Maurizio Landolina

Long term vagal stimulation in patients with advanced heart failure: first experience in man.

Experimentally, vagal stimulation (VS) is protective in chronic heart failure (HF). In man, VS is used in refractory epilepsy but has never been used in cardiovascular diseases. Increased sympathetic and reduced vagal activity predict increased mortality in HF.

Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies

OBJECTIVES The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. BACKGROUND Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiology setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases. METHODS Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype. RESULTS Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for >or=10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death. CONCLUSIONS Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation.

Who are the long-QT syndrome patients who receive an implantable cardioverter-defibrillator and what happens to them?: Data from the European Long-QT syndrome implantable cardioverter-defibrillator (LQTS ICD) registry

Background— A rapidly growing number of long-QT syndrome (LQTS) patients are being treated with an implantable cardioverter-defibrillator (ICD). ICDs may pose problems, especially in the young. We sought to determine the characteristics of the LQTS patients receiving an ICD, the indications, and the aftermath. Methods and Results— The study population included 233 patients. Beginning in 2002, data were collected prospectively. Female patients (77%) and LQT3 patients (22% of genotype positive) were overrepresented; mean QTc was 516±65 milliseconds; mean age at implantation was 30±17 years; and genotype was known in 59% of patients. Unexpectedly, 9% of patients were asymptomatic before implantation. Asymptomatic patients, almost absent among LQT1 and LQT2 patients, represented 45% of LQT3 patients. Patients with cardiac symptoms made up 91% of all study participants, but only 44% had cardiac arrest before ICD implantation. In addition, 41% of patients received an ICD without having first been on LQTS therapy. During follow-up, 4.6±3.2 years, at least 1 appropriate shock was received by 28% of patients, and adverse events occurred in 25%. Appropriate ICD therapies were predicted by age 500 milliseconds, prior cardiac arrest, and cardiac events despite therapy; within 7 years, appropriate shocks occurred in no patients with none of these factors and in 70% of those with all factors. Conclusions— Reflecting previous concepts, ICDs were implanted in some LQTS patients whose high risk now appears questionable. Refined criteria for implantation, reassessment of pros and cons, ICD reprogramming, and consideration for other existing therapeutic options are necessary. # Clinical Perspective {#article-title-18}Background— A rapidly growing number of long-QT syndrome (LQTS) patients are being treated with an implantable cardioverter-defibrillator (ICD). ICDs may pose problems, especially in the young. We sought to determine the characteristics of the LQTS patients receiving an ICD, the indications, and the aftermath. Methods and Results— The study population included 233 patients. Beginning in 2002, data were collected prospectively. Female patients (77%) and LQT3 patients (22% of genotype positive) were overrepresented; mean QTc was 516±65 milliseconds; mean age at implantation was 30±17 years; and genotype was known in 59% of patients. Unexpectedly, 9% of patients were asymptomatic before implantation. Asymptomatic patients, almost absent among LQT1 and LQT2 patients, represented 45% of LQT3 patients. Patients with cardiac symptoms made up 91% of all study participants, but only 44% had cardiac arrest before ICD implantation. In addition, 41% of patients received an ICD without having first been on LQTS therapy. During follow-up, 4.6±3.2 years, at least 1 appropriate shock was received by 28% of patients, and adverse events occurred in 25%. Appropriate ICD therapies were predicted by age <20 years at implantation, a QTc >500 milliseconds, prior cardiac arrest, and cardiac events despite therapy; within 7 years, appropriate shocks occurred in no patients with none of these factors and in 70% of those with all factors. Conclusions— Reflecting previous concepts, ICDs were implanted in some LQTS patients whose high risk now appears questionable. Refined criteria for implantation, reassessment of pros and cons, ICD reprogramming, and consideration for other existing therapeutic options are necessary.

A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long dEtection window programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary prevention treated with a biventricular ICD] study

Aims To investigate the efficacy and safety of a cardiac resynchronization therapy with cardioverter–defibrillator (CRT-D) device with simplified ventricular tachycardia management in patients with non-ischaemic heart failure (HF) and primary prevention implantable cardioverter defibrillator (ICD) indication. Methods and results Prospective, controlled, parallel, multicentre, non-randomized study enrolling 324 primary prevention non-ischaemic HF patients implanted with CRT-D devices from 2004 to 2007: Protect group, 164 patients implanted with a Medtronic Insync III Protect device and Control group, 160 patients utilizing other Medtronic CRT-D devices. Efficacy was assessed by computing appropriate and inappropriate detections and therapies during follow-up; safety compared hospitalizations and syncopal events between groups. Ninety per cent of both ventricular and supraventricular tachyarrhythmias terminated within the 13–29 beat detection interval with the Protect algorithm. The Protect group showed a significantly better event-free survival to first delivered therapy for total (P = 0.0001), appropriately treated (P = 0.002), and inappropriately treated episodes (P = 0.017). The total number of delivered shocks was significantly lower in the Protect group (22 vs. 59, P < 0.0001). In the Protect group, a significantly reduced HF hospitalization (hazard ratio 0.38, 95% CI 0.15–0.98, P = 0.044) was observed without any increase of syncope or death. Conclusion A simplified CRT-D device with fixed long detection reduced overall ICD therapy burden and HF hospitalizations without entailing any additional adverse events in primary prevention non-ischaemic HF patients.

Image integration increases efficacy of paroxysmal atrial fibrillation catheter ablation: Results from the CartoMerge™ italian Registry

AIMS The aim of this study was to investigate whether circumferential pulmonary vein (PV) isolation guided by image integration improves the procedural and clinical outcomes of atrial fibrillation (AF) ablation in comparison with segmental PV isolation and circumferential PV isolation guided by three-dimensional (3D) electroanatomical mapping alone. METHODS AND RESULTS Procedural and clinical outcomes of 573 patients who underwent their first catheter ablation for paroxysmal AF between January 2005 and April 2007 were collected from 12 centres. We evaluated three techniques: segmental ostial PV isolation (SOCA group, 240 patients), circumferential PV isolation guided by electroanatomical mapping (CARTO group, 107 patients), and circumferential PV isolation guided by electroanatomical mapping integrated with magnetic resonance/computed tomographic images of the left atrium (MERGE group, 226 patients). Procedure duration proved to be shorter in MERGE group patients than in CARTO group patients (P < 0.04), but longer than in SOCA group patients (P < 0.0001). During follow-up, atrial tachyarrhythmias relapsed more frequently in SOCA group patients (44.6%) and CARTO group patients (41.7%) than in MERGE group patients (22.6%; P < 0.0001). CONCLUSION In patients with paroxysmal AF, circumferential PV isolation guided by image integration significantly improves clinical outcome in comparison with both circumferential PV isolation guided by 3D mapping alone and with segmental electrophysiologically guided PV isolation.

Monitoring Intrathoracic Impedance with an Implantable Defibrillator Reduces Hospitalizations in Patients with Heart Failure

Purpose: Some implantable cardioverter‐defibrillators (ICDs) are now able to monitor intrathoracic impedance. The aim of the study was to describe the use of such monitoring in clinical practice and to evaluate the clinical impact of the fluid accumulation alert feature of these ICDs.

Device-detected atrial tachyarrhythmias predict adverse outcome in real-world patients with implantable biventricular defibrillators.

OBJECTIVES The purpose of this analysis was to evaluate the correlation between atrial tachycardia (AT) or atrial fibrillation (AF) and clinical outcomes in heart failure (HF) patients implanted with a cardiac resynchronization therapy defibrillator (CRT-D). BACKGROUND In HF patients, AT and AF have high prevalence and are associated with compromised hemodynamic function. METHODS Forty-four Italian cardiological centers followed up 1,193 patients who received a CRT-D according to current guidelines for advanced HF, New York Heart Association functional class ≥ II, left ventricular ejection fraction ≤ 35%, and QRS complex ≥ 120 ms. All patients were in sinus rhythm at implant. RESULTS During a median follow-up period of 13 months, AT/AF >10 min occurred in 361 of 1,193 (30%) patients. The composite end point (deaths or HF hospitalizations) occurred in 174 of 1,193 (14.6%). Multivariate time-dependent Cox regression analyses showed that composite end point risk was higher among patients with device-detected AT/AF (hazard ratio [HR]: 2.16, p = 0.032), New York Heart Association functional class III or IV compared with II (HR: 2.09, p = 0.002), and absence of beta-blockers (HR: 1.36, p = 0.036). Furthermore, the composite end point risk was inversely associated with left ventricular ejection fraction (HR: 1.04, p = 0.045), increasing by a factor of 4% for each 1% decrease in left ventricular ejection fraction. CONCLUSIONS In HF patients with CRT-D, device-detected AT/AF is associated with a worse prognosis. Continuous device diagnostics monitoring and Web-based alerts may inform the physician of AT/AF occurrences and identify patients at risk of cardiac deterioration or patients with suboptimal rate or rhythm control. (Italian ClinicalService Project; NCT01007474).

Baroreflex sensitivity, but not heart rate variability, is reduced in patients with life-threatening ventricular arrhythmias long after myocardial infarction

Low values of heart rate variability (HRV, a marker of vagal tone) and baroreflex sensitivity (BRS, a marker of vagal reflexes) identify patients at higher risk soon after myocardial infarction (MI). However, it is still unknown whether HRV and BRS correlate with malignant arrhythmias after the recovery from the transient post-MI autonomic disturbance. This study assessed whether HRV and BRS would differ in patients with malignant ventricular arrhythmias occurring long after MI compared with those in a control population. Twenty-eight patients entered the study: 14 patients with episodes of sustained ventricular tachycardia or ventricular fibrillation occurring more than 1 year after MI, age (mean +/- SEM) 64 +/- 2 years, and left ventricular ejection fraction 34% +/- 3% (VT/VF group) were compared with 14 similar patients with no ventricular tachycardia (control group). Mean RR interval was not different in the two groups (844 +/- 37 msec in VT/VF and 892 +/- 24 msec in control group). Also, no difference was found in any time- or frequency-domain measure of heart rate variability. However, patients in the VT/VF group had a significantly lower baroreflex sensitivity compared with patients in the control group (4.2 +/- 0.5 vs 8.0 +/- 1.1 msec/mm Hg, p = 0.008). Thus BRS but not HRV was reduced in patients with life-threatening ventricular arrhythmias occurring long after MI. A persistent depression of vagal reflexes may play a role in the occurrence of malignant arrhythmias, and analysis of BRS may potentially be helpful in the identification of patients at high risk long after myocardial infarction.

Impaired Baroreflex Sensitivity Is Correlated With Hemodynamic Deterioration of Sustained Ventricular Tachycardia

OBJECTIVES The goal of this study was to evaluate clinical and autonomic variables (heart rate variability and baroreflex sensitivity) related to hemodynamic tolerability of VT in patients with sustained monomorphic VT and a healed myocardial infarction. BACKGROUND Sustained ventricular tachycardia (VT) with hemodynamic deterioration is associated with a worse prognosis than that of well tolerated VT. The causes of hemodynamic deterioration of VT are incompletely understood. METHODS Twenty-four consecutive patients with sustained monomorphic VT and a healed myocardial infarction (mean age +/- SD 66 +/- 8 years, left ventricular [LV] ejection fraction 37 +/- 11%) were assigned to group 1 if the VT was well tolerated (n = 11) or to group 2 if faintness or syncope occurred or if systolic blood pressure was < 90 mm Hg with clinical signs of shock (n = 13). RESULTS No difference was found between the two groups in age, LV function, rate and duration of the VT or heart rate variability. However, patients in group 2 had a significantly lower baroreflex sensitivity (3.4 +/- 1.1 vs. 7.1 +/- 3.7 ms/mm Hg, p = 0.003). Multiple logistic regression analysis showed that only the value of baroreflex sensitivity (p = 0.0003)-but not age, LV ejection fraction, VT cycle length or SD of the RR interval (all p > 0.25)-correlated with the tolerability of the VT. Finally, LV ejection fraction (p = 0.0001) and baroreflex sensitivity (p = 0.0003)-but not age, cycle length of the tachycardia or SD of the RR interval-predicted cardiac death or unstable VT during follow-up. CONCLUSIONS These data suggest that an impaired cardiovascular reflex response may play a key role in the hemodynamic deterioration of sustained VT and that the evaluation of baroreflex sensitivity in patients at high risk for sustained VT may become useful both in risk stratification and in the individualization of treatment.

Long-Term Complications Related to Biventricular Defibrillator Implantation Rate of Surgical Revisions and Impact on Survival: Insights From the Italian ClinicalService Database

Background— Long-term data on device-related untoward events in patients receiving defibrillators for resynchronization therapy (CRT-D) are lacking. We quantified the frequency of repeat invasive procedures and the nature of long-term complications in current clinical practice and examined possible predictors of device-related events and their association with long-term patient outcome. Methods and Results— We analyzed data from 3253 patients who underwent de novo successful implantation of CRT-D and were followed up for a median of 18 months (25th to 75th percentiles: 9 to 30) in 117 Italian centers. Device-related events were reported in 416 patients, and, specifically, surgical interventions for system revision were described in 390 patients. Four years after the implantation procedure, 50% of patients underwent surgical revision for battery depletion and 14% for unanticipated events. For comparison, at 4 years battery depletion occurred in 10% and 13% of patients who received single- and dual-chamber defibrillators at the study centers, and unanticipated events were reported as 4% and 9%, respectively. In CRT-D, infections occurred at a rate of 1.0%/y, and the risk of infections increased after device replacement procedures (hazard ratio, 2.04; 95% confidence interval, 1.01 to 4.09; P =0.045). Left ventricular lead dislodgements were reported at a rate of 2.3%/y and were predicted by longer fluoroscopy time and higher pacing threshold on implantation. Device-related events were not associated with a worse clinical outcome; indeed, the risk of death was similar in patients with and without surgical revision (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.47; P =0.682). Conclusions— In current clinical practice device-related events are more frequent in CRT-D than in single- or dual-chamber defibrillators, and are frequently managed by surgical intervention for system revision. However, a worse clinical outcome is not associated with these events. Clinical Trial Registration— URL: . Unique identifier: [NCT01007474][1]. # Clinical Perspective {#article-title-32} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01007474&atom=%2Fcirculationaha%2F123%2F22%2F2526.atomBackground— Long-term data on device-related untoward events in patients receiving defibrillators for resynchronization therapy (CRT-D) are lacking. We quantified the frequency of repeat invasive procedures and the nature of long-term complications in current clinical practice and examined possible predictors of device-related events and their association with long-term patient outcome. Methods and Results— We analyzed data from 3253 patients who underwent de novo successful implantation of CRT-D and were followed up for a median of 18 months (25th to 75th percentiles: 9 to 30) in 117 Italian centers. Device-related events were reported in 416 patients, and, specifically, surgical interventions for system revision were described in 390 patients. Four years after the implantation procedure, 50% of patients underwent surgical revision for battery depletion and 14% for unanticipated events. For comparison, at 4 years battery depletion occurred in 10% and 13% of patients who received single- and dual-chamber defibrillators at the study centers, and unanticipated events were reported as 4% and 9%, respectively. In CRT-D, infections occurred at a rate of 1.0%/y, and the risk of infections increased after device replacement procedures (hazard ratio, 2.04; 95% confidence interval, 1.01 to 4.09; P=0.045). Left ventricular lead dislodgements were reported at a rate of 2.3%/y and were predicted by longer fluoroscopy time and higher pacing threshold on implantation. Device-related events were not associated with a worse clinical outcome; indeed, the risk of death was similar in patients with and without surgical revision (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.47; P=0.682). Conclusions— In current clinical practice device-related events are more frequent in CRT-D than in single- or dual-chamber defibrillators, and are frequently managed by surgical intervention for system revision. However, a worse clinical outcome is not associated with these events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01007474.