Active Arrhythmia Pattern: A Novel Predictor of ICD Shocks-A Subanalysis From the PARTITA Study.

BACKGROUND: In the PARTITA trial (Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator?), antitachycardia pacing (ATP) predicted the occurrence of implantable cardioverter defibrillator (ICD) shocks. Catheter ablation of ventricular tachycardia after the first shock reduced the risk of death or worsening heart failure. A threshold of ATPs that might warrant an ablation procedure before ICD shocks is unknown. Our aim was to identify a threshold of ATPs and clinical features that predict the occurrence of shocks and cardiovascular events. METHODS: We analyzed data from 517 patients in phase A of the PARTITA study. We used classification and regression tree analysis to develop and test a risk stratification model based on arrhythmia patterns and clinical data to predict ICD shocks. Secondary end points were worsening heart failure and cardiovascular hospitalization. RESULTS: Classification and regression tree classified patients into 6 leaves by increasing shock probability. Patients treated with ≥5 ATPs in 6 months (active arrhythmia pattern) had the highest risk of ICD shocks (93% and 86%, training and testing samples, respectively). Patients without ATPs had the lowest (1% and 2%). Other predictors included left ventricle ejection fraction<35%, age of <60 years, and obesity. Survival analysis revealed a higher risk of worsening heart failure (hazard ratio, 5.45 [95% CI, 1.62-18.4]; P=0.006) and cardiovascular hospitalization (hazard ratio, 7.29 [95% CI, 3.66-14.5]; P<0.001) for patients with an active arrhythmia pattern compared with those without ATPs. CONCLUSIONS: Patients with an active arrhythmia pattern (≥5 ATPs in 6 months) are associated with an increased risk of ICD shocks, as well as heart failure hospitalization and cardiovascular hospitalization. These data suggest that additional treatments may be helpful to this high-risk group as a preventive strategy to reduce the incidence of major events. Further prospective randomized trials are needed to confirm the benefits of early ventricular tachycardia ablation in this setting.

Device-detected atrial sensing amplitudes as a marker of increased risk for new onset and progression of atrial high-rate episodes.

BACKGROUND: Atrial high-rate episodes (AHREs) are frequent in patients with cardiac implantable electronic devices. A decrease in device-detected P-wave amplitude may be an indicator of periods of increased risk of AHRE. OBJECTIVE: The objective of this study was to assess the association between P-wave amplitude and AHRE incidence. METHODS: Remote monitoring data from 2579 patients with no history of atrial fibrillation (23% pacemakers and 77% implantable cardioverter-defibrillators, of which 40% provided cardiac resynchronization therapy) were used to calculate the mean P-wave amplitude during 1 month after implantation. The association with AHRE incidence according to 4 strata of daily burden duration (≥15 minutes, ≥6 hours, ≥24 hours, ≥7 days) was investigated by adjusting the hazard ratio with the CHA2DS2-VASc score. RESULTS: The adjusted hazard ratio for 1-mV lower mean P-wave amplitude during the first month increased from 1.10 (95% confidence interval [CI], 1.05-1.15; P < .001) to 1.18 (CI, 1.09-1.28; P < .001) with AHRE duration strata from ≥15 minutes to ≥7 days independent of the CHA2DS2-VASc score. Of 871 patients with AHREs, those with 1-month P-wave amplitude <2.45 mV had an adjusted hazard ratio of 1.51 (CI, 1.19-1.91; P = .001) for progression of AHREs from ≥15 minutes to ≥7 days compared with those with 1-month P-wave amplitude ≥2.45 mV. Device-detected P-wave amplitudes decreased linearly during the 1 year before the first AHRE by 7.3% (CI, 5.1%-9.5%; P < .001 vs patients without AHRE). CONCLUSION: Device-detected P-wave amplitudes <2.45 mV were associated with an increased risk of AHRE onset and progression to persistent forms of AHRE independent of the patient's risk profile.

Temporal relationship between haemodynamic changes and activation of closed-loop stimulation during a tilt-induced vasovagal syncope.

AIMS: A dual-chamber pacemaker with closed-loop stimulation (CLS) mode is effective in reducing syncopal recurrences in patients with asystolic vasovagal syncope (VVS). In this study, we explored the haemodynamic and temporal relationship of CLS during a tilt-induced vasovagal reflex. METHODS AND RESULTS: Twenty patients underwent a tilt test under video recording 3.9 years after CLS pacemaker implantation. Three patients were excluded from the analysis because of no VVS induced by the tilt test (n = 1) and protocol violation (n = 2). In 14 of the remaining 17 patients, CLS pacing emerged during the pre-syncopal phase of circulatory instability when the mean intrinsic heart rate (HR) was 88 ± 12 b.p.m. and systolic blood pressure (SBP) was 108 ± 19 mmHg. The CLS pacing rate thereafter rapidly increased to 105 ± 14 b.p.m. within a median of 0.1 min [inter-quartile range (IQR), 0.1-0.7 min] when the SBP was 99 ± 21 mmHg. At the time of maximum vasovagal effect (syncope or pre-syncope), SBP was 63 ± 17 mmHg and the CLS rate was 95 ± 13 b.p.m. The onset of CLS pacing was 1.7 min (IQR, 1.5-3.4) before syncope or lowest SBP. The total duration of CLS pacing was 5.0 min (IQR, 3.3-8.3). Closed-loop stimulation pacing was not observed in three patients who had a similar SBP decrease from 142 ± 22 mmHg at baseline to 69 ± 4 mmHg at the time of maximum vasovagal effect, but there was no significant increase in HR (59 ± 1 b.p.m.). CONCLUSION: The reproducibility of a vasovagal reflex was high. High-rate CLS pacing was observed early during the pre-syncopal phase in most patients and persisted, although attenuated, at the time of maximum vasovagal effect. REGISTRATION: ClinicalTrials.gov identifier: NCT06038708.

Predicting worsening heart failure hospitalizations in patients with implantable cardioverter defibrillators: is it all about alerts? A pooled analysis of nine trials.

AIMS: To predict worsening heart failure hospitalizations (WHFHs) in patients with implantable defibrillators and remote monitoring, the HeartInsight algorithm (Biotronik, Berlin, Germany) calculates a heart failure (HF) score combining seven physiologic parameters: 24 h heart rate (HR), nocturnal HR, HR variability, atrial tachyarrhythmia, ventricular extrasystoles, patient activity, and thoracic impedance. We compared temporal trends of the HF score and its components 12 weeks before a WHFH with 12-week trends in patients without WHFH, to assess whether trends indicate deteriorating HF regardless of alert status. METHODS AND RESULTS: Data from nine clinical trials were pooled, including 2050 patients with a defibrillator capable of atrial sensing, ejection fraction ≤ 35%, NYHA class II/III, no long-standing atrial fibrillation, and 369 WHFH from 259 patients. The mean HF score was higher in the WHFH group than in the no WHFH group (42.3 ± 26.1 vs. 30.7 ± 20.6, P < 0.001) already at the beginning of 12 weeks. The mean HF score further increased to 51.6 ± 26.8 until WHFH (+22% vs. no WHFH group, P = 0.003). As compared to the no WHFH group, the algorithm components either were already higher 12 weeks before WHFH (24 h HR, HR variability, thoracic impedance) or significantly increased until WHFH (nocturnal HR, atrial tachyarrhythmia, ventricular extrasystoles, patient activity). CONCLUSION: The HF score was significantly higher at, and further increased during 12 weeks before WHFH, as compared to the no WHFH group, with seven components showing different behaviour and contribution. Temporal trends of HF score may serve as a quantitative estimate of HF condition and evolution prior to WHFH.

Prognostic significance of remotely monitored nocturnal heart rate in heart failure patients with reduced ejection fraction.

BACKGROUND: Elevated resting heart rate is a risk factor for cardiovascular events. OBJECTIVE: The purpose of this study was to investigate the clinical significance of nocturnal heart rate (nHR) and 24-hour mean heart rate (24h-HR) obtained by continuous remote monitoring (RM) of implantable devices. METHODS: We analyzed daily-sampled trends of nHR, 24h-HR, and physical activity in patients on ß-blocker therapy for chronic heart failure and with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (CRT-Ds). Patients were grouped by average nHR and 24h-HR quartile during follow-up to estimate the respective incidence of nonarrhythmic death and device-treated ventricular tachycardia/fibrillation (VT/VF). RESULTS: The study cohort included 1330 patients (median age 69 years [interquartile range 61-77 years]; 41% [n = 550] with CRT-D; median follow-up 25 months [interquartile range 13-42 months]). Compared with patients in the lowest nHR quartile (≤57 beats/min) group, patients in the highest quartile group (>65 beats/min) had an increased risk of nonarrhythmic death (adjusted hazard ratio [AHR] 2.25; 95% confidence interval [CI] 1.13-4.50; P = .021) and VT/VF (AHR 1.98; 95% CI 1.40-2.79; P < .001) and were characterized by the lowest level of physical activity (P ≤ .0004 vs every other nHR quartiles). The highest 24h-HR quartile group (>75 beats/min) showed an increased risk of VT/VF (AHR 2.13; 95% CI 1.52-2.99; P < .001) and a weaker though significant association with nonarrhythmic mortality (AHR 1.80; 95% CI 1.00-3.22; P = .05) as compared with the lowest 24h-HR quartile group (≤65 beats/min). CONCLUSION: In remotely monitored patients with implantable cardioverter-defibrillator/CRT-D on ß-blocker therapy for heart failure, elevated heart rates (nHR >65 beats/min and 24h-HR >75 beats/min) were associated with increased mortality and VT/VF risk. nHR showed a stronger association than 24h-HR with worst prognosis and lowest physical activity.

Remote monitoring of implantable loop recorders reduces time to diagnosis in patients with unexplained syncope: a multicenter propensity score-matched study.

Background: There are little data on remote monitoring (RM) of implantable loop recorders (ILRs) in patients with unexplained syncope and whether it confers enhanced diagnostic power. Objective: To evaluate the effect of RM in ILR recipients for unexplained syncope for early detection of clinically relevant arrhythmias by comparison with a historical cohort with no RM. Methods: SyncRM is a propensity score (PS)-matched study prospectively including 133 consecutive patients with unexplained syncope and ILR followed up by RM (RM-ON group). A historical cohort of 108 consecutive ILR patients with biannual in-hospital follow-up visits was used as control group (RM-OFF group). The primary endpoint was the time to the clinician's evaluation of clinically relevant arrhythmias (types 1, 2, and 4 of the ISSUE classification). Results: The primary endpoint of arrhythmia evaluation was reached in 38 patients (28.6%) of the RM-ON group after a median time of 46 days (interquartile range, 13-106) and in 22 patients (20.4%) of the RM-OFF group after 92 days (25-368). The PS-matched adjusted ratio of rates of arrhythmia evaluation was 2.53 (95% confidence interval, 1.32-4.86) in the RM-ON vs. RM-OFF group (p = 0.005). Conclusion: In our PS-matched comparison with a historical cohort, RM of ILR patients with unexplained syncope was associated with a 2.5-fold higher chance of evaluations of clinically relevant arrhythmias as compared with biannual in-office follow-up visits.

Insertable cardiac monitor with a long sensing vector: Impact of obesity on sensing quality and safety.

Background: Fat layers in obese patients can impair R-wave detection and diagnostic performance of a subcutaneous insertable cardiac monitor (ICM). We compared safety and ICM sensing quality between obese patients [body mass index (BMI) ≥ 30 kg/m2] and normal-weight controls (BMI <30 kg/m2) in terms of R-wave amplitude and time in noise mode (noise burden) detected by a long-sensing-vector ICM. Materials and methods: Patients from two multicentre, non-randomized clinical registries are included in the present analysis on January 31, 2022 (data freeze), if the follow-up period was at least 90 days after ICM insertion, including daily remote monitoring. The R-wave amplitudes and daily noise burden averaged intraindividually for days 61-90 and days 1-90, respectively, were compared between obese patients (n = 104) and unmatched (n = 268) and a nearest-neighbour propensity score (PS) matched (n = 69) normal-weight controls. Results: The average R-wave amplitude was significantly lower in obese (median 0.46 mV) than in normal-weight unmatched (0.70 mV, P < 0.0001) or PS-matched (0.60 mV, P = 0.003) patients. The median noise burden was 1.0% in obese patients, which was not significantly higher than in unmatched (0.7%; P = 0.056) or PS-matched (0.8%; P = 0.133) controls. The rate of adverse device effects during the first 90 days did not differ significantly between groups. Conclusion: Although increased BMI was associated with reduced signal amplitude, also in obese patients the median R-wave amplitude was >0.3 mV, a value which is generally accepted as the minimum level for adequate R-wave detection. The noise burden and adverse event rates did not differ significantly between obese and normal-weight patients.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04075084 and NCT04198220.

Prevalence of asystole during tilt test-induced vasovagal syncope may depend on test methodology.

This review addresses tilt-testing methodology by searching the literature which reports timing of asystole and loss of consciousness (LOC). Despite the Italian protocol being the most widely adopted, its stipulations are not always followed to the letter of the European Society of Cardiology guidelines. The discrepancies permit reassessment of the incidence of asystole when tilt-down is early, impending syncope, compared with late, established LOC. Asystole is uncommon with early tilt down and diminishes with increasing age. However, if LOC is established as test-end, asystole is more common, and it is age-independent. Thus, the implications are that asystole is commonly under-diagnosed by early tilt-down. The prevalence of asystolic responses observed using the Italian protocol with a rigorous tilt down time is numerically close to that observed during spontaneous attacks by electrocardiogram loop recorder. Recently, tilt-testing has been questioned as to its validity but, in selection of pacemaker therapy in older highly symptomatic vasovagal syncope patients, the occurrence of asystole has been shown to be an effective guide for treatment. The use of head-up tilt test as an indication for cardiac pacing therapy requires pursuing the test until complete LOC. This review offers explanations for the findings and their applicability to practice. A novel interpretation is offered to explain why pacing induced earlier may combat vasodepression by raising the heart rate when sufficient blood remains in the heart.

Temporal association between drops in thoracic impedance and malignant ventricular arrhythmia: A longitudinal analysis of remote monitoring trends.

INTRODUCTION: Thoracic impedance (TI) drops measured by implantable cardioverter-defibrillators (ICDs) have been reported to correlate with ventricular tachycardia/fibrillation (VT/VF). The aim of our study was to assess the temporal association of decreasing TI trends with VT/VF episodes through a longitudinal analysis of daily remote monitoring data from ICDs and cardiac resynchronization therapy defibrillators (CRT-Ds). METHODS AND RESULTS: Retrospective data from 2384 patients were randomized 1:1 into a derivation or validation cohort. The TI decrease rate was defined as the percentage of rolling weeks with a continuously decreasing TI trend. The derivation cohort was used to determine a TI decrease rate threshold for a ≥99% specificity of arrhythmia prediction. The associated risk of VT/VF episodes was estimated in the validation cohort by dividing the available follow-up into 60-day assessment intervals. Analyses were performed separately for 1354 ICD and 1030 CRT-D patients. During a median follow-up of 2.0 years, 727 patients (30.4%) experienced 3298 confirmed VT/VF episodes. In the ICD group, a TI decrease rate of >60% was associated with a higher risk of VT/VF episode in a 60-day assessment interval (stratified hazard ratio, 1.42; 95% confidence interval (CI), 1.05-1.92; p = .023). The TI decrease preceded (40.8%) or followed (59.2%) the VT/VF episodes. In the CRT-D group, no association between TI decrease and VT/VF episodes was observed (p = .84). CONCLUSION: In our longitudinal analysis, TI decrease was associated with VT/VF episodes only in ICD patients. Preventive interventions may be difficult since episodes can occur before or after TI decrease.

A novel and practical method to add video monitoring to tilt table testing.

AIMS: We describe a novel, practical, and inexpensive method to add video recording during tilt table testing (TTT): Open-Access-Video-TTT. METHODS AND RESULTS: The Open-Access-Video-TTT set-up uses a personal computer (PC) to capture screen video data from a non-invasive-beat-to-beat (NIBTB) haemodynamic blood pressure (BP) device, combined with video recording of a patient, using Open Broadcaster Software (OBS®). The new Open-Access-Video-TTT set up was tested with both the Finometer (model Finapres Nova®, Medical Systems, the Netherlands) and the Task Force® Touch Cardio monitor (CNSystems, Austria). For this, the Finapres Nova® was enabled in 'remote' mode and Real Video Network Computing (RealVNC®) was installed on the PC/laptop. The Task Force® has a DisplayPort (DP) port, for which a DP/ high-definition multimedia interface (HDMI) cable and a video capture card is used to merge the signals to the PC/laptop. With this method the combined images are stored as a new video signal. TTT can be performed with any routine protocol. CONCLUSIONS: Open Access-Video-TTT worked well for both the Finapres NOVA® and the Task Force Monitor ®. This novel method can be used easily by all physicians who wish to add video recording during TTT who do not have access to an electroencephalogram machine.

Implantable cardioverter defibrillator lead performance: A systematic review and individual patient data Meta-analysis.

BACKGROUND: Reliable post-approval surveillance of implantable cardioverter-defibrillator (ICD) lead performance remains a challenge. In the past, two ICD leads were recalled due to a high frequency of failures. In this meta-analysis, we sought to provide a combined estimate of failure-free rate for ICD leads by reconstructing individual patient data from published Kaplan-Meier (KM) curves and to investigate whether estimates could be influenced by the characteristics of the study. METHODS: Observational studies assessing failure-free estimates of transvenous ICD leads with KM method, were identified through a systematic search up to November 2021. RESULTS: Forty-four studies were eligible that included 41,870 (63.1%) non-recalled leads and 24,493 (36.9%) recalled leads. The 8-year cumulative failure-free rate was 94.1% (CI, 93.6% - 94.6%) for contemporary non-recalled leads and 81.2% (80.3% - 82.0%) for recalled leads (hazard ratio [HR], 3.15 [2.85-3.47], p < 0.001). Failure-free rate was lower in single-center studies in both the non-recalled (HR, 0.28 [0.15-0.51], p < 0.001) and recalled (HR, 0.54 [0.33-0.88], p = 0.014) group compared with multicenter studies. Similarly, estimates were significantly lower in small (i.e. extracted KM curve with <312 leads) versus large studies (HR non-recalled group, 0.54 [CI, 0.33-0.89], p = 0.015; HR recalled group, 0.62 [CI, 0.43-0.89], p = 0.009). CONCLUSIONS: In this meta-analysis including >66,000 leads, we provide pooled survival curves that may play a role in generating evidence-based standards for assessing clinically acceptable failure rates for ICD leads. Lead performance was underestimated with single-center and small-sized studies; multicenter studies remain the main tool to reliably conduct post-market surveillance of ICD leads.

Ventricular Arrhythmias and Implantable Cardioverter-Defibrillator Therapy in Women: A Propensity Score-Matched Analysis.

BACKGROUND: Causes of sex differences in incidence of sustained ventricular arrhythmias (SVAs) are poorly understood. OBJECTIVES: This study aims to investigate sex-specific risk of SVAs and device therapies by balancing sex groups in relation to several baseline characteristics with the propensity score (PS). METHODS: We used a large remote monitoring dataset from implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds). Study endpoints were time to the first appropriate SVA, time to the first device therapy for SVA, and time to the first ICD shock. Results were compared between females and a PS-matched male subgroup. RESULTS: In a cohort of 2,532 patients with an ICD or CRT-D (median age, 70 years), 488 patients (19.3%) were women. After selecting 488 men PS-matched for 19 variables relative to baseline demographics, implant indications, principal comorbidities, and concomitant therapy, yet the SVA rate at the 2.1-year median follow-up was significantly lower in women than in man (adjusted HR: 0.65; 95% CI: 0.51-0.81; P < 0.001). Women also showed a reduced risk of any device therapy (HR: 0.59; 95% CI: 0.45-0.76; P < 0.001) and shocks (HR: 0.66; 95% CI: 0.47-0.94; P = 0.021). Differences in sex-specific SVA risk profile were not confirmed in CRT-D patients (HR: 0.78; 95% CI: 0.55-1.09; P = 0.14) nor in those with an ejection fraction <30% (HR: 0.80; 95% CI: 0.52-1.23; P = 0.31). CONCLUSIONS: After matching demographics, indications, principal comorbidities, and concomitant therapy, women still exhibited a lower SVA risk profile than men, except in the subgroups of CRT-D or/and ejection fraction <30%.

Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial.

BACKGROUND: Optimal timing for catheter ablation of ventricular tachycardia is an important unresolved issue. There are no randomized trials evaluating the benefit of ablation after the first implantable cardioverter defibrillator (ICD) shock. METHODS: We conducted a 2-phase, prospective, multicenter, randomized clinical trial. Patients with ischemic or nonischemic dilated cardiomyopathy and primary or secondary prevention indication for ICD were enrolled in an initial observational phase until first appropriate shock (phase A). After reconsenting, patients were randomly assigned 1:1 in phase B to immediate ablation (within 2 months from shock delivery) or continuation of standard therapy. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. Amiodarone intake was not allowed except for documented atrial tachyarrhythmias. On July 23, 2021, phase B of the trial was interrupted as a result of the first interim analysis on the basis of the Bayesian adaptive design. RESULTS: Of the 517 patients enrolled in phase A, 154 (30%) had ventricular tachycardia, 56 (11%) received an appropriate shock over a median follow-up of 2.4 years (interquartile range, 1.4-4.4), and 47 of 56 (84%) agreed to participate in phase B. After 24.2 (8.5-24.4) months, the primary end point occurred in 1 of 23 (4%) patients in the ablation group and 10 of 24 (42%) patients in the control group (hazard ratio, 0.11 [95% CI, 0.01-0.85]; P=0.034). The results met the prespecified termination criterion of >99% Bayesian posterior probability of superiority of treatment over standard therapy. No deaths were observed in the ablation group versus 8 deaths (33%) in the control group (P=0.004); there was 1 worsening heart failure hospitalization in the ablation group (4%) versus 4 in the control group (17%; P=0.159). ICD shocks were less frequent in the ablation group (9%) than in the control group (42%; P=0.039). CONCLUSIONS: Ventricular tachycardia ablation after first appropriate shock was associated with a reduced risk of the combined death or worsening heart failure hospitalization end point, lower mortality, and fewer ICD shocks. These findings provide support for considering ventricular tachycardia ablation after the first ICD shock. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01547208.

One-year mortality after implantable defibrillator implantation: do risk stratification models help improving clinical practice?

PURPOSE: The purpose of this study was to assess the available mortality risk stratification models for implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) patients. METHODS: We conducted a review of mortality risk stratification models and tested their ability to improve prediction of 1-year survival after implant in a database of patients who received a remotely controlled ICD/CRT-D device during routine care and included in the independent Home Monitoring Expert Alliance registry. RESULTS: We identified ten predicting models published in peer-reviewed journals between 2000 and 2021 (Parkash, PACE, MADIT, aCCI, CHA2DS2-VASc quartiles, CIDS, FADES, Sjoblom, AAACC, and MADIT-ICD non-arrhythmic mortality score) that could be tested in our database as based on common demographic, clinical, echocardiographic, electrocardiographic, and laboratory variables. Our cohort included 1,911 patients with left ventricular dysfunction (median age 71, 18.3% female) from sites not using any risk stratification score for systematic patient screening. Patients received an ICD (53.8%) or CRT-D (46.2%) between 2011 and 2017, after standard physician evaluation. There were 56 deaths within 1-year post-implant, with an all-cause mortality rate of 2.9% (95% confidence interval [CI], 2.3-3.8%). Four predicting models (Parkash, MADIT, AAACC, and MADIT-ICD non-arrhythmic mortality score) were significantly associated with increased risk of 1-year mortality with hazard ratios ranging from 3.75 (CI, 1.31-10.7) to 6.53 (CI 1.52-28.0, p ≤ 0.014 for all four). Positive predictive values of 1-year mortality were below 25% for all models. CONCLUSION: In our analysis, the models we tested conferred modest incremental predicting power to ordinary screening methods.

Combining home monitoring temporal trends from implanted defibrillators and baseline patient risk profile to predict heart failure hospitalizations: results from the SELENE HF study.

AIMS: We developed and validated an algorithm for prediction of heart failure (HF) hospitalizations using remote monitoring (RM) data transmitted by implanted defibrillators. METHODS AND RESULTS: The SELENE HF study enrolled 918 patients (median age 69 years, 81% men, median ejection fraction 30%) with cardiac resynchronization therapy (44%), dual-chamber (38%), or single-chamber defibrillators with atrial diagnostics (18%). To develop a predictive algorithm, temporal trends of diurnal and nocturnal heart rates, ventricular extrasystoles, atrial tachyarrhythmia burden, heart rate variability, physical activity, and thoracic impedance obtained by daily automatic RM were combined with a baseline risk-stratifier (Seattle HF Model) into one index. The primary endpoint was the first post-implant adjudicated HF hospitalization. After a median follow-up of 22.5 months since enrolment, patients were randomly allocated to the algorithm derivation group (n = 457; 31 endpoints) or algorithm validation group (n = 461; 29 endpoints). In the derivation group, the index showed a C-statistics of 0.89 [95% confidence interval (CI): 0.83-0.95] with 2.73 odds ratio (CI 1.98-3.78) for first HF hospitalization per unitary increase of index value (P < 0.001). In the validation group, sensitivity of predicting primary endpoint was 65.5% (CI 45.7-82.1%), median alerting time 42 days (interquartile range 21-89), and false (or unexplained) alert rate 0.69 (CI 0.64-0.74) [or 0.63 (CI 0.58-0.68)] per patient-year. Without the baseline risk-stratifier, the sensitivity remained 65.5% and the false/unexplained alert rates increased by ≈10% to 0.76/0.71 per patient-year. CONCLUSION: With the developed algorithm, two-thirds of first post-implant HF hospitalizations could be predicted timely with only 0.7 false alerts per patient-year.

Cardiac resynchronization therapy defibrillators in patients with permanent atrial fibrillation.

AIMS: There are conflicting data on the benefit of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with permanent atrial fibrillation (AF). We aimed to compare patient outcomes according to the presence or absence of permanent AF at device implantation. METHODS AND RESULTS: We retrospectively analysed remote monitoring data from 1141 CRT defibrillators. Propensity score with inverse-probability weighting method was used to balance AF and sinus rhythm (SR) groups. Analysis endpoints included total mortality, appropriate defibrillation shocks, and CRT percentage. There were 229 patients (20.1%) in the AF group and 912 patients (79.9%) in the SR group. Compared with SR patients, AF patients were older (median age, 77 vs. 72 years, P < 0.001), more frequently male (82.5% vs. 75.5%, P = 0.02), and had higher heart rate (75.7 vs. 71.0 b.p.m., P < 0.001). Of the 229 AF patients, 162 (70.7%) received suboptimal CRT (<98%) and 67 (29.3%) had adequate CRT (≥98%). During a median follow-up of 24 months, total mortality did not differ between AF and SR groups (propensity-score-weighted hazard ratio, HR 1.32 [95% confidence interval, 0.82-2.15], P = 0.25). The risk of appropriate shocks was significantly higher in the AF group with <98% CRT than in the SR group (weighted-HR, 1.99 [1.21-3.26], P = 0.006) and was similar in the AF group with ≥98% CRT versus the SR group (1.29 [0.66-2.53], P = 0.45). During follow-up, sinus rhythm was recovered in 23 patients in the AF group (10%) after a median time of 106 (42-256) days. The rate of sinus rhythm recovery in the AF group was 4.5 (95% CI, 2.8-6.7) per 100 patient-years; the rate of permanent AF occurrence in the SR group was 2.5 (95% CI, 1.9-3.3) per 100 patient-years. CONCLUSIONS: Although mortality was similar across patient groups, patients with permanent AF and suboptimal CRT had twofold higher risk of appropriate shocks than SR patients or AF patients with CRT ≥ 98%.

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

INTRODUCTION: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Heart rate distribution in paced and non-paced patients with severe recurrent reflex syncope and tilt-induced asystole: Findings from the BIOSync CLS study.

BACKGROUND: Undiagnosed sinus or atrioventricular node dysfunction may bias estimation of the real efficacy of cardiac pacing in preventing vasovagal reflex syncope. We assessed this hypothesis in the BIOSync CLS trial which showed that dual-chamber pacing with closed loop stimulation (CLS) remarkably reduced recurrences of syncope. METHODS AND RESULTS: In the study patients aged 40 years or older with ≥2 episodes of loss of consciousness in the last year and an asystolic response to Tilt-Table test were randomized to pacing ON (DDD-CLS mode) or pacing OFF (ODO mode). We utilized the available pacemaker diagnostic data in a total of 103 patients (52 pacing ON, 51 pacing OFF) to generate cumulative distribution charts for heart rate (HR) and percentage of pacing. At 12 months, we did not find evidence of suspected sinus or atrioventricular node dysfunction. Beats were similarly distributed between groups (p = 0.96), with an average HR of 76 ± 8 bpm (pacing ON) versus 77 ± 7 bpm (pacing OFF). In the active group, the median percentage of atrial and ventricular pacing was 47% and 0%, respectively. Intolerance to high pacing rates was reported in only one patient (1.6%) and was easily resolved by reprogramming the maximum CLS pacing rate. CONCLUSIONS: We did not find evidence of suspected sinus or atrioventricular node dysfunction in the BIOSync CLS patients. The benefit of pacing should be ascribed to pacing prevention of pure vasovagal episodes. CLS algorithm modulated pacing rates over a wide frequency range, consistently competing with sinus node.

Cardiac Pacing in Cardioinhibitory Reflex Syncope: Clinical Use of Closed-loop Stimulation.

Cardiac pacing has been studied extensively in patients with reflex syncope over the past two decades. The heterogeneity of the forms and clinical manifestations of reflex syncope explain the controversial results of older randomised clinical trials. New evidence from recent trials has changed medical practice, now leading to clear indications for pacing in patients with asystolic syncope documented during carotid sinus massage, implantable cardiac monitoring or tilt testing. Given that recent trials in reflex syncope have been performed using the closed-loop stimulation algorithm, the authors will briefly discuss this pacing mode, review hypotheses about the mechanisms underlying its activation during syncope and provide practical instructions for programming and troubleshooting.