M. Lunati

Device-detected atrial tachyarrhythmias predict adverse outcome in real-world patients with implantable biventricular defibrillators.

OBJECTIVESnThe 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).nnnBACKGROUNDnIn HF patients, AT and AF have high prevalence and are associated with compromised hemodynamic function.nnnMETHODSnForty-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.nnnRESULTSnDuring 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.nnnCONCLUSIONSnIn 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).

Antiarrhythmic Effect of Reverse Ventricular Remodeling Induced by Cardiac Resynchronization Therapy. The InSync ICD (Implantable Cardioverter-Defibrillator) Italian Registry

OBJECTIVESnWe investigated whether the reverse remodeling after cardiac resynchronization therapy (CRT) might reduce the occurrence of ventricular arrhythmias (VAs).nnnBACKGROUNDnIt is currently debated whether CRT has an effect on the burden of VAs.nnnMETHODSnThe study included 398 patients treated with a CRT defibrillator and with a follow-up of at least 12 months. Spontaneous VAs detected by the device were reviewed and validated.nnnRESULTSnA significant reduction in VA episodes and shock therapies was evident during the follow-up with greater decrease after 1 month. After 6 months of CRT, 227 patients (57%) showed a reduction in end-systolic volume of >or=10% and were defined as responders. The baseline characteristics were similar between the responders and the nonresponders. Nonetheless, the proportion of patients with recurrence of VA after 1 month of CRT was significantly lower in responders (32% vs. 43%, p = 0.024). Among baseline variables no parameters emerged as predictors of tachyarrhythmia recurrence. However, receiver-operating curve analysis recognized a reduction of left ventricular end-systolic volume at 6 months of 13% as the best cutoff to identify the reduction of VAs (with a sensitivity of 58% and a specificity of 54%).nnnCONCLUSIONSnIn patients treated with CRT defibrillators, a reduction in ventricular arrhythmic events occurs during the initial 12 months after implant and is correlated with the degree of ventricular remodeling induced by the therapy. Patients demonstrating reverse remodeling at midterm follow-up show a reduction in arrhythmias soon after the implant, pronounced improvements at long-term, and a better survival.

Early and late outcome of treated patients referred for syncope to emergency department: the EGSYS 2 follow-up study

AIMSnWe evaluated the early (1 month) and late (2 years) death rate and syncopal relapses of patients referred for syncope to 11 general hospitals emergency departments. Patients were enrolled in the Evaluation of Guidelines in SYncope Study 2 (EGSYS 2) study. The guidelines of the European Society of Cardiology were strictly followed in the management of patients.nnnMETHODS AND RESULTSnOut of the 465 patients enrolled in the EGSYS 2 study, 398 (86%) underwent a complete follow-up. We excluded 18 patients with non-syncopal attacks. Among the remaining 380 patients, death of any cause occurred in 35 (9.2%). The mean follow-up was 614 +/- 73 days. Six deaths (17% of total) occurred during the first month of follow-up. Patients who died were older, had a higher incidence of structural heart disease and/or abnormal ECG, had injuries related to syncope and higher EGSYS score. Syncope recurred in 63 (16.5%) patients. Syncopal relapses occurred in only one patient during the first month of follow-up. The incidence of syncopal recurrences was unrelated to the mechanism of syncope. No clinical differences were found between patients with or without syncopal recurrence and in patients with EGSYS score < or >or=3.nnnCONCLUSIONnA peak of cardiovascular mortality but not of syncopal recurrences was observed in patients attending to the emergency department for syncope within the first month. Late unfavourable outcomes were caused by associated cardiovascular diseases rather than by the mechanism of syncope. The causes of syncope did not determine the recurrence rate.

Persistent Atrial Fibrillation Worsens Heart Rate Variability, Activity and Heart Rate, as Shown by a Continuous Monitoring by Implantable Biventricular Pacemakers in Heart Failure Patients

Background: Atrial fibrillation (AF) induces loss of atrial contribution, heart rate irregularity, and fast ventricular rate.

Clinical and arrhythmic outcomes after implantation of a defibrillator for primary prevention of sudden death in patients with post-myocardial infarction cardiomyopathy: The Survey to Evaluate Arrhythmia Rate in High-risk MI patients (SEARCH-MI)

Aims To evaluate clinical and arrhythmic outcomes in post-infarction cardiomyopathy patients implanted with a defibrillator (ICD) for primary prevention of sudden death. Methods and results The SEARCH-MI registry is a European multi-centre, prospective, observational study enrolling patients after myocardial infarction, chronic left ventricular dysfunction and an ICD implanted for primary prevention of sudden death. Data on 556 patients with at least one recorded follow-up are presented. Survey to Evaluate Arrhythmia Rate in High-risk MI (SEARCH-MI) patients were sicker than those enrolled in MADIT-II with higher New York Heart Association class and left bundle branch block. Total mortality was 10.4%. Close to one-third (30%) of patients experienced episodes of sustained ventricular arrhythmia. One-quarter (23%) received at least one appropriate therapy and 10% inappropriate therapy. Gender (25% males vs. 5% females, P = 0.0009) and history of non-sustained ventricular tachycardia (24% with vs. 18% without P = 0.037) were predictive of appropriate ventricular therapy. Conclusion SEARCH-MI represents the current clinical management of post-MI patients with left ventricular dysfunction indicated to defibrillator implant for primary prevention. European routine clinical practice was influenced by landmark trials and guidelines which impacted on the implantation of cardiac resynchronization therapy in over 25% of such patients. Non-sustained ventricular tachycardia identifies subjects with a higher incidence of appropriate ICD therapy.

Assessment of a standardized algorithm for cardiac pacing in older patients affected by severe unpredictable reflex syncopes.

AIMSnOpinions differ regarding the effectiveness of cardiac pacing in patients affected by reflex syncope. We assessed a standardized guideline-based algorithm in different forms of reflex syncope.nnnMETHODS AND RESULTSnIn this prospective, multi-centre, observational study, patients aged >40 years, affected by severe unpredictable recurrent reflex syncopes, underwent carotid sinus massage (CSM), followed by tilt testing (TT) if CSM was negative, followed by implantation of an implantable loop recorder (ILR) if TT was negative. Those who had an asystolic response to one of these tests received a dual-chamber pacemaker.nnnPOPULATIONn253 patients, mean age 70 ± 12 years, median 4 (3-6) syncopes, 89% without or with short prodromes. Of these patients, 120 (47%) received a pacemaker and 106 were followed up for a mean of 13 ± 7 months: syncope recurred in 10 (9%). The recurrence rate was similar in 61 CSM+ (11%), 30 TT+ (7%), and 15 ILR+ (7%) patients. The actuarial total syncope recurrence rate was 9% (95% confidence interval (CI), 6-12) at 1 year and 15% (95% CI, 10-20) at 2 years and was significantly lower than that observed in the group of 124 patients with non-diagnostic tests who had received an ILR: i.e. 22% (95% CI, 18-26) at 1 year and 37% (95% CI, 30-43) at 2 years (P = 0.004).nnnCONCLUSIONnAbout half of older patients with severe recurrent syncopes without prodromes have an asystolic reflex for which cardiac pacing goes along with a low recurrence rate. The study supports the clinical utility of the algorithm for the selection of candidates to cardiac pacing in everyday clinical practice.nnnCLINICAL TRIAL REGISTRATIONnhttp://www.clinicaltrials.gov. Unique identifier: NCT01509534.

Comparison of the Usefulness of Cardiac Resynchronization Therapy in Three Age-Groups (<65, 65-74 and ≥75 Years) (from the InSync/InSync ICD Italian Registry)

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 (p <0.001). 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 aged <65 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.

Electrical storm in patients with biventricular implantable cardioverter defibrillator: Incidence, predictors, and prognostic implications

BACKGROUNDnThe aim of the present study was to evaluate the incidence, predictors, and related outcomes of patients with heart failure (HF) treated with cardiac resynchronization therapy with an implantable cardioverter defibrillator (CRT-D) who experienced electrical storm (ES). Electrical storm was defined as the occurrence of >or=3 episodes in 24 hours of sustained ventricular tachyarrhythmias.nnnMETHODSnA total of 631 patients with HF (90% male, mean 66+/-9 years) consecutively received a CRT-D device. At baseline, the mean left ventricular ejection fraction was 26%+/-7%, the QRS duration was 164+/-33 milliseconds, and the mean New York Heart Association class was 3.3+/-0.3.nnnRESULTSnDuring a mean follow-up of 19+/-11 months, 2,419 ventricular tachyarrhythmia episodes were appropriately detected in 141 (22%) patients. Electrical storm occurred in 45 (7%) of 631 patients. Kaplan-Meier analysis and multivariable Cox regression showed that ES is more frequent in secondary prevention (hazard ratio 2.3, 95% CI 1.2-4.3, P=.015) and in nonischemic patients (hazard ratio 2.0, 95% CI 1.1-3.8, P=.028). In patients who presented ES, CRT was associated with only marginal nonsignificant improvements of New York Heart Association class and left ventricular ejection fraction. Hospitalizations and death due to HF were more frequent in patients with ES compared with those without ES, amounting to 16.8 (4.3) versus 8.6 (0.9) per 100 patient-years (P = .018) and 7.7 versus 2.7 per 100 patient-years (P=.014), respectively.nnnCONCLUSIONSnElectrical storm affect only 7% of CRT-D recipients and occurred more frequently in nonischemic patients with HF with biventricular implantable cardioverter defibrillators implanted for secondary prevention. Electrical storm was associated with worse HF morbidity and mortality.

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry

Aims To analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients. Methods and results Patients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6–12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy. Conclusion In ‘real world’ clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available.

Benefit of dual-chamber pacing with Closed Loop Stimulation in tilt-induced cardio-inhibitory reflex syncope (BIOSync trial): study protocol for a randomized controlled trial

BackgroundThe efficacy of dual-chamber cardiac pacing in neuro-mediated reflex syncope with a cardio-inhibitory response to the Tilt-Table test (TT) has not been definitively assessed so far. The lack of reproducibility of results from previous studies may be partially explained by discrepancies in subject selection and some weaknesses in design and methods. The European Society of Cardiology (ESC) has set a class IIb indication to pacemaker implantation in this population recommending further research.Methods/designThe BIOSync study is a multicenter, patient- and outcome-assessor-blind, randomized, parallel-arm, placebo-controlled trial with the objective of assessing the clinical benefit of cardiac pacing in patients with frequently recurrent reflex syncope, suspected (but not proven) to be triggered by asystolic pauses as showing a VASIS 2B response to the TT (>3-s pause regardless of blood pressure drop). The primary and secondary endpoints are time to first post-implantation recurrence of syncope or the combination of pre-syncope or syncope, respectively. One hundred and twenty-eight consenting patients will be 1:1 randomized to dual-chamber cardiac pacing ‘on’ or ‘off’ after pacemaker implantation, and followed up until the first adjudicated primary endpoint event for a maximum of 2 years. The so-called Closed Loop Stimulation function on top of dual-chamber pacing is the pacing mode selected in the study active arm. Participating patients are asked to self-report syncopal symptoms at least every 3 months with self-administered questionnaires addressed to an independent Adjudication Committee. Patients and members of the Adjudicating Committee are blinded to randomization. The study is designed to detect a 40% relative reduction in the 2-year incidence of syncopal recurrences with 80% statistical power.DiscussionThe BIOSync study is designed to definitively assess the benefit of pacing against placebo in reflex syncope patients with a cardio-inhibitory response to the TT. The study will also provide important information on the efficiency of the TT in appropriately selecting reflex syncope patients for cardiac pacing.Trial registrationClinicalTrials.gov, identifier: NCT02324920 (27 October 2016, date last accessed).