"First-degree AV block-a benign entity?" Insertable cardiac monitor in patients with 1st-degree AV block reveals presence or progression to higher grade block or bradycardia requiring pacemaker implant.

BACKGROUND: First-degree AV block has in the past generally been considered a benign condition. A few recent studies have shown that 1st-degree AV block is associated with an increased risk for heart failure, pacemaker (IPG) implantation, and death. We investigated the outcomes of patients who received an insertable cardiac monitor (ICM) (Medtronic Reveal XT®) within the scope of the INSIGHT XT study and had 1st-degree AV block at baseline. METHODS: The observational, international, multi-center INSIGHT (R)XT study prospectively enrolled 1003 patients implanted with an ICM for arrhythmia diagnosis, irrespective of the clinical indication. This analysis includes 37 patients who had documented 1st-degree AV block at enrolment. Patients with known concurrent higher grade block at enrolment were excluded. RESULTS: The indications for rhythm monitoring and ICM implantation were syncope/pre-syncope in 54.1%, cryptogenic stroke in 18.9%, AF with rhythm control intervention in 21.6%, and unexplained palpitations in 5.4%. Mean age was 68 ± 14 years, 75.7% were male, and concurrent bundle branch block was present in 8.1%. The median follow-up time was 12.2 months (IQR3.9-15.9). Fifteen patients (40.5%) received an IPG during the follow-up, and in 93.3% of the cases, the implant was needed to treat a now detected more severe bradycardia or progression of the conduction disease. CONCLUSIONS: ICM either revealed progression of 1st-degree AV block to a higher grade block (53%) or detected an already existing more severe bradycardia warranting an IPG in 40.5% patients. This finding supports the conclusion that 1st-degree AV block might be a risk marker for more severe intermittent conduction disease and is not benign in all patients. Further studies may reveal patient subgroups which are at risk for demonstrating or developing higher grade AV block and may warrant a future IPG implantation.

Atrioventricular junction ablation in patients with atrial fibrillation treated with cardiac resynchronization therapy: positive impact on ventricular arrhythmias, implantable cardioverter-defibrillator therapies and hospitalizations.

AIMS: We sought to determine whether atrioventricular junction ablation (AVJA) in patients with cardiac resynchronization therapy (CRT) implantable cardioverter-defibrillator (ICD) and with permanent atrial fibrillation (AF) has a positive impact on ICD shocks and hospitalizations compared with rate-slowing drugs. METHODS AND RESULTS: This is a pooled analysis of data from 179 international centres participating in two randomized trials and one prospective observational research. The co-primary endpoints were all-cause ICD shocks and all-cause hospitalizations. Out of 3358 CRT-ICD patients (2720 male, 66.6 years), 2694 (80%) were in sinus rhythm (SR) and 664 (20%) had permanent AF-262 (8%) treated with AVJA (AF + AVJA) and 402 (12%) treated with rate-slowing drugs (AF + Drugs). Median follow-up was 18 months. The mean (95% confidence intervals) annual rate of all-cause ICD shocks per 100 patient years was 8.0 (5.3-11.9) in AF + AVJA, 43.6 (37.7-50.4) in AF + Drugs, and 34.4 (32.5-36.5) in SR patients, resulting in incidence rate ratio (IRR) reductions of 0.18 (0.10-0.32) for AF + AVJA vs. AF + Drugs (P < 0.001) and 0.48 (0.35-0.66) for AF + AVJA vs. SR (P < 0.001). These reductions were driven by significant reductions in both appropriate ICD shocks [IRR 0.23 (0.13-0.40), P < 0.001, vs. AF + Drugs] and inappropriate ICD shocks [IRR 0.09 (0.04-0.21), P < 0.001, vs. AF + Drugs]. Annual rate of all-cause hospitalizations was significantly lower in AF + AVJA vs. AF + Drugs [IRR 0.57 (0.41-0.79), P < 0.001] and SR [IRR 0.85 (073-0.98), P = 0.027]. CONCLUSION: In AF patients treated with CRT, AVJA results in a lower incidence and burden of all-cause, appropriate and inappropriate ICD shocks, as well as to fewer all-cause and heart failure hospitalizations. CLINICAL TRIAL REGISTRATION: NCT00147290, NCT00617175, NCT01007474.

Atrial antitachycardia pacing and atrial remodeling: A substudy of the international, randomized MINERVA trial.

BACKGROUND: Atrial tachycardia (AT) and atrial fibrillation (AF) are common in pacemaker patients and are associated with bad prognoses. OBJECTIVE: The purpose of this study was to evaluate atrial antitachycardia pacing impact on AT/AF-induced atrial remodeling, measured by early recurrence of AT/AF (ERAF) and by change in left atrial diameter (LAD), and to evaluate the impact of AT/AF duration on ERAF incidence. METHODS: Pacemaker patients were randomized to dual-chamber pacing (Control DDDR: 385 patients), managed ventricular pacing (MVP: 398 patients), or atrial antitachycardia pacing plus MVP (DDDRP+MVP: 383 patients). LAD change, estimated by echocardiography, was considered significant if the relative difference between baseline and 24-month measurements was >10%. RESULTS: At median follow-up of 34 months, ERAF incidence was significantly lower in the DDDRP+MVP arm for all AT/AF durations, in particular, ERAF followed AT/AF longer than 3 hours in 53% cases in Control DDDR, in 51% cases in MVP, and in 39% cases in DDDRP+MVP (P <.001 vs other groups). ERAF incidence showed a U-shaped pattern when evaluated as a function of previous AT/AF duration, decreasing for durations from 5 minutes to 12 hours and increasing for longer durations. Among patients with significant LAD change, the proportion of patients with a reduction in LAD was 35% in Control DDDR, 37% in MVP, and 70% in DDDRP+MVP (P <.05 vs other groups). CONCLUSION: Our data suggest that atrial electrical remodeling becomes important after about 12 hours of continuous arrhythmia. Compared to DDDR or MVP, DDDRP+MVP reduces ERAF and favors LAD reduction, suggesting that atrial antitachycardia pacing may reverse electrical and mechanical remodeling.

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.

Association between ventricular pacing and persistent atrial fibrillation in patients indicated to elective pacemaker replacement: Results of the Prefer for Elective Replacement MVP (PreFER MVP) randomized study.

BACKGROUND: Pacing in the right ventricle can cause a variety of detrimental effects, including atrial tachyarrhythmias (atrial tachycardia [AT]/atrial fibrillation [AF]). OBJECTIVE: The purpose of this study was to evaluate the incidence and predictors of persistent AT/AF in patients with long-term exposure to ventricular pacing. METHODS: In a multicenter international trial, 605 patients (age 75 ± 11 years, 240 women) referred for replacement of an implanted pacemaker or implantable cardioverter-defibrillator (ICD), with a history of high-percentage (>40%) ventricular pacing, were randomly allocated to standard dual-chamber pacing or managed ventricular pacing (MVP), a pacing modality that minimizes ventricular pacing. The main end-point of this secondary analysis of the PreFER MVP randomized study was persistent AT/AF, defined as ≥7 consecutive days with AT/AF or AT/AF interrupted by atrial cardioversion or AT/AF present during 2 consecutive follow-up visits. RESULTS: Persistent AT/AF was observed in 71 patients (11.7%) after 2 years of follow-up. At multivariable Cox regression analysis, prior AT/AF (hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.20-6.22, P = .017) and ventricular pacing percentage, estimated in the first 3 months, ≥10% (HR 3.24, 95% 95% CI 1.13-9.31, P = .029) were independent predictors for persistent AT/AF. MVP was associated with persistent AT/AF risk (HR 3.41, 95% 95% CI 1.10-10.6, P = .024) in the subgroup of patients with baseline long PR interval (PR >230 ms) but not in the whole population. CONCLUSION: In pacemaker and ICD replacement patients, a high percentage of ventricular pacing is associated with higher risk of persistent AT/AF. Use of algorithms that minimize right ventricular pacing may benefit patients with normal spontaneous AV conduction but should be evaluated with caution in patients with long PR interval.

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.

Determinants of all-cause mortality in different age groups in patients with severe systolic left ventricular dysfunction receiving an implantable cardioverter defibrillator (from the Italian ClinicalService Multicenter Observational Project).

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.

Ventricular rate monitoring as a tool to predict and prevent atrial fibrillation-related inappropriate shocks in heart failure patients treated with cardiac resynchronisation therapy defibrillators.

OBJECTIVE: Inappropriate implantable cardioverter defibrillators (ICD) therapies have been associated with multiple adverse effects, including worse quality of life and prognosis. We evaluated the possibility of predicting atrial fibrillation (AF)-related inappropriate ICD shocks through continuous monitoring of device diagnostics. METHODS: 1404 ICD patients were prospectively followed in an observational research by 74 Italian cardiology centres. Device diagnostics stored daily information on AF duration and ventricular rate (VR) during AF. Uncontrolled VR was defined as mean VR>80 beats per minute (bpm) and maximum VR>110 bpm. Expert electrophysiologists reviewed the ventricular tachycardia/ventricular fibrillation (VT/VF) episodes electrograms, stored in the device memory, and classified appropriate detections, inappropriate detection mechanisms and ICD therapy outcomes. RESULTS: Over a median follow-up of 31 months, 511 (36%) patients suffered spontaneous VT/VF, which were treated by ICD shocks in a subgroup of 189 (13%) patients. Inappropriate detections occurred in 232 (16%) patients, and inappropriate ICD shocks in 101 (7%) patients. AF was the cause of inappropriate shocks in 60 patients. AF caused 144 inappropriate shocks: 53% of all inappropriate shocks. The likelihood of experiencing AF-related inappropriate shocks was 2.4% at 1 year and 6% at 5 years. Uncontrolled VR during AF proved to be an independent predictor of AF-related inappropriate shocks (OR=3.02, p=0.006); an alarm set at a VR>90 bpm or 100 bpm was associated with prediction of AF-related inappropriate shocks with a sensitivity of 73% or 62%, respectively. CONCLUSIONS: AF is the most common cause of inappropriate shocks in ICD patients. Continuous remote monitoring of VR during AF would promptly and efficiently predict AF-related inappropriate shocks. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/ct2/show/NCT01007474.

Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial.

AIMS: Atrial fibrillation (AF) is a common comorbidity in bradycardia patients. Advanced pacemakers feature atrial preventive pacing and atrial antitachycardia pacing (DDDRP) and managed ventricular pacing (MVP), which minimizes unnecessary right ventricular pacing. We evaluated whether DDDRP and MVP might reduce mortality, morbidity, or progression to permanent AF when compared with standard dual-chamber pacing (Control DDDR). METHODS AND RESULTS: In a randomized, parallel, single-blind, multi-centre trial we enrolled 1300 patients with bradycardia and previous atrial tachyarrhythmias, in whom a DDDRP pacemaker had recently been implanted. History of permanent AF and third-degree atrioventricular block were exclusion criteria. After a 1-month run-in period, 1166 eligible patients, aged 74 ± 9 years, 50% females, were randomized to Control DDDR, DDDRP + MVP, or MVP. Analysis was intention-to-treat. The primary outcome, i.e. the 2-year incidence of a combined endpoint composed of death, cardiovascular hospitalizations, or permanent AF, occurred in 102/385 (26.5%) Control DDDR patients, in 76/383 (19.8%) DDDRP + MVP patients [hazard ratio (HR) = 0.74, 95% confidence interval 0.55-0.99, P = 0.04 vs. Control DDDR] and in 85/398 (21.4%) MVP patients (HR = 0.89, 95% confidence interval 0.77-1.03, P = 0.125 vs. Control DDDR). When compared with Control DDDR, DDDRP + MVP reduced the risk for AF longer than 1 day (HR = 0.66, 95% CI 0.52-0.85, P < 0.001), AF longer than 7 days (HR = 0.52, 95% CI 0.36-0.73, P < 0.001), and permanent AF (HR = 0.39, 95% CI 0.21-0.75, P = 0.004). CONCLUSION: In patients with bradycardia and atrial tachyarrhythmias, DDDRP + MVP is superior to standard dual-chamber pacing. The primary endpoint was significantly lowered through the reduction of the progression of atrial tachyarrhythmias to permanent AF. CLINICALTRIALSGOV IDENTIFIER: NCT00262119.

Acute kidney injury after transcatheter aortic valve implantation with self-expanding CoreValve prosthesis: results from a large multicentre Italian research project.

AIMS: Transcatheter aortic valve implantation (TAVI) can be associated with varying degrees of new renal impairment. The aim of this multicentre analysis was to determine the impact and predictors of periprocedural acute kidney injury (AKI) on prognosis after TAVI. METHODS AND RESULTS: From the ClinicalService (a nation-based data repository and medical care project) dataset, 1,157 patients with severe aortic stenosis treated with the third-generation CoreValve prosthesis in seven Italian sites, and with creatinine data available at baseline and during the post-TAVI in-hospital course, were included in this analysis. All outcomes were defined according to the VARC criteria. Overall, AKI occurred in 231 (20.0%): 15.4% stage 1, 2.7% stage 2, and 1.9% stage 3. Compared to patients without AKI, patients who suffered post-procedural AKI had significantly higher three-year all-cause mortality (31% vs. 12%; adjusted HR: 2.09; 95% CI: 1.52-2.87, p<0.001) and cardiovascular mortality (14% vs. 6%; adjusted HR: 2.28; 95% CI: 1.41-3.71, p=0.001). No significant differences in terms of stroke, spontaneous MI, and bleeding were reported. Female gender (adjusted OR: 1.37, 95% CI: 1.01-1.87; p=0.045), baseline renal insufficiency (adjusted OR: 11.02, 95% CI: 5.12-23.73; p<0.001), general anaesthesia (adjusted OR: 1.37, 95% CI: 1.00-1.87; p=0.050), and transfusion ≥3 red blood cell (RBC) units within 72 hrs from TAVI (adjusted OR: 1.65, 95% CI: 1.02-2.68; p=0.041) were found to be independent predictors of AKI. CONCLUSIONS: Acute kidney injury is a frequent complication and significantly impacts on both early and long-term TAVI survival. Females, subjects with impaired renal function at baseline, patients undergoing TAVI under general anaesthesia, and patients receiving ≥3 RBC units after the procedure should be considered populations at high risk for the development of AKI after TAVI.

Low-dose dobutamine test associated with interventricular dyssynchrony: a useful tool to identify cardiac resynchronization therapy responders: data from the LOw dose DObutamine stress-echo test in Cardiac Resynchronization Therapy (LODO-CRT) phase 2 study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in patients with heart failure, but 30% to 50% of subjects are classified as nonresponders. Identifying responders remains a challenging task. AIMS: The LODO-CRT trial investigated the association between left ventricular contractile reserve (LVCR) and clinical and echocardiographic long-term CRT response. METHODS: This is a multicenter, prospective, observational study. Left ventricular contractile reserve was detected using a dobutamine stress echocardiography test, defined as an ejection fraction increase of >5 points. Clinical CRT response was defined as the absence of major cardiovascular events (ie, cardiovascular death or heart failure hospitalization). Echocardiographic response was defined as a left ventricle end-systolic volume reduction of >10%. RESULTS: A total of 221 CRT-indicated patients were studied (80% presented LVCR). During a mean follow-up of 15 ± 5 months, 17 patients died and 16 were hospitalized due to heart failure. The proportion of clinical responders was 155 (88%) of 177 and 33 (75%) of 44 (P = .036) in the groups with and without LVCR, respectively. Kaplan-Meier analysis showed a significant difference in cardiac survival/hospitalization between patients with and without LVCR. The proportion of echocardiographic responders was 144 (87%) of 166 and 16 (42%) of 38 in the groups with and without LVCR (P < .001), respectively; LVCR showed 90% sensitivity and 87% positive predictive value to prefigure echocardiographic CRT responders. Multivariable analysis identified LVCR and interventricular dyssynchrony as independent predictors of CRT response. The concomitant presence of both factors showed 99% specificity and 83% sensitivity in detecting responders. CONCLUSION: The presence of LVCR helps in predicting a clinical and echocardiographic CRT response. Concomitant assessment of LVCR and interventricular dyssynchrony accurately stratifies responder and nonresponder patients.

Comparison between sensor-augmented insulin therapy with continuous subcutaneous insulin infusion or multiple daily injections in everyday life: 3-day analysis of glucose patterns and sensor accuracy in children.

BACKGROUND: Sensor-augmented continuous subcutaneous insulin infusion (CSII) therapy is superior to CSII therapy alone, but little is known on the effectiveness of sensor-augmented multiple daily injections (MDI) therapy. METHODS: We compared during everyday life mean glucose control and several variability indexes recorded for 3 days by a real-time glucose sensor (Medtronic, Northridge, CA) in two groups of children treated with either CSII or MDI. Fifty-five consecutive subjects were examined: 17 receiving CSII and 38 receiving MDI basal-bolus therapy (age range, 7-22 years). All subjects wore the sensor for 4 days, and 3 days were used for statistical analysis. Mean glucose and SD, coefficient of variation (CV), mean amplitude of glucose excursion (MAGE), mean of daily differences (MODD), continuous overall net glycemic action (CONGA) at 2 and 4 h, blood glucose (BG) rate, area under the curve (AUC) above 180 mg/dL and below 70 mg/dL, Low BG Index (LBGI), and High BG Index (HBGI) were calculated. RESULTS: Patients receiving CSII administered more daily boluses than patients receiving MDI (5.2±1.5 vs. 3.2±0.3, respectively; P=0.001). Mean glucose was lower in the CSII group. AUC above 180 mg/dL and HBGI were higher in the MDI group. CV, CONGA at 2 h, CONGA at 2 h during the day, and HBGI were worse in the MDI group, whereas MODD, LBGI, BG rate, and MAGE were similar. A positive correlation (r=0.95; P<0.05) was found between the paired sensor-meter values. For the glucose values <70 mg/dL, sensitivity was 40%, and specificity was 99%. CONCLUSIONS: In our pediatric patients during everyday life sensor-augmented CSII therapy seemed more effective than sensor-augmented MDI therapy, in terms both of glucose mean values and of intraday variability. Mild hypoglycemic episodes and indexes of low BG values were similar in the two groups, although the latter results may be inaccurate because of low sensor sensitivity at low glucose value.