Ernesto Ammendola

Longevity of implantable cardioverter-defibrillators for cardiac resynchronization therapy in current clinical practice: an analysis according to influencing factors, device generation, and manufacturer

Aims Device replacement at the time of battery depletion of implantable cardioverter-defibrillators (ICDs) may carry a considerable risk of complications and engenders costs for healthcare systems. Therefore, ICD device longevity is extremely important both from a clinical and economic standpoint. Cardiac resynchronization therapy defibrillators (CRT-D) battery longevity is shorter than ICDs. We determined the rate of replacements for battery depletion and we identified possible determinants of early depletion in a series of patients who had undergone implantation of CRT-D devices. Methods and results We retrieved data on 1726 consecutive CRT-D systems implanted from January 2008 to March 2010 in nine centres. Five years after a successful CRT-D implantation procedure, 46% of devices were replaced due to battery depletion. The time to device replacement for battery depletion differed considerably among currently available CRT-D systems from different manufacturers, with rates of batteries still in service at 5 years ranging from 52 to 88% (log-rank test, P < 0.001). Left ventricular lead output and unipolar pacing configuration were independent determinants of early depletion [hazard ratio (HR): 1.96; 95% 95% confidence interval (CI): 1.57–2.46; P < 0.001 and HR: 1.58, 95% CI: 1.25–2.01; P < 0.001, respectively]. The implantation of a recent-generation device (HR: 0.57; 95% CI: 0.45–0.72; P < 0.001), the battery chemistry and the CRT-D manufacturer (HR: 0.64; 95% CI: 0.47–0.89; P = 0.008) were additional factors associated with replacement for battery depletion. Conclusion The device longevity at 5 years was 54%. High left ventricular lead output and unipolar pacing configuration were associated with early battery depletion, while recent-generation CRT-Ds displayed better longevity. Significant differences emerged among currently available CRT-D systems from different manufacturers.

Is heart rate variability a valid parameter to predict sudden death in patients with Becker’s muscular dystrophy?

Becker’s muscular dystrophy (BMD) is an X linked recessive muscular dystrophy caused by dystrophin anomalies in striated muscles, with myocardial involvement1,2 and consequent dilated cardiomyopathy, rhythm and conduction disorders, and a high risk of sudden cardiac death.3,4 Heart rate variability (HRV) is a measure of the cyclical variations of beat-to-beat (RR) intervals that reflects cardiac autonomic function and sympathovagal balance.5,6 A predominance of sympathetic tone in cardiac activity induces tachycardia and reduced beat-to-beat variations, whereas parasympathetic nerve activity reduces heart rate and increases HRV.7 HRV is a well-correlated non-invasive parameter used to stratify arrhythmic risk in patients with chronic failure. In general, higher HRV is desirable, and lower HRV has been found to be a significant independent predictor of cardiac mortality and morbidity.8,9 The objective of our study was to evaluate the prognostic value of HRV for sudden death in a population of patients with BMD and dilated cardiomyopathy. The study population consisted in 30 men (mean age 44.2 (SD 12) years) with BMD and a variable stage of myocardial involvement. The control group consisted of 30 healthy men (age 39 (3.2) years). All patients included in study underwent physical …

Device Longevity in a Contemporary Cohort of ICD/CRT-D Patients Undergoing Device Replacement.

The longevity of defibrillators (ICD) is extremely important from both a clinical and economic perspective. We studied the reasons for device replacement, the longevity of removed ICD, and the existence of possible factors associated with shorter service life.

Implantable cardioverter-defibrillator programming and electrical storm: Results of the OBSERVational registry On long-term outcome of ICD patients (OBSERVO-ICD).

BACKGROUND Electrical storm (ES) is defined as 3 or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 hours and is associated with increased cardiac and all-cause mortality. OBJECTIVE The purpose of this study was to test whether aggressive implantable cardioverter-defibrillator (ICD) programming can be associated with ES. METHODS The OBSERVational registry On long-term outcome of ICD patients (OBSERVO-ICD) is a multicenter, retrospective registry enrolling all consecutive patients undergoing ICD implantation from 2010 to 2012 in 5 Italian high-volume arrhythmia centers. Clinical history and risk factors were collected for all patients, as were ICD therapy-related variables such as detection zones and delays. The total number of arrhythmic episodes and therapies delivered by the ICD were collected through out-of-hospital visits and remote monitoring. RESULTS The registry enrolled 1319 consecutive patients, of whom 62 (4.7%) experienced at least 1 ES during follow-up (median 39 months). Patients who experienced ES had a significantly lower VF detection zone (P = .002), more frequently had antitachycardia pacing therapies programmed off during capacitor charge (P = .001), and less frequently had an ICD set with delayed therapies for VT zones (P = .042) and VF zone (P = .036). Patients who experienced ES had a significantly higher incidence of death and heart failure-related death compared to patients with no ventricular arrhythmias and patients with unclustered VTs/VFs (P = .025 and P <.001, respectively). CONCLUSION Patients with ES had a more aggressive ICD programming setup, including lower VF detection rates, shorter detection times, and no antitachycardia pacing therapies during capacitor charge. This kind of ICD programming potentially could increase the likelihood of ES and the related risk of death.

Natriuretic peptides: molecular biology, pathophysiology and clinical implications for the cardiologist

Natriuretic peptides (NPs) counter the effects of volume overload or adrenergic activation of the cardiovascular system. They are able to induce arterial vasodilatations, natriuresis and diuresis, and they reduce the activities of the renin-angiotensin-aldosterone system and the sympathetic nervous system. However, in addition to wall stress, other factors have been associated with elevated natriuretic peptide levels. Since 2000, because of their characteristics, NPs have become quantitative plasma biomarkers of heart failure. Nowadays, NPs play an important role not only in the diagnosis of heart failure, but also for a prognostic purpose and a guide to medical therapy. Finally, a new drug that modulates the NP system or recombinant analogs of NPs are now available in patients with heart failure.

Effectiveness of a management program for outpatient clinic or remote titration of beta-blockers in CRT patients: The RESTORE study

BACKGROUND Many patients fail to receive β-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for β-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring. METHODS AND RESULTS 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group. A second group of 124 CRT-D candidates (Study Group) underwent up-titration visits every 2weeks after implantation (target dose: 10mg/day of bisoprolol or 50mg/day of carvedilol). In the Study Group, remote monitoring was undertaken in 66 patients, who received additional equipment for daily transmission of weight and blood pressure data, and scheduled titration telephone calls. In the Control Group, the maximal dose of β-blockers was being administered to 12 (9%) patients on implantation and 21 (16%) on 6-month follow-up examination (p>0.05). In the Study Group, 25 (20%) patients were receiving the maximal dose of β-blockers on implantation and 72 (58%) on follow-up examination (p<0.001). The 66 Study Group patients on remote monitoring underwent fewer in-clinic visits (p=0.034). Of these, 50 (76%) were on the maximal dose after remote up-titration (versus 38% of patients followed up conventionally, p<0.001). The decrease in left ventricular end-systolic volume was larger in the Study Group (p=0.040). CONCLUSIONS The program for β-blocker up-titration increased the number of patients reaching the target dose and improved the response to the therapy. The use of remote monitoring and daily transfer of weight and blood pressure data facilitated β-blocker titration. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/ Identifier: NCT02173028.

Cardiac resynchronization therapy and electrical storm: results of the OBSERVational registry on long-term outcome of ICD patients (OBSERVO-ICD)

Aims Electrical storm (ES) is a condition defined as three or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 h, and usually coexist with advanced heart failure in patients with structural heart disease. The aim of the present study is to test whether cardiac resynchronization therapy (CRT) can be associated with a lower incidence of ES. Methods and results The OBSERVO-ICD (NCT02735811) is a multicentre, retrospective registry, enrolling all consecutive patients undergoing ICD or CRT-D implantation from 2010 to 2012 in five Italian high-volume arrhythmia centres. Propensity score matching was used to compare two equally sized cohorts of ICD and CRT-D patients with similar characteristics. The primary endpoint was the time free from ES. Secondary endpoints were time free from unclustered VT/VF episodes and time free from ES in CRT-D patients according to clinical or echographic response. CRT-D was associated with a 45% relative risk reduction in ES when compared with ICD (5.6% vs. 12.3%; log rank P = 0.014). CRT-responders presented lower rates of ES when compared with non-responders and negative responders according to both clinical and echographic criteria (log-rank P = 0.017 and 0.023, respectively). No ES was detected in any of the 133 full responders to CRT-D. Clinical and echographic positive responses, but not CRT-implant per se, were associated with lower estimate rates of unclustered VTs/VFs. Conclusion Patients with CRT had a lower incidence of ES when compared with propensity-matched ICD patients. The long-term benefit of CRT seems to be due to the improved haemodynamics, as CRT-responders performed markedly better over a long-term follow-up.

Economic impact of remote monitoring after implantable defibrillators implantation in heart failure patients: an analysis from the EFFECT study

Aims Heart failure (HF) patients with implantable cardioverter-defibrillators (ICD) require admissions for disease management and out-patient visits for disease management and assessment of device performance. These admissions place a significant burden on the National Health Service. Remote monitoring (RM) is an effective alternative to frequent hospital visits. The EFFECT study was a multicentre observational investigation aiming to evaluate the clinical effectiveness of RM compared with in-office visits standard management (SM). The present analysis is an economic evaluation of the results of the EFFECT trial. Methods and results The present analysis considered the direct consumption of healthcare resources over 12-month follow-up. Standard tariffs were applied to hospitalizations, in-office visits and remote device interrogations. Economic comparisons were also carried out by means of propensity score (PS) analysis to take into account the lack of randomization in the study design. The analysis involved 858 patients with ICD or CRT-D. Of these, 401 (47%) were followed up via an SM approach, while 457 (53%) were assigned to RM. The rate of hospitalizations was 0.27/year in the SM group and 0.16/year in the RM group (risk reduction =0.59; P = 0.0004). In the non-adjusted analysis, the annual cost for each patient was €817 in the SM group and €604 in the RM group (P = 0.014). Propensity score analysis, in which 292 RM patients were matched with 292 SM patients, confirmed the results of the non-adjusted analysis (€872 in the SM group vs. €757 in the RM group; P < 0.0001). Conclusion There is a reduction in direct healthcare costs of RM for HF patients with ICDs, particularly CRT-D, compared with standard monitoring. Clinical Trial Registration http://clinicaltrials.gov/Identifier, NCT01723865.

Evaluation of Synergistic Effects of Resynchronization Therapy and a β-Blocker Up-titration Strategy Based on a Predefined Patient-Management Program: The RESTORE Study

Prior studies have suggested that a substantial number of eligible heart failure (HF) patients fail to receive β‐blocker therapy, or receive it at a suboptimal dose. The aim of this study is to assess the benefit of a predefined management program designed for β‐blocker up‐titration, evaluating the synergistic effect of cardiac resynchronization therapy (CRT) and β‐blockers in a HF population. The Resynchronization Therapy and β‐Blocker Titration (RESTORE) study is a prospective, case‐control, multicenter cohort study designed to test the hypothesis that a β‐blocker up‐titration strategy based on a predefined management program maximizes the beneficial effect of CRT, increasing the number of patients reaching the target dose of β‐blockers and improving their clinical outcome. All study patients receive an implantable defibrillator for CRT delivery in accordance with current guidelines. Enrollments started in December 2011 and are scheduled to end in December 2014. Approximately 250 consecutive patients will be prospectively enrolled in 6 Italian centers and followed up for 24 months after implantation. The primary endpoint is to demonstrate that CRT may allow titration of β‐blockers until the optimal dose, or at least to the effective dose, in patients with HF. This study might provide important information about the benefit of a predefined management program for β‐blocker up‐titration in patients receiving CRT. Moreover, assessment of health‐care utilization and the consumption of resources will allow estimating the potential utility of remote monitoring by means of an automated telemedicine system in facilitating the titration of β‐blockers in comparison with a standard in‐hospital approach.

Subcutaneous implantable cardioverter defibrillator eligibility according to a novel automated screening tool and agreement with the standard manual electrocardiographic morphology tool

PurposeSince subcutaneous implantable cardioverter defibrillator (S-ICD) introduction, the pre-implant screening based on a dedicated manual ECG tool (MST) was required to assure adequate sensing by the S-ICD. A novel automated screening tool (AST) has been recently developed. We assessed and compared the pass rate with AST and MST, and we measured the agreement between screening tools.MethodsThree electrodes were positioned at locations mimicking the placement of the S-ICD, and ECG recordings were collected in the supine and standing postures at rest. The three sensing vectors were analyzed with the MST and the AST. Eligibility was defined by the presence of at least one or two appropriate vectors in both postures.ResultsA total of 235 patients with an indication to ICD and no need for permanent pacing were enrolled. At least one suitable vector was identified in 214 (91%) patients with MST and 221 (94%) patients with AST (p = 0.219). At least two vectors were appropriate in 162 (69%) patients with MST and 187 (80%) patients with AST (p = 0.008). Overall, out of 1587 ECG analyzed, 1035 (65%) qualifying leads were identified with MST and 1111 (70%) with AST (p = 0.004). The agreement between the results of MST and AST ECG analysis was moderate (Kappa = 0.570; standard error = 0.022; CI = 0.526–0.613). The results were consistent regardless of the underlying cardiomyopathy. The most frequent reason for screening failure with MST was a high-amplitude T-wave (31% of failures). With AST, 23% of recordings that failed with MST for high-amplitude T-wave were classified as acceptable.ConclusionThe AST is associated with higher pass rate than the standard MST. It seems more tolerant of high-amplitude T-waves. Consequently, the agreement between MST and AST findings was only moderate.