Sex differences in implantable cardiac defibrillator therapy according to arrhythmia detection times.

OBJECTIVE: In 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. METHODS: The 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. RESULTS: Overall, 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). CONCLUSIONS: In 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 REGISTRATION: NCT00617175.

Implantable cardioverter-defibrillators in patients with long QT syndrome: a multicentre study.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy has been proven effective in the prevention of sudden cardiac death, but data on outcomes of ICD therapy in the young and otherwise healthy patients with long QT syndrome (LQTS) are limited. AIM: We sought to collect data on appropriate and inappropriate ICD discharges, risk factors, and ICD-related complications. METHODS: All LQTS patients implanted with an ICD in 14 centres were investigated. Demographic, clinical, and ICD therapy data were collected. RESULTS: The study included 67 patients (88% female). Median age at ICD implantation was 31 years (12-77 years). ICD indication was based on resuscitated cardiac arrest in 46 patients, syncope in 18 patients, and malignant family history in three patients. During a median follow-up of 48 months, 39 (58%) patients received one or more ICD therapies. Time to first appropriate discharge was up to 55 months. Inappropriate therapies were triggered by fast sinus rhythm, atrial fibrillation, and T-wave oversensing. No predictors of inappropriate shocks were identified. Risk factors for appropriate ICD therapy were: (1) recurrent syncope despite b-blocker treatment before ICD implantation, (2) pacemaker therapy before ICD implantation, (3) single-chamber ICD, and (4) noncompliance to b-blockers. In 38 (57%) patients, at least one complication occurred. CONCLUSIONS: ICD therapy is effective in nearly half the patient population; however, the rates of early and late complica-tions are high. Although the number of unnecessary ICD shocks and reimplantation procedures may be lowered by modern programming and increased longevity of newer ICD generators, other adverse events are less likely to be reduced.

Long Detection Programming in Single-Chamber Defibrillators Reduces Unnecessary Therapies and Mortality: The ADVANCE III Trial.

OBJECTIVES: This study sought to evaluate the effects of programming a long detection in single-chamber (VVI) implantable cardioverter-defibrillators (ICDs) in the multicenter prospective ADVANCE III (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III) trial. BACKGROUND: Programming strategies may reduce unnecessary ICD shocks and their adverse effects but to date have been described only for dual-chamber ICDs. METHODS: A total of 545 subjects (85% male; atrial fibrillation 25%, left ventricular ejection fraction 31%, ischemic etiology 68%, secondary prevention indications 32%) receiving a VVI ICD were randomized to long detection (30 of 40 intervals) or standard programming (18 of 24 intervals) based on device type, atrial fibrillation history, and indication. In both arms, antitachycardia pacing (ATP) therapy during charging was programmed for episodes with cycle length 320 to 200 ms and shock only for cycle length <200 ms. Wavelet and stability functions enabled. Therapies delivered were compared using a negative binomial regression model. RESULTS: A total of 267 patients were randomized to long detection and 278 to the control group. Median follow-up was 12 months. One hundred twelve therapies (shocks and ATP) occurred in the long detection arm versus 257 in the control arm, for a 48% reduction with 30 of 40 intervals (95% confidence interval [CI]: 0.36 to 0.76; p = 0.002). In the long detection arm, overall shocks were reduced by 40% compared to the control arm (48 vs. 24; 95% CI: 0.38 to 0.94; p = 0.026) and appropriate shocks by 51% (34 vs. 74; 95% CI: 0.26 to 0.94; p = 0.033). Syncopal events did not differ between arms, but survival improved in the long detection arm. CONCLUSIONS: Among patients implanted with a VVI ICD, programming with the long detection interval significantly reduced appropriate therapies, shocks, and all-cause mortality. (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III [ADVANCEIII]; NCT00617175).

Different impact of long-detection interval and anti-tachycardia pacing in reducing unnecessary shocks: data from the ADVANCE III trial.

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.

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 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.

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.

Comparison of the acute hemodynamic effect of right ventricular apex, outflow tract, and dual-site right ventricular pacing.

BACKGROUND: We studied the acute effect of pacing at the right ventricular outflow tract (RVOT), right ventricular apex (RVA) and simultaneous RVA and RVOT-dual-site right ventricular pacing (DuRV) in random order on systolic function using impedance cardiography. METHODS: Seventy-three patients (46 males), aged 52-89 years (mean 71.4 years) subjected to routine dual chamber pacemaker implantation with symptomatic chronic II or atrioventricular block, were included to the study. RESULTS: DuRV pacing resulted in significantly higher cardiac index (CI) in comparison to RVOT and RVA and CI at RVOT was higher than at RVA pacing (2.46 vs 2.35 vs 2.28; P < 0.001). In patients with ejection fraction >50% significantly higher CI was observed during DuRV pacing when compared to RVOT and RVA pacing and there was no difference of CI between RVOT and RVA pacing (2.53 vs 2.41 vs 2.37; P < 0.001). In patients with ejection fraction <50%, DuRV and RVOT pacing resulted in significantly higher CI in comparison to RVA pacing while no difference in CI was observed between RVOT and DuRV pacing (2.28 vs 2.21 vs 2.09; P < 0.001). CONCLUSION: Dual-site right ventricular pacing in comparison to RVA pacing improved cardiac systolic function. RVOT appeared to be more advantageous than RVA pacing in patients with impaired, but not in those with preserved left ventricular function. No clear hemodynamic benefit of DuRV in comparison to RVOT pacing in patients with impaired systolic function was observed.

Dual-site right ventricular pacing. A rescue alternative in cardiac resynchronisation therapy implantation failure? More efficient stimulation for patients with borderline cardiac resynchronisation therapy indication? Less harmful ventricular pacing?

Permanent cardiac pacing is nowadays a widespread method for the cure of conduction system diseases, improving quality of life and often saving patients' lives. In the twentieth century, scientific efforts were focused on extending battery life, improving sensitivity and reliability, minimizing the dimensions of the device and restoring atrio-ventricular synchrony and rate response. However, there is more and more evidence for the deleterious influence of chronic right ventricular pacing especially apical (RVA) pacing. DANISH, MOST, CTOPP and DAVID trials have proven univocally that right ventricular pacing increases risk of heart failure, atrial fibrillation and even mortality in patients with chronic heart failure. Such knowledge inspires the quest for alternative pacing sites. Right ventricular outflow tract (RVOT) became the most favourable non-apical pacing site. Since 1995 there have been several reports concerning dual-site right ventricular pacing (DuVP: RVOT plus RVA pacing) proving its beneficial clinical and hemodynamic outcome especially in the case of unsuccessful left ventricle implantation for cardiac resynchronisation therapy (CRT). (Cardiol J 2007; 14: 224-231).