Abstract: Background: An increased risk of delayed cardiac perforation (DCP) with active-fixation small-diameter ICD leads has recently been reported, especially with regard to the St. Jude Riata lead (St. Jude Medical, Sylmar, CA, USA). Few data on the risk of DCP in small versus standard-diameter leads implanted in a single high-volume center are available. Moreover, no data on the performances of St. Jude's new small-diameter Durata lead are as yet available. The aim of this study was to assess the incidence of DCP in small versus standard-diameter leads implanted in our center. Methods: Between January 2003 and October 2009, 437 small-diameter leads (190 Medtronic Sprint Fidelis [Medtronic Inc., Minneapolis, MN, USA], 196 Riata, 51 Durata) and 421 standard-diameter (>8 Fr) leads were implanted. Results: After a median follow-up of 421 days seven of 858 (0.8%) patients experienced DCP. The incidence of DCP was higher in patients with small-diameter leads than in those with standard-diameter leads (1.6% vs 0%, P = 0.01). No cases of DCP occurred among 371 passive-fixation leads versus 1.4% of events among active-fixation leads (P = 0.02). The incidence of DCP was 2.5% in Riata, 1% in Sprint Fidelis, 0% in Durata, and 0% in standard-diameter leads (P < 0.01 for Riata vs standard-diameter leads). Conclusions: Small-diameter active-fixation ICD leads are at increased risk of DCP, a finding mostly due to the higher incidence of events in the Riata family. By contrast, passive-fixation small-diameter leads and standard-diameter leads appear to be safe enough regarding the risk of DCP. Our preliminary data suggest that the new Durata lead is not associated with an increased risk of DCP. (PACE 2010; 1-9).
Abstract: AIMS: The purpose of this study was to evaluate adherence to national guidelines on the non-pharmacologic (ablative) treatment of atrial fibrillation (AF). METHODS AND RESULTS: This prospective, observational, transversal study enrolled 1256 consecutive in- and outpatients referred to 43 cardiology departments between 1 and 31 October 2008 for the management of AF as a primary diagnosis. A rhythm-control strategy (cardioversion, antiarrhythmic medication, pace-maker implantation, substrate ablation, alone or in combination) was prescribed in 865 (69%) of the patients and a rate-control strategy [drugs, atrioventricular junction ablation and pace-maker implantation (Ablate and Pace)] in 285 (23%). Specifically, substrate catheter ablation was indicated by the attending cardiologist in 187 (14.9%) patients and Ablate and Pace in 29 (2.3%). According to guideline indications, substrate catheter ablation would have been indicated in 183 (14.6%) patients, but only 105 (57%) of these were correctly identified by the attending cardiologist (K statistics for agreement for indications 0.49). Atrioventricular junction ablation and pace-maker implantation would have been indicated in 108 (8.6%) patients, but only 29 (27%) of these were correctly identified by the attending cardiologist (K statistics for agreement for indications 0.06). CONCLUSION: About a quarter of patients referred to cardiology departments for AF management have potential indications for non-pharmacological treatment according to the guidelines. Substrate catheter ablation was offered by the attending cardiologist in a percentage similar to that expected, but concordance with guideline indications was moderate. Atrioventricular junction ablation and pace-maker implantation was largely underused.
Abstract: Aims In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. Methods and results This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. Conclusions This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.
Abstract: Increased sympathetic and reduced vagal activity predict increased mortality in patients with congestive heart failure (CHF). Experimentally, vagal stimulation (VS) is protective both during acute myocardial ischemia and in chronic heart failure. In man, VS is used in refractory epilepsy but has never been used in cardiovascular diseases. Thus, there is a strong rationale to investigate the effects of chronic VS in patients with CHF. We assesses the feasibility and safety of chronic VS with CardioFit (BioControl Medical), a VS implantable system delivering pulses synchronous with heart beats to the right cervical vagus nerve in a preliminary pilot study in eight advanced CHF patients with favorable results, and subsequently in a larger multicenter study. Overall, 32 patients have been successfully implanted (mostly in NYHA Class III; mean age 56 years, ischemic etiology in 69%; prior implantable cardioverter-defibrillator (ICD) in 63%; concomitant beta blocker and angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) in 100%). Preliminary results confirm feasibility of the study, an acceptable side effect profile and promising preliminary efficacy data. Several mechanisms may contribute to the beneficial effect observed in patients with heart failure. Should these results be confirmed in larger controlled studies, chronic vagal stimulation could be a further treatment option for CHF patients, possibly integrated with defibrillator and resynchronization therapies.
Abstract: BACKGROUND: Prophylactic implantable cardioverter-defibrillator (ICD) therapy reduces mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF), but the absolute risk reduction is relatively small. Thus, there is a strong need to identify reliable risk stratifiers, particularly among patients with nonischemic cardiomyopathy (NIDCM), in whom the search for risk predictors has been particularly frustrating. OBJECTIVE: This study sought to review data regarding T-wave alternans (TWA) in patients with NIDCM and to discuss its potential role. METHODS: We included in a meta-analysis clinical trials that enrolled > or =50 NICDM patients, had a follow-up of > or =1 year, and provided detailed data on NIDCM patients, in case of mixed population. Relative risks were derived from absolute numbers of events in abnormal (positive + indeterminate test whenever possible) TWA versus normal (negative) TWA group. RESULTS: Eight studies with 1,456 patients (mean age 56 years, LVEF 30%, follow-up 25 months) were included. A negative TWA test occurred in 33%, and was indeterminate in 21% of the patients. The primary end point (VT+VF+sudden or all-cause death) occurred in 14.7% abnormal versus 3.8% normal TWA patients. The relative risk for the cumulative data was found to be 2.99 (95% confidence interval: 1.88 to 4.75). The negative predictive value was 96.2%. CONCLUSION: A normal TWA test identifies one-third of NIDCM patients who have a very good prognosis and are unlikely to significantly benefit from ICD therapy. A randomized clinical trial evaluating the utility of TWA in guiding therapy seems warranted, possibly a noninferiority trial of medical therapy only versus ICD in TWA-negative patients.
Abstract: BACKGROUND: 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. AIMS: This pilot study assessed feasibility and safety and tested possible efficacy of chronic VS in HF patients. METHODS: We studied 8 patients (mean age 54 years). CardioFit (BioControl Medical), a VS implantable system delivering pulses synchronous with heart beats through a multiple contact bipolar cuff electrode, was used. VS was started 2-4 weeks after implant, slowly raising intensity; patients were followed 1, 3 and 6 months thereafter. RESULTS: All procedures were successful: as sole surgical side effect, one patient had transient hoarseness. VS was well tolerated, with only mild side effects (cough and sensation of electrical stimulation). There was a significant improvement in NYHA class, Minnesota quality of life (from 52+/-14 to 31+/-18, p < 0.001), left ventricular end-systolic volume (from 208+/-71 to 190+/-83 ml, p = 0.03), and a favourable trend toward reduction in end-diastolic volume. CONCLUSIONS: This novel approach to the treatment of patients with HF is feasible, and appears safe and tolerable. The preliminary efficacy results appear promising. These findings suggest the opportunity to proceed with a larger multicentre study.
Abstract: OBJECTIVES: This study sought to assess the long-term predictive power of depressed baroreflex sensitivity (BRS) among post-myocardial infarction (MI) patients with preserved left ventricular function. BACKGROUND: Risk stratification after MI is primarily performed by identifying patients with depressed left ventricular ejection fraction (LVEF) because of their greater mortality. Autonomic markers can help refining risk stratification. Depressed BRS (<3 ms/mm Hg) correlated with cardiovascular mortality in 1,284 post-MI patients during a 21-month follow-up in the multicenter ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) study, but had no significant predictive power in patients with LVEF >35% or above age 65 years. METHODS: Two hundred forty-four consecutive post-MI patients (age 59 +/- 10 years) with LVEF >35% (average 54 +/- 8%) were enrolled. They underwent a complete assessment, including BRS 4 weeks after MI. RESULTS: During a 5-year mean follow-up, 14 (5.7%) patients died of cardiovascular causes. Multivariate analysis identified BRS (p = 0.0001), but not LVEF and age, as predictive of cardiovascular mortality. The relative risk (95% confidence interval [CI]) for depressed BRS was 11.4 (95% CI 3.3 to 39.0) for the overall population, 19.6 (95% CI 4.1 to 94.8) for patients </=65 years, and 7.2 (95% CI 1.3 to 39.9) for patients above age 65. CONCLUSIONS: Even among the large number of low-risk post-MI patients with preserved left ventricular function, depressed BRS identifies, independently of age, a subgroup at long-term high risk for cardiovascular mortality in which more aggressive preventive strategies should be considered.
Abstract: Oral estrogen treatment increases thrombotic risk. Tissue factor (TF), tissue factor pathway inhibitor (TFPI), and platelet interaction with leukocytes are important determinants of thrombogenesis. Therefore, the present study was designed to define and compare platelet TF and TFPI mRNA and adhesion protein expression in platelets derived from animals treated with different types of oral estrogens. Ovariectomized pigs were treated with 17beta-estradiol (2 mg/day), conjugated equine estrogen (CEE; 0.625 mg/day), or raloxifene (60 mg/day) for 4 wk. Compared with intact animals, ovariectomy and treatment differentially affected populations of leukocytes: neutrophils decreased whereas lymphocytes increased significantly 4 wk after ovariectomy and with 17beta-estradiol and CEE treatments; eosinophils increased only with 17beta-estradiol treatment. Content of TF protein increased in platelets from 17beta-estradiol- and raloxifene-treated pigs, whereas TF mRNA was detected only in platelets from 17beta-estradiol- and CEE treated pigs. TFPI mRNA increased in platelets after ovariectomy and estrogen treatment. Only a trace of TFPI protein was detected, but a higher-molecular-mass protein was observed in all treatment groups. Expression of CD40 and CD40 ligand increased with ovariectomy and decreased with 17beta-estradiol and CEE treatments more than with raloxifene. The ratio of activated to basal P-selectin expression decreased with ovariectomy and increased with raloxifene treatments. These results suggest that estrogenic formulations may affect individual thrombotic risk by different mechanisms that regulate TF and platelet-leukocytic interactions. These studies provide the rationale for evaluation of interactions among platelets and TF and TFPI expression on thrombin generation during estrogen treatment in humans.
