characteristics of mitral valve prolapse (MVP) in a post-mortem study of consecutive sudden cardiac deaths (SCDs) in subjects up to 90 years of age. Up to 2.3% of subjects with MVPs experience SCD, but by convention SCD is rarely confirmed by autopsy. In a post-mortem study of persons<40 years of age, 7% of SCDs were caused by MVP; bileaflet involvement, mitral annular disjunction (MAD), and replacement fibrosis were common. In the San Francisco POST SCD (Postmortem Systematic Investigation of Sudden Cardiac Death) study, autopsies have been performed on >1,000 consecutive World Health Organization-defined (presumed) cases of SCD in subjects aged 18 to 90 years since 2011; a total of 603 were adjudicated. Autopsy-defined sudden arrhythmic death (SAD) required absence of nonarrhythmic cause; MVP diagnosis required leaflet billowing. One hundred antemortem echocardiograms were revised to identify additional MVPs missed on autopsy. Among the 603 presumed SCDs, 339 (56%) were autopsy-defined SADs, with MVP identified in 7 (1%). Six additional MVPs were identified by review of echocardiograms, for a prevalence of at least 2% among 603 presumed SCDs and 4% among 339 SADs (vs. 264 non-SADs; p=0.02). All 6 additional MVPs had monoleaflet rather than bileaflet involvement and mild mitral regurgitation, ruling out hemodynamic cause. Less than one-half had MAD with replacement fibrosis, but all had multisite interstitial fibrosis. In a countywide post-mortem study of all adult cases of SCD, MVP prevalence was at least 4% of SADs,but one-half were missed on autopsy. Monoleaflet MVP was often underdiagnosed post-mortem. Compared withyoung cases of SCD, lethal MVP in older cases of SCD did not consistently have bileaflet anatomy, replacement fibrosis, or MAD.

Catheter ablation of ventricular tachycardia in patients with electrical storm, with a special focus on patients with Chagas disease.

There are few reports on the benefits of catheter ablation (CA) in patients with electrical storm (ES). None of these publications included patients with Chagas disease (ChD). Our aims areto analyze (1) all the cases of ES treated with CA and (2) the subgroup of patients with ChD. Prospective analysis of consecutive patients with ES due to monomorphic ventricular tachycardia (VT) treated with CA. We included 38 patients: 28 males; median age of 63.5 (IQR 55-71) years old; ejection fraction (LVEF) 0.30 (0.25-0.40). Sixteen patients (42.1%) had ChD. The patients experienced 21 (15-37) VT episodes and received 7 (3-13) ICD shocks before CA. Forty-six procedures were performed (7 required epicardial access). All patients experienced ES suppression after CA. After 35 (10-64) months of follow-up (1.21 procedures per patient), 23 patients (60.5%) remain free from any VT; 35 patients (92.1%) were free from ES, and 11 patients (28.9%) died from non-arrhythmic causes. One patient underwent heart transplantation. Patients with ChD were younger (60 vs. 67yearsold; p= 0.033), significantly morewomen (50% vs. 9.1%; p= 0.005), and had higher LVEF (0.40 vs. 0.28; p< 0.001) than the other patients. Long-term outcome of ChD patients was similar to that of the overall population. Only age and LVEF independently predicted mortality. CA was associated with acute ventricular arrhythmia suppression in all patients with ES. Freedom rates from ES and VT were 92.1% and 60.5% respectively. Despite having a lower-risk clinical profile, patients with ChD had a comparable outcome to that of the other patients.

Prevention of Sudden Cardiac Death: Focus on the Subcutaneous Implantable Cardioverter-Defibrillator.

The implantable cardioverter-defibrillator (ICD) is the most effective therapy to prevent sudden cardiac death (SCD) in high-risk patients. To overcome infections and failure of transvenous leads, the most frightening complications of conventional ICDs, a completely subcutaneous ICD (S-ICD) has been developed and is currently adopted in routine clinical practice. In view of their long life-expectancy, low competitive risk of dying from non-arrhythmic causes, and high lifetime risk of lead-related complications requiring surgical revisions, young patients with cardiomyopathies and inherited arrhythmia syndromes have traditionally been considered ideal candidates for the S-ICD. However, as growing evidence supported S-ICD safety and efficacy, initial niche implant indications were abandoned in favor of a widespread use of this technology, that is currently adopted in common ICD candidates with severe left ventricular dysfunction. Indeed, guidelines recommend S-ICD implantation as an alternative to TV-ICDs in all ICD candidates, unless pacing is required. This review focuses on the contemporary experience with the S-ICD and explores future scenarios in which device-to-device communication will enable to combine leadless therapies.

P529Efficacy and safety of S-ICD implantation without use of defibrillation threshold testing: a retrospective multicentric observational study

Abstract Introduction The subcutaneous ICD (S-ICD) is a valid alternative to transvenous systems (TV-ICD) for the treatment of life-threatening arrhythmias, and the extravascular position of the lead allows a significant reduction of the risk of infection. Current guidelines recommend defibrillation threshold testing (DFT) at the time of S-ICD implantation (class I). Although randomised trials have proven the safety of TV-ICD implantation with no DFT, it is unclear whether such an approach could be adopted for S-ICD as well. The PRAETORIAN score, based on post-implantation chest X-ray, can accurately predict a high defibrillation threshold after S-ICD implantation. The aim of this retrospective multicentre study was to evaluate the efficacy and safety of S-ICD implantation with no DFT. Methods We enrolled 203 consecutive patients undergoing S-ICD implantation in six different centres between October 2012 and January 2019. It was left at discretion of the operator whether performing or not DFT at the time of the procedure. Baseline device settings were collected, and the PRAETORIAN score was retrospectively calculated whenever chest X-ray was available. Both remote or in-clinic device interrogation reports were systemically analysed, and all the shocks and arrhythmia episodes identified. All the patients provided consent form and ethical approval was obtained. Results The population (mean age 57.6 ± 14.2) was divided in two groups, based on whether DFT was performed at the time of the S-ICD implantation: 72 patients (35.4%) underwent DFT (DFT+ group), while 131 patients (64.5%) did not (DFT- group). In the DFT- group, mean LVEF was lower (32 ± 8% vs 42 ± 17%, p &amp;lt; 0.0001) and prevalence of diabetes mellitus and atrial fibrillation higher compared to the DFT+ group (27.5% vs 13.9%, p = 0.04 and 38.9% vs 19.44%, p = 0.007; respectively). In addition, the indication for S-ICD was more frequently primary prevention in the DFT- vs DFT+ group (70.8% vs 90.8%, p = 0.0004; respectively). No differences in terms of device programming were identified between the two cohorts. The PRAETORIAN score was significantly higher in the DFT- vs DFT+ patients (50 ± 26 vs 36 ± 18, p = 0.032; respectively). After a median follow-up of … months, we observed 5 appropriate shocks in 3 patients from the DFT+ group vs. 15 shocks in 8 patients from the DFT- group (p = 0.81). All the life-threatening arrhythmias were successfully recognised and treated by the device. DFT was complicated by pulseless electrical activity in one patient. One patient in the DFT- group suffered from an episode of ventricular tachycardia requiring a total of 4 shocks for being terminated. Six patients in the DFT- group died for non-arrhythmic causes. On the Kaplan-Meier analysis, cumulative survival was comparable between the two groups (log rank p value = 0.13). Conclusions This study suggests that implantation of S-ICD with no DFT might be reasonable. These results should be confirmed in prospective randomised trials.

Protected risk stratification with the wearable cardioverter-defibrillator: results from the WEARIT-II-EUROPE registry

BackgroundThe prospective WEARIT-II-EUROPE registry aimed to assess the value of the wearable cardioverter-defibrillator (WCD) prior to potential ICD implantation in patients with heart failure and reduced ejection fraction considered at risk of sudden arrhythmic death.Methods and results781 patients (77% men; mean age 59.3 ± 13.4 years) with heart failure and reduced left ventricular ejection fraction (LVEF) were consecutively enrolled. All patients received a WCD. Follow-up time for all patients was 12 months. Mean baseline LVEF was 26.9%. Mean WCD wearing time was 75 ± 47.7 days, mean daily WCD use 20.3 ± 4.6 h. WCD shocks terminated 13 VT/VF events in ten patients (1.3%). Two patients died during WCD prescription of non-arrhythmic cause. Mean LVEF increased from 26.9 to 36.3% at the end of WCD prescription (p < 0.01). After WCD use, ICDs were implanted in only 289 patients (37%). Forty patients (5.1%) died during follow-up. Five patients (1.7%) died with ICDs implanted, 33 patients (7%) had no ICD (no information on ICD in two patients). The majority of patients (75%) with the follow-up of 12 months after WCD prescription died from heart failure (15 patients) and non-cardiac death (15 patients). Only three patients (7%) died suddenly. In seven patients, the cause of death remained unknown.ConclusionsMortality after WCD prescription was mainly driven by heart failure and non-cardiovascular death. In patients with HFrEF and a potential risk of sudden arrhythmic death, WCD protected observation of LVEF progression and appraisal of competing risks of potential non-arrhythmic death may enable improved selection for beneficial ICD implantation.Graphic abstract