Maurizio Lunati

Effect of Long-Detection Interval vs Standard-Detection Interval for Implantable Cardioverter-Defibrillators on Antitachycardia Pacing and Shock Delivery: The ADVANCE III Randomized Clinical Trial

IMPORTANCE Using more intervals to detect ventricular tachyarrhythmias has been associated with reducing unnecessary implantable cardioverter-defibrillator (ICD) therapies. OBJECTIVE To determine whether using 30 of 40 intervals to detect ventricular arrhythmias (VT) (long detection) during spontaneous fast VT episodes reduces antitachycardia pacing (ATP) and shock delivery more than 18 of 24 intervals (standard detection). DESIGN, SETTING, AND PARTICIPANTS Randomized, single-blind, parallel-group trial that enrolled 1902 primary and secondary prevention patients (mean [SD] age, 65 [11] years; 84% men; 75% primary prevention ICD) with ischemic and nonischemic etiology undergoing first ICD implant at 1 of 94 international centers (March 2008-December 2010). INTERVENTIONS Patients were randomized 1:1 to programming with long- (n = 948) or standard-detection (n = 954) intervals. MAIN OUTCOMES AND MEASURES Total number of ATPs and shocks delivered for all episodes (primary outcomes) and inappropriate shocks, mortality, and syncopal rate (secondary outcomes). RESULTS During a median follow-up of 12 months (interquartile range, 11-13), long-detection group had 346 delivered therapies (42 therapies per 100 person-years, 95% CI, 38-47) vs 557 in the standard-detection group (67 therapies per 100 person-years [95% CI, 62-73]; incident rate ratio [IRR], 0.63 [95% CI, 0.51-0.78]; P < .001). The long- vs the standard-detection group experienced 23 ATPs per 100 person-years (95% CI, 20-27) vs 37 ATPs per 100 person-years (95% CI, 33-41; IRR, 0.58 [95% CI, 0.47-0.72]; P < .001); 19 shocks per 100 person-years (95% CI, 16-22) vs 30 shocks per 100 person-years (95% CI, 26-34; IRR, 0.77 [95% CI, 0.59-1.01]; P = .06), with a significant difference in the probability of therapy occurrence (P < .001); and a reduction in first occurrence of inappropriate shock (5.1 per 100 patient-years [95% CI, 3.7-6.9] vs 11.6 [95% CI, 9.4-14.1]; IRR, 0.55 [95% CI, 0.36-0.85]; P = .008). Mortality (5.5 [95% CI, 4.0-7.2] vs 6.3 [95% CI, 4.8-8.2] per 100 patient-years; HR, 0.87; P = .50) and arrhythmic syncope rates (3.1 [95% CI, 2.6-4.6] vs 1.9 [95% CI, 1.1-3.1] per 100 patient-years; IRR, 1.60 [95% CI, 0.76-3.41]; P = .22) did not differ significantly between groups. CONCLUSIONS AND RELEVANCE Among patients receiving an ICD, the use of a long- vs standard-detection interval resulted in a lower rate of ATP and shocks, and inappropriate shocks. This programming strategy may be an appropriate alternative. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00617175.

Remote Monitoring of CRT-ICD: The Multicenter Italian CareLink Evaluation—Ease of Use, Acceptance, and Organizational Implications

Purpose: The Medtronic CareLink allows remote implantable device follow‐up. In this first European experience with CareLink, we assessed the ease of use of the system, the acceptance, and satisfaction of patients and clinicians.

Sequential Biventricular Pacing

The study evaluated the clinical safety, performance, and efficacy of sequential biventricular pacing in the InSync III (Model 8042) biventricular stimulator in a multicenter, prospective 3‐month study and assessed the proper functioning of features aiming at improving biventricular AV therapy delivery. The system was successfully implanted in 189 (95.9%) of 198 patients with symptomatic systolic heart failure and a prolonged QRS complex duration. Patients significantly improved their 6‐minute hall walk distance (baseline 339 ± 92 vs 3‐month 422 ± 127 meter, P < 0.001) and NYHA class (baseline 3.1 ± 0.5 vs 3‐month 1.9 ± 0.7, P < 0.001). Echocardiographic optimization of sequential biventricular pacing showed an improvement in stroke volume compared to simultaneous stimulation (sequential 68 ± 24 mL vs simultaneous 56 ± 23 mL, P < 0.001) at baseline and at 3 months. In 88% (30/34) of the patients these improvements were seen within a small range of V‐V delays of ±20 ms and in 94% (32/34) within V‐V delays of ±40 ms. In contrast, programming beyond this range reduced stroke volume below that during simultaneous biventricular pacing. The device functioned as expected. LV lead dislodgement was observed in 12 patients and phrenic nerve stimulation required lead repositioning in 2 patients. Eight patients died during the study. Patient survival at 3 and 6 months was 97 ± 2% and 94 ± 2%, respectively. Cause of death was cardiac (n = 7), heart failure related (n = 3), arrhythmia related (n = 2), and unknown (n = 2). In conclusion, this sequential biventricular pacemaker was safe and efficacious. (PACE 2004; 27:339–345)

Monitoring Intrathoracic Impedance with an Implantable Defibrillator Reduces Hospitalizations in Patients with Heart Failure

Purpose: Some implantable cardioverter‐defibrillators (ICDs) are now able to monitor intrathoracic impedance. The aim of the study was to describe the use of such monitoring in clinical practice and to evaluate the clinical impact of the fluid accumulation alert feature of these ICDs.

Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure

AIMS We performed a randomized, double blind, crossover study of cardiac contractility modulation (CCM) signals in heart failure patients. METHODS AND RESULTS One hundred and sixty-four subjects with ejection fraction (EF) < 35% and NYHA Class II (24%) or III (76%) symptoms received a CCM pulse generator. Patients were randomly assigned to Group 1 (n = 80, CCM treatment 3 months, sham treatment second 3 months) or Group 2 (n = 84, sham treatment 3 months, CCM treatment second 3 months). The co-primary endpoints were changes in peak oxygen consumption (VO2,peak) and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Baseline EF (29.3 +/- 6.7% vs. 29.8 +/- 7.8%), VO2,peak (14.1 +/- 3.0 vs. 13.6 +/- 2.7 mL/kg/min), and MLWHFQ (38.9 +/- 27.4 vs. 36.5 +/- 27.1) were similar between the groups. VO2,peak increased similarly in both groups during the first 3 months (0.40 +/- 3.0 vs. 0.37 +/- 3.3 mL/kg/min, placebo effect). During the next 3 months, VO2,peak decreased in the group switched to sham (-0.86 +/- 3.06 mL/kg/min) and increased in patients switched to active treatment (0.16 +/- 2.50 mL/kg/min). MLWHFQ trended better with treatment (-12.06 +/- 15.33 vs. -9.70 +/- 16.71) during the first 3 months, increased during the second 3 months in the group switched to sham (+4.70 +/- 16.57), and decreased further in patients switched to active treatment (-0.70 +/- 15.13). A comparison of values at the end of active treatment periods vs. end of sham treatment periods indicates statistically significantly improved VO2,peak and MLWHFQ (P = 0.03 for each parameter). CONCLUSION In patients with heart failure and left ventricular dysfunction, CCM signals appear safe; exercise tolerance and quality of life (MLWHFQ) were significantly better while patients were receiving active treatment with CCM for a 3-month period.

Prospective multicentre systematic guideline-based management of patients referred to the Syncope Units of general hospitals

AIMS Although an organizational model for syncope management facilities was proposed in the 2004 guidelines of the European Society of Cardiology (ESC), its implementation in clinical practice and its effectiveness are largely unknown. METHODS AND RESULTS This prospective study enrolled 941 consecutive patients referred to the Syncope Units of nine general hospitals from 15 March 2008 to 15 September 2008. A median of 15 patients per month were examined in each unit, but the five older units had a two-fold higher volume of activity than the four newer ones (instituted <1 year before): 23 vs. 12, P = 0.02. These figures give an estimated volume of 163 and 60 patients per 100,000 inhabitants per year, respectively. Referrals: 60% from out-of-hospital services, 11% immediate and 13% delayed referrals from the Emergency Department, and 16% hospitalized patients. A diagnosis was established on initial evaluation in 191 (21%) patients and early by means of 2.9 +/- 1.6 tests in 541 (61%) patients. A likely reflex cause was established in 67%, orthostatic hypotension in 4%, cardiac in 6% and non-syncopal in 5% of the cases. The cause of syncope remained unexplained in 159 (18%) patients, despite a mean of 3.5 +/- 1.8 tests per patient. These latter patients were older, more frequently had structural heart disease or electrocardiographic abnormalities, unpredictable onset of syncope due to the lack of prodromes, and higher OESIL and EGSIS risk scores than the other groups of patients. The mean costs of diagnostic evaluation was 209 euro per outpatient and 1073 euro per inpatient. The median cost of hospital stay was 2990 euro per patient. CONCLUSION We documented the current practice of syncope management in specialized facilities that have adopted the management model proposed by the ESC. The results are useful for those who wish to replicate this model in other hospitals. Syncope remains unexplained during in-hospital evaluation in more complex cases at higher risk.

Long-Term Complications Related to Biventricular Defibrillator Implantation Rate of Surgical Revisions and Impact on Survival: Insights From the Italian ClinicalService Database

Background— Long-term data on device-related untoward events in patients receiving defibrillators for resynchronization therapy (CRT-D) are lacking. We quantified the frequency of repeat invasive procedures and the nature of long-term complications in current clinical practice and examined possible predictors of device-related events and their association with long-term patient outcome. Methods and Results— We analyzed data from 3253 patients who underwent de novo successful implantation of CRT-D and were followed up for a median of 18 months (25th to 75th percentiles: 9 to 30) in 117 Italian centers. Device-related events were reported in 416 patients, and, specifically, surgical interventions for system revision were described in 390 patients. Four years after the implantation procedure, 50% of patients underwent surgical revision for battery depletion and 14% for unanticipated events. For comparison, at 4 years battery depletion occurred in 10% and 13% of patients who received single- and dual-chamber defibrillators at the study centers, and unanticipated events were reported as 4% and 9%, respectively. In CRT-D, infections occurred at a rate of 1.0%/y, and the risk of infections increased after device replacement procedures (hazard ratio, 2.04; 95% confidence interval, 1.01 to 4.09; P =0.045). Left ventricular lead dislodgements were reported at a rate of 2.3%/y and were predicted by longer fluoroscopy time and higher pacing threshold on implantation. Device-related events were not associated with a worse clinical outcome; indeed, the risk of death was similar in patients with and without surgical revision (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.47; P =0.682). Conclusions— In current clinical practice device-related events are more frequent in CRT-D than in single- or dual-chamber defibrillators, and are frequently managed by surgical intervention for system revision. However, a worse clinical outcome is not associated with these events. Clinical Trial Registration— URL: . Unique identifier: [NCT01007474][1]. # Clinical Perspective {#article-title-32} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01007474&atom=%2Fcirculationaha%2F123%2F22%2F2526.atomBackground— Long-term data on device-related untoward events in patients receiving defibrillators for resynchronization therapy (CRT-D) are lacking. We quantified the frequency of repeat invasive procedures and the nature of long-term complications in current clinical practice and examined possible predictors of device-related events and their association with long-term patient outcome. Methods and Results— We analyzed data from 3253 patients who underwent de novo successful implantation of CRT-D and were followed up for a median of 18 months (25th to 75th percentiles: 9 to 30) in 117 Italian centers. Device-related events were reported in 416 patients, and, specifically, surgical interventions for system revision were described in 390 patients. Four years after the implantation procedure, 50% of patients underwent surgical revision for battery depletion and 14% for unanticipated events. For comparison, at 4 years battery depletion occurred in 10% and 13% of patients who received single- and dual-chamber defibrillators at the study centers, and unanticipated events were reported as 4% and 9%, respectively. In CRT-D, infections occurred at a rate of 1.0%/y, and the risk of infections increased after device replacement procedures (hazard ratio, 2.04; 95% confidence interval, 1.01 to 4.09; P=0.045). Left ventricular lead dislodgements were reported at a rate of 2.3%/y and were predicted by longer fluoroscopy time and higher pacing threshold on implantation. Device-related events were not associated with a worse clinical outcome; indeed, the risk of death was similar in patients with and without surgical revision (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.47; P=0.682). Conclusions— In current clinical practice device-related events are more frequent in CRT-D than in single- or dual-chamber defibrillators, and are frequently managed by surgical intervention for system revision. However, a worse clinical outcome is not associated with these events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01007474.

Can monitoring of intrathoracic impedance reduce morbidity and mortality in patients with chronic heart failure? Rationale and design of the Diagnostic outcome Trial in Heart Failure (DOT-HF)

Chronic heart failure is associated with frequent hospitalisations which are often due to volume‐overload decompensation. Monitoring of intrathoracic impedance, measured from an implanted device, can detect increases in pulmonary fluid retention early and facilitate timely treatment interventions.

Efficacy of Long Detection Interval Implantable Cardioverter-Defibrillator Settings in Secondary Prevention Population Data From the Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) Trial

Background —Three trials recently demonstrated that a long detection window reduce ICD therapy in primary prevention (PP) patients. Advance III was the only trial enrolling both PP and secondary prevention (SP) patients. Methods and Results —Out of 1902 patients enrolled in the ADVANCEIII trial, 477 received a defibrillator for SP : 248 pts were randomly assigned to a long detection setting (30/40 intervals) and 229 pts to the nominal setting (18/24 intervals) for ventricular arrhythmias (VA) with cycle length ≤320 ms. Patients were 85% men with mean age of 65±12, previous history of ventricular fibrillation in 37% of the cases and mean ejection fraction of 38%±13%. ICD device mix was 37% single, 47% dual and 16% triple chamber. Over a median period of 12 months, the long detection was associated with a 25% reduction in the number of overall therapies (115.6 rate per 100/pts years vs 86.8; IRR: 0.75 95%CI:0.61-0.93, p=0.008) and 34% reduction in the number of shocks (51.2 rate per 100 pts years vs 38.1; IRR: 0.66; 95%CI:0.48-0.89, p=0.007). Appropriate therapies (89.7 vs 67.7; IRR: 0.77 95%CI:0.60-0.97, p=0.029) and appropriate shocks (37.1 vs 28.1; IRR:0.64 95%CI:0.45-0.93, p=0.018) were also reduced. Conclusions —Advance III is the first randomized trial that assessed an ICD long detection window setting in both PP and SP populations and demonstrates a reduction of overall therapies and shocks in the subgroup of SP patients. These data suggest that even SP population may benefit from a programming that combines a long detection with ATP during charging. Clinical Trial Registration Information —clinicaltrials.gov. Identifier: [NCT00617175][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00617175&atom=%2Fcirculationaha%2Fearly%2F2014%2F05%2F16%2FCIRCULATIONAHA.114.009468.atomBackground— Three trials demonstrated recently that a long detection window reduces implantable cardioverter-defibrillator (ICD) therapy in primary prevention patients. Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) was the only trial that enrolled both primary and secondary prevention patients. Methods and Results— Of the 1902 patients enrolled in the ADVANCE III trial, 477 received a defibrillator for secondary prevention; 248 patients were randomly assigned to a long detection setting (30 of 40 intervals) and 229 to the nominal setting (18 of 24 intervals) for ventricular arrhythmias with cycle length ⩽320 ms. Eight-five percent of patients were men, with a mean age of 65±12 years, a previous history of ventricular fibrillation in 37% of the cases, and a mean ejection fraction of 38±13%. The ICD device mix was 37% single chamber, 47% dual chamber, and 16% triple chamber. Over a median period of 12 months, the long detection period was associated with a 25% reduction in the number of overall therapies (115.6 versus 86.8 per 100 patient-years; incidence rate ratio, 0.75; 95% confidence interval, 0.61–0.93; P=0.008) and a 34% reduction in the number of shocks (rate per 100 patient-years, 51.2 versus 38.1; incidence rate ratio, 0.66; 95% confidence interval, 0.48–0.89; P=0.007). Appropriate therapies (89.7 versus 67.7; incidence rate ratio, 0.77; 95% confidence interval, 0.60–0.97; P=0.029) and appropriate shocks (37.1 versus 28.1; incidence rate ratio, 0.64; 95% confidence interval, 0.45–0.93; P=0.018) were also reduced. Conclusions— ADVANCE III is the first randomized trial to assess a long detection window setting in ICDs in both primary and secondary prevention populations and demonstrates a reduction of overall therapies and shocks in the subgroup of secondary prevention patients. These data suggest that even the secondary prevention population may benefit from programming that combines a long detection period with antitachycardia pacing during charging. Clinical Trial Registration— URL: http://www/clinicaltrials.gov. Unique identifier: NCT00617175.

Follow‐Up of CRT‐ICD: Implications for the Use of Remote Follow‐Up Systems. Data from the InSync ICD Italian Registry

Background: Launch of remote follow‐up systems in Europe is currently underway. However, there is insufficient understanding of postimplant practices with respect to device follow‐up, reprogramming of device features, and postshock clinic visits.