Search

Background: Cardiac resynchronization therapy (CRT) involves stimulation of both right ventricle (RV) and left ventricle (LV). LV pacing from the sites of delayed electrical activation improves CRT response. The RV-LV conduction is typically measured in intrinsic rhythm. The differences in RV-LV conduction patterns and timing between intrinsic rhythm and during paced RV activation, these differences are not fully understood. Methods: Enrolled patients were implanted with a de novo CRT device and quadripolar LV lead, with lead implant locations at the implanting physician's discretion. QRS duration and conduction delay between the RV lead and each of the four LV electrodes (D1, M2, M3, and P4) were measured during intrinsic conduction and RV pacing. Results: Conduction measurements were collected from 275 patients across 14 international centers (68 ± 13 years of age, 73% male, 45% ischemic, 158 ± 22ms QRS duration). Mean RV-LV conduction time was shorter during intrinsic conduction versus RV pacing by 59.6ms (106.5 ± 36.5versus 166.1 ± 32.1ms, p&nbsp

About one-third of patients receiving cardiac resynchronization therapy (CRT) are not responders, due to either patient selection or technical issues. Left ventricular quadripolar passive fixation leads (QPL) and bipolar active fixation (BAF) leads have been designed to ensure a targeted left ventricular stimulation area, minimizing lead dislodgments and phrenic nerve stimulation (PNS). The aim was to compare real-world safety and efficacy of BAF (Attain Stability, Medtronic Plc.) and QPL (Attain Performa, Medtronic Plc.).We performed a retrospective analysis examining procedural and follow-up data of 261 BAF and 124 QPL (programmed to single-site left ventricular pacing), included in the ClinicalService project from 16 Italian hospitals.At median follow-up of 12 months, no difference in left ventricular pacing threshold was recorded between BAF and QPL (1.3 ± 0.9 V @0.4 ms vs. 1.3 ± 1.0 V @0.4 ms; P = 0.749). Total left ventricular lead dislodgement rate was 1.43/100 patient-years in BAF vs. 2.9/100 patient-years in QPL (P = 0.583). However, no dislodgements occurred among BAF after hospital discharge. Events requiring repeated surgery or permanently turning CRT off occurred in 0.8% of BAF, as compared with 4.0% of QPL (P = 0.025). There was no difference between groups in the echo CRT responders' rate (70% of BAF and 66% of QPL; P = 0.589) or in the annual rate of heart failure hospitalization (P = 0.513).BAF resulted in noninferior clinical outcome and CRT responders' rate in comparison to QPL. Moreover, BAF ensured more precise and stable placement in cardiac veins, with comparable electrical performance and less than 1% patients with unsolved PNS.

Surface electrocardiograms, both resting 12-lead electrocardiographs and ambulatory electrocardiograph monitoring, play an essential role in establishing indications for cardiac implantable electronic devices (pacemakers, cardiac implantable defibrillators, and cardiac resynchronization therapies), and in the evaluation of patients already implanted. Current devices have prolonged memory capabilities (defined as Holter functions) and remote monitoring functions, to evaluate the electrical properties and the automatic detection of arrhythmias. Nonetheless, surface electrocardiography remains the critical tool to detect device malfunction, evaluate programming and function, verify the automatic arrhythmia analysis and the delivered electric therapy, and prevent inappropriate intervention.

Background Atrial tachyarrhythmias (AT/AF) have been associated with an increased risk of mortality, morbidity and ischemic stroke. Up to now, single chamber ICD diagnostics was not able to detect AT/AF, therefore the incidence of new onset AT/AF in patients with single chamber ICD is not known. Objective To evaluate incidence and predictors of AT/AF occurrence in patients with dual-chamber ICD with no pacing indications and no history of AT/AF that strictly mimic single chamber ICD recipient. Methods & results Consecutive dual-chamber ICD patients were prospectively followed by 47 Italian cardiologic centers in an observational research. Clinical and device data were reviewed by expert cardiologists to assess AT/AF occurrence. Multivariate regression analysis evaluated the risk of new-onset AT/AF and its association with patients' baseline characteristics and with CHADS 2 score. 428 (13.4% female, 64years old) patients were followed for a median observation period of 31months. AT/AF episodes occurred in 160 (37.4%) patients when considering at least 5min duration, in 95 (22.2%) for AT/AF ≥6h, in 47 (11.0%) for AT/AF ≥1day, in 29 (6.8%) for AT/AF ≥7days. Patients with CHADS 2 ≥2, who comprised 36% of the whole population, showed higher incidence of AT/AF ≥6h compared with patients with CHADS 2 p =0.011). Conclusions Our observations in a population of dual-chamber ICD patients with no pacing indications and no history of AT/AF, who strictly mimic single–chamber ICD recipients, highlight that AT/AF episodes occurred in the 37.5% of the population and CHADS 2 score is predictive of new-onset AT/AF.

Background Catheter ablation (CA) is recommended for patients with drug refractory symptomatic atrial fibrillation (AF). “One Shot” catheters have been introduced to simplify CA and cryoballoon ablation (CBA) is spreading rapidly. Few real-world data are available on standard clinical practice, mainly from single-center experience. We aimed to evaluate clinical settings, demographics, and acute procedural outcomes in a large cohort of patients treated with CBA. Methods A total of 903 patients (73% male, mean age 59 ± 11) underwent pulmonary vein CBA. Correlations between the patient's inclusion time and clinical characteristics, procedure duration, acute success rate, and intraprocedural complications were evaluated. Results Seventy-seven percent of patients were affected by paroxysmal AF and 23% by persistent AF. Overall, acute success rate was 97.9% and periprocedural complications were observed in 35 (3.9%) patients, 13 (1.4%) of which were classified as major complications. With respect to the patient's inclusion time analysis, an increase in treatment of persistent AF was observed, a significant decrease in CBA times (procedure, ablation, and fluoroscopy: 136.0 ± 46.5 minutes, 28.8 ± 19.6 minutes, and 34.3 ± 15.4 minutes, respectively) was observed, with comparable acute success rate and intraprocedural complications over time. The rate of major complications was extremely low (1.4%); no death, atrioesophageal fistula, stroke, or other major periinterventional or late complications occurred. Conclusion This series represents the largest experience of CBA in the treatment of AF that also describes the adoption curve of this relatively recent technology. CBA showed an excellent safety profile when performed in a large real-world clinical setting, with satisfactory acute success rate and, on average, short procedural times. Clinical Trial Registration clinicaltrials.gov (NCT01007474)

ObjectiveIn implantable cardiac defibrillators (ICDs), long-detection times safely reduce unnecessary and inappropriate therapies. We aimed to evaluate ICD treatment of ventricular arrhythmias in women, compared with men, also taking into account ICD detection.MethodsThe Advance III trial randomised patients implanted with an ICD for primary or secondary prevention in two arms—long and nominal ventricular arrhythmias detection times before therapy delivering (number of intervals needed to detect (NID) 30/40 and 18/24, respectively). The main endpoint of this post hoc analysis was the incidence of ICD therapies evaluated through Kaplan-Meier method and univariate Cox regression models.ResultsOverall, 1902 patients (304 women, 65±11 years) were randomised. Women showed a lower risk of ICD therapy (HR 0.63, 95% CI 0.43 to 0.93, p=0.022); this difference was observed only in the long-detection arm (HR 0.37, p=0.013) and not in the short detection arm (HR 0.82, p=0.414). No significant sex differences were observed concerning inappropriate therapies and mortality rate. Long-detection settings significantly reduced overall ICD therapies and appropriate ICD therapies, both in women (overall HR 0.31, p=0.007; appropriate HR 0.33, p=0.033) and in men (overall HR 0.69, p=0.006; appropriate HR 0.73, p=0.048).ConclusionsIn patients with ICDs, the strategy of setting a long-detection time to treat ventricular arrhythmias (NID 30/40) reduces overall delivered therapies, both in women and men, when compared with nominal setting (NID 18/24). The reduction was significantly higher in women. Overall, women were less likely to experience ICD therapies than men; this result was only observed in the long-detection arm.Clinical trial registrationNCT00617175.

Background The AdaptivCRT (aCRT) algorithm continuously adjusts cardiac resynchronization therapy (CRT) according to intrinsic atrioventricular conduction, providing synchronized left ventricular pacing in patients with normal PR interval and adaptive BiV pacing in patients with prolonged PR interval. Previous analyses demonstrated an association between aCRT and clinical benefit. We evaluated the incidence of patient mortality and atrial fibrillation (AF) with aCRT compared with standard CRT in a real‐world population. Methods and Results Patients enrolled in the Medtronic Personalized CRT Registry and implanted with a CRT from 2013‐2018 were divided into aCRT ON or standard CRT groups based upon device‐stored data. A Frailty survival model was used to evaluate the potential survival benefit of aCRT, accounting for patient heterogeneity and center variability. Daily AF burden and first device‐detected AF episodes of various durations were recorded by the device during follow‐up. A total of 1814 CRT patients with no reported long‐standing AF history at implant were included. Mean follow‐up time was 26.1 ± 16.5 months and 1162 patients (64.1%) had aCRT ON. Patient survival probability at 36 months was 88.3% for aCRT ON and 83.7% for standard CRT (covariate‐adjusted hazard ratio [HR] = 0.71, 95% CI: 0.53‐0.96, P = .028). Mean AF burden during follow‐up was consistently lower in aCRT ON patients compared with standard CRT. At 36 months, the probability of AF was lower in patients with aCRT ON, regardless of which AF definition threshold was applied (6 minutes‐30 days, all P

Objectives The aim of the study was to confirm the value of the VALID‐cardiac resynchronization therapy (CRT) risk score in predicting outcome and to assess its association with clinical response (CR) in an unselected real‐world CRT population. Methods and Results The present analysis comprised all consecutive CRT patients (pts) enrolled in the CRT‐MORE registry from 2011 to 2013. Pts were stratified into five groups (quintiles 1‐5) according to the VALID‐CRT risk predictor index applied to the CRT‐MORE population. In the analysis of clinical outcome, adverse events comprised death from any cause and non‐fatal heart failure (HF) events requiring hospitalization. CR at 12‐month follow‐up was also assessed. We enrolled 905 pts. During a median follow‐up of 1005 [627‐1361] days, 134 patients died, and 79 had at least one HF hospitalization. At 12 months, 69% of pts displayed an improvement in their CR. The mean VALID‐CRT risk score derived from the CRT‐MOdular Registry (MORE) population was 0.317, ranging from −0.419 in Q1 to 2.59 in Q5. The risk‐stratification algorithm was able to predict total mortality after CRT (survival ranging from 93%‐Q1 to 77%‐Q5; hazards ratio [HR] = 1.42, 95% confidence interval [CI]: 1.25‐1.61, P

Several acquired and congenital disease conditions and many cardiac and noncardiac drugs affect ventricular repolarization and increase susceptibility to ventricular arrhythmias. Abnormal ventricular repolarization can be reflected on the surface ECG by prolonged or shortened QT interval, early repolarization, and abnormal T-wave configuration. Reduced outward K+ currents and abnormal or increased sodium or calcium currents increase the vulnerability to ventricular arrhythmias. Multiple mechanisms give rise to ventricular arrhythmias in conditions of congenital or acquired abnormal ventricular repolarization. Ventricular arrhythmias associated with abnormalities of ventricular repolarization typically are rapid, usually polymorphic, ventricular tachycardia or torsades de pointes, often degenerating into ventricular fibrillation.

International audience; BackgroundCardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint Pacing [MPP]) improves acute hemodynamics and chronic outcomes in comparison to conventional biventricular pacing (BiV), though MPP programming questions persist.ObjectivesIn this multicenter feasibility study, we evaluated the feasibility of using noninvasive systolic blood pressure (SBP) to guide MPP programming and assessed the chronic 6-month echocardiographic CRT response.MethodsPatients implanted with MPP-enabled CRT-defibrillator devices underwent noninvasive hemodynamic assessment (finger arterial pressure) during a pacing protocol that included atrial-only pacing and various BiV and MPP configurations. Each configuration was repeated 4 times, alternating with a reference pacing configuration, to calculate the SBP difference relative to reference (ΔSBP). CRT configurations with the greatest ΔSBP were programmed. An independent core laboratory analyzed baseline and 6-month echocardiograms, with CRT response defined as a 6-month reduction in LV end-systolic volume ≥ 15%.ResultsForty-two patients (71% male; LV ejection fraction 30.3% ± 7.5%; QRS duration 161 ± 19 ms; 26% had ischemic cardiomyopathy) were enrolled in 4 European centers. Relative to atrial-only pacing, the best BiV and best MPP configurations produced significant SBP elevations of 3.1 ± 4.2 (P < .01) and 4.1 ± 4.1 mm Hg (P < .01), respectively (BiV vs MPP; P < .01). Greater SBP elevations were associated with the best MPP compared with the best BiV configurations in 29 of 37 patients completing the pacing protocol (78%). Of MPP-programmed patients completing the 6-month follow-up visit, 23 of 27 (85%) were classified as CRT responders (6-month reduction in LV end-systolic volume 37.0% ± 13.6%).ConclusionAcute noninvasive hemodynamics after CRT device implantation predominantly favored MPP over BiV programming. MPP programming guided by noninvasive hemodynamics resulted in positive LV structural remodeling.

Aims A long-detection interval (LDI) (30/40 intervals) has been proved to be superior to a standard-detection interval (SDI) (18/24 intervals) in terms of reducing unnecessary implantable cardioverter defibrillator (ICD) therapies. To better evaluate the different impact of LDI and anti-tachycardia pacing (ATP) on reducing painful shocks, we assessed all treated episodes in the ADVANCE III trial. Methods and results A total of 452 fast (200 ms < cycle length ≤ 320 ms) arrhythmic episodes were recorded: 284 in 138 patients in the SDI arm and 168 in 82 patients in the LDI arm (106/452 inappropriate detections). A total of 346 fast ventricular tachycardias (FVT) were detected in 169 patients: 208 in 105 patients with SDI and 138 in 64 patients with LDI. Setting LDI determined a significant reduction in appropriate but unnecessary therapies [208 in SDI vs. 138 in LDI; incidence rate ratio (IRR): 0.61 (95% CI 0.45–0.83), P = 0.002]. Anti-tachycardia pacing determined another 52% reduction in unnecessary shocks [208 in SDI with hypothetical shock-only programming vs. 66 in LDI with ATP; IRR: 0.37 (95% CI 0.25–0.53, P < 0.001)]. The efficacy of ATP in terminating FVT was 63% in SDI and 52% in LDI ( P = 0.022). No difference in the safety profile (acceleration/degeneration and death/cardiovascular hospitalizations) was observed between the two groups. Conclusion The combination of LDI and ATP during charging is extremely effective and significantly reduces appropriate but unnecessary therapies. The use of LDI alone yielded a 39% reduction in appropriate but unnecessary therapies; ATP on top of LDI determined another 52% reduction in unnecessary shocks. The strategy of associating ATP and LDI could be considered in the majority of ICD recipients.

AIM Mitral regurgitation (MR) is a common finding in patients with heart failure with debatable effects on prognosis. Reduction in MR is one of the mechanisms by which cardiac resynchronization therapy (CRT) exerts its beneficial effects. We investigated the prognostic impact of baseline MR and MR persistence after CRT on outcomes of treated patients. METHODS AND RESULTS We prospectively followed 1122 CRT patients (66.4 ± 10.3 years, 78% male) who were stratified according to baseline MR severity as having MR- (degree 0-1; n = 508, 45%) or MR+ (degrees 2-3-4; n = 614, 55%). In 916 patients (82%) with MR severity data available at 1-year follow-up, the annual mortality rate was 3.4 and 6.0 per patient-year in the MR- and MR+ group, respectively, with a 1-year incidence rate ratio (IRR) of 1.76 (P

It is generally accepted that the current guidelines for the primary prevention of sudden arrhythmic death, which are based on ejection fraction, do not allow the optimal selection of patients with low left ventricular ejection fraction of ischemic and nonischemic etiology for implantation of a cardioverter-defibrillator. Ejection fraction alone is limited in both sensitivity and specificity. An analysis of the risk of sudden arrhythmic death with a combination of multiple tests (ejection fraction associated with one or more arrhythmic risk markers) could partially compensate for these limitations. We propose a polyparametric approach for defining the risk of sudden arrhythmic death using ejection fraction in combination with other clinical and arrhythmic risk markers (i.e. late gadolinium enhancement cardiac magnetic resonance, T-wave alternans, programmed ventricular stimulation, autonomic tone, and genetic testing) that have been validated in nonrandomized trials. In this article, we examine these approaches to identify three subsets of patients who cannot be comprehensively assessed by the current guidelines: patients with ejection fraction of 35% or less and a relatively low risk of sudden arrhythmic death despite the ejection fraction value; patients with ejection fraction of 35% or less and high competitive risk of death due to evolution of heart failure or noncardiac causes; and patients with ejection fraction between 35 and 45% with relatively high risk of sudden arrhythmic death despite the ejection fraction value.

Aims Implantable cardioverter defibrillators improve survival of patients at risk for ventricular arrhythmias, but inappropriate shocks occur in up to 30% of patients and have been associated with worse quality of life and prognosis. In heart failure patients with cardiac resynchronization therapy defibrillators (CRT-Ds), we evaluated whether a new generation of detection and discrimination algorithms reduces inappropriate shocks. Methods and results We analysed 1983 Medtronic CRT-D patients (80% male, 67 ± 10 years), 1368 with standard devices (Control CRT-D) and 615 with new generation devices (New CRT-D). Expert electrophysiologists reviewed and classified the electrograms of all device-detected ventricular tachycardia/fibrillation episodes. Total follow-up was 3751 patients-years. Incidence of inappropriate shocks at 1 year was 2.8% [95% confidence interval (CI) = 2.0–3.5] in Control CRT-D and 0.9% (CI = 0.4–2.2) in New CRT-D (hazard ratio = 0.37, CI = 0.21–0.66, P < 0.001). In New CRT-D, inappropriate shocks were reduced by 77% [incidence rate ratio (IRR) = 0.23, CI = 0.16–0.35, P < 0.001] and inappropriate anti-tachycardia pacing by 81% (IRR = 0.19, CI = 0.11–0.335, P < 0.001). Annual rate per 100 patient-years for appropriate VF detections was 3.0 (CI = 2.1–4.2) in New CRT-D and 3.2 (CI = 2.1–5.0) in Control CRT-D ( P = 0.68), for syncope was 0.4 (CI = 0.2–0.9) in New CRT-D and 0.7 (CI = 0.5–1.0) in Control CRT-D ( P = 0.266), and for death was 1.0 (CI = 0.6–1.6) in New CRT-D and 3.5 (CI = 3.0–4.1) in Control CRT-D ( P < 0.001). Conclusion Detection and discrimination algorithms used in new generation CRT-D significantly reduced inappropriate shocks when compared with standard CRT-D. This result, with no compromise on VF sensitivity or risk of syncope, has important implications for patients' quality of life and prognosis.

OBJECTIVES: The purpose of this study is to determine whether, in patients with atrial fibrillation (AF) undergoing cardiac resynchronization therapy (CRT), atrioventricular junction ablation (AVJA) is associated with a better outcome than treatment with rate-slowing drugs. BACKGROUND: Different trials have demonstrated that CRT is effective in treating heart failure (HF) patients who are in sinus rhythm (SR). No trials have addressed whether CRT confers similar benefits on AF patients, with or without AVJA. METHODS: The clinical outcomes of CRT for patients with permanent AF undergoing CRT combined with either AVJA (n = 443) or rate-slowing drugs (n = 895) were compared with those of SR patients (n = 6,046). RESULTS: Median follow-up was 37 months. Total mortality (6.8 vs. 6.1 per 100 person-years) and cardiac mortality (4.2 vs. 4.0) were similar for patients with AF+AVJA and patients in SR (both p = NS). In contrast, the AF+drugs group had a higher total and cardiac mortality than the SR group and the AF+AVJA group (11.3 and 8.1, respectively; p < 0.001). On multivariable analysis, AF+AVJA had total mortality (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.74 to 1.67) and cardiac mortality (HR: 0.88, 95% CI: 0.66 to 1.17) similar to that of the SR group, independent of known confounders. The AF+drugs group, however, had a higher total mortality (HR: 1.52, 95% CI: 1.26 to 1.82) and cardiac mortality (HR: 1.57, 95% CI: 1.27 to 1.94) than both the SR group and the AF+AVJA group (both p < 0.001). CONCLUSIONS: Long-term survival after CRT among patients with AF+AVJA is similar to that observed among patients in SR. Mortality is higher for AF patients treated with rate-slowing drugs. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

In patients with left ventricular assist device (LVAD), a minority of post-operative ventricular tachycardias (VTs) is caused by contact between the inflow cannula and the endocardium. Currently, electrophysiologic characteristics and pathologic features of this condition are lacking. We report on a case of a successfully ablated mechanical VT. After VT recurrence, heart transplantation took place. Pathologic observations were consistent with direct tissue injury and inflammation, eventually contributing to persisting arrhythmias. Radiofrequency catheter ablation can be a safe and effective option to treat arrhythmias caused by inflow cannula interference in the short term, although a high recurrence rate is expected.

Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF); however, PVI-C can become a challenging procedure due to the anatomy of the left atrium and pulmonary veins (PVs). Importantly, the utility of imaging before the procedure is still unknown regarding the long-term clinical outcomes following PVI-C. The aim of the analysis is to evaluate the impact of imaging before PVI-C on procedural data and AF recurrence. Patients with paroxysmal AF underwent an index PVI-C. Data were collected prospectively in the framework of 1STOP ClinicalService® project. Patients were divided into two groups according to the utilization of pre-procedural imaging of PV anatomy (via CT or MRI) or the non-usage of pre-procedural imaging. Out of 912 patients, 461 (50.5%) were evaluated with CT or MRI before the PVI-C and denoted as the imaging group. Accordingly, 451 (49.5%) patients had no pre-procedural imaging and were categorized as the no imaging group. Patient baseline characteristics were comparable between the two cohorts, but the ablation centers that comprised the imaging group had fewer PVI-C cases per year than the no imaging group (p

BACKGROUND: Late gadolinium enhancement (LGE) assessed with cardiovascular magnetic resonance (CMR) correlates with ventricular arrhythmias and survival in patients with structural heart disease. Whether some LGE characteristics may specifically improve prediction of arrhythmic outcomes is unknown. HYPOTHESIS: We sought to evaluate scar characteristics assessed with CMR to predict implantable cardioverter‐defibrillator (ICD) interventions in dilated cardiomyopathy of different etiology. METHODS: 96 consecutive patients evaluated with CMR received an ICD. Biventricular volumes, ejection fraction, and myocardial LGE were evaluated. LGE was defined as “complex” (Cx‐LGE) in presence of ≥1 of the following: ischemic pattern, involving ≥2 different coronary territories; epicardial pattern; global endocardial pattern; and presence of ≥2 different patterns. The primary endpoint was occurrence of any appropriate ICD intervention. A composite secondary endpoint of cardiovascular death, cardiac transplantation, or ventricular assist device implantation was also considered. RESULTS: During a median follow‐up of 75 months, 30 and 25 patients reached the primary and secondary endpoints, respectively. Cx‐LGE was correlated with a worse primary endpoint survival (log‐rank P < 0.001). Cx‐LGE and right ventricular end‐diastolic volume were independently associated with the primary endpoint (HR: 3.22, 95% CI: 1.56–6.65, P = 0.002; and HR: 1.06, 95% CI: 1.00–1.12, P = 0.045, respectively), but not with the secondary endpoint. CONCLUSIONS: Cx‐LGE identified at CMR imaging seems promising as an independent and specific prognostic factor of ventricular arrhythmias requiring ICD therapy in dilated cardiomyopathy of different etiologies.

Aims Mortality after cardiac resynchronization therapy (CRT) is difficult to predict. We sought to design and validate a simple prognostic score for patients implanted with CRT, based on readily available clinical variables, including age, gender, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class, presence/absence of atrial fibrillation, presence/absence of atrioventricular junction ablation, coronary heart disease, diabetes, and implantation of a CRT device with defibrillation. Methods For predictive modelling, 5153 consecutive patients enrolled in 72 European centres (79% male; LVEF 25.9 ± 6.85%; NYHA class III–IV 77.5%; QRS 158.4 ± 32.3 ms) were randomly split into derivation (70%) and validation (30%) samples. The primary endpoint was total mortality and the secondary endpoint was cardiovascular mortality. The final predictive model fit was assessed by plotting observed vs. predicted survival. Results In the entire cohort, 1004 deaths occurred over a follow-up of 14 409 person years. Total mortality ranged from 3.1% to 28.2% at 2 years in the first and fifth quintile of the risk score, respectively. At 5 years, total mortality was 10.3%, 18.6%, 27.6%, 36.1%, and 58.8%, from the first to the fifth quintile. Compared with the lowest quintile (Q), total mortality was significantly higher in the other four quintiles [Q2 hazard ratio (HR) = 1.71; Q3 HR = 2.20; Q4 HR = 4.03; Q5 HR = 8.03; all P < 0.001). The final model, which was based on the entire cohort using the above variables, showed a good discrimination (Harrell's c = 0.70) and high explained variation (0.26). The mean predicted survival fitted well with the observed survival for up to 6 years of follow-up. Conclusions The VALID-CRT risk score, which is based on routine, readily available clinical variables, reliably predicted the long-term total and cardiovascular mortality in patients undergoing CRT. While this score cannot be used to predict the benefit of CRT, it may be useful for predicting survival after CRT. This may have useful implications for follow-up.

Background— Cardiac resynchronization therapy (CRT) can improve ventricular size, shape, and mass and reduce mitral regurgitation by reverse remodeling of the failing ventricle. About 30% of patients do not respond to this therapy for unknown reasons. In this study, we aimed at the identification and classification of CRT responder by the use of genetic variants and clinical parameters. Methods and Results— Of 1421 CRT patients, 207 subjects were consecutively selected, and CRT responder and nonresponder were matched for their baseline parameters before CRT. Treatment success of CRT was defined as a decrease in left ventricular end-systolic volume >15% at follow-up echocardiography compared with left ventricular end-systolic volume at baseline. All other changes classified the patient as CRT nonresponder. A genetic association study was performed, which identified 4 genetic variants to be associated with the CRT responder phenotype at the allelic ( P P ATPIB1 ), rs5443 ( GNB3 ), rs5522 ( NR3C2 ), and rs7325635 ( TNFSF11 ). Machine learning algorithms were used for the classification of CRT patients into responder and nonresponder status, including combinations of the identified genetic variants and clinical parameters. Conclusions— We demonstrated that rule induction algorithms can successfully be applied for the classification of heart failure patients in CRT responder and nonresponder status using clinical and genetic parameters. Our analysis included information on alleles and genotypes of 4 genetic loci, rs3766031 ( ATPIB1 ), rs5443 ( GNB3 ), rs5522 ( NR3C2 ), and rs7325635 ( TNFSF11 ), pathophysiologically associated with remodeling of the failing ventricle.

Background In patients with cardiac implanted electronic devices, detection of new atrial fibrillation (AF) is associated with an increased risk of stroke. Objective To characterize daily AF burden at first detection and the rate of temporal transition to higher device-detected AF burden. Methods A pooled analysis of data from 3 prospective projects was analyzed, and 6580 patients (mean age 68 ± 12 years, 72% male) with no history of AF and no use of anticoagulants at baseline were identified. Various thresholds of daily AF burden (5 minutes and 1, 6, 12, and 23 hours) were analyzed. Results Among the study population of 6580 patients, a new AF, with an AF burden of ≥5 minutes, was detected in 2244 patients (34%) during a follow-up period of 2.4 ± 1.7 years. Among these patients, 1091 (49.8%) transitioned to a higher AF-burden threshold during follow-up. A higher duration of daily AF burden manifest at first detection and CHADS2 score ≥2 were associated with faster transition to a subsequent higher burden. Approximately 24% of patients transitioned from a lower threshold to a daily AF burden of ≥23 hours during follow-up. Conclusion More than one-third of patients with no history of AF developed device-detected AF, with attainment of different thresholds of daily AF burden over time. Continuous long-term monitoring, especially when the initial detection corresponds to a higher daily AF burden and the CHADS2 score is ≥2, could support timely clinical decisions on anticoagulation by capturing transitions to higher AF-burden thresholds.

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into clinical practice has revolutionized the prevention and the therapeutic approaches to thromboembolic events in patients with nonvalvular atrial fibrillation and represents with no doubts one of the most remarkable advances in the history of cardiovascular medicine over the last years. NOACs beyond a comparable efficacy with vitamin K antagonists allow to overcome the limitations of this last category of drugs owing to their less drug to drug interactions and a predictable anticoagulant effect that allows a fixed dose administration without the need for continuous monitoring. However, the penetration of NOACs into the Italian market is still lower than predicted with respect to their use in other European countries.The aim of this review is to critically analyze the reasons behind this attitude through the adoption of the nominal group technique, a methodology that permits to reach an official consensus.

Aims To evaluate if the increased thromboembolic risk in female patients may be related to a higher burden of atrial fibrillation (AF). Methods and results Data collected in a prospective observational research of patients implanted with a cardiac implantable electrical device (CIED) were analysed. We included 2398 patients: 489 (20.4%) were female and 1909 (79.6%) were male (oral anticoagulants treatment in 23.2%, independent of gender). During the follow-up (mean 42.8, median 37.7 months), 26 thromboembolic events occurred in 22 patients, with an incidence rate ratio of both stroke and stroke/transient ischemic attack (TIA) significantly higher in females compared with males [2.00, 95% confidence interval (CI) 1.53–2.61, P

Heart failure (HF) is a common condition in elderly patients. Despite great improvements in medical therapy, HF mortality remains high. Implantable cardioverter defibrillator (ICD) significantly lengthens the survival rate of subjects with severe HF, but little evidence exists on its effect in elderly persons. Aim of this study was to compare the age-related determinants of prognosis in a large population of patients with ICD. We divided all patients who underwent an ICD implantation in 117 Italian centers of the "ClinicalService Project" into 3 age groups (65, 65 to 74, ≥ 75 years), and collected clinical and instrumental variables at baseline and during follow-up (median length: 27 months). Between 2004 and 2011, 6,311 patients were enrolled (5,174 men; left ventricular ejection fraction 29% ± 9%); 1,510 subjects were ≥ 75 years (23.9%; mean age 78 ± 3 years). The prevalence of co-morbidities increased with age. HF was most frequently due to coronary artery disease in the elderly, who also showed the worst New York Heart Association class. At multivariate analysis, older age, coronary artery disease, chronic obstructive pulmonary disease, chronic renal failure, diabetes, complex ventricular arrhythmias, and left ventricular ejection fraction were significant predictors of all-cause mortality. After adjustment, the hazard ratio(age group) for mortality was 22.6% less than at univariate analysis. When groups were analyzed separately, age alone predicted mortality in the oldest. In conclusion, a large proportion of our population was aged ≥ 75 years. Mortality was related to age and several co-morbidities, except for the oldest patients in whom age alone resulted predictive.

WereadwithinteresttworecentpublicationsbyDr.Zusterzeeletal.on the impact of cardiac resynchronization therapy (CRT) in womencompared with men based on individual patient pooled data from 3CRT-defibrillators(CRT-D)versus,implantablecardioverterdefibrillator(ICD) trials (4076 patients) and 31,892 CRT-D patients in the NationalCardiovascular Data Registry (NCDR), ICD registry between 2006 and2009[1,2]. The authorsconcludedthat amongpatientswithleft bundlebranch block (LBBB) and a QRS of 130 to 149 ms who received CRT-D,mortality is lower in women than men, with a hazard ratio (HR) of0.24 (95%confidence interval[CI], 0.06–0.89; p =0.03)[2]. Additional-ly,longerQRSdurationinLBBBisassociatedwithbettersurvivalinbothsexes. In the population of patients with primarily mild heart failure(HF) derived by the 3 CRT-D trials it was evident that women withLBBB benefited from CRT-D at a shorter QRS duration than men withLBBB.Similarly, we have recently observed in a prospective analysis in-cluding 507 patients receiving a CRT with LBBB and QRS longer than130 ms that female CRT recipients achieve greater long-term benefitin terms of reduced mortality, and that benefit appears to be more evi-dent in non-ischemic patients [3].To further contextualize our findings and results by Zusterzeel wemade a cumulative analysis of the 5 largest studies published in thelast 3 years (2011–2014) on 4802 patients who had undergone CRT(by Leyva et al. [4],Arshadetal.,Xuetal.[5] [6],Zabarovskajaetal.[7],andMooyaartetal.[8])thatassessedtheeffectoffemalesexonsur-vival. Trials, which did not provide the HR and CI in their evaluation ofthe effect of female sex on all-cause mortality as a single outcome, orwherethefemalepopulationwasunderrepresented(nb 100) wereex-cluded [9,10]. All of the studies provided the following information:number of patients (male/female), follow-up length (years), HRconcerning the impact of female sex on “all-cause mortality” and theirCI, and mean age and standard deviation (SD). In order to evaluate theeffect of female-sex on all-cause mortality, we performed the cumula-tive analysis on HR and their CI. The heterogeneity of the studies ana-lyzed was checked by means of a heterogeneity test. In all statisticaltests, values of p b 0.05 were considered statistically significant (whennot specifiedotherwise, the p-value is2-tailed).The studiesprovedho-mogeneous (Heterogeneity test p = 0.341). Moreover, no publicationbias emerged (Begg's test p = 0.133). All analyses were performed bymeans of the StataSE 12.0 statistical software (StataCorp, College Sta-tion, TX, USA).In Table1,theprincipalbaselinecharacteristicsof the variouspopu-lations are shown. In Fig. 1, the Forest plot of HR in females and malesregarding mortality after CRT is shown together with the combinedHR that was statistically significant (p b 0.001). Overall, the female sexconstituted a protective factor (HR = 0.50; CI 0.42–) against all-0.60cause mortality among HF patients on CRT with LBBB and QRS longerthan 130 ms. Our cumulative analysis of these recent studies, whichcomprised 4802 patients, further corroborates the robustness and re-producibility of this finding by Zusterzeel et al., which is in contrastwith early analyses of the female-sex effect on CRT response [9].Itmust be underlined that our cumulative analysis on female-sex effecton the CRT response includes also 1860 patients from the MADIT-CRTpreviously published by Arshad et al. [5] that were also included inthe individual pooled data analysis by Zusterzeel.Our data indicate that women benefit from CRT more than men interms of survival. However, this female-associated reduction in both

AIMS: SYNARR-Flash study (Monitoring of SYNcopes and/or sustained palpitations of suspected ARRhythmic origin) is an international, multicentre, observational, prospective trial designed to evaluate the role of external 4-week electrocardiogram (ECG) monitoring in clinical work-up of unexplained syncope and/or sustained palpitations of suspected arrhythmic origin. METHODS AND RESULTS: Consecutive patients were enrolled within 1 month after unexplained syncope or palpitations (index event) after being discharged from emergency room or hospitalization without a conclusive diagnosis. A 4-week ECG monitoring was obtained by external high-capacity loop recorder (SpiderFlash-T(®), Sorin) storing patient-activated and auto-triggered tracings. Diagnostic monitorings included (i) conclusive events with reoccurrence of syncope or palpitation with concomitant ECG recording (with/without arrhythmias) and (ii) events with asymptomatic predefined significant arrhythmias (sustained supraventricular or ventricular tachycardia, advanced atrio-ventricular block, sinus bradycardia 6 s). SYNARR-Flash study enrolled 395 patients (57.7% females, 56.9 ± 18.7 years, 28.1% with syncope, and 71.9% with palpitations) from 10 European centres. For syncope, the 4-week diagnostic yield was 24.5%, and predictors of diagnostic events were early start of recording (0-15 vs. >15 days after index event) (OR 6.2, 95% CI 1.3-29.6, P = 0.021) and previous history of supraventricular arrhythmias (OR 3.6, 95% CI 1.4-9.7, P = 0.018). For palpitations, the 4-week diagnostic yield was 71.6% and predictors of diagnostic events were history of recurrent palpitations (P < 0.001) and early start of recording (P = 0.001). CONCLUSION: The 4-week external ECG monitoring can be considered as first-line tool in the diagnostic work-up of syncope and palpitation. Early recorder use, history of supraventricular arrhythmia, and frequent previous events increased the likelihood of diagnostic events during the 4-week external ECG monitoring. info:eu-repo/semantics/publishedVersion

Background Despite an intensive search for predictors of the response to cardiac resynchronization therapy (CRT), the QRS duration remains the simplest and most robust predictor of a positive response. QRS duration of ≥ 130 ms is considered to be a prerequisite for CRT; however, some studies have shown that CRT may also be effective in heart failure (HF) patients with a narrow QRS (15% from the baseline. Discussion This feasibility study will determine whether MPP improves reverse remodeling, as compared with standard ICD, in HF patients who have a narrow QRS complex (100–130 ms). Trial registration ClinicalTrials.gov, NCT02402816. Registered on 25 March 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1698-1) contains supplementary material, which is available to authorized users.

Background: We assessed the influence of clinically significant mitral regurgitation (MR) on clinical-echocardiographic response and outcome in heart failure (HF) patients treated with a biventricular defibrillator (cardiac resynchronization therapy defibrillator [CRT-D]). Methods and Results: A total of 659 HF patients underwent successful implantation of CRT-D and were enrolled in a multicenter prospective registry (median follow-up of 15 months). Following baseline echocardiographic evaluation, patients were stratified into two groups according to the severity of MR: 232 patients with more than mild MR (Group MR+: grade 2, 3, and 4 MR) versus 427 patients with mild (grade 1) or no functional MR (Group MR−). On 6- and 12-month echocardiographic evaluation, MR was seen to have improved in the vast majority of MR+ patients, while it remained unchanged in most MR− patients. On 12-month follow-up evaluation, a comparable response to CRT was observed in the two groups, in terms of the extent of left ventricular reverse remodeling and combined clinical and echocardiographic response. During long-term follow-up, event-free survival did not differ between MR+ and MR− patients, even when subpopulations of patients with ischemic heart disease and with dilated cardiomyopathy were analyzed separately. On multivariate analysis, the only independent predictor of death from any cause was the lack of β-blocker use. Conclusions: This observational analysis supports the use of CRT-D in HF patients with clinically significant MR; MR had no major influence on patient outcome. (PACE 2012; 35:146–154)

Background— Heart failure is associated with frequent hospitalizations, often resulting from volume overload. Measurement of intrathoracic impedance with an implanted device with an audible patient alert may detect increases in pulmonary fluid retention early. We hypothesized that early intervention could prevent hospitalizations and affect outcome. Methods and Results— We studied 335 patients with chronic heart failure who had undergone implantation of an implantable cardioverter-defibrillator alone (18%) or with cardiac resynchronization therapy (82%). All devices featured a monitoring tool to track changes in intrathoracic impedance (OptiVol) and other diagnostic parameters. Patients were randomized to have information available to physicians and patients as an audible alert in case of preset threshold crossings (access arm) or not (control arm). The primary end point was a composite of all-cause mortality and heart failure hospitalizations. During 14.9±5.4 months, this occurred in 48 patients (29%) in the access arm and in 33 patients (20%) in the control arm ( P =0.063; hazard ratio, 1.52; 95% confidence interval, 0.97–2.37). This was due mainly to more heart failure hospitalizations (hazard ratio, 1.79; 95% confidence interval, 1.08–2.95; P =0.022), whereas the number of deaths was comparable (19 versus 15; P =0.54). The number of outpatient visits was higher in the access arm (250 versus 84; P Conclusion— Use of an implantable diagnostic tool to measure intrathoracic impedance with an audible patient alert did not improve outcome and increased heart failure hospitalizations and outpatient visits in heart failure patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT 00480077.

Chronic heart failure is one of the most important geriatric syndromes, associated with disability, increased hospital admissions, and high mortality. The aim of this study was to evaluate the existence of age-related differences in clinical effectiveness and outcomes of cardiac resynchronization therapy (CRT), alone or in combination with an implantable cardioverter-defibrillator (CRT-D), in a large, real-world registry. A total of 1,787 patients admitted for CRT or CRT-D to the 117 centers participating in the InSync/InSync ICD Italian Registry from 1999 to 2005 were evaluated. Patients were divided into 3 age groups:65 years (n = 571), 65 to 74 years (n = 740), and ≥75 years (n = 476). The left ventricular ejection fraction did not differ in the 3 groups (26 ± 8% vs 26 ± 7% vs 27 ± 8%, p = 0.123). Atrial fibrillation prevalence demonstrated an age-related increase. The use of recommended medical therapy for chronic heart failure decreased with age, as well as CRT-D implantation (p0.001). The percentage of echocardiographic responders to CRT was similar in the 3 groups, and New York Heart Association class significantly improved independent of age. During the follow-up period (19 ± 13 months), all-cause mortality was higher in patients aged ≥75 years than in those aged65 years (p = 0.005). In the whole population, mortality was associated with the nonresponder condition, the presence of atrial fibrillation and the lack of prescription of recommended medical therapy. In conclusion, CRT improved left ventricular performance and functional capacity independent of age. The proportion of the responder condition to CRT was the same in all groups. Pharmacologic undertreatment is an important issue in a "real-world" geriatric population.

Background Algorithms for automatic pacing output adjustment have been implemented in pacemakers and implantable defibrillators (ICD) and recently in cardiac resynchronization therapy defibrillators (CRT-D). We assessed the impact and effectiveness of these automatic features. Method and resuls We prospectively enrolled patients successfully implanted with the following Medtronic CRT-Ds: Concerto [with automatic left ventricular (LV) output management algorithm], Consulta [automatic management of atrial, right ventricular (RV) and LV voltage], and Sentry (only manual voltage adjustments). Patients with complete device data available for at least 12 months were included in the analysis. We analysed data from 739 patients (360 Sentry, 335 Concerto, 44 Consulta). During the first 6 months, the LV pacing amplitude underwent more frequent adjustments in Concerto (63%, P < 0.001) and Consulta (64%, P = 0.047) patients than in Sentry (48%). Similarly, RV and atrial amplitude at 6 months differed from the pre-discharge value more frequently in Consulta (61 and 50%, respectively) than in Sentry patients (33 and 28%, both P < 0.01). The LV pulse amplitude for Concerto and the voltages in the three chambers of Consulta were significantly lower than the corresponding values programmed in Sentry at 6 and 12 months. The proportion of CRT-D interrogations involving manual reprogramming was 97 ± 8% for Sentry, 79 ± 20% for Concerto, and 56 ± 16% for Consulta (all P < 0.001). Conclusions Algorithms for the automatic management of the pacing output reduced pacing output in comparison with the standard manual management approach, with potential optimization of battery longevity. Moreover, they reduced the need to manually reprogram CRT-Ds, suggesting the possibility to simplify CRT-D management and facilitate remote monitoring.

Objectives The purpose of this analysis was to evaluate the correlation between atrial tachycardia (AT) or atrial fibrillation (AF) and clinical outcomes in heart failure (HF) patients implanted with a cardiac resynchronization therapy defibrillator (CRT-D). Background In HF patients, AT and AF have high prevalence and are associated with compromised hemodynamic function. Methods Forty-four Italian cardiological centers followed up 1,193 patients who received a CRT-D according to current guidelines for advanced HF, New York Heart Association functional class ≥II, left ventricular ejection fraction ≤35%, and QRS complex ≥120 ms. All patients were in sinus rhythm at implant. Results During a median follow-up period of 13 months, AT/AF >10 min occurred in 361 of 1,193 (30%) patients. The composite end point (deaths or HF hospitalizations) occurred in 174 of 1,193 (14.6%). Multivariate time-dependent Cox regression analyses showed that composite end point risk was higher among patients with device-detected AT/AF (hazard ratio [HR]: 2.16, p = 0.032), New York Heart Association functional class III or IV compared with II (HR: 2.09, p = 0.002), and absence of beta-blockers (HR: 1.36, p = 0.036). Furthermore, the composite end point risk was inversely associated with left ventricular ejection fraction (HR: 1.04, p = 0.045), increasing by a factor of 4% for each 1% decrease in left ventricular ejection fraction. Conclusions In HF patients with CRT-D, device-detected AT/AF is associated with a worse prognosis. Continuous device diagnostics monitoring and Web-based alerts may inform the physician of AT/AF occurrences and identify patients at risk of cardiac deterioration or patients with suboptimal rate or rhythm control. (Italian ClinicalService Project; NCT01007474 )