A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Differential apicomplexan presence predicts thermal stress mortality in the Mediterranean coral Paramuricea clavata.

Paramuricea clavata is an ecosystem architect of the Mediterranean temperate reefs that is currently threatened by episodic mass mortality events related to global warming. The microbiome may play an active role in the thermal stress susceptibility of corals, potentially holding the answer as to why corals show differential sensitivity to heat stress. To investigate this, the prokaryotic and eukaryotic microbiome of P. clavata collected from around the Mediterranean was characterised before experimental heat stress to determine if its microbial composition influences the thermal response of the holobiont. We found that members of P. clavata's microeukaryotic community were significantly correlated with thermal stress sensitivity. Syndiniales from the Dino-Group I Clade 1 were significantly enriched in thermally resistant corals, while the apicomplexan corallicolids were significantly enriched in thermally susceptible corals. We hypothesise that P. clavata mortality following heat stress may be caused by a shift from apparent commensalism to parasitism in the corallicolid-coral host relationship driven by the added stress. Our results show the potential importance of corallicolids and the rest of the microeukaryotic community of corals to understanding thermal stress response in corals and provide a useful tool to guide conservation efforts and future research into coral-associated microeukaryotes.

Baseline left atrial low-voltage area predicts recurrence after pulmonary vein isolation: WAVE-MAP AF results.

AIMS: Electro-anatomical mapping may be critical to identify atrial fibrillation (AF) subjects who require substrate modification beyond pulmonary vein isolation (PVI). The objective was to determine correlations between pre-ablation mapping characteristics and 12-month outcomes after a single PVI-only catheter ablation of AF. METHODS AND RESULTS: This study enrolled paroxysmal AF (PAF), early persistent AF (PsAF; 7 days-3 months), and non-early PsAF (>3-12 months) subjects undergoing de novo PVI-only radiofrequency catheter ablation. Sinus rhythm (SR) and AF voltage maps were created with the Advisor HD Grid™ Mapping Catheter, Sensor Enabled™ for each subject, and the presence of low-voltage area (LVA) (low-voltage cutoffs: 0.1-1.5 mV) was investigated. Follow-up visits were at 3, 6, and 12 months, with a 24-h Holter monitor at 12 months. A Cox proportional hazards model identified associations between mapping data and 12-month recurrence after a single PVI procedure. The study enrolled 300 subjects (113 PAF, 86 early PsAF, and 101 non-early PsAF) at 18 centres. At 12 months, 75.5% of subjects were free from AF/atrial flutter (AFL)/atrial tachycardia (AT) recurrence. Univariate analysis found that arrhythmia recurrence did not correlate with AF diagnosis, but LVA was significantly correlated. Low-voltage area (<0.5 mV) >28% of the left atrium in SR [hazard ratio (HR): 4.82, 95% confidence interval (CI): 2.08-11.18; P = 0.0003] and >72% in AF (HR: 5.66, 95% CI: 2.34-13.69; P = 0.0001) was associated with a higher risk of AF/AFL/AT recurrence at 12 months. CONCLUSION: Larger extension of LVA was associated with an increased risk of arrhythmia recurrence. These subjects may benefit from substrate modification beyond PVI.

Marine heatwaves drive recurrent mass mortalities in the Mediterranean Sea.

Climate change is causing an increase in the frequency and intensity of marine heatwaves (MHWs) and mass mortality events (MMEs) of marine organisms are one of their main ecological impacts. Here, we show that during the 2015-2019 period, the Mediterranean Sea has experienced exceptional thermal conditions resulting in the onset of five consecutive years of widespread MMEs across the basin. These MMEs affected thousands of kilometers of coastline from the surface to 45 m, across a range of marine habitats and taxa (50 taxa across 8 phyla). Significant relationships were found between the incidence of MMEs and the heat exposure associated with MHWs observed both at the surface and across depths. Our findings reveal that the Mediterranean Sea is experiencing an acceleration of the ecological impacts of MHWs which poses an unprecedented threat to its ecosystems' health and functioning. Overall, we show that increasing the resolution of empirical observation is critical to enhancing our ability to more effectively understand and manage the consequences of climate change.

Climate change transforms the functional identity of Mediterranean coralligenous assemblages.

Quantifying changes in functional community structure driven by disturbance is critical to anticipate potential shifts in ecosystem functioning. However, how marine heatwaves (MHWs) affect the functional structure of temperate coral-dominated communities is poorly understood. Here, we used five long-term (> 10 years) records of Mediterranean coralligenous assemblages in a multi-taxa, trait-based analysis to investigate MHW-driven changes in functional structure. We show that, despite stability in functional richness (i.e. the range of species functional traits), MHW-impacted assemblages experienced long-term directional changes in functional identity (i.e. their dominant trait values). Declining traits included large sizes, long lifespans, arborescent morphologies, filter-feeding strategies or calcified skeletons. These traits, which were mostly supported by few sensitive and irreplaceable species from a single functional group (habitat-forming octocorals), disproportionally influence certain ecosystem functions (e.g. 3D-habitat provision). Hence, MHWs are leading to assemblages that are deficient in key functional traits, with likely consequences for the ecosystem functioning.

Wearable cardioverter-defibrillator in patients with a transient risk of sudden cardiac death: the WEARIT-France cohort study.

AIMS: We aimed to provide contemporary real-world data on wearable cardioverter-defibrillator (WCD) use, not only in terms of effectiveness and safety but also compliance and acceptability. METHODS AND RESULTS: Across 88 French centres, the WEARIT-France study enrolled retrospectively patients who used the WCD between May 2014 and December 2016, and prospectively all patients equipped for WCD therapy between January 2017 and March 2018. All patients received systematic education session through a standardized programme across France at the time of initiation of WCD therapy and were systematically enrolled in the LifeVest Network remote services. Overall, 1157 patients were included (mean age 60 ± 12 years, 16% women; 46% prospectively): 82.1% with ischaemic cardiomyopathy, 10.3% after implantable cardioverter-defibrillator explant, and 7.6% before heart transplantation. Median WCD usage period was 62 (37-97) days. Median daily wear time of WCD was 23.4 (22.2-23.8) h. In multivariate analysis, younger age was associated with lower compliance [adjusted odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95-0.99, P < 0.01]. A total of 18 participants (1.6%) received at least one appropriate shock, giving an incidence of appropriate therapy of 7.2 per 100 patient-years. Patient-response button allowed the shock to be aborted in 35.7% of well-tolerated sustained ventricular arrhythmias and in 95.4% of inappropriate ventricular arrhythmia detection, finally resulting in an inappropriate therapy in eight patients (0.7%). CONCLUSION: Our real-life findings reinforce previous studies on the efficacy and safety of the WCD in the setting of transient high-risk group in selected patients. Moreover, they emphasize the fact that when prescribed appropriately, in concert with adequate patient education and dedicated follow-up using specific remote monitoring system, compliance with WCD is high and the device well-tolerated by the patient.

Prophylactic implantable cardioverter-defibrillator in the very elderly.

AIMS: Current guidelines do not propose any age cut-off for the primary prevention implantable cardioverter-defibrillator (ICD). However, the risk/benefit balance in the very elderly population has not been well studied. METHODS AND RESULTS: In a multicentre French study assessing patients implanted with an ICD for primary prevention, outcomes among patients aged ≥80 years were compared with <80 years old controls matched for sex and underlying heart disease (ischaemic and dilated cardiomyopathy). A total of 300 ICD recipients were enrolled in this specific analysis, including 150 patients ≥80 years (mean age 81.9 ± 2.0 years; 86.7% males) and 150 controls (mean age 61.8 ± 10.8 years). Among older patients, 92 (75.6%) had no more than one associated comorbidity. Most subjects in the elderly group got an ICD as part of a cardiac resynchronization therapy procedure (74% vs. 46%, P < 0.0001). After a mean follow-up of 3.0 ± 2 years, 53 patients (35%) in the elderly group died, including 38.2% from non cardiovascular causes of death. Similar proportion of patients received ≥1 appropriate therapy (19.4% vs. 21.6%; P = 0.65) in the elderly group and controls, respectively. There was a trend towards more early perioperative events (P = 0.10) in the elderly, with no significant increase in late complications (P = 0.73). CONCLUSION: Primary prevention ICD recipients ≥80 years in the real world had relatively low associated comorbidity. Rates of appropriate therapies and device-related complications were similar, compared with younger subjects. Nevertheless, the inherent limitations in interpreting observational data on this particular competing risk situation call for randomized controlled trials to provide definitive answers. Meanwhile, a careful multidisciplinary evaluation is needed to guide patient selection for ICD implantation in the elderly population.

Implantable cardioverter-defibrillator therapy among patients with non-ischaemic vs. ischaemic cardiomyopathy for primary prevention of sudden cardiac death.

Aim: The magnitude of benefit related to implantable cardioverter defibrillator (ICD) therapy for primary prevention of sudden cardiac death (SCD) in non-ischaemic cardiomyopathy (NICM) and ischaemic cardiomyopathy (ICM) has not been evaluated extensively in clinical practice. Methods and results: Of the 5539 consecutive patients enrolled in the multicentre Défibrillateur Automatique Implantable-Prévention Primaire (DAI-PP) study (2002-12), 5485 patients (with information on underlying heart disease) were included in the present analysis: 2181 (39.8%) had NICM and 3304 (60.2%) had ICM. ICM patients were older (63.7 ±10.3 vs. 60.6 ± 12.2 years, P < 0.0001), with a higher ejection fraction [27% (25-30) vs. 25% (20-30), P < 0.0001], narrower QRS (37.3% vs. 21.4% with QRS <120, P < 0.0001), and higher prevalence of sinus rhythm (77.3% vs. 74.0%, P = 0.009). During a mean follow-up of 3.1 ± 2.2 years, 814 patients died, giving a mortality incidence of 48.6 per 1000 person-years [95% confidence interval (CI) 45.2-51.9], higher among ICM patients (52.3, 95% CI 47.8-56.7) than in NICM patients (42.4, 95% CI 37.3-47.6; P = 0.008) (adjusted hazard ratio 1.31, 95% CI 1.06-1.61, P = 0.01). The increase in mortality among ICM patients was mainly due to non-cardiovascular mortality (P = 0.0002), whereas incidences of cardiovascular mortality (including ICD-unresponsive SCD) were similar in the two groups. Incidences of appropriate ICD interventions (anti-tachycardia pacing, shocks) were similar, but inappropriate therapies were more frequent in NICM (7.94 vs. 5.96%; P = 0.005). Conclusion: NICM and ICM patients had a same rate of ICD therapy for primary prevention of SCD in everyday practice. But, ICM patients more often died of a non- cardiovascular cause of death. Clinical Trial Registration: NCT 01992458.

Long-term electrical performance of Attain Performa quadripolar left ventricular leads with all steroid-eluting electrodes: Results from a large worldwide clinical trial.

BACKGROUND: Steroid-eluting (SE) electrodes suppress local inflammation and lower pacing capture thresholds (PCT); however, their effectiveness on quadripolar left ventricular (LV) leads in the cardiac vein is not fully studied. We evaluated the effectiveness of SE on all four LV pacing electrodes in human subjects enrolled in the Medtronic Attain® Performa™ quadripolar LV lead study. METHODS: A total of 1,097 subjects were included in this evaluation. At each follow-up visit (1, 3, 6, and 12 months), LV PCT and pacing impedance were measured using either manual or automated testing methods. Summary statistics for PCT and impedance values were obtained for implant and each scheduled follow-up visit for all lead models. RESULTS: Average extended bipolar (LV electrode to right ventricular Coil) PCTs for the four LV SE pacing electrodes (LV1, LV2, LV3, and LV4) on the three shapes of the quadripolar LV leads were 1.06 ± 0.97 V, 1.38 ± 1.26 V, 1.51 ± 1.33 V, and 2.25 ± 1.63 V, respectively, at 0.5-ms pulse width. PCTs remained low and stable throughout the 12-month follow-up period. CONCLUSION: This clinical trial demonstrated that SE on all LV pacing electrodes is associated with low and stable PCTs for all quadripolar LV lead electrodes, resulting in multiple viable vectors for LV pacing. The large number of available vectors facilitates basal pacing, avoidance of PNS, and potentially prolongs generator longevity due to lower PCTs.

Prognostic implications of left ventricular global longitudinal strain in heart failure patients with narrow QRS complex treated with cardiac resynchronization therapy: a subanalysis of the randomized EchoCRT trial.

AIM: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic function and correlates inversely with the extent of LV myocardial scar and fibrosis. The present subanalysis of the Echocardiography Guided CRT trial investigated the prognostic value of LV GLS in patients with narrow QRS complex. METHODS AND RESULTS: Left ventricular (LV) global longitudinal strain (GLS) was measured on the apical 2-, 4- and 3-chamber views using speckle tracking analysis. Measurement of baseline LV GLS was feasible in 755 patients (374 with cardiac resynchronization therapy (CRT)-ON and 381 with CRT-OFF). The median value of LV GLS in the overall population was 7.9%, interquartile range 6.2-10.1%. After a mean follow-up period of 19.4 months, 95 patients in the CRT-OFF group and 111 in the CRT-ON group reached the combined primary endpoint of all-cause mortality and heart failure hospitalization. Each 1% absolute unit decrease in LV GLS was independently associated with 11% increase in the risk to reach the primary endpoint (Hazard ratio 1.11; 95% confidence interval 95% 1.04-1.17, P < 0.001), after adjusting for ischaemic cardiomyopathy and randomization treatment among other clinically relevant variables. When categorizing patients according to quartiles of LV GLS, the primary endpoint occurred more frequently in patients in the lowest quartile (<6.2%) treated with CRT-ON vs. CRT-OFF (45.6% vs. 28.7%, P = 0.009) whereas, no differences were observed in patients with LV GLS ≥6.2% treated with CRT-OFF vs. CRT-ON (23.7% vs. 24.5%, respectively; P = 0.62). CONCLUSION: Low LV GLS is associated with poor outcome in heart failure patients with QRS width <130 ms, independent of randomization to CRT or not. Importantly, in the group of patients with the lowest LV GLS quartile, CRT may have a detrimental effect on clinical outcomes.

Temporal Trends Over a Decade of Defibrillator Therapy for Primary Prevention in Community Practice.

BACKGROUND: Technology and clinical practice surrounding the use of the primary prevention implantable cardioverter defibrillator (ICD) are in a state of constant evolution. The purpose of the study was to test the hypothesis of significant temporal trends in characteristics and outcomes over a decade of ICD therapy. METHODS: Between 2002 and 2012, 5,539 consecutive patients (age 62.5 ± 11 years, 84.9% male), with ischemic or nonischemic cardiomyopathy, implanted with a primary prevention ICD from 12 centers in France were included. Information on characteristics and outcomes (including causes of death) were evaluated over a median follow-up of 994 days (466-1,667). RESULTS: In addition to a shift in the type of devices implanted with a significant increase in cardiac resynchronization therapy-defibrillator (CRT-D) over time (43.6 to 60.4%, P = 0.0001), an increase in mean age (from 61.5 ± 11.6 to 63.2 ± 10.9 years, P = 0.0016), proportion of nonischemic cardiomyopathy (31.0 to 44.7%, P <0.0001) and women recipients (11.4 to 15.8%, P = 0.004) was observed. A total of 1,181 patients (22.3%) received ≥1 appropriate therapy, inappropriate therapies occurred in 355 patients (6.7%) and 826 patients (15.2%) died, mainly from cardiovascular causes (49.3%). Annual mortality incidence (5.4% to 4.3%, P = 0.05), as well as incidence of appropriate therapy (10.4% to 7.1%, P = 0.0004), significantly decreased over the decade. By contrast, incidence of ICD-related late (>30 days after implant) complications significantly increased (4.6 to 7.6%, P = 0.003). CONCLUSION: Our findings demonstrate significant changes in patterns of use and outcomes in primary prevention ICD over the last decade with reductions in mortality and appropriate therapies, counterbalanced by an increase in complications.

Dual- vs. single-chamber defibrillators for primary prevention of sudden cardiac death: long-term follow-up of the Défibrillateur Automatique Implantable-Prévention Primaire registry.

AIMS: Implantable cardioverter defibrillators (ICDs) are an effective primary prevention of sudden cardiac death. We examined whether dual-chamber (DC) ICDs confer a greater benefit than single-chamber (SC) ICDs, and compared the long-term outcomes of recipients of each type of device implanted for primary prevention. METHODS AND RESULTS: Between 2002 and 2012, the DAI-PP registry consecutively enrolled 1258 SC- and 1280 DC-ICD recipients at 12 French medical centres. The devices were interrogated at 4- to 6-month intervals during outpatient visits, with a focus on the therapies delivered. The study endpoints were incidence of appropriate therapies, ICD-related morbidity, and deaths from all and from specific causes. The mean age of the SC- and DC-ICD recipients was 59 ± 12 and 62 ± 11 years, respectively (P< 0.0001). The distribution of genders, New York Heart Association functional classes and glomerular filtration rates, and the rates of ischaemic vs. dilated cardiomyopathies and of defibrillation tests at implant, were similar in both study groups. The rates of periprocedural complications were 12.1% in the DC- vs. 8.8% in the SC-ICD groups (P= 0.008). Over a mean follow-up of 3.1 ± 2.2 years, pulse generators were replaced in 21.9% of the DC- vs. 13.6% of the SC-ICD group (P< 0.0001). The proportions of patients treated with ≥1 appropriate therapies (24.7 vs. 23.8%) and ≥1 inappropriate shocks (8.4 vs. 7.8%), and all-cause mortality (12.4 vs. 13.2%) were similar in both groups. CONCLUSION: In this large registry of ICD implanted for primary prevention, DC-ICDs were associated with higher rates of peri-implant complications and generator replacements, whereas the survival and rates of inappropriate shocks were similar in both groups. CLINICAL TRIAL NUMBER: NCT#01992458.

Association of persistent or worsened echocardiographic dyssynchrony with unfavourable clinical outcomes in heart failure patients with narrow QRS width: a subgroup analysis of the EchoCRT trial.

AIMS: EchoCRT was a randomized trial of cardiac resynchronization therapy (CRT) in severely symptomatic heart failure (HF) patients with narrow QRS width <130 ms, ejection fraction ≤35%, and echocardiographic dyssynchrony. All received CRT implants which were then randomized to CRT-On or CRT-Off. While the trial showed no benefit of CRT to these patients, the aim of this subgroup analysis was to test the hypothesis that persistent or worsening dyssynchrony is associated with unfavourable clinical outcomes. METHODS AND RESULTS: We studied 614 EchoCRT patients with baseline and 6-month echocardiograms. Baseline dyssynchrony required for study inclusion was either tissue Doppler imaging longitudinal velocity delay ≥80 ms or speckle-tracking radial strain delay ≥130 ms. Persistent dyssynchrony at 6 months was observed similarly in both groups (77% in CRT-On; 76% in CRT-Off). Persistent dyssynchrony was associated with a significantly higher primary end point of death or HF hospitalization (HR = 1.54, 95% CI 1.03-2.30, P = 0.03), and in particular secondary endpoint of HF hospitalization (HR = 1.66, 95% CI 1.07-2.57, P = 0.02). HF hospitalizations were also associated with worsening longitudinal dyssynchrony (HR = 1.45, 95% CI 1.02-2.05, P = 0.037), and worsening radial dyssynchrony (HR = 1.81, 95% CI 1.16-2.81, P = 0.008). Associations of persistent or worsening dyssynchrony with outcomes were similar in CRT-Off and CRT-On groups. CONCLUSIONS: Persistent or worsening echocardiographic dyssynchrony in HF patients with narrow QRS width was a marker for unfavourable clinical outcomes unaffected by CRT. In particular, echocardiographic dyssynchrony on follow-up was strongly associated with HF hospitalizations and appears to be a prognostic marker of disease severity.

Cardiac-resynchronization therapy in heart failure with a narrow QRS complex.

BACKGROUND: Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients. METHODS: We conducted a randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 msec, and echocardiographic evidence of left ventricular dyssynchrony. All patients underwent device implantation and were randomly assigned to have CRT capability turned on or off. The primary efficacy outcome was the composite of death from any cause or first hospitalization for worsening heart failure. RESULTS: On March 13, 2013, the study was stopped for futility on the recommendation of the data and safety monitoring board. At study closure, the 809 patients who had undergone randomization had been followed for a mean of 19.4 months. The primary outcome occurred in 116 of 404 patients in the CRT group, as compared with 102 of 405 in the control group (28.7% vs. 25.2%; hazard ratio, 1.20; 95% confidence interval [CI], 0.92 to 1.57; P=0.15). There were 45 deaths in the CRT group and 26 in the control group (11.1% vs. 6.4%; hazard ratio, 1.81; 95% CI, 1.11 to 2.93; P=0.02). CONCLUSIONS: In patients with systolic heart failure and a QRS duration of less than 130 msec, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality. (Funded by Biotronik and GE Healthcare; EchoCRT ClinicalTrials.gov number, NCT00683696.).

The effect of QRS duration on cardiac resynchronization therapy in patients with a narrow QRS complex: a subgroup analysis of the EchoCRT trial.

AIMS: In EchoCRT, a randomized trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of <130 ms and echocardiographic evidence of left ventricular dyssynchrony, the primary outcome occurred more frequently in the CRT when compared with the control group. According to current heart failure guidelines, CRT is recommended in patients with a QRS duration of ≥120 ms. However, there is some ambiguity from clinical trial data regarding the benefit of patients with a QRS duration of 120-130 ms. METHODS AND RESULTS: The main EchoCRT trial was prematurely terminated due to futility. For the current subgroup analysis we compared data for CRT-ON vs. -OFF in patients with QRS < 120 (n = 661) and QRS 120-130 ms (n = 139). On uni- and multivariable analyses, no significant interaction was observed between the two groups and randomized treatment for the primary or any of the secondary endpoints. On multivariable analysis, a higher risk for the primary endpoint was observed in patients with a QRS duration of 120-130 ms randomized to CRT-ON vs. CRT-OFF (hazard ratio 2.18, 95% CI 1.02-4.65; P = 0.044). However, no statistically significant interaction, compared with patients with QRS < 120 ms randomized to CRT-ON vs. CRT-OFF, was noted (P-interaction = 0.160). CONCLUSIONS: In this pre-specified subgroup analysis of EchoCRT, no benefit of CRT was evident in patients with a QRS duration of 120-130 ms. These data further question the usefulness of CRT in this patient population.

Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study.

AIMS: The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice. METHODS AND RESULTS: A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P < 0.0001), less often male (P < 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P < 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41-94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56-2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07-2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death. CONCLUSION: When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator.

A review of multisite pacing to achieve cardiac resynchronization therapy.

Non-response to cardiac resynchronization therapy remains a significant problem in up to 30% of patients. Multisite stimulation has emerged as a way of potentially overcoming non-response. This may be achieved by the use of multiple leads placed within the coronary sinus and its tributaries (dual-vein pacing) or more recently by the use of multipolar (quadripolar) left ventricular pacing leads which can deliver pacing stimuli at multiple sites within the same vein. This review covers the role of multisite pacing including the interaction with the underlying pathophysiology, the current and planned studies, and the potential pitfalls of this technology.

State of the art of leadless pacing.

Despite undisputable benefits, conventional pacemaker therapy is associated with specific complications related to the subcutaneous device and the transvenous leads. Recently, two miniaturized leadless pacemakers, Nanostim™ (St. Jude Medical) and Micra™ (Medtronic), which can be completely implanted inside the right ventricle using steerable delivery systems, entered clinical application. The WiCS™-cardiac resynchronisation therapy (CRT) system (wireless cardiac stimulation for CRT, EBR Systems) delivers leadless left ventricular endocardial stimulation for cardiac resynchronization. In addition to obvious cosmetic benefits, leadless pacing systems may have the potential to overcome some complications of conventional pacing. However, acute and long-term complications still remains to be determined, as well as the feasibility of device explantation years after device placement.

Utility of a guiding catheter for conduction system pacing: An early multicenter experience.

Background: Conduction system pacing (CSP), either as His bundle pacing (HBP) or as left bundle branch area pacing (LBBAP), may be superior to right ventricular apical or septal pacing. Objective: The study sought to present acute results for a new guiding catheter (Biotronik Selectra 3D) designed for CSP implantations of a retractable screw-in lead (Biotronik Solia S). Methods: The primary endpoint of the prospective, international nonrandomized BIO|MASTER.Selectra 3D study was freedom from catheter-related serious adverse device effects (SADEs) within 1 week of lead implantation. Results: Of 157 enrolled patients, CSP was achieved in 147 (93.6%) patients. No SADEs occurred within 7 days. LBBAP was achieved in 82 patients (45 as crossover from an HBP attempt) and HBP in 65 (44.2%) patients. In centers considering both HBP and LBBAP, the CSP implantation success approached 99%. Successful CSP implantations lasted on average ∼50 minutes (fluoroscopy ∼6 minutes). Most procedures (87.9%) needed only 1 catheter, even after switch from HBP to LBBAP. The catheter's handling was rated largely positive. In patients without bundle branch block, mean QRS duration increased from 106 ms (intrinsic) to 122 ms (CSP) (P = .001). In patients with bundle branch block, mean QRS duration decreased from 151 ms (intrinsic) to 137 ms (CSP) (P = .004). Conclusion: The Selectra 3D catheter is a valuable tool for HBP and LBBAP implantations of the stylet-supported pacemaker leads. When implanters considered both HBP and LBBAP, the success rate was ∼99%. Flexibility to change between different approaches may be advisable in heterogeneous and challenging areas, such as CSP implantations.

Pre-emptive treatment of heart failure exacerbations in patients managed with the HeartLogic™ algorithm.

AIMS: Heart failure (HF) is a chronic disease affecting 64 million people worldwide and places a severe burden on society because of its mortality, numerous re-hospitalizations and associated costs. HeartLogic™ is an algorithm programmed into implanted devices incorporating several biometric parameters which aims to predict HF episodes. It provides an index which can be monitored remotely, allowing pre-emptive treatment of congestion to prevent acute decompensation. We aim to assess the impact and security of pre-emptive HF management, guided by the HeartLogic™ index. METHODS AND RESULTS: The HeartLogic™ France Cohort Study is an investigator-initiated, prospective, multi-centre, non-randomized study. Three hundred ten patients with a history of HF (left ventricular ejection fraction ≤40%; or at least one episode of clinical HF with elevated NT-proBNP ≥450 ng/L) and implanted with a cardioverter defibrillator enabling HeartLogic™ index calculation will be included across 10 French centres. The HeartLogic™ index will be monitored remotely for 12 months and in the event of a HeartLogic™ index ≥16, the local investigator will contact the patient for assessment and adjust HF treatment as necessary. The primary endpoint is unscheduled hospitalization for HF. Secondary endpoints are all-cause mortality, cardiovascular death, HF-related death, unscheduled hospitalizations for ventricular or atrial arrhythmia and HeartLogic™ index evolution over time. Blood samples will be collected for biobanking, and quality of life will be assessed. Finally, the safety of a HeartLogic™-triggered strategy for initiating or increasing diuretic therapy will be assessed. A blind and independent committee will adjudicate the events. CONCLUSIONS: The HeartLogic™ France Cohort Study will provide robust real-world data in a cohort of HF patients managed with the HeartLogic™ algorithm allowing pre-emptive treatment of heart failure exacerbations.