Randomized evaluation of vessel preparation with orbital atherectomy prior to drug-eluting stent implantation in severely calcified coronary artery lesions: Design and rationale of the ECLIPSE trial.

BACKGROUND: Severe coronary artery calcification has been associated with stent underexpansion, procedural complications, and increased rates of early and late adverse clinical events in patients undergoing percutaneous coronary intervention. To date, no lesion preparation strategy has been shown to definitively improve outcomes of percutaneous coronary intervention for calcified coronary artery lesions. STUDY DESIGN AND OBJECTIVES: ECLIPSE (NCT03108456) is a prospective, randomized, multicenter trial designed to evaluate two different vessel preparation strategies in severely calcified coronary artery lesions. The routine use of the Diamondback 360 Coronary Orbital Atherectomy System is compared with conventional balloon angioplasty prior to drug-eluting stent implantation. The trial aims to enroll approximately 2000 subjects with a primary clinical endpoint of target vessel failure, defined as the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization assessed at 1 year. The co-primary endpoint is the acute post-procedural in-stent minimal cross-sectional area as assessed by optical coherence tomography in a 500-subject cohort. Enrollment is anticipated to complete in 2022 with total clinical follow-up planned for 2 years. CONCLUSIONS: ECLIPSE is a large-scale, prospective randomized trial powered to demonstrate whether a vessel preparation strategy of routine orbital atherectomy system is superior to conventional balloon angioplasty prior to implantation of drug-eluting stents in severely calcified coronary artery lesions.

Long-term efficacy and safety of sacral nerve stimulation for fecal incontinence.

BACKGROUND AND OBJECTIVE: Sacral nerve stimulation is effective in the treatment of urinary incontinence and is currently under Food and Drug Administration review in the United States for fecal incontinence. Previous reports have focused primarily on short-term results of sacral nerve stimulation for fecal incontinence. The present study reports the long-term effectiveness and safety of sacral nerve stimulation for fecal incontinence in a large prospective multicenter study. DESIGN AND METHODS: Patients with fecal incontinent episodes more than twice per week were offered participation in this multicentered prospective trial. Patients showing ≥ 50% improvement during test stimulation were offered chronic implantation of the InterStim Therapy system (Medtronic; Minneapolis, MN). The aims of the current report were to provide 3-year follow-up data on patients from that study who underwent sacral nerve stimulation and were monitored under the rigors of an Food and Drug Administration-approved investigational protocol. RESULTS: One hundred thirty-three patients underwent test stimulation with a 90% success rate, of whom 120 (110 females) with a mean age of 60.5 years and a mean duration of fecal incontinence of 7 years received chronic implantation. Mean length of follow-up was 3.1 (range, 0.2-6.1) years, with 83 patients completing all or part of the 3-year follow-up assessment. At 3 years follow-up, 86% of patients (P < .0001) reported ≥ 50% reduction in the number of incontinent episodes per week compared with baseline and the number of incontinent episodes per week decreased from a mean of 9.4 at baseline to 1.7. Perfect continence was achieved in 40% of subjects. The therapy also improved the fecal incontinence severity index. Sacral nerve stimulation had a positive impact on the quality of life, as evidenced by significant improvements in all 4 scales of the Fecal Incontinence Quality of Life instrument at 12, 24, and 36 months of follow-up. The most common device- or therapy-related adverse events through the mean 36 months of follow-up included implant site pain (28%), paresthesia (15%), change in the sensation of stimulation (12%), and infection (10%). There were no reported unanticipated adverse device effects associated with sacral nerve stimulation therapy. CONCLUSIONS: Sacral nerve stimulation using InterStim Therapy is a safe and effective treatment for patients with fecal incontinence. These data support long-term safety and effectiveness to 36 months.

Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study.

BACKGROUND: Sacral nerve stimulation has been approved for use in treating urinary incontinence in the United States since 1997, and in Europe for both urinary and fecal incontinence (FI) since 1994. The purpose of this study was to determine the safety and efficacy of sacral nerve stimulation in a large population under the rigors of Food and Drug Administration-approved investigational protocol. METHODS: Candidates for SNS who provided informed consent were enrolled in this Institutional Review Board-approved multicentered prospective trial. Patients showing > or =50% improvement during test stimulation received chronic implantation of the InterStim Therapy (Medtronic; Minneapolis, MN). The primary efficacy objective was to demonstrate that > or =50% of subjects would achieve therapeutic success, defined as > or =50% reduction of incontinent episodes per week at 12 months compared with baseline. RESULTS: A total of 133 patients underwent test stimulation with a 90% success rate, and 120 (110 females) of a mean age of 60.5 years and a mean duration of FI of 6.8 years received chronic implantation. Mean follow-up was 28 (range, 2.2-69.5) months. At 12 months, 83% of subjects achieved therapeutic success (95% confidence interval: 74%-90%; P < 0.0001), and 41% achieved 100% continence. Therapeutic success was 85% at 24 months. Incontinent episodes decreased from a mean of 9.4 per week at baseline to 1.9 at 12 months and 2.9 at 2 years. There were no reported unanticipated adverse device effects associated with InterStim Therapy. CONCLUSION: Sacral nerve stimulation using InterStim Therapy is a safe and effective treatment for patients with FI.

Short-long sequences prior to ventricular tachycardia onset: analysis of VAST trial electrograms.

BACKGROUND: The recently published Ventricular Arrhythmia Suppression Trial (VAST) found no effect of rate-smoothing (RS) algorithm on frequency of ventricular tachycardia (VT) episodes in patients with implantable defibrillator. A similar recent trial reported an opposite result. In order to determine possible reasons for the discrepancy between the trials and achieve better understanding of events preceding VT onset, we analyzed stored device electrograms preceding 162 VT episodes from 50 VAST trial patients with dual-chamber devices. RESULTS: In this analysis, short-long sequences were more common prior to polymorphic VTs than before monomorphic VTs. The proportion of VT episodes preceded by short-long sequences was lower during randomization to RS ON (5.3% vs 31.3%, P < 0.001). For patients with multiple episodes of monomorphic VT, there was higher interpatient than intrapatient variability in preceding RR intervals. When adjusting for this similarity of RR interval sequences preceding VT onset in individual patients, the difference in proportion short-long sequences between RS ON and RS OFF programming was no longer significant. CONCLUSION: Episodes of VT were preceded by stereotypic, patient-specific sequences of RR intervals in several VAST trial patients. RS reduced the percentage of VTs preceded by short-long sequences, but did not change overall VT incidence.

Is dual-chamber programming inferior to single-chamber programming in an implantable cardioverter-defibrillator? Results of the INTRINSIC RV (Inhibition of Unnecessary RV Pacing With AVSH in ICDs) study.

BACKGROUND: The INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AVSH in ICDs) study tested the hypothesis that dual-chamber rate-responsive (DDDR) with atrioventricular search hysteresis (AVSH) 60-130 programming is not inferior to single-chamber (VVI)-40 programming in an implantable cardioverter defibrillator with respect to all-cause mortality and heart failure hospitalizations using an equivalence margin of 5%. METHODS AND RESULTS: At 108 centers, 1530 patients with an implantable cardioverter defibrillator indication received a VITALITY AVT (Guidant Corporation, St. Paul, Minn) implantable cardioverter defibrillator programmed consistently to DDDR AVSH 60-130 for the first week. Of those, 988 patients with <20% right ventricular pacing at 1 week were randomized to DDDR AVSH 60-130 or to VVI-40 programming. Among those randomized, 502 were assigned to DDDR AVSH and 486 to VVI. Groups were similar with regard to coronary disease (68%), gender (21% female), and New York Heart Association functional class >I (79%). A total of 32 patients (6.4%) in the DDDR AVSH arm and 46 patients (9.5%) in the VVI arm died or were hospitalized for heart failure during a mean follow-up of 10.4 months (relative risk=0.67, P=0.072 in favor of DDDR AVSH). DDDR AVSH was not inferior to VVI programming (P<0.001). All-cause mortality was not significantly different between the DDDR AVSH arm (3.6%) and the VVI arm (5.1%; P=0.23). The mean percent right ventricular pacing in the DDDR AVSH arm was 10% (median 4%) versus 3% (median 0%) in the VVI arm. CONCLUSIONS: In the INTRINSIC RV trial, among those randomized, DDDR AVSH was associated with similar outcomes as with VVI backup pacing.

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. Among enrolled patients, 59 (3.9%) did not initially meet the 10 J safety margin criterion. In these 59 patients, a 10 J safety margin was achieved by making at least one system revision: reversing shocking polarity (n = 33, 56%), right ventricular lead repositioning (n = 19, 32%), repeat testing at a later date (n = 1, 2%), adding a subcutaneous array (n = 1, 2%), or other means (n = 10, 17%). Only New York Heart Association class (P = 0.001) and no previous myocardial infarction (P = 0.044) predicted a failed initial conversion test. There were no reported complications from ICD shock testing. CONCLUSION: Successful defibrillation conversion criteria with the first configuration tested with a standard energy device is almost always met with modern dual-chamber ICD systems. The need for revising the initial ICD shock configuration to achieve a 10 J safety margin appears extremely low and of low risk.

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. METHODS: Seven hundred fifteen patients consistently programmed to DDDR mode throughout follow-up (mean 11.6 months) were examined. The relationship between RV pacing tier and death and heart failure hospitalization was determined and compared with patient characteristics. RESULTS: Across the six RV pacing tiers, patients differed significantly with respect to age, clinical history of ventricular tachycardia, atrial fibrillation, and atrial flutter, and amiodarone use. When controlling for these baseline differences, the best outcome was seen in the group with RV pacing between 10% and 19% (2.8% event rate; n = 106). Increasing levels of RV pacing were generally predictive of higher event rates (death or heart failure hospitalization; P = 0.003), except for the group (n = 344) with the least amount of RV pacing (0-9%). This group exhibited poorer outcomes than otherwise expected (P = 0.016), with 8.1% of these patients experiencing an event. CONCLUSIONS: High levels of RV pacing are associated with heart failure hospitalization and mortality in a large ICD population. However, ICD patients with some RV pacing (10%-19%) exhibit lower event rates compared with those with very low levels (0-9%), possibly due to the physiologically appropriate nature of that RV pacing.

Longitudinal changes in quality of life following ICD implant and the impact of age, gender, and ICD shocks: observations from the INTRINSIC RV trial.

PURPOSE: ICDs can improve survival in at-risk patients but no consensus exists with respect to their impact on health-related quality of life (QOL). Moreover, the data are unclear on QOL benefits in specific patient subgroups. We sought to analyze, in the INTRINSIC RV ICD trial population, health-related QOL longitudinally following ICD implant and consider impact of age, gender, and ICD shocks on QOL by employing a global measure of health-related QOL. METHODS: One thousand five hundred thirty patients had an ICD implanted. One week after implant (n = 1461), 988 patients were randomized to DDDR with AV search hysteresis (n = 502) or VVI (n = 486) programming. QOL data, using the SF-36 short form, were obtained for the 1461 patient cohort, irrespective of randomization status, at baseline and prospectively for 1 year following ICD implant. RESULTS: Longitudinal mixed-effect analyses revealed significant improvements from baseline across all SF-36 subscales and component scores for the overall study cohort. Women had a substantially lower QOL at baseline, although their improvement after implant was similar to men. Patients <50 years scored consistently worse at baseline but experienced the greatest QOL improvement versus other age groups. Patients with higher NYHA class, angina, and diabetes had greater QOL improvements. There was no significant difference in QOL between patients with and without ICD shocks. CONCLUSIONS: Our findings indicate that QOL was reportedly better post-implant and suggest that benefits associated with ICD implantation go beyond the direct treatment of arrhythmias, with benefits seen across genders and different age groups. These results further highlight that ICD implantation, in and of itself, does not reduce QOL.

Effects of a rate smoothing algorithm for prevention of ventricular arrhythmias: results of the Ventricular Arrhythmia Suppression Trial (VAST).

BACKGROUND: Rate smoothing, which is available in some pacemakers and implantable cardioverter defibrillators (ICDs), has been used to prevent Torsades de Pointes in patients with long QT syndrome. Its efficacy in general ventricular arrhythmia prevention has not been determined. OBJECTIVES: The purpose of the Ventricular Arrhythmia Suppression Trial (VAST) was to prospectively investigate whether rate smoothing could significantly reduce the incidence of ventricular tachyarrhythmias in a large, broad population of patients with ICDs. METHODS: Five hundred sixty-nine patients were enrolled at 57 participating centers and implanted with a commercially available Guidant ICD. A single-blinded crossover design was used in which each patient was randomized at implant to one of two treatment sequences: either rate smoothing on (RS On) followed by rate smoothing off (RS Off), or RS Off followed by RS On. This mode sequence was randomly determined and assigned in a 1:1 fashion using randomized permuted blocks by site. Each mode was followed for 6 months. Programming of rate smoothing was prescribed as 12% Down and 12% Up for the duration of the RS On period. RESULTS: Of enrolled patients, 281 were randomized to RS Off followed by RS On, and 288 to RS On followed by RS Off. With RS On, 75 (23%) patients experienced a reduction in arrhythmias, 76 (23%) saw an increase in arrhythmias, and the remaining 176 (54%) had no difference. No significant difference (P = .58) in frequency of arrhythmias with RS On vs RS Off was found. CONCLUSION: Rate smoothing does not result in a reduction in ventricular arrhythmias in a heterogeneous population of patients receiving ICDs.

Latent structure of anxiety: taxometric exploration.

Taxometrics is a statistical tool that can be used to discern categories from continua. Taxometric analyses (MAXCOV and MAXEIG) were conducted in a large nonclinical sample (N=1,215) to determine whether extreme anxiety forms a distinct psychopathological category, an anxiety taxon. Anxiety was operationalized with self-report measures of subjective anxiety, anxious cognitive style, physiological arousal, and anxiety-related impairment. Procedures consistently identified a taxon with a prevalence of approximately 11%. Examination of the taxon's convergent and discriminant validity revealed that it reflects general distress rather than physiological arousal. Taxon membership showed some evidence of incremental validity.

Infection rates in a large investigational trial of sacral nerve stimulation for fecal incontinence.

INTRODUCTION: Treatment options for patients with fecal incontinence (FI) are limited, and surgical treatments can be associated with high rates of infection and other complications. One treatment, sacral nerve stimulation (SNS), is approved for FI in Europe. A large multicenter trial was conducted in North America and Australia to assess the efficacy of SNS in patients with chronic fecal incontinence. The aim of this report was to analyze the infectious complication rates in that trial. METHODS: Adult patients with a history of chronic fecal incontinence were enrolled into this study. Those patients who fulfilled study inclusion/exclusion criteria and demonstrated greater than two FI episodes per week underwent a 2-week test phase of SNS. Patients who showed a > or = 50% reduction in incontinent episodes and/or days per week underwent chronic stimulator implantation. Adverse events were reported to the sponsor by investigators at each study site and then coded. All events coded as implant site infection were included in this analysis. RESULTS: One hundred twenty subjects (92% female, 60.5 +/- 12.5 years old) received a chronically implanted InterStim Therapy device (Medtronic, Minneapolis, MN, USA). Patients were followed for an average of 28 months (range 2.2-69.5). Thirteen of the 120 implanted subjects (10.8%) reported infection after the chronic system implant. One infection spontaneously resolved and five were successfully treated with antibiotics. Seven infections (5.8%) required surgical intervention, with infections in six patients requiring full permanent device explantation. The duration of the test stimulation implant procedure was similar between the infected group (74 min) and the non-infected group (74 min). The average duration of the chronic neurostimulator implant procedure was also similar between the infected (39 min) and non-infected group (37 min). Nine infections occurred within a month of chronic system implant and the remaining four infections occurred more than a year from implantation. While the majority (7/9) of the early infections was successfully treated with observation, antibiotics, or system replacement, all four of the late infections resulted in permanent system explantation. CONCLUSION: SNS for FI resulted in a relatively low infection rate. This finding is especially important because the only other Food and Drug Administration-approved treatment for end-stage FI, the artificial bowel sphincter, reports a much higher rate. Combined with its published high therapeutic success rate, this treatment has a positive risk/benefit profile.

The Rhythm ID Going Head to Head Trial (RIGHT): design of a randomized trial comparing competitive rhythm discrimination algorithms in implantable cardioverter defibrillators.

BACKGROUND: The implantable cardioverter defibrillator (ICD) has become primary therapy for the prevention of sudden death. One of the major morbidities of ICD use remains inappropriate therapy for supraventricular arrhythmias (SVA). Detection enhancements have increased therapy specificity, but their impact on inappropriate therapy is not well studied. Moreover, ICD manufacturers have developed unique algorithms to meet this goal, with no previous clinical direct comparisons. RIGHT is a randomized, prospective study that will assess the differential efficacy of ICDs from two different manufacturers. It is the first trial to compare directly competitive ICD rhythm discrimination algorithms on a large scale. OBJECTIVE: The primary objective of this study is to assess arrhythmia discrimination in Guidant versus Medtronic ICDs by comparing the time to first inappropriate therapy after the predischarge visit. METHODS: The study will enroll approximately 2,000 patients in 100 centers. Patients will be randomized to Guidant or Medtronic using a permuted block design, stratified by center and by single/dual chamber device types. Patients will receive a commercially available Guidant VITALITY 2 family ICD with Rhythm ID or a Medtronic ICD using the Enhanced PR Logic or Wavelet discrimination algorithms, and will be followed according to the schedule shown until a common closing date with a minimum follow-up of 12 months. All events will be reviewed by an independent committee to determine the appropriateness of rhythm classification and therapy delivery. CONCLUSION: RIGHT is the first randomized, large scale, head-to-head comparison of ICD discrimination algorithms.

Reduction of right ventricular pacing in patients with dual-chamber ICDs.

BACKGROUND: Unnecessary right ventricular (RV) pacing in patients with implantable cardioverter defibrillators (ICD) may adversely affect heart failure morbidity and total mortality. Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) is a prospective, multicenter, randomized trial evaluating outcomes in ICD recipients programmed to single-chamber pacing (VVI) versus dual-chamber (DDDR) pacing with AV search hysteresis (AVSH). METHODS: Patients underwent ICD implant (for standard indications). The ICD was programmed to DDDR with AVSH regardless of any need for pacing. Rate-adaptive pacing was set at 60-130 ppm with dynamic AV delay from 200 to 90 ms. AVSH was programmed to search every 32 intervals and extend the AV delay by 50%. One week post-implant patients with ICDs were interrogated to assess the percentage of RV pacing with the expectation that most would have <20% RV pacing and would be randomized into INTRINSIC RV. Early analysis showed that targets for randomization were not met. AVSH parameters were modified under a protocol amendment to increase AV delay extension to 100%. We report findings related to this programming change based upon analyses of (nonrandomized) data pre- and post-amendment. RESULTS: Twenty-one percent of patients (n = 314) were enrolled pre-amendment and 79% (n = 1,216) were enrolled post-amendment. The mean percentage of RV pacing at the 1-week visit was 41.4 +/- 29.6% pre-amendment and 14.7 +/- 22.6% post-amendment (P < 0.0001). The proportion of patients eligible for randomization (RV pacing <20% at the 1-week visit) was 31.2% pre-amendment and 76.8% post-amendment (P < 0.0001). CONCLUSION: AVSH can dramatically reduce the percentage of RV pacing among ICD recipients.