Comparison of Transcatheter Arterialization of Deep Veins to Standard of Care in Patients with No-Option Chronic Limb Threatening Ischemia.

BACKGROUND: Patients with no-option chronic limb-threatening ischemia (no-option CLTI) have limited therapeutic options. The PROMISE II study evaluated, transcatheter arterialization of deep veins (TADV) as a treatment option for no-option CLTI. In the current study patients from PROMISE II were compared to patients from a registry of untreated no-option CLTI patients (CLariTI: Natural Progression of High-Risk Chronic Limb-Threatening Ischemia). METHODS: We used propensity matching to compare patients from the PROMISE II prospective study of the TADV intervention with simultaneously enrolled CLTI patients that were note candidates for PROMISE II but were enrolled in to CLariTI natural history registry. Untreated no-option CLTI (CLariTI) patients could either be no-option or patients who did not meet PROMISE II entry criteria. Risk difference between groups was calculated using common risk difference and P values were provided by propensity-score stratified Mantel-Haenszel test. The primary endpoint was amputation-free survival (AFS). RESULTS: Diabetes was present in over 75% of patients. All patients had tissue loss and 35-46% had extensive tissue loss (Rutherford 6). The unadjusted AFS at 6 months, was 66.1% by Kaplan-Meier estimate for PROMISE II patients (n = 105) compared to 39.1% in the no-option cohort of CLariTI (n = 121) and 44.0% in the full cohort (no-option and patients not meeting entry criteria combine, n = 180). The treatment group who underwent TADV for no-option CLTI had an absolute difference of 29% improved (P < 0.0001) propensity-adjusted risk difference in AFS and a relative event rate reduction of 45% compared to the no-option control patients. CONCLUSIONS: Transcatheter arterialization of deep veins (TADV) resulted in improved 6 month AFS in no-option CLTI patients and appears to be a promising therapy in patients with no-option CLTI.

Mortality in randomised controlled trials using paclitaxel-coated devices for femoropopliteal interventional procedures: an updated patient-level meta-analysis.

BACKGROUND: Numerous randomised clinical trials and real-world studies have supported the safety of paclitaxel-coated devices for the treatment of femoropopliteal occlusive disease. However, a 2018 summary-level meta-analysis suggested an increased mortality risk for paclitaxel-coated devices compared with uncoated control devices. This study presents an updated analysis of deaths using the most complete and current data available from pivotal trials of paclitaxel-coated versus control devices. METHODS: Ten trials comparing paclitaxel-coated versus control devices were included in a patient-level pooled analysis. Cox regression models were used to evaluate the effect of paclitaxel exposure on risk of death in both intention-to-treat (ITT; primary analysis) and three as-treated analysis sets accounting for treatment group crossover at the index procedure and over time. The effect of paclitaxel dose and baseline covariates were also evaluated. FINDINGS: A total of 2666 participants were included with a median follow-up of 4·9 years. No significant increase in deaths was observed for patients treated with paclitaxel-coated devices. This was true in the ITT analysis (hazard ratio [HR] 1·14, 95% CI 0·93-1·40), the as-treated analysis (HR 1·13, 95% CI 0·92-1·39), and in two crossover analyses: 1·07 (0·87-1·31) when late crossovers were censored and 1·04 (0·84-1·28) when crossovers were analysed from the date of paclitaxel exposure. There was no significant effect of paclitaxel dose on mortality risk. INTERPRETATION: This meta-analysis found no association between paclitaxel-coated device exposure and risk of death, providing reassurance to patients, physicians, and regulators on the safety of paclitaxel-coated devices. FUNDING: Becton Dickinson, Boston Scientific, Cook, Medtronic, Philips, Surmodics, and TriReme Medical.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials.

Importance: Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. Objective: To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. Data Sources: A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Study Selection: Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Data Extraction and Synthesis: Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. Main Outcomes and Measures: The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. Results: A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Conclusions and Relevance: Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

Mortality and Paclitaxel-Coated Devices: An Individual Patient Data Meta-Analysis.

BACKGROUND: Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality. METHODS: Manufacturers of US Food and Drug Administration-approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed. RESULTS: A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%-58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose-mortality association was identified. CONCLUSIONS: This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.

Patient-level meta-analysis of 999 claudicants undergoing primary femoropopliteal nitinol stent implantation.

CONDENSED ABSTRACT: The factors that impact the clinical effectiveness of bare nitinol stents in claudicants with symptomatic femoropopliteal atherosclerosis are incompletely known. The authors analyzed variables that may influence stent durability and provide a benchmark for their effectiveness. Data analyzed from six studies (999 patients) included baseline noninvasive hemodynamic tests, angiographic characteristics, ultrasound defined stent patency and target lesion revascularization through 12-months. Baseline ankle-brachial index and lesion length predicted stent patency and target lesion revascularization and when combined interacted significantly to better predict outcomes. This meta-analysis provides an important comparator against which emerging therapies that treat claudicants with femoropopliteal atherosclerosis can be assessed. SUBJECT CODE: Peripheral Artery Disease BACKGROUND: The performance of bare metal nitinol stents in patients with symptomatic femoropopliteal peripheral artery disease (PAD) is not well defined. METHODS: Patient-level data from six large prospective trials sponsored by medical device manufacturers was abstracted and analyzed to identify a cohort of patients with claudication and femoropopliteal artery occlusive disease. Twelve-month binary patency and target lesion revascularization (TLR) rates were primary outcomes. Stent patency was assessed by duplex ultrasonography (DUS) and TLR was a clinically driven intervention. To characterize the effects of patient characteristics on the outcomes, meta-regression was performed via mixed effects logistic regression models with patient-level covariates. RESULTS: About 999 patients were analyzed; the mean ABI was 0.68 ± 0.18, the mean lesion length was 84 ± 53 mm, the mean lesion stenosis was 78%, and nearly two thirds of patients had mild to severe calcification. The mean Rutherford clinical category was 2.7 ± 0.6 and ranged from 2.6 to 2.8 in all studies. The 12-month patency across all studies was 69.8% and TLR rates ranged from 9.2% to 19.7%. Multivariable analysis demonstrated that baseline ABI and baseline target lesion length predicted both primary patency and TLR. Further, these two variables interacted significantly to better predict TLR outcomes when used in combination. CONCLUSION: The 12-month clinical effectiveness of bare nitinol stents to treat patients with symptomatic femoropopliteal PAD is acceptable and is impacted by clinical and lesion-specific characteristics. These data provide an important and useful benchmark to compare the clinical benefit of emerging endovascular PAD therapies. © 2017 Wiley Periodicals, Inc.

Validation of a Novel Monitoring System to Measure Contrast Volume Use During Invasive Angiography.

BACKGROUND: Multiple studies have demonstrated the relationship between contrast volume (CV) and the risk of acute kidney injury (AKI). Quantification of total CV is often estimated and therefore may be inaccurate. We describe validation of a novel contrast monitoring system (CMS) (Osprey Medical), which is designed to detect and display injection by injection and total CV use on a monitor system in real time. METHODS: Thirty patients undergoing a coronary or peripheral angiogram were included. Ten patients underwent procedures using the CMS only and 20 underwent procedures using both the CMS and the AVERT Plus contrast modulation system (Osprey Medical). Total CV used during these cases was measured using direct measurement via a graduated cylinder (CVDM). This was compared with the CMS-reported CV and with the operator's assessment of CV (CVPE) used during the case. Intraclass correlation coefficient (ICC) and Pearson correlation coefficient (PCC) were used for analysis and the results displayed using Bland-Altman plots. RESULTS: Twenty-one cases were diagnostic and 9 were interventional. The ICC/PCC (confidence interval [CI]) for the comparison of CVDM to CMS and CVPE were 0.96/0.97 [CI, 0.94-0.99] and 0.89/0.90 [CI, 0.80-0.95], respectively, with a P=.01 for difference between the correlations. The average absolute difference between the CVDM and CMS readout and the CVPE was 12.0 ± 13.7 mL and 22.8 ± 15.3 mL, respectively; P=.01. CONCLUSIONS: The CMS was accurate when compared with the direct measurement of CV used. This accuracy was superior to physician estimation of CV.

Clinical predictors of risk for atrial fibrillation: implications for diagnosis and monitoring.

OBJECTIVE: To create a risk score using clinical factors to determine whom to screen and monitor for atrial fibrillation (AF). PATIENTS AND METHODS: The AF risk score was developed based on the summed odds ratios (ORs) for AF development of 7 accepted clinical risk factors. The AF risk score is intended to assess the risk of AF similar to how the CHA2DS2-VASc score assesses stroke risk. Seven validated risk factors for AF were used to develop the AF risk score: age, coronary artery disease, diabetes mellitus, sex, heart failure, hypertension, and valvular disease. The AF risk score was tested within a random population sample of the Intermountain Healthcare outpatient database. Outcomes were stratified by AF risk score for OR and Kaplan-Meier analysis. RESULTS: A total of 100,000 patient records with an index follow-up from January 1, 2002, through December 31, 2007, were selected and followed up for the development of AF through the time of this analysis, May 13, 2013, through September 6, 2013. Mean ± SD follow-up time was 3106±819 days. The ORs of subsequent AF diagnosis of patients with AF risk scores of 1, 2, 3, 4, and 5 or higher were 3.05, 12.9, 22.8, 34.0, and 48.0, respectively. The area under the curve statistic for the AF risk score was 0.812 (95% CI, 0.805-0.820). CONCLUSION: We developed a simple AF risk score made up of common clinical factors that may be useful to possibly select patients for long-term monitoring for AF detection.

Interpreting changes in quality of life in atrial fibrillation: how much change is meaningful?

BACKGROUND: The Atrial Fibrillation Effect on QualiTy of Life (AFEQT) questionnaire is a novel quality of life (QOL) measure previously shown to be valid, reliable, and sensitive to clinical change in patients with atrial fibrillation (AF). The clinical relevance of a given change in the score is not known. The most useful "anchor" for a measure of meaningful change in QOL is patient-reported magnitude of change. OBJECTIVE: The aim of this study was to define the interpretability of changes in the AFEQT score from the patients' perspective. METHODS: With the use of the original validation study of AFEQT, in which 210 patients completed the questionnaire at baseline and at 3 months, we estimated the AFEQT score corresponding to a meaningful improvement in QOL using the patients' assessments of global change in QOL, AF symptoms from the Atrial Fibrillation Severity Scale (AFSS), and physicians' assessment of global QOL over the 3 months, as anchors. RESULTS: In patients with a moderate improvement in global QOL, the AFEQT scores increased from 51.9 ± 21.8 to 70.8 ± 17.4 (an increase of 18.9 ± 20.7), compared with an increase of 6.9 ± 16.9 units in patients with "unimportant change" in global QOL. Physicians' global assessment yielded a similar change in AFEQT score corresponding to a moderate change in global QOL (21.3 ± 20.2 units). Patients with moderate improvement in AF symptom severity using the AFSS scale had an increase of 17.9 ± 11.8 units on the AFEQT scale. A change in 19 units in the AFEQT score corresponded to a 0.9 SD unit change or greater than a minimal important difference from a distribution based method. CONCLUSIONS: A meaningful improvement in QOL in patients with AF can be measured from a change in the AFEQT score. These results can assist in monitoring patient progress and interpreting the effects of interventions in patients with AF.

Device diagnostics and long-term clinical outcome in patients receiving cardiac resynchronization therapy.

AIMS: This retrospective analysis sought to develop and validate a model using the measured diagnostic variables in cardiac resynchronization therapy (CRT) devices to predict mortality. METHODS AND RESULTS: Data used in this analysis came from two CRT studies: Cardiac Resynchronization Therapy Registry Evaluating Patient Response with RENEWAL Family Devices (CRT RENEWAL) (n = 436) and Heart Failure-Heart Rate Variability (HF-HRV) (n = 838). Patients from CRT RENEWAL were used to create a model for risk of death using logistic regression and to create a scoring system that could be used to predict mortality. Results of both the logistic regression and the clinical risk score were validated in a cohort of patients from the HF-HRV study. Diagnostics significantly improved over time post-CRT implant (all P < 0.001) and were correlated with a trend of decreased risk of death. The regression model classified CRT RENEWAL patients into low (2.8%), moderate (6.9%), and high (13.8%) risk of death based on tertiles of their model predicted risk. The clinical risk score classified CRT RENEWAL patients into low (2.8%), moderate (10.1%), and high (13.4%) risk of death based on tertiles of their score. When both the regression model and the clinical risk score were applied to the HF-HRV study, each was able to classify patients into appropriate levels of risk. CONCLUSION: Device diagnostics may be used to create models that predict the risk of death.

Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial.

BACKGROUND: In patients with non-valvular atrial fibrillation, embolic stroke is thought to be associated with left atrial appendage (LAA) thrombi. We assessed the efficacy and safety of percutaneous closure of the LAA for prevention of stroke compared with warfarin treatment in patients with atrial fibrillation. METHODS: Adult patients with non-valvular atrial fibrillation were eligible for inclusion in this multicentre, randomised non-inferiority trial if they had at least one of the following: previous stroke or transient ischaemic attack, congestive heart failure, diabetes, hypertension, or were 75 years or older. 707 eligible patients were randomly assigned in a 2:1 ratio by computer-generated randomisation sequence to percutaneous closure of the LAA and subsequent discontinuation of warfarin (intervention; n=463) or to warfarin treatment with a target international normalised ratio between 2.0 and 3.0 (control; n=244). Efficacy was assessed by a primary composite endpoint of stroke, cardiovascular death, and systemic embolism. We selected a one-sided probability criterion of non-inferiority for the intervention of at least 97.5%, by use of a two-fold non-inferiority margin. Serious adverse events that constituted the primary endpoint for safety included major bleeding, pericardial effusion, and device embolisation. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00129545. FINDINGS: At 1065 patient-years of follow-up, the primary efficacy event rate was 3.0 per 100 patient-years (95% credible interval [CrI] 1.9-4.5) in the intervention group and 4.9 per 100 patient-years (2.8-7.1) in the control group (rate ratio [RR] 0.62, 95% CrI 0.35-1.25). The probability of non-inferiority of the intervention was more than 99.9%. Primary safety events were more frequent in the intervention group than in the control group (7.4 per 100 patient-years, 95% CrI 5.5-9.7, vs 4.4 per 100 patient-years, 95% CrI 2.5-6.7; RR 1.69, 1.01-3.19). INTERPRETATION: The efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. Although there was a higher rate of adverse safety events in the intervention group than in the control group, events in the intervention group were mainly a result of periprocedural complications. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation. FUNDING: Atritech.

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. Compared with men, women were less likely to have coronary disease, ischemic cardiomyopathy, and hyperlipidemia, and were more likely to have congestive heart failure and diabetes. Women were less likely to receive beta blockers and ACE inhibitors, and more likely to receive diuretics. Over 10.8 +/- 3.5 months of follow-up, unadjusted mortality was higher in women than men (6.8% vs 4.1%, P = 0.04). Heart failure hospitalizations occurred in 7.9% of women versus 5.7% of men (P = 0.13). After adjustment for baseline differences and drug therapy, there was no significant difference in mortality between men and women. Adverse events were observed more often in women. There were no gender differences in the percentage of patients receiving appropriate or inappropriate ICD shocks. CONCLUSIONS: In INTRINSIC RV, women receiving ICDs differed from men regarding baseline characteristics and drug therapy. After adjusting for baseline differences and medical therapy, there were no differences in heart failure hospitalization, survival, or ICD shock therapy during follow-up. Apparent undertreatment of heart failure and greater frequency of adverse advents in women receiving ICDs warrant further investigation.

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. The relationships between AF and endpoints (total mortality, ICD shocks, and HF hospitalizations) were analyzed retrospectively with proportional-hazards models. RESULTS: At 108 centers, 1530 patients meeting VITALITY AVT ICD indications were followed for 12 months. Of these, 1356 (89%) had no history of AF at the time of implant. Patients with a history of AF had a higher prevalence of HF (52% vs. 36%; P <.01) and had higher rates of HF hospitalization (hazard ratio [HR] 2.14 [1.29-3.54], P <.01), death (HR 2.22 [1.26-3.92], P <.01), and any ICD shock (HR 1.75 [1.19-2.58], P <.01) compared with those with no history. AF incidence during the first 3 months of implant was available in 1317 (86%; 1170 no AF, 147 history of AF) patients. New-onset AF during the first 3 months of implant (45 of 1170, 4%) was associated with a significant increased risk of death (HR 2.86 [1.02-8.05], P = .05) but not with inappropriate ICD shock (HR 2.43 [0.87-6.75], P = .09) or HF hospitalization (HR 1.17 [0.28-4.82], P = .83). CONCLUSION: History of AF at the time of ICD implant identifies additional risk of HF and death. Newly detected AF is associated with significantly higher rates of death. The relationship between newly detected AF and inappropriate ICD shock or HF hospitalization is uncertain and requires further study.

Remote Active Monitoring in Patients with Heart Failure (RAPID-RF): design and rationale.

BACKGROUND: Heart failure (HF) ambulatory disease management programs appear to offer the greatest benefit to HF patients at highest risk, defined as having New York Heart Association (NYHA) functional Class III or IV symptoms. The Latitude Patient Management System is the first HF management tool to use wireless telemetry present in a cardiac resynchronization therapy defibrillator (CRT-D) device that is linked to remotely collect blood pressure and weight measures, permitting a single transmission reporting device data. Potential advantages of this system include ease of data transmissions, correlation among measures of HF status, arrhythmic events, and device performance. However, the use and ultimate utility of these combined features for patient management are untested. METHODS AND RESULTS: The Remote Active Monitoring in Patients with Heart Failure (RAPID-RF) study is a multicenter registry that will enroll up to 1000 patients on the Latitude Patient Management System from approximately 100 centers. The primary objective is to examine physician responses to Latitude Active Monitoring data alerts by assessing alert-related medical interventions. Minimum follow-up will be 3 months after implant with a maximum follow-up time of 24 months after implant. CONCLUSIONS: The RAPID-RF study will provide important preliminary data on how remotely collected HF and arrhythmic surveillance data alter the management of HF patients with CRT-D devices.

Prognostic value of heart rate variability footprint and standard deviation of average 5-minute intrinsic R-R intervals for mortality in cardiac resynchronization therapy patients.

BACKGROUND: Cardiac resynchronization therapy devices provide effective therapy for heart failure. Heart rate variability (HRV) parameters in the device such as HRV footprint and SD of average 5-minute intrinsic R-R intervals (SDANN) are related to autonomic function and may be used to identify patients with a higher risk of mortality. METHODS: We examined the relationship between HRV and mortality in a prospective cohort study. The 842 patients (mean age, 67.7 +/- 11.2; 23.5 % female; New York Heart Association class III, 88.6%; class IV, 11.4%) included in the analysis were implanted with a cardiac resynchronization therapy with defibrillation device and had baseline HRV measurements available. RESULTS: During a median of 11.6 months of follow-up, 7.8% (66/842) of patients died. Heart rate variability footprint and SDANN were significant predictors of mortality (all P < .05); patients with lower HRV values were at greater risk for death, compared with patients with higher HRV values. Heart rate variability changes over time tended to predict the risk of mortality in follow-up (P = nonsignificant); patients with low baseline HRV and small changes in HRV during the follow-up period were at the highest risk for death (7% mortality for SDANN and 8.9% for HRV footprint), and patients with high baseline HRV and large changes in HRV were at the lowest risk (1.5% mortality for SDANN and 2.4% for HRV footprint). Results were consistent when adjusted for age, sex, body mass index, and diastolic blood pressure. CONCLUSIONS: Continuously measured device HRV parameters provide prognostic information about patient mortality that may be helpful for risk stratification.

Changes in heart rate variability, quality of life, and activity in cardiac resynchronization therapy patients: results of the HF-HRV registry.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a viable therapy in the treatment of heart failure (HF). Heart rate variability (HRV) is a prognostic marker of HF and mortality and is a sign of autonomic dysfunction. Acute improvements in measures of HRV have been demonstrated after CRT in small clinical studies. The purpose of the present study was to evaluate changes in HRV and patient outcomes over time and the relationship between these changes in a large generalized sample of patients who received CRT with defibrillator (CRT-D). METHODS: The Heart Failure-Heart Rate Variability (HF-HRV) registry enrolled 1,421 patients who received a CRT-D device capable of measuring HRV. Patients were followed for a 1-year period. Device diagnostics, including HRV footprint; standard deviation of averaged normal R to R intervals (SDANN); and mean, minimum, and maximum heart rate were measured at each visit, in addition to activity log, New York Heart Association (NYHA) class, and quality of life (QOL) data. RESULTS: This large sample of HF patients showed an overall improvement in SDANN (69.2 +/- 25.5, 78.5 +/- 27.8, 79.4 +/- 27.2, 80.7 +/- 28.2) and HRV footprint (31.5 +/- 11.8, 33.4 +/- 12.3, 34.2 +/- 12.2, 34.5 +/- 12.3) at the 2 week, 3 month, 6 month, and 12 month visits, respectively (both P < 0.001). There were also significant changes over time in clinical status (improved QOL, increased activity, and improved NYHA, all P < 0.0001), with the greatest changes occurring between the 2 week and 3 month visits. CONCLUSION: In conclusion, these study results demonstrate that device measured HRV parameters and patient outcomes significantly improve after receipt of CRT.

Sex differences in the associations of HIV disease characteristics and body composition in antiretroviral-naive persons.

BACKGROUND: Data on associations of body composition with HIV disease characteristics are limited. OBJECTIVE: We compared sex-specific associations between HIV disease characteristics and body composition in an racially-ethnically diverse cohort of antiretroviral-naive patients. DESIGN: The study was a cross-sectional analysis of participants enrolled in a metabolic substudy of a multicenter trial. Regional fat was measured, and total body fat (TBF) was derived by using the Durnin-Womersley formula (DWF) and bioelectrical impedance analysis (BIA). Body cell mass (BCM) was measured by BIA. RESULTS: Among 422 participants, 22% were women, 60% were African American, and 36% had prior AIDS-defining illnesses. Mean (+/-SD) age was 38.2 +/- 9.6 y, CD4+ count was 215 +/- 184 cells/mm3, and HIV RNA log10 was 5.0 +/- 0.8 copies/mL. On multivariate analysis, women with AIDS-defining illness had significantly (P < 0.005) lower regional body fat and TBF (BIA: -9.5 kg; DWF: -7.3 kg) but nonsignificantly lower BCM (-1.3 kg) than did women without such illnesses, whereas men with AIDS-defining illness had significantly (P < 0.005) lower BCM (-1.7 kg) but nonsignificantly lower TBF (BIA: -1.3 kg; DWF: -1.83 kg) than did men without such illnesses (P < 0.05 for sex differences in TBF). Significant negative associations of HIV RNA with BCM (-0.9 kg/log RNA; P = 0.03), TBF by BIA (-1.4 kg/log RNA; P = 0.05) and by DWF (-1.6 kg/log RNA; P = 0.01), and regional fat were observed in men only. CONCLUSIONS: The effect of prior AIDS illness on body fat differed significantly between the sexes: women with prior AIDS-defining illness had significantly less fat than did women without such illnesses. An independent effect of HIV viremia on BCM and fat was seen in men. These distinctions may be due to inherent biological differences between the sexes.

Comparison of prognostic importance of latest CD4+ cell count and HIV RNA levels in patients with advanced HIV infection on highly active antiretroviral therapy.

UNLABELLED: The comparative prognostic importance of latest plasma HIV RNA levels (viral loads) and CD4+ cell counts among patients prescribed highly active antiretroviral therapy (HAART) has not been well characterized. METHOD: We assessed the prognostic value of latest CD4+ cell counts and latest viral loads for progression to AIDS or death and explored their interaction among 432 HIV-infected persons with advanced HIV who were prescribed a protease inhibitor (PI) as their first HAART regimen. RESULTS: Pre-HAART median CD4+ cell count and viral load were 41 cells/mm3 and 126,331 copies/mL, respectively. After 12 months of HAART, the median CD4+ cell count was 154 cells/mm3; 39% of patients had a viral load of 400 copies/mL or lower. Over a median follow-up of 33 months, 109 (25%) of the 432 patients experienced an AIDS event or died. The hazard ratio for AIDS or death for those with latest CD4+ cell count <50 cells/mm3 versus > or =200 cells/mm3 was 13.9 (95% CI 6.5 to 29.7) without adjustment for latest viral load measurements and 9.5 (95% CI 4.0 to 22.5) after adjustment for latest viral load. In contrast, the hazard ratio for AIDS or death for those with viral load > or =100,000 versus <400 copies/mL was 4.2 (95% CI 2.3 to 7.7) without adjustment for latest CD4+ level and 1.2 (95% CI 0.6 to 2.4) with adjustment for latest CD4+ cell count. CONCLUSION: We conclude that when latest CD4+ cell count and viral load are considered separately, both are significantly related to AIDS or death; when these markers are jointly considered, the association of viral load with AIDS or death is substantially diminished. Latest CD4+ levels are more strongly related to AIDS or death than latest viral load levels in patients on HAART.

CD4(+) cell count increase predicts clinical benefits in patients with advanced HIV disease and persistent viremia after 1 year of combination antiretroviral therapy.

The relationship between 12-month CD4(+) cell count response and clinical outcome (AIDS-defining event or death) in a subset of 228 patients with a human immunodeficiency virus load >400 copies/mL despite receiving combination antiretroviral therapy as part of a larger randomized trial was defined by use of Cox models. The 12-month CD4(+) cell count responses were divided into 5 categories, ranging from decrease or no change (29% of patients) to a > or =100-cell/mm(3) increase (27% of patients). There was a lower risk of clinical progression for each incremental increase in CD4(+) cell count response. A 25-cell/mm(3) increase in CD4(+) cell count was associated with a 21% reduction in the risk of an AIDS-defining event or death (P<.0001).