Rationale and design of an implant procedure and pivotal study to evaluate safety and effectiveness of Medtronic's tibial neuromodulation device.

Percutaneous tibial neuromodulation is a medical guideline recommended therapy for treating symptoms of overactive bladder. Stimulation is delivered to the tibial nerve via a thin needle placed percutaneously for 30 min once a week for 12-weeks, and monthly thereafter. Studies have shown that this therapy can effectively relieve symptoms of overactive bladder; however, the frequent office visits present a barrier to patients and can impact therapy effectiveness.

A prospective, multicenter, international study to explore the effect of three different amplitude settings in female subjects with urinary urge incontinence receiving interstim therapy.

Aims: The aim of this study is to evaluate the effect of sub-sensory amplitude settings of sacral neuromodulation therapy on overactive bladder symptoms in subjects with urinary urge incontinence.

Methods: Subjects who qualified for a neurostimulator device implant were randomized to one of three amplitude settings (50% of sensory threshold [ST], 80% of ST, and ST). Subjects completed urinary voiding diaries (3-day), International consultation on incontinence modular questionnaire-overactive bladder symptoms quality of life questionnaire, and patient global impression of improvement (PGI-I) to assess change in voiding symptoms and quality of life (QoL) from baseline through 12 weeks.

Does change in device detected frequency of non-sustained or diverted episodes serve as a marker for inappropriate shock therapy? Analyses from the INTRINSIC RV and ALTITUDE-REDUCES Trials.

Aims: Implantable cardioverter-defibrillators (ICDs) treat ventricular tachycardia or fibrillation but may also deliver unnecessary shocks. We sought to determine if the frequency of ICD-detected non-sustained or diverted (NSD) episodes increases before appropriate or inappropriate ICD shocks.

Methods And Results: We evaluated NSD episodes in the INTRINSIC RV Trial and their relationship to ICD shocks (appropriate and inappropriate).

Atrial support pacing in heart failure: results from the multicenter PEGASUS CRT trial.

Introduction: Cardiac resynchronization therapy (CRT) efficacy trials to date used atrial-synchronous biventricular pacing wherein there is no or minimal atrial pacing. However, bradycardia and chronotropic incompetence are common in this patient population. This trial was designed to evaluate the effect of atrial support pacing among heart failure patients receiving a CRT defibrillator.

Arrhythmia rate distribution and tachyarrhythmia therapy in an ICD population: results from the INTRINSIC RV trial.

Background: Appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) depends, in part, on the programming of tachycardia zones.

Objective: We assessed events treated with ICD shocks or antitachycardia pacing (ATP) in the Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) trial.

Methods: ATP and shock episodes from 1530 patients with dual-chamber ICDs were analyzed.

Design and rationale of the assessment of proper physiologic response with rate adaptive pacing driven by minute ventilation or accelerometer (APPROPRIATE) trial.

Rate-adaptive sensors are designed to restore a physiologic heart rate response to activity, in particular for patients that have chronotropic incompetence (CI). Limited data exist comparing two primary types of sensors; an accelerometer (XL) sensor which detects activity or motion and a minute ventilation (MV) sensor, which detects the product of respiration rate and tidal volume. The APPROPRIATE study will evaluate the MV sensor compared with the XL sensor for superiority in improving functional capacity (peak VO(2)) in pacemaker patients that have CI.

Older persons with diabetes receive fewer inappropriate ICD shocks: results from the INTRINSIC RV trial.

In patients with heart disease, diabetes and age predict adverse outcomes. It remains unclear whether persons with diabetes who have implantable cardioverter defibrillators (ICDs) have fewer appropriate and inappropriate ICD shocks. The objective of this study is to determine if persons with diabetes who have ICDs receive a similar amount of appropriate and inappropriate shocks compared to persons without diabetes.

Heart rate predicts outcomes in an implantable cardioverter-defibrillator population.

Background: Elevated heart rate (HR) is associated with adverse cardiovascular events and total mortality in the general population and in individuals with heart disease. Our hypothesis was that mean HR predicts total mortality and heart failure hospitalization in patients undergoing implantable cardioverter-defibrillator (ICD) implantation.

Methods And Results: The Inhibition of Unnecessary RV Pacing With AV Search Hysteresis in ICDs (INTRINSIC RV) trial included 1530 patients undergoing ICD implantation.

Fractal scaling properties of heart rate dynamics and myocardial efficiency in dilated cardiomyopathy.

Introduction: Since altered heart rate (HR) fluctuations provide prognostic information in heart failure, we examined the associations between HR dynamics, myocardial efficiency and perfusion, among patients with dilated cardiomyopathy.

Methods: Sixteen patients with dilated cardiomyopathy were enrolled. Patients received supervised strength and aerobic training for 5 months (n = 9) or standard care (n = 7).

Implantable cardioverter defibrillators: do women fare worse than men? Gender comparison in the INTRINSIC RV trial.

Introduction: Due to limited enrollment of women in previous trials, there is a paucity of data comparing outcome and arrhythmic events in men versus women with implantable cardioverter defibrillators (ICDs).

Methods And Results: We analyzed outcome of patients in the INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs) trial based on gender. Women comprised 19% (293/1530) of the INTRINSIC RV population.

Newly detected atrial fibrillation in patients with an implantable cardioverter-defibrillator is a strong risk marker of increased mortality.

Background: Atrial fibrillation (AF) has been associated with higher rates of all-cause mortality in patients with heart failure (HF). The risk of newly detected AF in patients receiving implantable cardioverter-defibrillator (ICD) therapy is unknown.

Methods: Newly detected AF was evaluated in all patients enrolled in the Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) study.

A blended sensor restores chronotropic response more favorably than an accelerometer alone in pacemaker patients: the LIFE study results.

Background: Adaptive rate sensors used in permanent pacemakers incorporate an accelerometer (XL) to increase heart rate with activity. Limited data exists regarding the relative benefit of a blended sensor (BS) (XL and minute ventilation) versus XL alone in restoring chronotropic response (CR) in chronotropically incompetent (CI) patients.

Methods: One thousand five hundred thirty-eight patients from the limiting chronotropic incompetence for pacemaker recipients (LIFE) study were implanted with a pacemaker and 1,256 patients had data collected at 1 month.

High defibrillation energy requirements are encountered rarely with modern dual-chamber implantable cardioverter-defibrillator systems.

Aims: Defibrillation conversion testing to assure a 10 J safety margin is a standard practice during implantable cardioverter-defibrillator (ICD) implantation. Little data are available on the number of patients who do not have a 10 J margin initially and therefore require system revisions, further testing, or a higher energy output device.

Methods And Results: The INTRINSIC RV study enrolled 1530 new ICD recipients who were not in permanent atrial fibrillation who received a VITALITY AVT (Guidant, St Paul, MN, USA) standard energy (31 J maximum) ICD and underwent defibrillation conversion testing at the time of implantation from 108 centres.

Eliminating right ventricular pacing may not be best for patients requiring implantable cardioverter-defibrillators.

Background: Excessive right ventricular (RV) pacing has been associated with adverse clinical outcomes in patients receiving pacemakers or implantable cardioverter-defibrillators (ICDs). It remains uncertain how much RV pacing is clinically deleterious.

Objective: This retrospective analysis assessed the relationship between the amount of RV pacing and the composite of all-cause mortality and heart failure hospitalization in all patients programmed DDDR in the Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) study.

Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene: a positron emission tomography study.

Background: The relationship between myocardial metabolic changes and the severity of left ventricular (LV) hypertrophy in patients with hypertrophic cardiomyopathy (HCM) is largely unknown. We characterized metabolic abnormalities in patients with a genetically identical cause for HCM but with variable LV hypertrophy.

Methods And Results: Eight patients with HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene underwent myocardial perfusion, oxidative, and free fatty acid (FFA) metabolism measurements via positron emission tomography and oxygen 15-labeled water, carbon 11 acetate, and fluorine 14(R,S)-[18F] Fluoro-6-thia-heptadecanoic acid (18 FTHA).

Pacing Evaluation-Atrial SUpport Study in Cardiac Resynchronization Therapy (PEGASUS CRT): design and rationale.

Background: Cardiac resynchronization therapy (CRT) has been demonstrated to be an effective heart failure (HF) therapy. All pivotal trials of CRT to date have used atrial-synchronous biventricular pacing wherein there is no or minimal atrial pacing. In clinical practice, however, physicians often program CRT devices to have atrial rate support pacing, either by increasing the lower rate limit or by activating the rate sensor.

Assessment of right ventricular oxidative metabolism by PET in patients with idiopathic dilated cardiomyopathy undergoing cardiac resynchronization therapy.

Purpose: Right ventricular (RV) performance is known to have prognostic value in patients with congestive heart failure (CHF). Cardiac resynchronization therapy (CRT) has been found to enhance left ventricular (LV) energetics and metabolic reserve in patients with heart failure. The interplay between the LV and RV may play an important role in CRT response.

Myocardial perfusion reserve and oxidative metabolism contribute to exercise capacity in patients with dilated cardiomyopathy.

Background: Exercise intolerance is a hallmark symptom in patients with heart failure; however, myocardial factors contributing to the limited exercise capacity are not fully characterized.

Methods: Twenty patients with stable heart failure resulting from idiopathic dilated cardiomyopathy (DCM) and 13 controls were studied. Myocardial perfusion, biventricular oxidative metabolism, and insulin-stimulated glucose uptake were measured using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate, and [(18)F]FDG.

The effects of cardiac resynchronization therapy on left ventricular function, myocardial energetics, and metabolic reserve in patients with dilated cardiomyopathy and heart failure.

Objectives: The effects of long-term cardiac resynchronization therapy (CRT) on left ventricular (LV) energetics and metabolic reserve were evaluated.

Background: Cardiac resynchronization therapy is a new therapy for patients with drug-refractory severe heart failure (HF).

Methods: Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of biventricular pacemaker 8 +/- 5 months earlier were studied during two conditions: CRT switched on, and after CRT was switched off for 24 h.

Myocardial perfusion reserve and peripheral endothelial function in patients with idiopathic dilated cardiomyopathy.

The aim of this study was to assess the relation between peripheral endothelial function and myocardial perfusion reserve in patients with mild heart failure due to idiopathic dilated cardiomyopathy (IDC). Myocardial perfusion and brachial artery flow mediated dilation (FMD) were measured in 20 clinically stable patients with IDC (New York Heart Association classes I to III, ejection fraction 35 +/- 9%) and 13 apparently healthy subjects who were matched for age and lipid profile. Resting and hyperemic (dipyridamole; 0.

Exercise training improves insulin-stimulated myocardial glucose uptake in patients with dilated cardiomyopathy.

Background: The effects of exercise training on myocardial substrate utilization have not previously been studied in patients with idiopathic dilated cardiomyopathy and mild heart failure.

Methods And Results: Myocardial glucose uptake was studied in 15 clinically stable patients with dilated cardiomyopathy (New York Heart Association class I-II, ejection fraction 34% +/- 8%) with the use of 2-[fluorine 18]fluoro-2-deoxy-d-glucose ([F-18]FDG) and positron emission tomography under euglycemic hyperinsulinemia. Eight of these patients participated in a 5-month endurance and strength training program, whereas seven patients served as nontrained subjects.

Exercise training improves insulin stimulated skeletal muscle glucose uptake independent of changes in perfusion in patients with dilated cardiomyopathy.

Objective: The purpose of the present study was to investigate the effects of a 5-month exercise training program on skeletal muscle perfusion and insulin sensitivity at rest and during exercise in patients with idiopathic dilative cardiomyopathy (DCM).

Background: Patients with chronic heart failure are characterized by impaired insulin sensitivity and endothelial function. It is hypothesized that exercise training improves metabolism by enhancing perfusion in patients with heart failure.

Insulin signalling and resistance in patients with chronic heart failure.

We investigated whether insulin resistance in patients with chronic heart failure (CHF) is associated with impaired insulin signalling in skeletal muscle and whether exercise training would lead to an improvement in insulin signalling, concomitant with enhanced insulin action. Fourteen men with CHF due to idiopathic dilated cardiomyopathy, with mild-to-moderate limitation of physical activity and a left-ventricular ejection fraction of less than 45 %, were studied before and after either a 5 month exercise training programme (n = 7) or standard care (n = 7). Seven healthy men participated as controls.

Exercise training improves biventricular oxidative metabolism and left ventricular efficiency in patients with dilated cardiomyopathy.

Objectives: The aim of this study was to determine the effect of exercise training on myocardial oxidative metabolism and efficiency in patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (HF).

Background: Exercise training is known to improve exercise tolerance and quality of life in patients with chronic HF. However, little is known about how exercise training may influence myocardial energetics.