Gianluca Botto

Conversion of recent-onset atrial fibrillation to sinus rhythm: effects of different drug protocols.

In a population of 417 hospitalized patients, the efficacy and safety of different drug regimens administered to convert atrial fibrillation (AF) of recent anset (≤ 7 days duration) to sinus rhythm were evaluated. All patients were in NYHA Class ≤ 2, and free of heart failure. They were randomly allocated to treatment with placebo in 121 patients; IV amiodarone, 5 mg/kg bolus, followed by 1.8 g/24 hours in 51 patients; IV propafenone, 2 mg/kg bolus, followed by 0.0078 mg/kg/min in 57 patients; p.o. propafenone, 600 mg p.o. in a single dose in 119 patients; and p.o. flecainide, 300 mg p.o. in a single dose in 69 patients. All patients were continuously monitored by Holter ECG, and the number of conversions to sinus rhythm was measured at 1, 3, and 8 hours. Results: (1) IV propafenone resulted in a higher conversion rate within 1 hour compared with the oral loading regimens of propafenone or flecainide, but the conversion rates at 3 and 8 hours were comparable, approximately 75% at 8 hours; 2) IV amiodarone was not different from placebo until 8 hours when it was associated with 57% of conversions; (3) conversion to sinus rhythm at 8 hours was observed in 37% of the placebo treated patients. Serious adverse effects occurred in few patients: two patients treated with flecainide and one treated with IV propafenone experienced left ventricular decompensation; one patient treated with placebo and two treated with flecainide had atrial flutter with rapid ventricular response. In conclusion, single‐dose, oral loading with propafenone or flecainide are acceptable alternatives to conventional drug regimens in selected hospitalized patients. In addition, the measure of a placebo effect is mandatory in studies of recent‐onset AF.

Consensus statement of the European Heart Rhythm Association: updated recommendations for driving by patients with implantable cardioverter defibrillators

Patients with an implantable cardioverter defibrillator (ICD) have an ongoing risk of sudden incapacitation that might cause harm to others while driving a car. Driving restrictions vary across different countries in Europe. The most recent recommendations for driving of ICD patients in Europe were published in 1997 and focused mainly on patients implanted for secondary prevention. In recent years there has been a vast increase in the number of patients with an ICD and in the percentage of patients implanted for primary prevention. The EHRA task force on ICD and driving was formed to reassess the risk of driving for ICD patients based on the literature available. The recommendations are summarized in the following table and are further explained in the document. [table: see text] Driving restrictions are perceived as difficult for patients and their families, and have an immediate consequence for their lifestyle. To increase the adherence to the driving restrictions, adequate discharge of education and follow-up of patients and family are pivotal. The task force members hope this document may serve as an instrument for European and national regulatory authorities to formulate uniform driving regulations.

Clinical and arrhythmic outcomes after implantation of a defibrillator for primary prevention of sudden death in patients with post-myocardial infarction cardiomyopathy: The Survey to Evaluate Arrhythmia Rate in High-risk MI patients (SEARCH-MI)

Aims To evaluate clinical and arrhythmic outcomes in post-infarction cardiomyopathy patients implanted with a defibrillator (ICD) for primary prevention of sudden death. Methods and results The SEARCH-MI registry is a European multi-centre, prospective, observational study enrolling patients after myocardial infarction, chronic left ventricular dysfunction and an ICD implanted for primary prevention of sudden death. Data on 556 patients with at least one recorded follow-up are presented. Survey to Evaluate Arrhythmia Rate in High-risk MI (SEARCH-MI) patients were sicker than those enrolled in MADIT-II with higher New York Heart Association class and left bundle branch block. Total mortality was 10.4%. Close to one-third (30%) of patients experienced episodes of sustained ventricular arrhythmia. One-quarter (23%) received at least one appropriate therapy and 10% inappropriate therapy. Gender (25% males vs. 5% females, P = 0.0009) and history of non-sustained ventricular tachycardia (24% with vs. 18% without P = 0.037) were predictive of appropriate ventricular therapy. Conclusion SEARCH-MI represents the current clinical management of post-MI patients with left ventricular dysfunction indicated to defibrillator implant for primary prevention. European routine clinical practice was influenced by landmark trials and guidelines which impacted on the implantation of cardiac resynchronization therapy in over 25% of such patients. Non-sustained ventricular tachycardia identifies subjects with a higher incidence of appropriate ICD therapy.

Far-field R wave oversensing in dual chamber pacemakers designed for atrial arrhythmia management: Effect of pacing site and lead tip to ring distance

The aim of the study was to determine the incidence and practical implications of far‐field R wave oversensing (FFRWO) and its association with pacing site and lead tip to ring spacing (TTRS) in implantable devices designed to diagnose and treat atrial tachyarrhythmias and programmed with a fixed and short postventricular blanking period. The study included 395 patients who were implanted with a DDDRP pacemaker and prospectively followed. At implant and follow‐up visits FFRWO was assessed by analyzing lead electrical measures and atrial tachyarrhythmic episodes collected in the device diagnostics. During a median follow‐up of 12 months 11 (2.8%) of 395 patients showed a clinically significant FFRWO that induced inappropriate detection or pacemaker malfunctioning. The atrial pacing site of these 11 patients was right atrium appendage (RAA) for 3 patients, representing 1.1% of 254 RAA patients, coronary sinus ostium (CSO) for 7 patients, representing 7.4% of 94 CSO patients (P < 0.005 vs RAA), and lateral wall (LW) for 1 (2.9%) of 34 LW patients. The minimal value of the FFRWO to P wave ratio, measured at implant, associated with a clinically significant FFRWO was 0.6; therefore, a value of 0.5 was used as a cutoff to identify patients at risk of undesirable device behavior induced by FFRWO: there were 11 (9.6%) of 114 of RAA patients with short (≤ 10 mm) TTRS, 22 (18.8%) of 117 of RAA patients with long (≥ 17 mm) TTRS (P < 0.05 vs short TTRS), 21 (30.6%) of 64 of CSO patients short TTRS (P < 0.001 vs RAA patients with short TTRS) and 3 (30%) of 10 of CSO patients with long TTRS. The analysis showed that, despite the short postventricular blanking time, FFRWO inducing undesired functioning in AT500 pacemakers is infrequent (2.8% of patients). Compared to RAA, the CSO lead position was more frequently associated with FFRWO.TTRS < 10 mm was associated with lower risk of clinically significant FFRWO in RAA.

Cardiac Resynchronization Therapy MOdular REgistry: ECG and Rx predictors of response to cardiac resynchronization therapy (NCT01573091).

Aims A variable proportion, up to 30%, of patients who undergo cardiac resynchronization therapy (CRT) do not benefit from treatment. The aim of the Cardiac Resynchronization Therapy MOdular REgistry (CRT MORE) is to determine whether specific electrocardiographic and radiographic parameters can be used to predict clinical and echocardiographic response to CRT. Methods The CRT MORE is a prospective, single-arm, multicenter cohort study designed to evaluate the electrocardiographic and radiographic predictors of response to CRT. All study patients receive a pacemaker or implantable defibrillator for CRT delivery in accordance with current guidelines. Enrolment started in December 2011 and is scheduled to end in November 2013. Approximately 1100 consecutive patients will be enrolled in 30 Italian centers and will be followed up for 60 months after implantation. The primary endpoint is the improvement in clinical (Clinical Composite Score) and echocardiographic (a decrease of ≥15% in left ventricular end-systolic volume) parameters at the 6-month follow-up visit. Conclusion This study might provide important information about which electrocardiographic and radiographic parameters better predict CRT response.

Impact of Mitral Regurgitation on the Outcome of Patients Treated with CRT-D: Data from the InSync ICD Italian Registry

Background: We assessed the influence of clinically significant mitral regurgitation (MR) on clinical‐echocardiographic response and outcome in heart failure (HF) patients treated with a biventricular defibrillator (cardiac resynchronization therapy defibrillator [CRT‐D]).

Consensus statement of the European Heart Rhythm Association: Updated recommendations for driving by patients with implantable cardioverter defibrillators

Patients with an implantable cardioverter defibrillator (ICD) have an ongoing risk of sudden incapacitation that might cause harm to others while driving a car. Driving restrictions vary across different countries in Europe. The most recent recommendations for driving of ICD patients in Europe were published in 1997 and focused mainly on patients implanted for secondary prevention. In recent years there has been a vast increase in the number of patients with an ICD and in the percentage of patients implanted for primary prevention. The EHRA task force on ICD and driving was formed to reassess the risk of driving for ICD patients based on the literature available. The recommendations are summarized in the following table and are further explained in the document. Restriction for private driving Restriction for professional driving ICD implantation for secondary prevention Three months Permanent ICD implantation for primary prevention Four weeks Permanent After appropriate ICD therapy Three months Permanent After inappropriate ICD therapy Until measures to prevent inappropriate therapy are taken Permanent After replacement of the ICD One week Permanent After replacement of the lead system Four weeks Permanent Patients refusing ICD for primary prevention No restriction Permanent Patients refusing ICD implantation for secondary prevention Seven months Permanent Driving restrictions are perceived as difficult for patients and their families, and have an immediate consequence for their lifestyle. To increase the adherence to the driving restrictions, adequate discharge of education and follow-up of patients and family are pivotal. The task force members hope this document may serve as an instrument for European and national regulatory authorities to formulate uniform driving regulations.

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry

Aims To analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients. Methods and results Patients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6–12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy. Conclusion In ‘real world’ clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available.

Managed ventricular pacing vs. conventional dual-chamber pacing for elective replacements: the PreFER MVP study: clinical background, rationale, and design

AIMS Several clinical studies have shown that, in patients with intact atrioventricular (AV) conduction, unnecessary chronic right ventricular (RV) pacing can be detrimental. The managed ventricular pacing (MVP) algorithm is designed to give preference to spontaneous AV conduction, thus minimizing RV pacing. The clinical outcomes of MVP are being studied in several ongoing trials in patients undergoing a first device implantation, but it is unknown to what extent MVP is beneficial in patients with a history of ventricular pacing. The purpose of the Prefer for Elective Replacement MVP (PreFER MVP) study is to assess the superiority of the MVP algorithm to conventional pacemaker and implantable cardioverter-defibrillator programming in terms of freedom from hospitalization for cardiovascular causes in a population of patients exposed to long periods of ventricular pacing. METHODS AND RESULTS PreFER MVP is a prospective, 1:1 parallel, randomized (MVP ON/MVP OFF), single-blinded multi-centre trial. The study population consists of patients with more than 40% ventricular pacing documented with their previous device. Approximately, 600 patients will be randomized and followed for at least 24 months. The primary endpoint comprises cardiovascular hospitalization. CONCLUSION The PreFER MVP trial is the first large prospective randomized clinical trial evaluating the effect of MVP in patients with a history of RV pacing.

Primary Prevention of Sudden Cardiac Death: Can We Afford the Cost of Cardioverter-Defibrillators? Data from the Search-MI Registry-Italian Sub-study

Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter‐defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD‐HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay‐off in terms of clinical benefits. Cost‐effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies.