Acute safety, effectiveness, and real-world clinical usage of ultra-high density mapping for ablation of cardiac arrhythmias: results of the TRUE HD study.

AIMS: The objective of this study was to verify acute safety, performance, and usage of a novel ultra-high density mapping system in patients undergoing ablation procedure in a real-world clinical setting. METHODS AND RESULTS: The TRUE HD study enrolled patients undergoing catheter ablation with mapping for all arrhythmias (excluding de novo atrial fibrillation) who were followed for 1 month. Safety was determined by collecting all serious adverse events and adverse events associated with the study devices. Performance was determined as the composite of: ability to map the arrhythmia/substrate, complete the ablation applications, arrhythmia termination (where applicable), and ablation validation. Use of mapping system in the ablation validation workflow was also evaluated. Among the 519 patients who underwent a complete (504) or attempted (15) procedure, 21 (4%) serious ablation-related complications were collected, with 3 (0.57%) potentially related to the mapping catheter. Four hundred and twenty treated patients resulted in a successful procedure confirmed by arrhythmia-specific validation techniques (83.3%; 95% confidence interval: 79.8-86.5%). A total of 1419 electroanatomical maps were created with a median acquisition time of 9:23 min per map. Of these, 372 maps in 222 (44%) patients were collected for ablation validation purposes. Following validation mapping, 162/222 (73%) patients required additional ablation. CONCLUSION: In the TRUE HD study mapping was associated with rates of acute success and complications consistent with previously published reports. Importantly, a low percentage of events (0.57%) was attributed to the mapping catheter. When performed, validation mapping was useful for identifying additional targets for ablation in the majority of patients.

Preliminary findings on the safety of 1.5 and 3 Tesla magnetic resonance imaging in cardiac pacemaker patients.

INTRODUCTION: Modern pacemakers are designed to allow patients to undergo magnetic resonance imaging (MRI) under a set of specific conditions. Aim of this study is to provide confirmatory evidence of safety and performance of a new pacing system (ImageReady™, Boston Scientific) in patients undergoing 1.5 and 3T MRI. METHODS AND RESULTS: Two prospective, nonrandomized, single-arm studies were designed to provide confirmatory data of no impact of MRI on device function, lead parameters, and patient conditions in subjects implanted with the system undergoing a clinically non-indicated 1.5T and 3T MRI, respectively. Device measurements were done within 1 hour before and after the scan and at 1 month follow-up. Thirty-two subjects underwent MRI visit (17 subjects with 1.5T MRI and 15 subjects with 3T MRI). There were no unanticipated adverse effects related to the pacemaker. Device measurements taken pre- and post-MRI scan did not show any clinical relevant change that could indicate an effect of the MRI on the device or at the lead-tissue interface (RV threshold change: 0.01 ± 0.13 V, P = 0.60; RA threshold change: 0.01 ± 0.11 V, P = 0.53; R wave change: -0.44 ± 1.73 mV, P = 0.36; R wave change: 0.12 ± 1.67 mV, P = 0.73), with data confirmed at 1-month follow-up visit. CONCLUSION: The study documented safety of the pacing system in the 1.5T and 3T MRI environment by showing no adverse events related to device or MRI scan. Additional data are required to cover the more complex scenarios involving different diagnostic needs, conditions of use, clinical conditions, and new emerging technologies.

Electrical treatment of atrial arrhythmias in heart failure patients implanted with a dual defibrillator CRT device. Results from the TRADE-HF study.

BACKGROUND: Ventricular and atrial arrhythmias commonly occur in heart failure patients and are a significant source of symptoms, morbidity and mortality. Some specific generators referred to as dual defibrillators, Dual CRT-Ds, have the ability to treat atrial and ventricular arrhythmias. TRADE-HF is a prospective two-arm randomized study aimed at assessing the benefits of complete automatic management of atrial arrhythmias in patients implanted with a dual CRT-D. METHODS: Primary objective of the TRADE-HF study was to document reduction of unplanned hospital admission for cardiac reasons or death for cardiovascular causes or progression to permanent AF, by comparing fully-automatic device driven therapy for atrial tachycardia or fibrillation (AT/AF) to an in-hospital approach for treatment of symptomatic AT/AF. Randomized Patients were followed every 6months for 3years to assess the primary objective. RESULTS: Four-hundred-twenty patients have been enrolled in the study. At the end of the study 30 subjects died for cardiovascular causes, 60 had at least one hospitalization for cardiovascular causes and 14 developed permanent AF. Eighty-seven patients experienced a composite event. Hazard Ratio for device-managed automatic therapy arm compared to traditional was 0.987 (95% CI: 0.684-1.503; p=0.951). The primary endpoint analysis resulted in no difference between the device managed and in-hospital treatment arm. CONCLUSION: The TRADE-HF study failed to demonstrate a reduction in the composite of unplanned hospitalizations for cardiovascular causes or death for cardiovascular causes or progression to permanent AF using automatic atrial therapy compared to a traditional approach including hospitalization for symptomatic episodes and/or in-hospital treatment of AT/AF.

Prevention of syncope through permanent cardiac pacing in patients with bifascicular block and syncope of unexplained origin: the PRESS study.

BACKGROUND: Syncope in patients with bifascicular block (BFB) is a common event whose causes might be difficult to assess. METHODS AND RESULTS: Prevention of syncope through permanent cardiac pacing in patients with bifascicular block (PRESS) is a multicenter, prospective, randomized, single-blinded study designed to demonstrate a reduction in symptomatic events in patients with bifascicular block and syncope of undetermined origin implanted with permanent pacemaker. Device programming mode (NASPE/BPEG code) at DDD with a lower rate of 60 ppm is compared with backup pacing at DDI with a lower rate of 30 ppm. The end point consisted of (1) syncope, (2) symptomatic presyncopal episodes associated with a device intervention (ventricular pacing), and (3) symptomatic episodes associated with intermittent or permanent atrioventricular block (any degree). One hundred one patients were enrolled and randomized. Primary end point events at 2 years were observed in 23 patients, with a significant lower incidence in the study group (hazard ratio, 0.32; 95% confidence interval [CI], 0.10-0.96; P=0.042). Reduction of any symptoms, associated or not with device intervention, was superior in DDD60 compared with DDI30 (hazard ratio, 0.4; 95% confidence interval, 0.25-0.78; P=0.0053). Fourteen patients developed other rhythm diseases and met class I indication for pacing. The annual incidence of rhythm disease development was 7.4%. CONCLUSIONS: In patients with bifascicular block and syncope of undetermined origin, the use of a dual chamber pacemaker programmed to DDD60 led to a significant reduction of syncope or symptomatic events associated with a cardioinhibitory origin, compared with DDI30 programming. Symptoms associated with a new onset of rhythm disease were found in 15% of the population at 2 years.

Clinical characteristics, mortality, cardiac hospitalization, and ventricular arrhythmias in patients undergoing CRT-D implantation: results of the ACTION-HF study.

INTRODUCTION: The characteristics and outcomes of patients who undergo cardiac resynchronization therapy (CRT) device implantation in current clinical practice may differ from those of reference trial populations. Study objectives were to assess 2-year outcomes in a population implanted with a CRT plus defibrillator device in accordance with the standard of care and to evaluate any independent association between clinical variables and outcome. METHODS AND RESULTS: A total of 406 patients enrolled at 35 centers in Italy were followed up prospectively for 2 years. All patient management decisions were left to the treating physician's discretion, in accordance with clinical practice. ACTION-HF patients had a better baseline clinical status than patients enrolled in the COMPANION study: shorter HF history (1 vs 3.5 years, P < 0.01), less advanced NYHA functional class (III-IV: 73% vs 100%, P < 0.01), higher LVEF (26% vs 21%, P < 0.01), higher SBP (122 vs 112 mmHg, P < 0.01), and less diabetes (27% vs 41%, P < 0.01). This status was reflected in lower mortality (11.5% vs 26%) and a lower incidence of appropriate ICD shocks (12.1% vs 19.3%). AF history was an independent predictor of the combination of all-cause mortality and cardiac-cause hospitalization (HR: 3.31; P < 0.001). Recurrent or new atrial arrhythmias were independently associated with the development of ventricular arrhythmias (HR: 3.4; P < 0.001). CONCLUSIONS: This population appears clinically less compromised and had a lower incidence of adverse clinical outcomes than those of reference trials. However, we recorded a substantial burden of atrial arrhythmias, which was independently associated with a higher incidence of ventricular arrhythmias.

Treatment of atrial fibrillation with a dual defibrillator in heart failure patients (TRADE HF): protocol for a randomized clinical trial.

BACKGROUND: Heart failure(HF) and atrial fibrillation(AF) frequently coexist in the same patient and are associated with increased mortality and frequent hospitalizations. As the concomitance of AF and HF is often associated with a poor prognosis, the prompt treatment of AF in HF patients may significantly improve outcome. METHODS/DESIGN: Recent implantable cardiac resynchronization (CRT) devices allow electrical therapies to treat AF automatically. TRADE-HF (trial registration: NCT00345592; http://www.clinicaltrials.gov) is a prospective, randomized, double arm study aimed at demonstrating the efficacy of an automatic, device-based therapy for treatment of atrial tachycardia and fibrillation(AT/AF) in patients indicated for CRT. The study compares automatic electrical therapy to a traditional more usual treatment of AT/AF: the goal is to demonstrate a reduction in a combined endpoint of unplanned hospitalizations for cardiac reasons, death from cardiovascular causes or permanent AF when using automatic atrial therapy as compared to the traditional approach involving hospitalization for symptoms and in-hospital treatment of AT/AF. DISCUSSION: CRT pacemaker with the additional ability to convert AF as well as ventricular arrhythmias may play a simultaneous role in rhythm control and HF treatment. The value of the systematic implantation of CRT ICDs with the capacity to deliver atrial therapy in HF patients at risk of AF has not yet been explored. The TRADE-HF study will assess in CRT patients whether a strategy based on automatic management of atrial arrhythmias might be a valuable option to reduce the number of hospital admission and to reduce the progression the arrhythmia to a permanent form. TRIAL REGISTRATION: NCT00345592.

Baseline heart rate variability predicts clinical events in heart failure patients implanted with cardiac resynchronization therapy: validation by means of related complexity index.

BACKGROUND: Studies on the physiology of the cardiovascular system suggest that generation of the heart rate (HR) signal is governed by nonlinear dynamics. Linear and nonlinear indices of HR variability (HRV) have been shown to predict outcome in heart failure (HF). Aim of the present study is to assess if a HR-related complexity predicts adverse clinical and cardiovascular events at 1 year in patients implanted with cardiac resynchronization therapy (CRT). METHODS: In sixty patients implanted with CRT (Renewal), 24-hour HR data were retrieved at patient discharge and 1-year follow-up. A set of linear indices of HRV were considered: mean HR, standard deviation of normal beat to normal beat (SDANN), and HR footprint. Two novel nonlinear indices were calculated by means of a specific algorithm (OntoSpace): HR-complexity (HR-Co) and HR-entropy (HR-En). Predictors of adverse clinical outcome (functional class deterioration or major hospitalizations for cardiovascular causes or all-cause mortality) and of HRV recovery were sought by means of multivariate analysis. RESULTS: HR-Co and HR-En were found to be highly correlated with the other traditional indices of HRV. Lower baseline values of COMPLEXITY WERE ASSOCIATED WITH ADVERSE CLINICAL OUTCOMES (HAZARD RATIO [HR] 0.71; 95% CONFIDENCE INTERVAL [CI] 0.54-0.95; P < 0.02). CONCLUSION: Complexity and entropy indices, calculated from 24-hour normal beat to normal beat (RR) intervals well represent patient's autonomic function. In this limited set of data, HF patients with lower baseline complexity-related indices, representing a more compromised autonomic function, present worse clinical outcome at 1-year follow-up.

Proportion of patients needing an implantable cardioverter defibrillator on the basis of current guidelines: impact on healthcare resources in Italy and the USA. Data from the ALPHA study registry.

AIMS: Implantable cardioverter defibrillators (ICD) improve survival in selected patients with left ventricular dysfunction or heart failure (HF). The objective is to estimate the number of ICD candidates and to assess the potential impact on public health expenditure in Italy and the USA. METHODS AND RESULTS: Data from 3513 consecutive patients (ALPHA study registry) were screened. A model based on international guidelines inclusion criteria and epidemiological data was used to estimate the number of eligible patients. A comparison with current ICD implant rate was done to estimate the necessary incremental rate to treat eligible patients within 5 years. Up to 54% of HF patients are estimated to be eligible for ICD implantation. An implantation policy based on guidelines would significantly increase the ICD number to 2671 implants per million inhabitants in Italy and to 4261 in the USA. An annual increment of prophylactic ICD implants of 20% in the USA and 68% in Italy would be necessary to treat all indicated patients in a 5-year timeframe. CONCLUSION: Implantable cardioverter defibrillator implantation policy based on current evidence may have significant impact on public health expenditure. Effective risk stratification may be useful in order to maximize benefit of ICD therapy and its cost-effectiveness in primary prevention.

Compliance to MADIT and MUSTT criteria for implantable cardioverter defibrillator therapy in the pre-SCD-Heft and MADIT II era. Data from a multicenter Italian study.

The follow-up of 1440 consecutive post-MI patients (68.9 ± 10.9 years) with an LVEF ≤ 40% was analyzed in 19 Italian hospitals to evaluate how many patients with clinical nonsustained VT and inducible sustained VT or VF underwent post-discharge risk assessment (RA). During 38 (range, 4-76) months follow-up, 611 patients (42.4%) qualified for and 294 (20.4%) effectively underwent RA combining LVEF assessment and Holter monitoring, 29 (2.0%) subsequently underwent programmed electrical stimulation and 19 (1.3%) received an ICD.

Product-experience reporting on endocardial defibrillation leads: a 4-year national perspective.

The medical device industry must implement accurate programs to monitor product performance once the product is released into the market. Product-experience reports provide a means for physicians who use medical devices to provide continuous feedback to manufacturers in order to monitor device performance. We examined product-experience reports sent from Italy over 4 years (2004-2007) related to a single manufacturer's family of permanent endocardial leads (Endotak Reliance, Boston Scientific, MA, USA) used with implantable cardioverter-defibrillators. Out of 15,772 implanted leads, physicians sent in 454 (2.87%) product-experience reports. Only 126 out of 454 (28%) leads were returned to the company; most of these (101 out of 126; 80%) were related to implant procedure. Laboratory analyses of returned leads rarely showed loss of integrity (0.01%). The practice of reporting product performance and returning the device to companies should be strongly encouraged in order to better identify potential issues affecting implantable devices.

Performance of a ventricular automatic-capture algorithm in a wide clinical setting.

BACKGROUND: The optimal programming of a pacemaker (PM) voltage output considers both efficiency (prolonging battery cell longevity) and patient safety (adequate safety margin). Currently, automatic capture (AC) algorithms are designed to ensure safe automatic stimulation threshold determination and pacing with a safety margin. METHODS: The aims of this prospective observational study were (1) to evaluate, over a short-term follow-up, the extent of backup pacing in patients implanted with an AC-featured PM produced by Boston Scientific (Insignia) and a wide range of ventricular leads; (2) to identify patient- or lead-specific predictors of ventricular threshold increase or missed detection of the ventricular pacing threshold; and (3) to analyze day-to-day fluctuations in the ventricular pacing threshold and the relationship between their magnitude, the characteristics of patients, and the system implanted. RESULTS: Five hundred and seventy-nine patients implanted with 89 different leads were followed up for a median of 2.1 months. Five hundred and thirty-six patients (92.5%) never experienced failure of automatic threshold testing; 571 (98.6%) did not experience permanent failure requiring continuous backup pacing at high energy. On multivariate analysis, none of the patient or lead characteristics predicted the occurrence of high-energy backup pacing during the study period. Day-to-day threshold fluctuations were associated only with higher thresholds (>1 V). CONCLUSION: AC algorithm reliably measures ventricular pacing thresholds in most patients: in only 1.4% of patients the system is permanently unable to detect the ventricular threshold. Backup pacing is not dependent on lead or patient characteristics, including lead polarization, polarity, and maturation.

Defibrillation testing at the time of implantation of cardioverter defibrillator in the clinical practice: a nation-wide survey.

AIMS: Despite an effective defibrillation testing (DT) is considered mandatory to be consistent with the rules of good clinical practice, some physicians are concerned about the risk of complications related to the induction test, and in real world clinical practice, several implant procedures are performed without any induction test. We conducted a systematic nation-wide retrospective survey in order to determine the DT rate and its complications. METHODS AND RESULTS: An ad hoc questionnaire was sent to all 343 Italian implanting centres and the data from the 229 (67%) centres that answered were analysed. During the year 2005, a total of 7857 patients underwent a first implantation of cardioverter defibrillator (ICD), 38% of which with cardiac resynchronization therapy (CRT). Of these, 2356 (30%) were implanted without any induction test. In 35 (15%) centres, the induction test was performed in < 25% of the patients, whereas in 136 (59%) centres, it was performed in > 75% of the patients. At multivariable analysis, performed in a subset of 1206 patients from 107 centres, CRT device (OR = 1.82) and primary prevention (OR = 1.47) were independent predictors of the decision to not perform DT. However, altogether, the clinical variables accounted only for 35% of the total variance, whereas the remaining 65% was probably unrelated to clinical factors. There was a total of 22 (0.4%) life-threatening complications as a consequence of the induction test: 4 deaths (0.07%), 8 cardiopulmonary arrests requiring resuscitation manoeuvres (0.15%), 6 cardiogenic shocks (0.11%), 3 strokes (0.05%), and 1 pulmonary embolism (0.02%). CONCLUSION: In real world practice, DT is not performed in a substantial number of patients, most of these in the absence of legitimate reasons. The clinical impact of DT vs. no DT remains unclear until the not negligible complication rate is compared against the long-term potential benefit.

Prognostic role of post-infarction C-reactive protein in patients undergoing implantation of cardioverter-defibrillators: design of the C-reactive protein Assessment after Myocardial Infarction to GUide Implantation of DEfibrillator (CAMI GUIDE) study.

BACKGROUND: Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can currently be offered effective means of prevention, such as implantable cardioverter-defibrillators (ICD). However, predictors of SCD able to identify those patients who are at higher risk are still lacking. Whether C-reactive protein (CRP), a serum inflammatory marker with established prognostic accuracy after MI, can also be a predictor of SCD is unclear. METHODS: The CAMI GUIDE study is designed to evaluate the prognostic role of CRP in patients undergoing ICD implantation after MI according to MADIT II criteria (i.e. left ventricular ejection fraction

Role of rate control and regularization through pacing in patients with chronic atrial fibrillation and preserved ventricular function: the VRR study.

AIM: High heart rates in chronic atrial fibrillation (CAF) is one of the factors responsible for hemodynamic alterations and may lead to tachycardiomyopathies. The ventricular rate regulation (VRR) study evaluates the effect of ventricular rate regularization in CAF patients with preserved ventricular function, marked ventricular rate variability, and indications for pacemaker (PM) implantation owing to symptomatic pauses. Rate regularization was achieved using VRR algorithm (INSIGNIA pacemakers, Guidant Corp., St. Paul, MN, USA). METHODS: One month after PM implantation, 58 patients followed two 3-month crossover periods (VRR-OFF; VRR-ON) in which the VRR algorithm was randomized and compared to fixed rate stimulation at 60 ppm. During follow-up visits a 6-minute walk test was performed under partially inhibited conditions (PM at 40 ppm) and ventricular response was recorded. The following parameters were measured: mean ventricular rate (MR), rate variability (RR30), rate recovery after exercise (SLOPE = (R-END - R-REC)/(R-END - 40)), R-END being the rate at end of walk and R-REC the rate 1 minute after exercise. RESULTS: The VRR algorithm decreased rate variability (RR30: -7.36 +/- 8.8; P < 0.01) without increasing ventricular rate (MR: -1.11 +/- 8.3 P = NS), while SLOPE improved significantly (SLOPE: +15.41 +/- 16.8 P < 0.01). CONCLUSIONS: VRR effectively stabilizes rate, without increasing pacing rate above spontaneous rhythm and helps achieve a more favorable autonomic balance, improving rate recovery after exercise.

Is a dual-sensor pacemaker appropriate in patients with sino-atrial disease? Results from the DUSISLOG study.

BACKGROUND: Rate-responsive pacemakers (PMs) are often supplied with accelerometer (XL) and minute ventilation (MV) sensors to provide a physiologic rate response according to patient needs. No information is available about the real benefit of dual-sensor rate-responsive pacing on the daily life of patients. METHODS: DUSISLOG (Dual Sensor vs Single Sensor comparison using patient activity LOGbook) is a two-arm prospective, randomized, multicenter study that enrolled 105 patients who received a rate-responsive PM (Insignia), Guidant Corp.). After 1 month of DDD pacing at 60 ppm lower rate, a single sensor (XL or MV, randomized) was activated for 3 months at the manufacturer's suggested nominal settings, followed by a 3-month period with dual sensors optimized with automatic response. During the last month of each period, the following data concerning patient physical activity were retrieved from PM diagnostics (Activity Log): mean percentage of physical activity, mean intensity of activity. Quality of life (QoL) scores and 6-minute walk test (WT) were also recorded. RESULTS: Single-sensor rate-responsive pacing resulted in symptomatic benefit equally with XL and MV sensors while no additional benefit was found using dual sensor. In a subgroup analysis, patients (17%) with marked chronotropic incompetence and with 0% atrial sensing received benefits from single sensor with an additional advantage from sensor (QoL: +21 +/- 14% P < 0.05; WT: +17 +/- 7% P < 0.02). CONCLUSION: In most patients with rate-responsive devices, a single sensor is sufficient to achieve a satisfactory rate response. A dual sensor combination and optimization provides an additional benefit only in a selected population with an advanced atrial chronotropic disease.

Atrial fibrillation in patients with a dual defibrillator: characteristics of spontaneous and induced episodes and effect of ventricular tachyarrhythmia induction.

BACKGROUND: The pattern of FF intervals during atrial fibrillation (AF) has been analyzed in induced and spontaneous AF episodes, after the induction of ventricular fibrillation (VF) and after atrial shock, in order to suggest practical considerations for AF management in patients implanted with antitachycardia devices. METHODS: In 13 patients implanted with a dual-chamber defibrillator, FF intervals were analyzed during two separate induced AF episodes, before and after VF induction over AF, as well as during spontaneous AF episodes and after unsuccessful atrial shocks. The following parameters were considered: mean atrial cycle length (CL), atrial CL stability, and standard deviation of the atrial cycle. RESULTS: The AF pattern had comparable characteristics considering two separate inductions of AF, as well as spontaneous AF episodes. Ventricular tachyarrhythmia induction resulted in a shortening of atrial CL (P < 0.02) and in a less organized AF pattern (P < 0.005). Changes in the FF interval after ineffective shock therapy showed a shortening of AF cycles after shocks with energies far below the defibrillation threshold. CONCLUSIONS: (a) The AF pattern is reproducible in separate inductions of sustained AF and in spontaneous episodes, (b) dynamic changes involving a shortening of the AF cycle and an evolution to a less homogeneous pattern occur after VF induction, revealing a complex interplay between AF and VF, and (c) FF interval analysis after ineffective shock delivery may allow the relationship between delivered shock energy and effective defibrillation energy to be estimated, thereby providing practical suggestions for step-up protocols in atrial cardioversion.