The utilization and safety of apixaban for therapeutic anticoagulation in heart transplant population requiring routine endomyocardial biopsies.

PURPOSE: Routine endomyocardial (EM) biopsies pose a challenge in the management of heart transplant recipients requiring anticoagulation. Apixaban is a direct-acting oral anticoagulant (DOAC) with a short half-life allowing for brief interruptions of anticoagulation for procedures. The study objective was to determine the safety and efficacy of apixaban in heart transplant patients undergoing EM biopsies. METHODS: This retrospective case series evaluated patients with a heart transplant from April 1, 2017 to July 30, 2020 who were treated with apixaban within 90 days post-transplant. The primary outcome was the occurrence of a bleeding or thrombotic event. RESULTS: A total of 12 patients with >100 biopsies were included. The median age was 54 years (IQR 37-59) with a mean weight of 91 ± 20 kg. There were no bleeding or thrombotic events. During therapy, patients underwent an average of eight biopsies. The median time from transplant to initiation of apixaban was 39.5 days (range 9-77). Therapy was maintained without any need for reversal for a median of 276 days (IQR 45-245). CONCLUSIONS: Apixaban is safe to use for anticoagulation of heart transplant recipients undergoing routine biopsies. Using apixaban allows for a short interruption of therapeutic anticoagulation to accommodate a biopsy without increased risk of bleeding.

Safety and efficacy of a totally subcutaneous implantable-cardioverter defibrillator.

BACKGROUND: The most frequent complications associated with implantable cardioverter-defibrillators (ICDs) involve the transvenous leads. A subcutaneous implantable cardioverter-defibrillator (S-ICD) has been developed as an alternative system. This study evaluated the safety and effectiveness of the S-ICD System (Cameron Health/Boston Scientific) for the treatment of life-threatening ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation). METHODS AND RESULTS: This prospective, nonrandomized, multicenter trial included adult patients with a standard indication for an ICD, who neither required pacing nor had documented pace-terminable ventricular tachycardia. The primary safety end point was the 180-day S-ICD System complication-free rate compared with a prespecified performance goal of 79%. The primary effectiveness end point was the induced ventricular fibrillation conversion rate compared with a prespecified performance goal of 88%, with success defined as 2 consecutive ventricular fibrillation conversions of 4 attempts. Detection and conversion of spontaneous episodes were also evaluated. Device implantation was attempted in 321 of 330 enrolled patients, and 314 patients underwent successful implantation. The cohort was followed for a mean duration of 11 months. The study population was 74% male with a mean age of 52±16 years and mean left ventricular ejection fraction of 36±16%. A previous transvenous ICD had been implanted in 13%. Both primary end points were met: The 180-day system complication-free rate was 99%, and sensitivity analysis of the acute ventricular fibrillation conversion rate was >90% in the entire cohort. There were 38 discrete spontaneous episodes of ventricular tachycardia/ventricular fibrillation recorded in 21 patients (6.7%), all of which successfully converted. Forty-one patients (13.1%) received an inappropriate shock. CONCLUSIONS: The findings support the efficacy and safety of the S-ICD System for the treatment of life-threatening ventricular arrhythmias.

Torsemide vs Furosemide Among Patients With New-Onset vs Worsening Chronic Heart Failure: A Substudy of the TRANSFORM-HF Randomized Clinical Trial.

Importance: Differences in clinical profiles, outcomes, and diuretic treatment effects may exist between patients with de novo heart failure (HF) and worsening chronic HF (WHF). Objectives: To compare clinical characteristics and treatment outcomes of torsemide vs furosemide in patients hospitalized with de novo HF vs WHF. Design, Setting, and Participants: All patients with a documented ejection fraction who were randomized in the Torsemide Comparison With Furosemide for Management of Heart Failure (TRANSFORM-HF) trial, conducted from June 18 through March 2022, were included in this post hoc analysis. Study data were analyzed March to May 2023. Exposure: Patients were categorized by HF type and further divided by loop diuretic strategy. Main Outcomes and Measures: End points included all-cause mortality and hospitalization outcomes over 12 months, as well as change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results: Among 2858 patients (mean [SD] age, 64.5 [14.0] years; 1803 male [63.1%]), 838 patients (29.3%) had de novo HF, and 2020 patients (70.7%) had WHF. Patients with de novo HF were younger (mean [SD] age, 60.6 [14.5] years vs 66.1 [13.5] years), had a higher glomerular filtration rate (mean [SD], 68.6 [24.9] vs 57.0 [24.0]), lower levels of natriuretic peptides (median [IQR], brain-type natriuretic peptide, 855.0 [423.0-1555.0] pg/mL vs 1022.0 [500.0-1927.0] pg/mL), and tended to be discharged on lower doses of loop diuretic (mean [SD], 50.3 [46.2] mg vs 63.8 [52.4] mg). De novo HF was associated with lower all-cause mortality at 12 months (de novo, 65 of 838 [9.1%] vs WHF, 408 of 2020 [25.4%]; adjusted hazard ratio [aHR], 0.50; 95% CI, 0.38-0.66; P < .001). Similarly, lower all-cause first rehospitalization at 12 months and greater improvement from baseline in KCCQ-CSS at 12 months were noted among patients with de novo HF (median [IQR]: de novo, 29.94 [27.35-32.54] vs WHF, 23.68 [21.62-25.74]; adjusted estimated difference in means: 6.26; 95% CI, 3.72-8.81; P < .001). There was no significant difference in mortality with torsemide vs furosemide in either de novo (No. of events [rate per 100 patient-years]: torsemide, 27 [7.4%] vs furosemide, 38 [10.9%]; aHR, 0.70; 95% CI, 0.40-1.14; P = .15) or WHF (torsemide 212 [26.8%] vs furosemide, 196 [24.0%]; aHR, 1.08; 95% CI, 0.89-1.32; P = .42; P for interaction = .10), In addition, no significant differences in hospitalizations, first all-cause hospitalization, or total hospitalizations at 12 months were noted with a strategy of torsemide vs furosemide in either de novo HF or WHF. Conclusions and Relevance: Among patients discharged after hospitalization for HF, de novo HF was associated with better clinical and patient-reported outcomes when compared with WHF. Regardless of HF type, there was no significant difference between torsemide and furosemide with respect to 12-month clinical or patient-reported outcomes.

Clinical outcomes of ventricular assist device support by HIV infection status: An STS-INTERMACS analysis.

BACKGROUND: Cardiovascular disease remains the leading cause of mortality in human immunodeficiency virus-infected (HIV-positive) patients. Ventricular assist device therapy is rarely offered to these patients and data on outcomes are sparse. We investigated outcomes following ventricular assist device implants for HIV-positive as compared to non-HIV-infected (HIV-negative) patients. METHODS: We analyzed 22,065 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry for outcomes by HIV status. A propensity-matched analysis adjusting for 21 preimplant risk factors was also conducted. RESULTS: Compared with 21,980 HIV-negative device recipients, the 85 HIV-positive recipients were younger (median age 58 years vs 59 years, p = 0.02), had lower body mass index (26 kg/m2 vs 29 kg/m2, p = 0.001), and had higher rates of prior stroke (8% vs 4%, p = 0.02). In the matched HIV-positive and HIV-negative cohorts, there was significantly higher mortality in HIV-positive patients in earlier implant years, however, this association was not seen in later implant years (2018-2020). In both unmatched and matched cohorts, no significant differences in postimplantation stroke, major bleeding, or major infection were noted. CONCLUSIONS: With recent advancements in mechanical circulatory support and HIV treatment, ventricular assist device therapy is a viable therapeutic option for HIV-positive patients with end-stage heart failure.

Postapproval Study of a Subcutaneous Implantable Cardioverter-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to avoid complications related to transvenous implantable cardioverter-defibrillator (TV-ICD) leads. Device safety and efficacy were demonstrated previously with atypical clinical patients or limited follow-up. OBJECTIVES: The S-ICD PAS (Subcutaneous Implantable Cardioverter-Defibrillator System Post Approval Study) is a real-world, multicenter, registry of U.S. centers that was designed to assess long-term S-ICD safety and efficacy in a diverse group of patients and implantation centers. METHODS: Patients were enrolled in 86 U.S. centers with standard S-ICD indications and were observed for up to 5 years. Efficacy endpoints were first and final shock efficacy. Safety endpoints were complications directly related to the S-ICD system or implantation procedure. Endpoints were assessed using prespecified performance goals. RESULTS: A total of 1,643 patients were prospectively enrolled, with a median follow-up of 4.2 years. All prespecified safety and efficacy endpoint goals were met. Shock efficacy rates for discrete episodes of ventricular tachycardia or ventricular fibrillation were 98.4%, and they did not differ significantly across follow-up years (P = 0.68). S-ICD-related and electrode-related complication-free rates were 93.4% and 99.3%, respectively. Only 1.6% of patients had their devices replaced by a TV-ICD for a pacing need. Cumulative all-cause mortality was 21.7%. CONCLUSIONS: In the largest prospective study of the S-ICD to date, all study endpoints were met, despite a cohort with more comorbidities than in most previous trials. Complication rates were low and shock efficacy was high. These results demonstrate the 5-year S-ICD safety and efficacy for a large, diverse cohort of S-ICD recipients. (Subcutaneous Implantable Cardioverter-Defibrillator [S-ICD] System Post Approval Study [PAS]; NCT01736618).

Protocol-based anticoagulation management for mechanical circulatory support patients can be safe and efficient.

BACKGROUND: Achieving optimal anticoagulation remains a significant challenge in managing patients on left ventricular assist device (LVAD) support. Maintaining tight control of anticoagulation can be time-consuming but essential in preventing serious complications such as pump thrombosis and bleeding. OBJECTIVES: The efficacy and safety of a nurse coordinator-driven outpatient protocol (NCDOP) was evaluated for managing anticoagulation for LVAD patients. METHODS: A retrospective analysis was performed as part of a single-center quality improvement project. The primary outcome was time in therapeutic range (TTR), a measure of anticoagulation target efficacy before and after the implementation of the protocol. RESULTS: Among 47 patients, who served as their own control, there was no significant change in TTR or proportion of hospitalizations following institution of the protocol. Pre-NCDOP, there were six major bleeding and two thrombotic events, and none during the post-NCDOP period. CONCLUSIONS: A NCDOP is a reliable method to manage anticoagulation in LVAD patients and facilitates efficient care delivery. Future multicenter studies with larger patient cohorts are warranted to expand on the findings outlined in this manuscript.

Development of donor specific antibodies after SARS-CoV-2 vaccination in kidney and heart transplant recipients.

This study examined the development of new or changes in donor specific antibodies (DSA) mean-fluorescence intensity (MFI) after SARS-CoV-2 vaccination in 100 kidney and 50 heart transplant recipients. The study was performed when the Center for Disease Control and Prevention (CDC) recommended two doses of Pfizer/BioNTech [BNT162b2] and Moderna [mRNA-1273 SARS-CoV-2] vaccine or 1 dose Johnson & Johnson/Janssen [Ad26.COV2·S] vaccines for full vaccination in transplant recipients. A novel assay bead-based platform for detecting antibodies against 4 domains of the SARS-CoV-2 spike protein to determine vaccine response (SA) and one nucleocapsid protein (NC) to determine prior SARS-CoV-2 infection was utilized. These assays were performed on the multiplex, bead-based platform utilized to assay DSA levels. 61/150 patients (40.7%) had successful vaccination. 18 patients had confirmed SARS-CoV-2 infection based on positive NC assay or previous Covid-19 oropharyngeal swab. 138 patients had no DSA prior to vaccination but 3 heart recipients developed new DSA's. Among 12 patients with known DSA prior to vaccination, 4 developed new DSA's or increased MFI. All 7 patients with new or increased DSA had stable graft function without rejection and had no changes in immunosuppression. All 8 patients with stable post vaccine DSA had stable graft function and immunosuppression was not changed. The presence of DSA before vaccination was associated with subsequent development of increased MFI or new DSA's (p = 0.001). There was no association between pre-vaccine DSA and positive vaccine response (NS). There was no association with successful vaccination or prior SARS-CoV-2 infection and DSA changes (NS).

Gastrointestinal Bleeding Rates in Left Ventricular Assist Device Population Reduced with Octreotide Utilization.

Patients with continuous-flow left ventricular assist devices have a high risk of gastrointestinal bleeding (GIB) and recurrent bleeding. Studies have shown octreotide can reduce the risk of GIB. This retrospective, case-crossover study, evaluated the efficacy of octreotide for the prevention of recurrent GIB in patients with left ventricular assist devices between August 2008 and October 2018. A total of 32 patients received octreotide and were included in the study. Hospital admission for GIB was evaluated before and after the initiation of octreotide. Each case served as his/her own control. Most patients were on a reduced aspirin dose (56.2%) and had a reduced international normalized ratio goal (59.4%) before starting monthly octreotide. The most common dose of long-acting octreotide was 30 mg every 28 days. Overall, octreotide decreased the frequency of GIB (4.3 vs. 0.9 events/year, p < 0.001). Nineteen (59.4%) patients did not have a subsequent gastrointestinal bleed. Of the 13 patients who rebled after initiation of octreotide, the frequency of events decreased by 2.6 bleeds per patient per year (4.8 vs. 2.2; p = 0.043). In high-risk patients who have failed conventional therapy, octreotide can be useful for the prevention of recurrent GIB.

Intoxicated Donors and Heart Transplant Outcomes: Long-Term Safety.

BACKGROUND: The opioid crisis has led to an increase in available donor hearts, although questions remain about the long-term outcomes associated with the use of these organs. Prior studies have relied on historical information without examining the toxicology results at the time of organ offer. The objectives of this study were to examine the long-term survival of heart transplants in the recent era, stratified by results of toxicological testing at the time of organ offer as well as comparing the toxicology at the time of donation with variables based on reported history. METHODS: The United Network for Organ Sharing database was requested as well as the donor toxicology field. Between 2007 and 2017, 23 748 adult heart transplants were performed. United Network for Organ Sharing historical variables formed a United Network for Organ Sharing Toxicology Score and the measured toxicology results formed a Measured Toxicology Score. Survival was examined by the United Network for Organ Sharing Toxicology Score and Measured Toxicology Score, as well as Cox proportional hazards models incorporating a variety of risk factors. RESULTS: The number and percent of donors with drug use has significantly increased over the study period (P<0.0001). Cox proportional hazards modeling of survival including toxicological and historical data did not demonstrate differences in post-transplant mortality. Combinations of drugs identified by toxicology were not associated with differences in survival. Lower donor age and ischemic time were significantly positively associated with survival (P<0.0001). CONCLUSIONS: Among donors accepted for transplantation, neither history nor toxicological evidence of drug use was associated with significant differences in survival. Increasing use of such donors may help alleviate the chronic donor shortage.

Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves LV structure, function, and clinical outcomes in New York Heart Association class III/IV heart failure with prolonged QRS. It is not known whether patients with New York Heart Association class I/II systolic heart failure exhibit left ventricular (LV) reverse remodeling with CRT or whether reverse remodeling is modified by the cause of heart failure. METHODS AND RESULTS: Six hundred ten patients with New York Heart Association class I/II heart failure, QRS duration > or =120 ms, LV end-diastolic dimension > or =55 mm, and LV ejection fraction < or =40% were randomized to active therapy (CRT on; n=419) or control (CRT off; n=191) for 12 months. Doppler echocardiograms were recorded at baseline, before hospital discharge, and at 6 and 12 months. When CRT was turned on initially, immediate changes occurred in LV volumes and ejection fraction; however, these changes did not correlate with the long-term changes (12 months) in LV end-systolic (r=0.11, P=0.31) or end-diastolic (r=0.10, P=0.38) volume indexes or LV ejection fraction (r=0.07, P=0.72). LV end-diastolic and end-systolic volume indexes decreased in patients with CRT turned on (both P<0.001 compared with CRT off), whereas LV ejection fraction in CRT-on patients increased (P<0.0001 compared with CRT off) from baseline through 12 months. LV mass, mitral regurgitation, and LV diastolic function did not change in either group by 12 months; however, there was a 3-fold greater reduction in LV end-diastolic and end-systolic volume indexes and a 3-fold greater increase in LV ejection fraction in patients with nonischemic causes of heart failure. CONCLUSIONS: CRT in patients with New York Heart Association I/II resulted in major structural and functional reverse remodeling at 1 year, with the greatest changes occurring in patients with a nonischemic cause of heart failure. CRT may interrupt the natural disease progression in these patients. Clinical Trial Registration- Clinicaltrials.gov Identifier: NCT00271154.

Clinical performance of the St. Jude Medical Riata defibrillation lead in a large patient population.

OBJECTIVE: The purpose of this large multicenter study was to evaluate the long-term reliability of an implantable cardioverter defibrillator (ICD) lead to determine the incidence of adverse events (AEs). BACKGROUND: A recent concern has been the performance of cardiac defibrillator leads. There have been conflicting reports regarding the rate of lead perforation and other AEs. METHODS: Medical records from patients implanted from 6-1-2001 to 11-27-2007 with the St. Jude Medical Riata family of RV leads at 23 US (N = 12,969) and 5 German (N = 2,418) centers were reviewed for chronic lead-related AEs. These included perforation, dislodgment, conductor fracture and insulation damage. The mean follow-up period was 18.0 months. AEs were defined as those that required Riata lead revision, extraction, or replacement. RESULTS: The incidence of lead AEs was <1% for each AE type. Perforation occurred in 0.38%, dislodgement in 0.93%, conductor fracture in 0.18%, and insulation damage in 0.21% of patients studied. CONCLUSIONS: During the follow-up of the 15,387 patients with Riata leads, the incidence of AEs which included perforation, dislodgement, conductor fraction and insulation damage was low and within the range of what is considered clinically acceptable.

The effect of left ventricular pacing site on cardiac resynchronization therapy outcome and mortality: the results of a PROSPECT substudy.

AIMS: Left ventricular pacing site (LV-PS) was prospectively collected to test the influence of the anatomical LV-PS on the outcome of cardiac resynchronization therapy (CRT) and mortality. METHODS AND RESULTS: Four hundred and twenty-six patients with standard indications for CRT underwent echocardiographic and clinical evaluation before and after CRT implantation. The LV-PS was determined from fluoroscopy using the clockwise principle (CP). The LV-PS was categorized into three prospectively defined groups: between 3 and 5 o'clock and longitudinal basal/mid-position (Group A, 'optimal'); between 12 and 2 o'clock and longitudinal mid-apical anterior position (Group B, 'non-optimal'); and all other (Group C, 'other'). Of 333 patients, followed for 0.9 years (mean), adequate images were available to define the LV-PS. Left ventricular pacing site was Group A for 118 patients, Group B for 56, and Group C for 159. The three groups were comparable regarding gender, aetiology, and NYHA class; however, patients in Group A were younger. No relation was found between the LV-PS groups and CRT outcome or all-cause mortality. However, further exploratory subanalyses suggest that LV-PS may impact outcomes in non-ischaemic patients, those with left bundle branch block, and when LV-PS is apical in location. CONCLUSION: Using the CP to define anatomical LV-PS, no relation was found between the LV-PS groups and CRT outcome and mortality. Exploratory analyses warrant further studies.

Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with persistent myocarditis.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare serious adverse effect associated with a variety of medications. We present a case of minocycline-induced DRESS syndrome, which resulted in acute renal failure, transient thyroiditis, and transaminitis, and a persistent lymphocytic myocarditis resulting in congestive heart failure. To our knowledge, this is the third reported case of minocycline-induced myocarditis. Additionally, we report successful plasmapheresis and rituximab treatment for minocycline-induced myocarditis associated with the DRESS syndrome.

Outcomes of subcutaneous implantable cardioverter-defibrillator in dialysis patients: Results from the S-ICD post-approval study.

BACKGROUND: Patients with chronic renal disease on hemodialysis (HD) have limited vascular access and are at high risk of bacteremia. The subcutaneous implantable cardioverter-defibrillator (S-ICD) avoids vascular access, so it may be advantageous in this patient population. OBJECTIVE: The purpose of this study was to report outcomes of patients with end-stage renal disease enrolled in the multicenter S-ICD post-approval study (PAS). METHODS: S-ICD PAS patients were stratified on the basis of the presence (group 1) or absence (group 2) of HD at the time of implantation. Baseline demographic and clinical characteristics were collected. Perioperative and intermediate-term outcomes 365 days postimplantation were compared between the 2 groups. RESULTS: There were 220 patients on HD (13.4%) at the time of implantation out of 1637 patients enrolled in the S-ICD PAS. Patients on HD (group 1) were older (57.4 ± 13.2 years vs 52.5 ± 15.2 years; P < .0001), more likely to be of African descent (48.6% vs 25.1%; P < .0001), and had lower ejection fraction (28.6% ± 11.3% vs 32.6% ± 14.9%; P < .0001) as compared with patients not on HD (group 2). Group 1 had more comorbidities and mortality was higher (17.4% vs 3.7%) than did group 2. The rate of complications calculated using the Kaplan-Meier estimate did not differ between the 2 groups (overall P = .9169), with a 1-year rate of 7.9% and 7.7% for groups 1 and 2, respectively. The rate of appropriate shocks was significantly higher in group 1 (Kaplan-Meier analysis, P = .0003), as was inappropriate shocks (P = .0137). CONCLUSION: S-ICD is associated with similar adverse event rates but a higher risk of inappropriate and appropriate therapy in dialysis patients than in nondialysis patients.

Performance of the subcutaneous implantable cardioverter-defibrillator in patients with a primary prevention indication with and without a reduced ejection fraction versus patients with a secondary prevention indication.

BACKGROUND: The subcutaneous implantable defibrillator (S-ICD) provides an alternative to the transvenous ICD for the prevention of sudden cardiac death, but has not been well studied in the most commonly treated transvenous ICD patient population, namely, primary prevention (PP) patients with left ventricular dysfunction. OBJECTIVE: The analyses in the present study were designed to compare clinical outcomes for PP patients with and without a reduced ejection fraction (EF) and secondary prevention (SP) patients implanted with the S-ICD. METHODS: All patients 18 years and older from the S-ICD IDE study and the EFFORTLESS Registry with available data as of November 18, 2013, were included (n = 856; mean follow-up duration 644 days). Outcomes were evaluated in 2 analyses: (1) comparing all PP patients (n = 603, 70.4%) with all SP patients (n = 253, 29.6%) and (2) comparing all PP patients with an EF ≤35% (n = 379) with those with an EF >35% (n = 149, 17.4%). RESULTS: No differences were observed in mortality, complications, inappropriate therapy, or ability to convert ventricular tachyarrhythmias between SP and PP patients. However, SP patients had a higher incidence of appropriate therapy than did PP patients (11.9% vs 5.0%; P = .0004). In the PP subanalysis, the cohort with an EF ≤35% had significantly older patients with more comorbidities and higher mortality (3.0% annually vs 0.0%). Despite these differences, device-related complications, conversion efficacy, and incidence of inappropriate shock therapies were not significantly different between PP subgroups. CONCLUSION: The S-ICD performs well in protecting patients with either PP or SP implant indications from sudden cardiac death. Within PP patients, device performance was independent of EF.

A comparison of the AVID and DAVID trials of implantable defibrillators.

We compared 2 studies of implantable cardiac defibrillators (ICDs) to determine the effects of device mode on outcomes. The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial (1993 to 1997) demonstrated improved survival with the ICD compared with antiarrhythmic drug therapy. The Dual-chamber And VVI Implantable Defibrillator (DAVID) trial (2000 to 2002) showed that VVI pacing at 40 beats/min in patients with ICDs reduced the combined end point of death and hospitalization for congestive heart failure compared with DDDR pacing at 70 beats/min. Patients in the AVID trial (631 of 1,016) and the DAVID trial (221 of 506) meeting common inclusion and all exclusion criteria were studied. The major end points were the time to death, and the composite end point of time to death or hospitalization for congestive heart failure. Patients in the AVID and DAVID trials were similar, but more AVID patients had coronary artery disease (p = 0.04), history of myocardial infarction (p = 0.005), and previous ventricular arrhythmias (p = 0.03). DAVID patients underwent more previous revascularization procedures (coronary artery bypass surgery, p = 0.03; percutaneous coronary intervention, p = 0.001), and were more often taking beta-blocking drugs at hospital discharge (p <0.001). The backup VVI ICD groups in both studies had similar outcomes (p = 0.4), even when corrected for the previous demographic differences. The time-to- composite end point was similar in AVID patients treated with antiarrhythmic drugs and DAVID patients treated with DDDR ICDs (p = 0.6). Despite improved pharmacologic therapy and revascularization, outcomes have not improved with backup VVI pacing ICDs. If DDDR ICDs had been used in the AVID trial, benefit from ICDs for patients with serious ventricular arrhythmias could have been missed.

Accurate monitoring of intravascular fluid volume: A novel application of intrathoracic impedance measures for the guidance of volume reduction therapy.

BACKGROUND: A significant proportion of patients admitted for acute decompensated heart failure (ADHF) that undergo volume reduction therapy are discharged with unchanged or increased bodyweight suggesting that the endpoints for these therapies are not optimally defined. We aimed to identify vectors that can help monitor changes in intravascular fluid volume, that in turn may more accurately guide volume reduction therapy. METHODS: Data from six different impedance vectors and corresponding changes in intravascular volume derived from changes in hematocrit were obtained from 132 clinical congestion events in 56 unique patients enrolled in a multisite trial of early detection of clinical congestion events (DEFEAT PE). Mixed effects regression models were used to determine the relation between changes in impedance derived from six different vectors and changes in intravascular plasma volume. RESULTS: Changes in impedance were negatively associated with changes in plasma volume. Two vectors, the right atrial ring to left ventricular ring and the left ventricular ring to the right ventricular ring, were most closely associated with changes in intravascular plasma volume. CONCLUSION: Impedance vectors derived from a multivector monitoring system reflect changes in intravascular plasma volume. Two of these vectors most closely track changes in plasma volume and may be used to more accurately guide and optimize volume reduction therapy.

Safety and Efficacy of the Totally Subcutaneous Implantable Defibrillator: 2-Year Results From a Pooled Analysis of the IDE Study and EFFORTLESS Registry.

BACKGROUND: The entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) is the first implantable defibrillator that avoids placing electrodes in or around the heart. Two large prospective studies (IDE [S-ICD System IDE Clinical Investigation] and EFFORTLESS [Boston Scientific Post Market S-ICD Registry]) have reported 6-month to 1-year data on the S-ICD. OBJECTIVES: The objective of this study was to evaluate the safety and efficacy of the S-ICD in a large diverse population. METHODS: Data from the IDE and EFFORTLESS studies were pooled. Shocks were independently adjudicated, and complications were measured with a standardized classification scheme. Enrollment date quartiles were used to assess event rates over time. RESULTS: Eight hundred eighty-two patients who underwent implantation were followed for 651±345 days. Spontaneous ventricular tachyarrhythmia (VT)/ventricular fibrillation (VF) events (n=111) were treated in 59 patients; 100 (90.1%) events were terminated with 1 shock, and 109 events (98.2%) were terminated within the 5 available shocks. The estimated 3-year inappropriate shock rate was 13.1%. Estimated 3-year, all-cause mortality was 4.7% (95% confidence interval: 0.9% to 8.5%), with 26 deaths (2.9%). Device-related complications occurred in 11.1% of patients at 3 years. There were no electrode failures, and no S-ICD-related endocarditis or bacteremia occurred. Three devices (0.3%) were replaced for right ventricular pacing. The 6-month complication rate decreased by quartile of enrollment (Q1: 8.9%; Q4: 5.5%), and there was a trend toward a reduction in inappropriate shocks (Q1: 6.9% Q4: 4.5%). CONCLUSIONS: The S-ICD demonstrated high efficacy for VT/VF. Complications and inappropriate shock rates were reduced consistently with strategic programming and as operator experience increased. These data provide further evidence for the safety and efficacy of the S-ICD. (Boston Scientific Post Market S-ICD Registry [EFFORTLESS]; NCT01085435; S-ICD® System IDE Clinical Study; NCT01064076).

Influence of wall motion score on mortality after coronary bypass surgery in the CABG-patch trial.

BACKGROUND: It was hypothesized that a wall motion score (WMS) of 16% (n=108), respectively, calculated from a preoperative RAO ventriculogram. There was no difference in EF between the two groups (26.5+/-5.5 vs. 27.8+/-5.3%, respectively). Eight (9.9%) versus three (2.8%) patients died perioperatively in the low versus the high WMS group, respectively. The relative risk for perioperative death in the low WMS group was 3.6 (P<0.04). Kaplan-Meier estimates of cumulative survival did not reveal any statistical difference between the two groups over 4 years (P=0.11). Subgroup analysis revealed that patients with a WMS of 16% were not significantly different, although subgroup analysis revealed that patients with a WMS

Analysis of different device-based intrathoracic impedance vectors for detection of heart failure events (from the Detect Fluid Early from Intrathoracic Impedance Monitoring study).

Detect Fluid Early from Intrathoracic Impedance Monitoring (DEFEAT-PE) is a prospective, multicenter study of multiple intrathoracic impedance vectors to detect pulmonary congestion (PC) events. Changes in intrathoracic impedance between the right ventricular (RV) coil and device can (RVcoil→Can) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs (CRT-Ds) are used clinically for the detection of PC events, but other impedance vectors and algorithms have not been studied prospectively. An initial 75-patient study was used to derive optimal impedance vectors to detect PC events, with 2 vector combinations selected for prospective analysis in DEFEAT-PE (ICD vectors: RVring→Can + RVcoil→Can, detection threshold 13 days; CRT-D vectors: left ventricular ring→Can + RVcoil→Can, detection threshold 14 days). Impedance changes were considered true positive if detected <30 days before an adjudicated PC event. One hundred sixty-two patients were enrolled (80 with ICDs and 82 with CRT-Ds), all with ≥1 previous PC event. One hundred forty-four patients provided study data, with 214 patient-years of follow-up and 139 PC events. Sensitivity for PC events of the prespecified algorithms was as follows: ICD: sensitivity 32.3%, false-positive rate 1.28 per patient-year; CRT-D: sensitivity 32.4%, false-positive rate 1.66 per patient-year. An alternative algorithm, ultimately approved by the US Food and Drug Administration (RVring→Can + RVcoil→Can, detection threshold 14 days), resulted in (for all patients) sensitivity of 21.6% and a false-positive rate of 0.9 per patient-year. The CRT-D thoracic impedance vector algorithm selected in the derivation study was not superior to the ICD algorithm RVring→Can + RVcoil→Can when studied prospectively. In conclusion, to achieve an acceptably low false-positive rate, the intrathoracic impedance algorithms studied in DEFEAT-PE resulted in low sensitivity for the prediction of heart failure events.