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Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections.We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months.A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98).Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).

Aims Per standard of care, dual-chamber pacemakers are programmed in DDDR mode with fixed atrioventricular (AV) delay or with long AV delay to minimize ventricular pacing. We aimed to evaluate whether the PR interval may be a specific criterion of choice between standard DDDR, to preserve AV synchrony in long PR patients, and managed ventricular pacing (MVP), to avoid ventricular desynchronization imposed by right ventricle apical pacing, in short PR patients. Methods and results In the MINERVA trial, 1166 patients were randomized to Control DDDR, MVP, or atrial anti-tachycardia pacing plus MVP (DDDRP + MVP). We evaluated the interaction of PR interval with pacing mode by comparing the risk of atrial fibrillation (AF) longer than 7 consecutive days as a function of PR interval. Out of 906 patients with available data, the median PR interval was 180ms. The PR interval was found to significantly (P=0.012) interact with pacing mode for AF incidence: the risk of AF>7days was lower [hazard ratio (HR) 0.58, 95% confidence interval (95% CI) 0.34-0.99; P=0.047] in patients with short PR (shorter than median PR) if programmed in MVP mode compared with DDDR mode and it was lower (HR 0.65, 95% CI 0.43-0.99; P=0.049) in patients with long PR (equal to or longer than median PR) if programmed in DDDR mode compared with MVP. Conclusion Our data show that PR interval may be used as a selection criterion to identify the optimal physiological pacing mode. Persistent AF incidence was lower in short PR patients treated by right ventricular pacing minimization and in long PR patients treated by standard dual-chamber pacing.

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, 66.6years), 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 18months. 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

The replacement of implantable cardioverter‐defibrillators (ICDs) may give rise to considerable clinical consequences, the importance of which is underrated by the medical community. Replacement‐related adverse events are difficult to identify and require monitoring of both short‐term complications and long‐term patient outcome. The aim of this study is to perform a structured evaluation of both short‐ and long‐term adverse events and a cost analysis of consecutive ICD replacement procedures. Detect Long‐term Complications After ICD Replacement (DECODE) is a prospective, single‐arm, multicenter cohort study designed to estimate long‐term complication rates (at 12 months and 5 years) in patients undergoing ICD generator replacement. The study will also evaluate predictors of complications, patient management before and during the replacement procedure in clinical practice, and the costs related to use of health care resources. About 800 consecutive patients with standard indications for ICD generator replacement will be enrolled in this study. The decision to undertake generator replacement/upgrade will be made according to the investigators' own judgment (which will be recorded). Patients will be followed for 60 months through periodic in‐hospital examinations or remote monitoring. Detailed data on complications related to ICD replacement in current clinical practice are still lacking. The analysis of adverse events will reveal the value of new preventive strategies, thereby yielding both clinical and economic benefits. Moreover, assessment of complication rates after ICD replacement in a real‐life setting will help estimate the actual long‐term cost of ICD therapy and assess the real impact of increasing ICD longevity on cost‐effectiveness.

To understand the impact of a quadripolar left ventricular (LV) lead on reverse remodeling and phrenic nerve stimulation (PNS) in congestive heart failure patients treated by cardiac resynchronization therapy at 8-month follow-up (FU).One hundred and fifty-eight patients received an LV Medtronic Performa lead (Medtronic Inc., Minneapolis, MN, USA) and were reevaluated at FU by echocardiography and measurement of electrical parameters.A targeted LV lead placement was achieved in 140 (89%) patients. Super responders and responders were 76 (50%) and 26 (18%), respectively, at FU; seven (4%) died and 13 (8%) were hospitalized for any cause. Nonischemic etiology was the only independent predictor of reverse remodeling. The configurations available only with the Performa leads reduced PNS occurrence at 8 V@0.4 ms from 43 (27%) to 14 (9%) of patients at implantation, and from 44 (28%) to 19 (12%) at last FU, compared to configurations available with bipolar leads. Patients with detectable PNS had10/16 pacing configurations with a PNS safety margin2 V both at implantation and at FU. During FU 16 (10%) patients had an adverse event possibly related to the lead or to modification of the underlying heart disease but 99% of these events were fixed by reprogramming of the pacing vector.Performa Lead enables an increased capability to achieve a targeted lead positioning in the broad clinical scenario of large- and small-volume implanting centers, with a relevant impact on the occurrence of reverse remodeling compared to literature data. The enhanced management of PNS resulted in a dislodgement rate of only 1%.

The searches for drugs that exhibit antineoplastic activity and regulate blood pressure are among the most prevalent and compelling research activities today. Amazingly, there is ample precedence for the antiproliferative action of vitamin-D-related compounds and their role as endocrine suppressors of renin biosynthesis. We have recently synthesized a number of novel calcitriol analogs of the gemini family and originally selected for further studies an epimeric pair related to 19-nor-calcitriol whose 21-methyl group was replaced by a 5,5,5-trifluoro-4-hydroxy-4-(trifluoromethyl)-2-pentynyl group. While maintaining the acceptable calcemic responses, the IC50 concentrations of interferon-gamma release were reduced and the antiproliferative activity and inhibition of renin mRNA expression enhanced. Replacing the geminal methyl groups on the calcitriol-related side chain of these gemini compounds with trideuteriomethyl moieties further boosted the potency in the colon cancer model in mice some 10-fold, reduced NMU-induced breast cancer carcinogenesis in rats and decreased the IC(50) values for renin mRNA inhibition into the pM range.

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Cardiac resynchronization therapy (CRT) is an effective and useful electrical treatment for appropriately selected heart failure patients with complete left bundle branch block, even for those with mild symptoms. It has been calculated that 3-12% of heart failure patients could benefit from a CRT device. According to the results of a series of trials, biventricular pacing improves quality of life and haemodynamic parameters and this is associated with a reduction in heart failure hospitalizations and mortality. The efficacy of CRT has been proven by a series of randomized controlled studies, and consensus guidelines now give precise recommendations for selecting candidates for CRT not only among patients with moderate to severe heart failure, but also among patients with mild heart failure. Despite some uncertainties concerning a series of issues (selection of candidates, prediction of response, phrenic nerve stimulation, optimization of device programming), CRT is now an accepted treatment for selected patients with heart failure and specific indications are included in consensus guidelines for heart failure treatment. Devices for CRT have a relatively high upfront cost, but when CRT is applied to appropriately selected patients it may be a worthwhile investment not only for our patients but also for our healthcare systems.

Comment on: Potpara TS, Stankovic GR, Beleslin BD, Polovina MM, Marinkovic JM, Ostojic MC, Lip GY A 12-year follow-up study of patients with newly diagnosed lone atrial fibrillation: implications of arrhythmia progression on prognosis: the Belgrade Atrial Fibrillation study. Chest. 2012 Feb;141(2):339-47. .

Background And Purpose- In patients with atrial fibrillation (AF), stroke risk stratification schema do not consider AF parameters. The aim of the study is to assess the impact of combining risk factors with continuous AF burden monitoring. Methods- In this retrospective study 568 patients implanted with a DDDR-P pacemaker (AT-500; Medtronic) and a history of AF were continuously monitored for 1 year. Results- During follow-up, 14 patients (2.5%) had a thromboembolic event. Patients were divided into 3 groups: AF burden ≤5 minutes per day (AF-free; n=223 [39%]), AF burden >5 minutes but

Background: We studied long-term right ventricular (RV) pacing threshold (RVPT) behavior in patients consecutively implanted with pacemakers capable of automatic output reprogramming tracked by automatic RV threshold measurement (automatic verification of capture [AVC]). Methods: All the patients had state-of-the art steroid-eluting bipolar pacing leads and were RV-paced by an AVC algorithm from the three American manufacturers. Follow-up occurred twice in the first year after implantation, then yearly until approaching elective replacement indicator. Results: Three hundred and twenty-one patients aged 73 ± 12 years were observed for 49 ± 26 months on average. At implantation, RVPT was 0.54 ± 0.2 V at 0.4 ms at an average 774 ± 217 Ω impedance. Forty-one of the 321 patients (12.8%) had a permanent RVPT increase above 1.5 V at 0.4 ms: RVPT was between 1.6 and 2.5 V in 29 of 321 (9%) patients, whereas it was between 2.6 and 3.5 V in seven of 321 (2.2%) patients, and >3.5 V in five of 321 (1.5%) patients. No exit block occurred because of automatic RV output adjustment by AVC algorithms. No predictor of RVPT increase was found at multivariable analysis. The maximum RVPT increase occurred within 12 months from implantation in 19 of 321 (5.9%) patients, between the first and the second year in 12 of 321 (3.7%), between the second and the sixth year in eight of 321 (2.5%), and after the sixth year in two of 321 (0.6%). Conclusion: Despite technologic improvement in lead manufacturing, long-term increase of the RVPT occurs in about 13% of patients, possibly representing a serious safety issue in 3.7% when 2.5 V at 0.4 ms is exceeded. AVC algorithms can improve patients' safety by automatic tailoring of the pacing output to threshold fluctuations, while maximizing device longevity

The search for effective treatment for preventing sudden cardiac death (SCD) initially started with anti-arrhythmic agents in high-risk patients, but the use of randomized controlled trials clearly led to the conclusion that an approach based on anti-arrhythmic agents is not useful, and sometimes potentially harmful (the risk of arrhythmic death was increased up to 159% in CAST study). Today the approach to SCD prevention includes considering both the setting of patients who have already presented a cardiac arrest or a malignant ventricular tachyarrhythmias (secondary prevention of SCD) and the much broader setting of primary prevention in patients at variable degrees of identifiable risk. For secondary prevention of SCD, implantable cardioverter defibrillation is now the standard of care (the risk of overall mortality may be reduced by 20-31%), and anti-arrhythmic agents, specifically amiodarone, have only a complementary role (for reducing device activations or for preventing atrial fibrillation). For primary prevention of SCD in high-risk patients, cardioverter defibrillators have nowadays specific indications in patients with left ventricular dysfunction (often in combination with cardiac resynchronization therapy), where the risk of overall mortality may be reduced by 23-54%. For the large number of subjects who have some risk of SCD, but are not identified as at high risk of SCD, a series of drugs could exert a favorable effect (beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker agents, statins, omega-3 fatty acids and aldosterone antagonists), and for some of them evidence is emerging, from subgroup analysis, of possible SCD prevention capabilities.

Trattazione completa sulla problematche della sindrome da pacemaker, con focus su diagnosi e trattamento.

Background: Although left ventricular (LV) pacing has been proposed as an alternative to biventricular (BIV) pacing for heart failure (HF) patients, few comparative data are available on the electromechanical effects of these pacing modalities at mid-term follow-up. Aim: To investigate the clinical and echocardiographic effects of LV versus BIV pacing in a mid-term randomized study. Methods: After implantation of a device with LV/BIV pacing capabilities, 22 patients with chronic HF and left bundle branch block were randomized to LV or BIV pacing. Patients were assessed both preimplantation and after 3 months by clinical examination, ECG and echocardiography with pulsed tissue Doppler imaging. Results: At 3 months LV pacing improved clinical parameters, LV ejection fraction (+5%, range 5-8%, P = 0.007) and intraventricular dyssynchrony (-40 ms, range -50 to -15 ms, in septal to lateral delay, P = 0.008) to a similar extent to BIV pacing. A decrease in interventricular mechanical delay (-25 ms, range -40 to -5 ms, P = 0.008) and QRS duration (-28 ms, range -40 to -5 ms, P = 0.008) was observed in BIV, but not in LV patients. Conclusion: In this pilot evaluation, LV pacing appeared to be associated with clinical benefits similar to BIV pacing at mid-term follow-up, and this was combined with an improvement in intraventricular dyssynchrony, regardless of variations in interventricular dyssynchrony and QRS duration. Echocardiographic evaluation of intraventricular dyssynchrony seems to be an appropriate method for assessing the chronic response to LV pacing.

Automatic management of atrial stimulation by verification of atrial threshold (ACM) has recently been made feasible. We investigated circadian atrial threshold variability over the long term and the predictors of successful automatic atrial threshold measurement, in order to provide practical clues for programming ACM features, in such a way as to achieve daily threshold verification and99% effective atrial stimulation.Six daily attempts to measure atrial threshold were programmed in patients receiving an EnPulse pacemaker (Medtronic Inc., Minneapolis, MN, USA). Atrioventricular (AV) conduction was maximized by programming Search AV+ (SAV+) to a resting Paced AV delay = 400 ms in the first month, and 600 ms thereafter.Seventy-six patients had a median follow-up of 12 months. Median ACM success was 77%. Concordance between automatically and manually measured thresholds was observed during the entire follow-up (Rho = 0.82, P0.001). Daily variability in atrial threshold was0.5 V in94% of measurements in the first trimester after implantation, and0.5 V in99% of measurements thereafter, as well as any time after pacemaker replacement. Atrial threshold was measured on 86% of days: the predictors of ACM failure were AV block (AVB), high%Atrial pacing, and atrial fibrillation. Programming SAV+ to achieve 600 ms resting Paced AV decreased%Vpacing in patients with normal AV conduction and first-degree AVB, improving the ability to detect atrial threshold.The reliability of ACM is high over a long follow-up. On the basis of atrial threshold variability, a practical approach to ACM programming should be two daily atrial threshold measurements in patients with normal AV conduction and%Apor = 40%, or with normal sinus activity and AVB, whereas 3-4 measurements should be recommended in patients with first-degree AVB and%Ap40% or with recurrent atrial fibrillation and AVB. The lowest adapted stimulation output should achieve at least threshold +1 V in the first trimester after implantation, then threshold +0.5 V thereafter, in order to achieve99.5% effective atrial stimulation.