Implantable Defibrillator Therapy Research Articles

The correlation between cardiac magnetic resonance imaging and echocardiography in patients with severe ischaemic cardiomyopathy

Abstract Background Left ventricular ejection fraction is the single metric that guides therapeutic decision-making, risk stratification and prognosis in patients with severely impaired systolic function. Although cardiac magnetic resonance imaging (CMR) is the current reference standard for quantification of ventricular volume and function, echocardiography is used more often as it is more widely available and less expensive.(1) Aims To evaluate the correlation between CMR and echocardiography in quantifying left ventricular (LV) volume and function and to determine whether these measurements are associated with clinical outcomes in patients with severe ischemic cardiomyopathy (ICM). Methods Participants recruited to the REVIVED-BCIS2 trial who had undergone baseline CMR or echocardiography were included in this analysis. All scans were analyzed in blinded core laboratories as previously reported.(2,3) All volumes were indexed to body surface area. Spearman correlation, Bland Altman analysis and coverage probability methods were performed to assess the correlation between the two modalities. A Cox proportional hazards model was used to assess the association between imaging metrics and the primary outcome, a composite of all-cause death and aborted sudden death. A sensitivity analysis was conducted a priori, restricted to patients undergoing both scans within 60 days of each other. Results A total of 373 participants with paired imaging data were included: mean age 69±9 years, 87% male, BMI 28±5. A moderate correlation was detected for volume measurements between the modalities (end diastolic volume index (EDVI) r=0.66 end systolic volume index (ESVI) r=0.68), with a weaker correlation for LV ejection fraction (EF) (r=0.41). Bland-Altman plots showed moderate agreement in LVEF measurements (Table 1). The sensitivity analysis included 199 patients, and showed similar results (EDVI r=0.72, ESVI r=0.73 LVEF r=0.43, all p<0.000). Only 7.5% of the paired LVEF measurements were within 5% of each other. 30% of participants were misclassified by echocardiography as having an LVEF>35%. (Figure 1) CMR ESVI was associated with the occurrence of the primary outcome (HR 1.05 per 10ml increment, 95% CI 1.00-1.10) however echo ESVI (HR 1.05 per 10ml increment 95% CI 0.99 – 1.10) and all other imaging metrics were not. Conclusion Left ventricular volumes and ejection fraction on CMR and echocardiography were only modestly correlated in this population with severe ICM. When using the binary EF threshold of 35% that is commonly used to select patients of implantable defibrillator therapy, almost a third of patients at risk would have been missed by echocardiography alone. The additional insights provided by CMR, including scar burden, further support preferential use of this modality in the assessment such patients.

First human safety and effectiveness study of defibrillation with a novel patch wearable cardioverter-defibrillator.

Wearable cardioverter-defibrillators (WCDs) are indicated in patients at risk of sudden cardiac arrest who are not immediate candidates for implantable defibrillator therapy. Limitations of existing WCDs include poor compliance and high false alarm rates. The Jewel is a novel patch-WCD (P-WCD) that addresses these limitations with an adhesive-based design for near-continuous wear and a machine learning algorithm designed to minimize inappropriate detections. This was a first-in-human study of the Jewel P-WCD conducted in an electrophysiology (EP) lab to determine the safety and effectiveness of the device in terminating ventricular tachycardia/ventricular fibrillation (VT/VF) with a single shock. The aim was to evaluate the safety and effectiveness of terminating VT/VF with a single shock using the Jewel P-WCD. This was a first-in-human, prospective, single-arm, single-centre study in patients scheduled for an EP procedure in which VT/VF was expected to either spontaneously occur or be induced. The Jewel P-WCD was placed on consented patients; upon confirmation of VT/VF, a single shock (150 J) was delivered via the device. A group sequential design and Pocock alpha spending function was used to measure the observed proportion of successful VT/VF single-shock terminations. The endpoint was achieved if the lower confidence limit exceeded the performance goal of 62%, using a one-sided lower 97.4% exact confidence bound. Of 18 eligible subjects, 16 (88.9%, 97.4% confidence bound: 65.4%) were successfully defibrillated with a single shock, exceeding the primary endpoint performance goal with no adverse events. This first-in-human evaluation of the Jewel P-WCD demonstrated the safety and effectiveness of terminating VT/VF. URL: https://clinicaltrials.gov/; Unique identifier: NCT05490459.

Clinical findings and outcomes of Brugada syndrome in women

Abstract Introduction Brugada syndrome (BrS) is a genetic disorder characterized by typical ECG changes and association with spontaneous ventricular tachyarrhythmia (VTA) and sudden death in young patients. BrS has been widely established to be particularly prevalent in men, however less information exists regarding female patients and their long-term risk. Objectives The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS. Methods This study includes a retrospective analysis of a single-center cohort of patients followed and observed for relevant clinical outcomes. The data collected included demographic data, severity of symptoms (e.g. syncope, VTA), cardioverter-defibrillator logs and occurrence of sudden cardiac death. Results 317 patients were diagnosed with BrS between 1998 and 2023. Among those, 112 (36%) were female. At presentation, 5 patients (4%) were symptomatic with history of survived cardiac arrest and/or documented VTA. 29 (26%) had history of unexplained syncope and 78 (70%) were asymptomatic. The average age at diagnosis was 42.1±15.1 yrs. as opposed to 40.1±14.2 yrs. in men. Females presented less frequently with a type 1 ECG pattern (5% vs 21%; p<0.01), had a trend to a higher rate of family history of sudden cardiac death (31% vs 25%; p=n.s.), and had less sustained VTA during programmed ventricular stimulation (4% vs 19%; p<0.01). Genetic testing was performed in 89 females (79% of the sample) and pathogenic variants were present in 36 (40%) women. An implantable cardioverter defibrillator was inserted in 24 (31%) females for primary prevention. During mean follow-up of 138±72 months, 11 women had cardiovascular events (syncope, VT/VF or death). Syncope was most common and occurred in 8 cases. No VTA were documented in any female patient. In the group of ICD patients, 8 shocks have occurred. None of these were deemed appropriate by medical controls. There were 3 deaths. Two were considered non-arrhythmic due to pulmonary embolism and breast carcinoma. One ICD patient died suddenly during sleep. Unfortunately, no device interrogation data was available. Conclusion Women typically present less symptomatic and demonstrate a reduced incidence of life-threatening arrhythmias during follow-up , often experiencing a frequent occurrence of inappropriate implantable defibrillator therapy. The less frequent prevalence of the BrS ECG pattern in women adds complexity to the diagnostic process. Further studies are still needed to elucidate gender differences for risk stratification of BrS.

Early Ventricular Arrhythmias After Left Ventricular Assist Device Implantation

BackgroundAlthough sustained ventricular arrhythmias (VAs) are a common complication after durable left ventricular assist device (LVAD) implantation, the incidence, risk factors, and prognostic implications of postoperative early VAs (EVAs) in contemporary patients with LVAD are poorly understood. Methods and ResultsA single-center retrospective analysis was performed of patients who underwent LVAD implantation from October 1, 2006, to October 1, 2022. EVA was defined as an episode of sustained VA identified ≤30 days after LVAD implantation. A total of 789 patients underwent LVAD implantation (mean age 62.9 ± 0. years 5, HeartMate 3 41.4%, destination therapy 43.3%). EVAs occurred in 100 patients (12.7%). A history of end-stage renal disease (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.45–21.70), preoperative electrical storm (OR 2.82, 95% CI 1.11–7.16), and appropriate implantable cardiac defibrillator therapy before implantation (OR 2.8, 95% CI 1.26–6.19) are independently associated with EVAs. EVA was associated with decreased 30-day survival (hazard ratio 3.02, 95% CI 1.1–8.3, P = .032). There was no difference in transplant-free survival time between patients with and without EVAs (hazard ratio 0.82, 95% CI 0.5–1.4, P = .454). ConclusionsEVAs are common after durable LVAD implantation and are associated with an increased risk of 30-day mortality.

Abstract 15106: Echocardiography versus Cardiac Magnetic Resonance-Quantification of Right Ventricular Function to Stratify the Risk of Appropriate Defibrillator Therapy

Background: Right ventricular dysfunction is recently referred as an independent predictor of sudden cardiac death. The purpose of this study was to evaluate the efficiency of risk stratification methods for appropriate implantable cardiac defibrillator (ICD) therapy using two different modalities to quantify the right ventricular function. Methods: Consecutive patients undergoing ICD implantations who completed both preprocedural echocardiography and cardiac magnetic resonance (CMR) were retrospectively enrolled. Any channelopathy or arrhythmogenic right ventricular disease were excluded. The right ventricular fractional area change (RVFAC) and estimated pulmonary artery pressure (EPAP) were calculated from echocardiography. The contraction-pressure index (CPI) was defined as the quotient of the RVFAC divided by EPAP. The right ventricular ejection fraction (RVEF) was automatically provided by CMR. Both were evaluated to predict the initial appropriate ICD therapy. Results: In total, 111 patients (59.5±14.9 years, 79 males) including 20 with ischemic cardiomyopathy were retrospectively enrolled. Fifty-six patients received an ICD as secondary prophylaxis. The mean RVFAC, CPI, and RVEF were 36.7±8.9%, 1.4±0.7%, and 39.9±13.8%, respectively. Regarding appropriate ICD therapy events, the best cut-off value of the RVFAC was 34.8 (specificity 0.63, sensitivity 0.65, ROC-AUC 0.64), CPI 1.59 (specificity 0.42, sensitivity 0.94, ROC-AUC 0.61) and RVEF 43.0 (specificity 0.48, sensitivity 0.87, ROC-AUC 0.64). The hazard ratio of a low RVFAC was 3.13 (95%CI: 1.32-7.44, P<0.01, concordance=0.62), that of low CPI was 9.60 (95%CI: 1.27-72.4, P=0.03, c=0.65), and that of reduced RVEF was 5.55 (95%CI: 1.64-18.7, P<0.01, c=0.67). Conclusion: CPI and RVEF were similarly associated with an increased appropriate ICD therapy. The CPI seemed to provide an equivalent stratification for the risk of appropriate ICD therapy as compared to a CMR indicator.

Current management of inherited arrhythmia syndromes associated with the cardiac ryanodine receptor.

Gain-of-function variants in the gene encoding the cardiac ryanodine receptor (RYR2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). The exercise stress test (EST) has long been fundamental in diagnosis and management, but recent work has further explored its role. A new entity termed calcium release deficiency syndrome (CRDS) has been associated with loss-of-function RYR2 variants and a different arrhythmic phenotype. Standard EST is not perfectly reproducible with regards to provocation of arrhythmia in CPVT. A newly described burst EST protocol may be more sensitive in this regard. Nadolol is the most effective beta blocker in CPVT, though arrhythmic events remain frequent and dual therapy with flecainide and/or left cardiac sympathetic denervation may add protection. A recent report renews debate regarding the use of implantable defibrillator therapy in CPVT. CRDS is characterized by later age of presentation, normal/near normal EST, and ventricular arrhythmia induced by a novel ventricular stimulation protocol. Burst EST may aid in the diagnosis and management of CPVT. Nadolol is the preferred beta blocker in CPVT, and consideration should be given to early dual therapy. CRDS should be suspected in patients with arrhythmic events, rare RYR2 variants, and a phenotype inconsistent with CPVT.

Abstract 14931: Frailty Status Modifies the Efficacy of ICD Therapy Among Patients With Chronic Heart Failure With Reduced Ejection Fraction

Introduction: Frailty is common in patients with heart failure with reduced ejection fraction (HFrEF) and is independently associated with mortality. Implantable cardiac defibrillator (ICD) therapy is recommended to reduce mortality risk in patients with HFrEF. Whether baseline frailty modifies the efficacy of ICD therapy in HFrEF is not known. Methods: Stable outpatients with HFrEF randomized to ICD vs. placebo in the SCD-HeFT trial were included. Baseline frailty was estimated using Rockwood’s Frailty Index (FI) by dividing the number of deficits present by the number of variables considered (n=37). Participants were categorized into tertiles of FI. Multivariable adjusted Cox proportional hazard models with multiplicative interaction terms (frailty*treatment arm) were constructed to evaluate whether frailty modified the treatment effect of ICD therapy on the primary outcome all-cause mortality and secondary outcomes of cardiovascular (CV) mortality and sudden cardiac death (SCD). Results: Among 1,673 participants (age: 59±12 y, 23% women), the median [IQR] FI ranged from 0.19 [0.14-0.23] in tertile 1 (lower frailty burden) to 0.51 [0.47-0.56] in tertile 3 (higher frailty burden). Baseline frailty significantly modified the treatment effect of ICD therapy (P-interaction: 0.03) ( Fig. A ). Specifically, ICD therapy was associated with a lower risk of all-cause mortality in tertile 1 [HR (95% CI) = 0.55 (0.37-0.80)] but not in tertile 3 participants [HR (95% CI) = 0.90 (0.67-1.22)] ( Fig. B ). Among secondary outcomes, frailty status modified the association of both CV mortality and SCD (P-interaction = 0.007 and 0.04, respectively). Similar results were observed in landmark analyses at 12 months. Conclusions: Among patients with chronic stable HFrEF, baseline frailty modified the treatment effect of ICD therapy with a greater reduction in the risk of CV mortality and SCD in patients with a lower burden of frailty.

Remote monitoring in patients with heart failure with cardiac implantable electronic devices: a systematic review and meta-analysis

BackgroundRemote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is now the standard of care, but whether the demonstrated benefits of RM translate into improvements in heart failure (HF) management...

Implantable defibrillator therapy and mortality in patients with non-ischaemic dilated cardiomyopathy : Anupdated meta-analysis and effect on Dutch clinical practice by the Task Force of the Dutch Society of Cardiology.

Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit of ICD therapy with or without cardiac resynchronisation therapy (CRT) in patients with NICMP. In addition, data were compared with real-world clinical data to perform arisk/benefit analysis. Relevant randomised clinical trials (RCTs) published in meta-analyses since DANISH, and in PubMed, EMBASE and Cochrane databases from 2016 to 2020 were identified. The benefit of ICD therapy stratified by CRT use was assessed using random effects meta-analysis techniques. Six RCTs were included in the meta-analysis. Among patients without CRT, ICD use was associated with a24% reduction in mortality (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62-0.93; P = 0.008). In contrast, among patients with CRT, aCRT-defibrillator was not associated with reduced mortality (HR: 0.74, 95% CI 0.47-1.16; P = 0.19). For ICD therapy without CRT, absolute risk reduction at 3‑years follow-up was 3.7% yielding anumber needed to treat of27. ICD use significantly improved survival among patients with NICMP who are not eligible for CRT. Considering CRT, the addition of defibrillator therapy was not significantly associated with mortality benefit compared with CRT pacemaker.

Subcutaneous Versus Transvenous Implantable Defibrillator Therapy: A Systematic Review and Meta-Analysis of Randomized Trials and Propensity Score-Matched Studies.

BackgroundSubcutaneous implantable cardioverter‐defibrillators (S‐ICDs) have been of great interest as an alternative to transvenous implantable cardioverter‐defibrillators (TV‐ICDs). No meta‐analyses synthesizing data from high‐quality studies have yet been published.Methods and ResultsAn electronic literature search was conducted to retrieve randomized controlled trials or propensity score–matched studies comparing S‐ICD against TV‐ICD in patients with an implantable cardioverter‐defibrillator indication. The primary outcomes were device‐related complications and lead‐related complications. Secondary outcomes were inappropriate shocks, appropriate shock, all‐cause mortality, and infection. All outcomes were pooled under random‐effects meta‐analyses and reported as risk ratios (RRs) and 95% CIs. Kaplan–Meier curves of device‐related complications were digitized to retrieve individual patient data and pooled under a 1‐stage meta‐analysis using Cox models to determine hazard ratios (HRs) of patients undergoing S‐ICD versus TV‐ICD. A total of 5 studies (2387 patients) were retrieved. S‐ICD had a similar rate of device‐related complications compared with TV‐ICD (RR, 0.59 [95% CI, 0.33–1.04]; P=0.070), but a significantly lower lead‐related complication rate (RR, 0.14 [95% CI, 0.07–0.29]; P<0.0001). The individual patient data–based 1‐stage stratified Cox model for device‐related complications across 4 studies yielded no significant difference (shared‐frailty HR, 0.82 [95% CI, 0.61–1.09]; P=0.167), but visual inspection of pooled Kaplan–Meier curves suggested a divergence favoring S‐ICD. Secondary outcomes did not differ significantly between both modalities.ConclusionsS‐ICD is clinically superior to TV‐ICD in terms of lead‐related complications while demonstrating comparable efficacy and safety. For device‐related complications, S‐ICD may be beneficial over TV‐ICD in the long term. These indicate that S‐ICD is likely a suitable substitute for TV‐ICD in patients requiring implantable cardioverter‐defibrillator implantation without a pacing indication.

Phenotypic characteristics of patients with arrhythmogenic left ventricular cardiomyopathy and sustained ventricular tachycardias

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The Padua criteria proposed for the diagnostic approach to Arrhythmogenic Cardiomyopathy (AMC) introduced new diagnostic criteria to recognize patients with a phenotype of the left ventricular variants of AMC (ALVC). Unlike ARVC, the arrhythmogenicity of this left phenotype has not yet been established. Objectives This study aims to analyze the phenotypic characteristics in a group of patients with ALVC and ventricular arrhythmias (VA). Methods Thirty-seven related patients with ALVC and VA were included and these were evaluated at the Inherited Cardiac Disease Unit of a Tertiary Hospital. Results Between 2000 and 2021, a total of 207 patients were diagnosed with ALVC. Thirty-seven patients (18%) presented VA; 25 ( 67%) sustained ventricular tachycardia (SVT), 10 ( 27 %) non sustained ventricular tachycardia (NSVT) and 2 ventricular fibrillation (VF). Eighteen 18/37 (49%) biventricular and 19/37 (51%) dominant . Twenty-five, 67 % male, aged 41.8 ± 13.4 years. A genetic study was performed in 36 ( 97%), and the pathogenic mutations were identified in desmoplakin in eighteen, plakophilin-2, desmoglein-2 and phospholamb in three, titin and filamine in two; desmin, plakoglobin and lamin A in one. There was one variant of uncertain significance in desmocollin-2, desmoplakin and titin. A low amplitude QRS voltages (LAQRS) in limb leads was present in 14/33 patients . Inverted T waves in right (V1-V3) in 4/33 patients and in left precordial (V4-V6) were present in 9/33 patients. The average left ventricular ejection fraction (LVEF) was 41%± 14 and myocardial fibrosis evidenced by contrast-enhanced CMR as LGE was presented in 22 patients. Ventricular arrhythmias with a right bundle branch block (RBBB) morphology were most frequent (7/12 ), denoting the origin from LV. All VT with LBBB morphology appeared in biventricular cases (5/12). Reverse pattern break was present in three patients. EAM showed bipolar or unipolar endocardial scar left ventricle in 6/10 and bipolar or unipolar endocardial scar right ventricle in 3/10 patients. Epicardial scar was present in 4 patients ( 3 LV, 2 RV). An implantable cardioverted defibrillator (ICD) therapy was performed in 25 patients for primary or secondary prevention of sudden death. Heart transplantation was carried out for three patients. Conclusions A substancial number of patients with ALVC have presented ventricular arrhythmias. Ventricular arrhythmias with a right bundle branch block (RBBB) morphology were the most frequent. All of VT with LBBB morphology appeared in biventricular cases. The mutation in DSP was the most prevalent in patients with ALVC and VT. Patients with ALVC and VA are characterized by a ventricular function that is not significantly impaired; however, fibrosis in LGE is widespread.

Device-detected sleep-disordered breathing predicts implantable defibrillator therapy in patients with heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Sleep-disordered breathing is highly prevalent in heart failure (HF) and it has been suggested as a risk factor for malignant ventricular arrhythmias. The Respiratory Disturbance Index (RDI) algorithm computed by select implantable cardioverter defibrillators (ICDs) can identify severe sleep apnea (SA). Purpose In the present analysis we evaluated the association between ICD-detected SA and the incidence of appropriate ICD therapy in patients with HF. Methods We enrolled 411 HF patients (age 69±10years, 77% male, ejection fraction 32±8%), implanted with an ICD endowed with an algorithm (ApneaScan, Boston Scientific) that calculates the RDI each night. In this analysis the weekly mean RDI value was considered. The endpoint was the first appropriate ICD shock. The median follow-up was 26 months [25th–75th percentile: 16-35]. Results During follow-up, one or more ICD shocks were documented in 58 (14%) patients. Patients with shocks were younger (66±13years versus 70±10years, p=0.038), and more frequently implanted for secondary prevention (21% versus 10%, p=0.026). The maximum RDI value calculated during the entire follow-up period did not differ between patients with and without shocks (55±15episodes/h versus 54±14episodes/h, p=0.539). However, the ICD-detected RDI showed a considerable variability during follow-up. The overall median of the weekly RDI was 33episodes/h [25th–75th percentile: 24-45]. Using a time-dependent Cox regression model, the continuously measured weekly mean RDI≥45episodes/h was independently associated with shock occurrence (HR:4.63, 95%CI:2.54-8.43, p&amp;lt;0.001), after correction for baseline confounders (age, secondary prevention). Conclusions In HF patients, patients were more likely to receive appropriate ICD shocks during periods of time when they exhibited more sleep-disordered breathing.

Short-time ventricular tachycardia ablation for cardiac sarcoidosis using coherent map.

A 69‐year‐old woman with isolated cardiac sarcoidosis was hospitalized for frequent appropriate implantable converter defibrillator therapies for ventricular tachycardia (VT) despite of favorably controlled condition with oral prednisolone. The patient underwent urgent catheter ablation with CARTO 3D mapping system. Although the voltage map, activation map, and propagation map during VT could not visualize the tachycardia circuit, the coherent map clarified entrance and exit sites of the tachycardia circuit with slow or nonconducting (SNO) zones, which seemed like a figure‐of‐eight circuit. Considering the risk of VT termination or acceleration to rapid unstable VT, neither entrainment nor pacing studies were performed. The VT was terminated near the exit site of the isthmus where tiny pre‐systolic potential was detected. Any diastolic potentials could not be detected. This meant that the critical isthmus might be located at the epicardium or deep incite of the left‐ventricular myocardium where the coherent map showed as SNO zones. We should recognize coherent map as artificial that may represent VT circuit as if complete endocardial reentry even if not. The procedural time from mapping to termination of VT was only 22 minutes. The patient has been free from any cardiovascular events after the procedure. Coherent map might be feasible for revealing the critical isthmus of hemodynamically stable VTs without using electrophysiological techniques, including entrainment, pacing study, and voltage map during own beats, and would enable us to achieve successful VT ablation in a short time.

An Unusual Cause of Superior Vena Cava Stenosis

<h3>Introduction</h3> An unusual cause of superior vena cava stenosis following heart transplantation. <h3>Case Report</h3> A sixty-five year old female underwent orthotopic heart transplantation for chemotherapy-induced cardiomyopathy after treatment for breast cancer in 2008. She required peripheral veno-arterial extracorporeal membrane oxygenation for primary graft dysfunction immediately post-transplantation. Venous access proved challenging due to a combination of implantable defibrillator therapy (extracted at transplant) and left sided mastectomy with lymph node clearance. Attempts at floating a pulmonary artery catheter were unsuccessful. Three days later she developed clinical signs of superior vena cava (SVC) obstruction, with head and upper limb oedema and elevated central venous pressure at 25mmHg. Echocardiography showed a moderate pericardial effusion but no tamponade and an underfilled right heart. Venography confirmed stenosis of the SVC during contrast injection, and measurement of central venous pressures demonstrated a pressure gradient of >4mmHg across the narrowing, with dampening of the pressure waveform distally (Figures). Surgical exploration of the SVC anastomosis site identified a haematoma causing external venous compression. Evacuation of the haematoma resulted in full resolution of symptoms. <h3>Summary</h3> Superior vena cava stenosis is an uncommon complication following heart transplantation, characterized by elevated central venous pressures and upper body oedema. Venography and direct intravenous pressure measurements are diagnostic. Surgical exploration or revision of the anastomosis may be indicated.

Previous pacemaker therapy was not associated with the risk of clinical events in patients with atrial fibrillation: the Fushimi AF Registry

Abstract Background Patients with atrial fibrillation (AF) occasionally require pacemaker implantation. Meanwhile, patients with implanted pacemaker are occasionally found to have subclinical AF and develop clinical AF. However, little is known about the clinical outcomes of AF patients with implanted pacemaker. Purpose We aimed to investigate the clinical outcomes in AF patients undergoing previous pacemaker therapy. Methods The Fushimi AF Registry is a community-based prospective survey of the AF patients in a city of Japan. Follow-up data including prescription status were available for 4,447 patients. After exclusion of patients with implantable cardioverter defibrillator and cardiac resynchronization therapy, we investigated 293 AF patients with pacemaker implantation at baseline. We performed propensity score-matching analysis to assess the impact of pacemaker therapy in AF patients. Results Of a total cohort, patients with pacemaker were more often female (51.2% vs. 39.7%; p&amp;lt;0.01) and older (78.0 vs. 73.3 years of age; p&amp;lt;0.01). Patients with pacemaker were more likely to have pre-existing heart failure (33.1% vs. 26.6%; p&amp;lt;0.01), valvular heart disease (22.9% vs. 16.8%; p&amp;lt;0.01), chronic kidney disease (48.8% vs. 34.7%; p&amp;lt;0.01), and history of performing direct current cardioversion (7.2% vs. 3.1%; p&amp;lt;0.01), compared with patients without pacemaker. Mean CHA2DS2-VASc score was higher in patients with pacemaker (3.80 vs. 3.34; p&amp;lt;0.01). Patients with pacemaker were more often prescribed oral anticoagulants (62.1% vs. 55.2%; p=0.02), verapamil (13.3% vs. 9.4%; p=0.03), and loop diuretics (30.7% vs. 21.8%; p&amp;lt;0.01). Using propensity score-matching, 291 patients with pacemaker and 291 without pacemaker were matched and baseline characteristics were comparable. The median follow-up period was 1,819 days. All-cause death occurred in 91 patients with pacemaker (6.0 /100 person-years) and 79 patients without pacemaker (5.9 /100 person-years), with a hazard ratio (HR) for patients with pacemaker of 1.01 (95% confidence interval [CI], 0.75 to 1.37; p=0.93). Furthermore, HR of cardiac death for patients with pacemaker was 1.00 (95% CI, 0.23 to 4.32; p=0.99), that of stroke or systemic embolism was 0.69 (95% CI, 0.44 to 1.07; p=0.10) and that of hospitalization for heart failure was 0.94 (95% CI, 0.65 to 1.37; p=0.76). Conclusion We identified that patients undergoing previous pacemaker therapy were not associated with the incidence of various adverse clinical events in Japanese AF patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi Sankyo, Novartis Pharma, MSD, Sanofi-Aventis, Takeda Pharmaceutical, and the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development.

Association between cardiac autonomic function and physical activity in patients at high risk of sudden cardiac death: a cohort study

BackgroundHigh levels of physical activity (PA) and heart rate variability (HRV) are associated with cardiovascular benefits in patients with cardiovascular diseases. HRV, representing cardiac autonomic function, is positively associated with PA. However, the impacts of PA and cardiac autonomic function on cardiovascular outcomes were not analysed in the same study population. This lack of evidence supported our hypothesis that PA might contribute to cardiovascular benefits via enhanced cardiac autonomic function.MethodsPatients with implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy defibrillator (CRT-D) implantation were included from the SUMMIT registry. HRV and PA values were assessed during the first 30–60 days post device implantation using a continuous home monitoring system. Causal mediation analysis was conducted to explore the possible mediation function of HRV in the association of PA with long-term cardiac death and all-cause mortality in patients at a high risk of sudden cardiac death.ResultsOver a mean follow-up period of 47.7 months, 63 cardiac deaths (18.9%) and 85 all-cause death events (25.5%) were observed among 342 patients with ICD/CRT-D implantation. A positive linear association between HRV and PA was demonstrated and the β value of HRV was 0.842 (95% confidence interval [CI]: 0.261–1.425, P = 0.005) in the multiple linear regression analysis. Multivariable Cox proportional hazards analysis revealed that high levels of PA (≥11.0%) and HRV (≥75.9 ms) were independent protective factors against cardiac death (PA: hazard ratio [HR] = 0.273; 95% CI, 0.142–0.526, P < 0.001; HRV: HR = 0.224; 95% CI, 0.103–0.489, P < 0.001) and all-cause mortality (PA: HR = 0.299; 95% CI, 0.177–0.505, P < 0.001; HRV: HR = 0.394; 95% CI, 0.231–0.674, P = 0.001). Causal mediation analysis demonstrated partial mediation effects of PA that were mediated through HRV on cardiac death (mediation proportion = 12.9, 95%CI: 2.2–32.0%, P = 0.006) and all-cause mortality (mediation proportion = 8.2, 95%CI: 1.6–20.0%, P = 0.006).ConclusionsHRV might be a modest mediator in the association between high levels of PA and the reduced risks of cardiac death and all-cause mortality in ICD/CRT-D recipients. This finding supports that enhanced cardiac autonomic function might be one of the underlying mechanisms by which regular PA contributes to cardiovascular benefits.

Implantable Cardiac Device Infections Prevalence: Diagnostic and Therapeutic Implications

Background: It has been demonstrated that the use of cardiac implanted electronic devices (CIED) improve mortality and survivability in a variety of patient populations. Nevertheless, CIED related infection is a serious complication characterized by a high rate of mortality and morbidity.&#x0D; Objectives: To evaluate the prevalence of CIED related infections, risk factors, clinical and demographic characteristics, causative organisms, and the management and outcome of patients presented in the Critical Care Department, Cairo University.&#x0D; Methods: A retrospective analysis was conducted in 1871 individuals who had been implanted with a cardiac device with a total number of devices of 1968 and 2270 procedures performed from January 2007 to December 2017.&#x0D; Results: 59 infectious episodes were identified with an estimated incidence of 2.99% of inserted devices and 2.6% of total procedures. The infection rate was considerably higher in patients with multiple procedures than those who had a single procedure (9.27% vs. 1.18%; P&lt;0.001). The individuals with a dual-chamber implantable cardiac defibrillator (ICD) and cardiac resynchronization therapy devices (CRTD) had the highest infection rate of 6.25% &amp; 6.85%, respectively. The rate of pocket infection (PI) and CIED related endocarditis (CDE) was 1.54% &amp; 1.06% of total devices respectively. Numerous risk factors have been found; the most significant of those are diabetes mellitus, recurrent procedures, the device's complexity, and the existence of more than one lead. Gram-positive cocci were the most isolated organisms in all positive cultures (69.23%). Echocardiography revealed lead vegetations and valvular vegetations in 22 patients and 2 patients respectively. In 53 cases (89.83%), the devices were removed; in 41 cases, the entire system was removed; and in 12 cases, only the generator was removed. The mortality rate was found to be 10.17%, having a considerably higher prevalence in CDE individuals than in pocket infection individuals (20.83% vs. 2.86%; P=0.025).&#x0D; Conclusion: In our center, while the rate of CIED implantation continues to increase, the incidence rate of CIED-related infection continues to decline. Until now, the infection burden associated with secondary intervention is still significantly high. The management strategy of selection is to eliminate the entire system for patients presented with infection especially those with CDE. However, the mortality rate is still high.

Circadian periodicity affects the type of ventricular arrhythmias and efficacy of implantable defibrillator therapies.

Factors influencing malignant arrhythmia onset are not fully understood. We explored the circadian periodicity of ventricular arrhythmias (VAs) in patients with implantable cardioverter and cardiac resynchronization defibrillators (ICD/CRT-D). Time, morphology (monomorphic/polymorphic), and mode of termination (anti-tachycardia pacing [ATP] or shock) of VAs stored in a database of remote monitoring data were adjudicated. Episodes were grouped in six 4-h timeslots from 00:00 to 24:00. Circadian distributions and adjusted marginal odds ratios (ORs), with 95% confidence interval (CI), were analyzed using mixed-effect models and logit generalized estimating equations, respectively, to account for within-subject correlation of multiple episodes. Among 1303 VA episodes from 446 patients (63% ICD and 37% CRT-D), 120 (9%) self-extinguished, and 842 (65%) were terminated by ATP, 343 (26%) by shock. VAs clustered from 08:00 to 16:00 with 44% of episodes, as compared with 22% from 00:00 to 08:00 (p < .001) and 34% from 16:00 to 24:00 (p = .005). Episodes were more likely to be polymorphic at night with an adjusted marginal OR of 1.66 (CI, 1.15-2.40; p = .007) at 00:00-04:00 versus other timeslots. Episodes were less likely to be terminated by ATP in the 00:00-04:00 (success-to-failure ratio, 0.67; CI, 0.46-0.98; p = .039) and 08:00-12:00 (0.70; CI, 0.51-0.96; p = .02) timeslots, and most likely to be terminated by ATP between 12:00 and 16:00 (success-to-failure ratio 1.42; CI, 1.06-1.91; p = .02). VAs did not distribute uniformly over the 24 h, with a majority of episodes occurring from 08:00 to 16:00. Nocturnal episodes were more likely to be polymorphic. The efficacy of ATP depended on the time of delivery.

Sudden cardiac death risk stratification in patients with a preserved or mildly reduced ejection fraction: role of cardiac magnetic resonance and electrophysiological study

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Patients presenting with syncope of suspected arrhythmogenic origin or symptomatic documented non sustained ventricular tachycardia (NSVT) may represent a population with higher risk for sudden cardiac death (SCD). However today there are still no defined criteria to stratify the risk of SCD in this population. PURPOSE To assess the prognostic value of magnetic resonance (MRI) and electrophysiological study (EPS) in the risk stratification for SCD of patients with a preserved or mildly-reduced ejection fraction (EF) that may benefit from implantable cardiac defibrillator (ICD) therapy. METHODS We selected ischemic and non-ischemic patients with a preserved or mildly-reduced ejection fraction who came to our attention either after a probably arrhythmogenic syncopal event or a documented NSVT between 12/2018 and 09/2020. Patients with other ICD indications following current guideline-criteria were excluded (id est Brugada syndrome, Long QT and hypertrophic cardiomyopathy). All patients underwent an echocardiography, a coronary angiography, and an MRI with gadolinium, those among them with a positive LGE also underwent an induction EPS. Non inducible patients were followed-up clinically or with an implantable event-recorder, while inducible patients received an ICD. RESULTS In our observational study seventeen patients with preserved or only mildly-reduced EF were enrolled (13 males and 5 females; mean age 68 years). Among these patients, nine were identified with an underlying myocardial scar with positive Late-Gadolinium-Enhancement (LGE) in MRI. Based on the clinical orientation and the MRI LGE pattern patients were divided in ischemic group (5 patients) and non-ischemic group (4 patients). All 9 patients underwent an induction EPS. Three of them, 2 with non-ischemic and 1 with an ischemic pattern, demonstrated a reproducible inducibility of a sustained ventricular tachycardia or ventricular fibrillation and were implanted with an ICD. During our follow-up two of the three patients had an adequate shock within a year from the ICD implantation. Among the 6 patients with negative induction EPS there were no clinical events in the follow up, except one death for unknown causes. CONCLUSION Our preliminary results demonstrated that in patients with ischemic or non ischemic cardiopathy with preserved or mildly reduced EF, a positive MRI LGE pattern and the inducibility of ventricular arrhythmias during induction EPS identify a population at higher risk for clinical recurrence of ventricular arryhthmic events. Further investigation is needed to validate this combined diagnostic strategy as new SCD prevention tool.

Long-Term clinical outcomes of subcutaneous implantable defibrillator therapy in patients with heart failure and reduced ejection fraction: a single center experience

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): P. JACON consultant: Boston Scientific France Introduction The implantable cardioverter defibrillator (ICD) is the most effective therapy for prevention of sudden cardiac death in high-risk patients with heart failure and reduced ejection fraction (HFrEF). The subcutaneous implantable cardioverter defibrillator (S-ICD) has been considered as a comparable and relatively safer alternative to transvenous ICD in patients (pts) without pacing indication. Purpose Our aim was to assess the clinical "real-life" outcomes of S-ICD in patients with HFrEF and primary or secondary prevention, over a long-term follow-up (FU) period after S-ICD implantation. Methods All pts with HFrEF (left ventricular ejection fraction ≤35%) implanted with a S-ICD and a FU above 6 months were included in a cross-sectional monocentric study. Pts were followed by remote monitoring. Results 88 pts were included (52 ± 12.8 years old, male 87.5%). Indications were: primary 92% and secondary 8% prevention (ischemic cardiopathy 46%; dilated 46%; hypertrophic 5%; congenital 2%; valvular 1%). The mean left ventricular ejection fraction was 27%. 9 pts had a previous transvenous ICD implanted, but required revision because of infection or lead defects. The mean FU period was 33 ± 18 months with a mortality rate of 10% (S-ICD-related death secondary to inappropriate (inap) shocks for one patient). 5 pts underwent S-ICD system extraction after a mean FU period of 30 ± 21 months. Reasons were infectious complication (1 pt), pacing indication (2 pts) and S-ICD lead dysfunction (2 pts). Extraction after heart transplant was performed in 4 pts. During FU, 18 pts (20.5%) experienced at least one therapy: 8 pts (9%) with appropriate (ap) (3.3% per year) and 11 pts (12%) with inap shocks (4.36% per year). A total number of 24 ap shocks have been observed (3 ± 4 ap shocks per patient, several shocks for 3 pts), the first shock occurred after a mean FU period of 24 ± 14 months. 2 pts were referred to VT ablation and no recurrence of events was observed after medical therapy modification for the other pts. For the 11 pts with inap shocks, time to the first event was 19 ± 20 months. Reasons were: supraventricular arrhythmias (18%), T wave (36%) and noise (54%) oversensing. There was 1.8 ± 1.6 shock per patient with several shocks for 4 pts. Among pts with inap shocks, 2 pts required S-ICD system extraction, 1 pt died, while reprogramming and medical therapy options were efficient in other pts. Conclusion In pts with HFrEF at high risk of sudden cardiac death, S-ICD has proven to be effective in treating ventricular arrhythmias. However, more investigations must be conducted to explain the real-life high rate of inappropriate therapies. Abstract Figure. Survival-free from therapies curve