PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure: Results of the PRIME-HF Trial.

BACKGROUND: Ivabradine is guideline-recommended to reduce heart failure (HF) hospitalization in patients with stable chronic HF with reduced ejection fraction (EF). Ivabradine initiation following acute HF has had limited evaluation, and there are few randomized data in US patients. The PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) study was conducted to address predischarge ivabradine initiation in stabilized acute HF patients. METHODS: PRIME-HF was an investigator-initiated, randomized, open-label study of predischarge initiation of ivabradine versus usual care. Eligible patients were hospitalized for acute HF but stabilized, with EF ≤35%, on maximally tolerated ß-blocker and in sinus rhythm with heart rate ≥70 beats/min. Ivabradine was acquired per routine care. The primary end point was the proportion of patients on ivabradine at 180 days. Additional end points included heart rate change, patient-reported outcomes, ß-blocker use/dose, and safety events (symptomatic bradycardia and hypotension). RESULTS: Overall, 104 patients (36% women, 64% African American) were randomized, and the study was terminated early because of funding limitations. At 180 days, 21 of 52 (40.4%) of patients randomized to predischarge initiation were treated with ivabradine compared with 6 of 52 (11.5%) randomized to usual care (odds ratio 5.19, 95% CI 1.88-14.33, P = .002). The predischarge initiation group experienced greater reduction in heart rate through 180 days (mean -10.0 beats/min, 95% CI -15.7 to -4.3 vs 0.7 beats/min, 95% CI -5.4 to 6.7, P = .011). Patient-reported outcomes, ß-blocker use/dose, and safety events were similar (all P > .05). CONCLUSIONS: Ivabradine initiation prior to discharge among stabilized HF patients increased ivabradine use at 180 days and lowered heart rates without reducing ß-blockers or increasing adverse events. As the trial did not achieve the planned enrollment, additional studies are needed.

Japan-United States of America Harmonized Assessment by Randomized Multicentre Study of OrbusNEich's Combo StEnt (Japan-USA HARMONEE) study: primary results of the pivotal registration study of combined endothelial progenitor cell capture and drug-eluting stent in patients with ischaemic coronary disease and non-ST-elevation acute coronary syndrome.

Aims: Harmonized Assessment by Randomized Multicentre Study of OrbusNEich's Combo StEnt (HARMONEE) (NCT02073565) was a randomized pivotal registration trial of the Combo stent, which combined sirolimus and an abluminal bioabsorbable polymer with a novel endoluminal anti-CD34+ antibody coating designed to capture endothelial progenitor cells (EPC) and promote percutaneous coronary intervention (PCI) site healing. Methods and results: Clinically stabilized PCI subjects were randomized 1:1 to receive Combo or everolimus-eluting stents (EES). Between February 2014 and June 2016, 572 subjects with 675 coronary lesions underwent 1-year angiography and fractional flow reserve, with optical coherence tomography (OCT) in the first 140 patients. The primary clinical endpoint was non-inferior 1-year target vessel failure (TVF). The primary mechanistic endpoint of EPC capture activity was superior strut coverage by OCT. Target vessel failure occurred in 7.0% Combo (20/287) vs. 4.2% EES (12/285), a 2.8% [95% confidence interval (95% CI) -1.0%, 6.5%] difference, meeting the non-inferiority hypothesis (P = 0.02). There were no cardiac deaths, with one stent thrombosis observed in the EES group. Quantitative coronary angiography late loss with Combo was equivalent to EES. Optical coherence tomography strut coverage at 1 year was superior with Combo vs. EES [91.3% (95% CI 88.7%, 93.8%) vs. 74.8% (95% CI 70.0%, 79.6%), P < 0.001], with homogeneous tissue in 81.2% vs. 68.8%, respectively. Conclusion: Combo stent demonstrated non-inferior 1-year TVF and late loss in a randomized comparison to EES, with superior strut-based tissue coverage by OCT as a surrogate of EPC capture technology activity.

Treatment of sleep-disordered breathing in heart failure impacts cardiac remodeling: Insights from the CAT-HF Trial.

BACKGROUND: Sleep-disordered breathing (SDB), including central and obstructive sleep apnea, is a marker of poor prognosis in heart failure (HF) and may worsen cardiac dysfunction over time. Treatment of SDB with adaptive servoventilation (ASV) may reverse pathologic cardiac remodeling in HF patients. METHODS: The Cardiovascular Improvements with Minute Ventilation-targeted Adaptive Servo-Ventilation Therapy in Heart Failure (CAT-HF) trial randomized patients with acute decompensated HF and confirmed SDB to either optimal medical therapy (OMT) or treatment with ASV and OMT. Patients with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) were included. Echocardiograms, performed at baseline and 6 months, assessed cardiac size and function and evaluated cardiac remodeling over time. The CAT-HF trial was stopped early in response to the SERVE-HF trial, which found increased mortality among HFrEF patients with central sleep apnea treated with ASV. RESULTS: Of the 126 patients enrolled prior to trial cessation, 95 had both baseline and 6-month echocardiograms (77 HFrEF and 18 HFpEF). Among HFrEF patients, both treatment arms demonstrated a significant increase in EF: +4.3% in the ASV group (.0004) and +4.6% in OMT alone (P = .007) and a significant decrease in LV end-systolic volume index: -9.4 mL/m2 in the ASV group (P = .01) and -8.6 mL/m2 in OMT alone (P = .003). Reductions in left atrial (LA) volume and E/e' were greater in the ASV arm, whereas patients receiving OMT alone demonstrated more improvement in right ventricular function. HFpEF patients treated with ASV also had a decrease in LA size that was greater than those receiving OMT alone. Although there were significant intragroup changes within the ASV + OMT and OMT-alone groups, there were no significant intergroup differences at 6 months. CONCLUSIONS: Significant reverse LV remodeling was seen among HFrEF patients with SDB regardless of treatment allocation. Substantial reductions in LA volume among HFrEF and HFpEF patients receiving ASV suggest that ASV treatment may also improve diastolic function and warrant further investigation.

Cangrelor Use Patterns and Transition to Oral P2Y12 Inhibitors Among Patients With Myocardial Infarction: Initial Results From the CAMEO Registry.

Background In clinical trials, cangrelor has been shown to reduce percutaneous coronary intervention-related ischemic complications without increasing major bleeding. This study was performed to examine cangrelor use and transition to oral P2Y12 inhibitors in routine clinical practice. Methods and Results The CAMEO (Cangrelor in Acute Myocardial Infarction: Effectiveness and Outcomes) registry is a multicenter, retrospective observational study of platelet inhibition strategies for patients with myocardial infarction undergoing percutaneous coronary intervention. In phase 1, data were collected on consecutive patients with myocardial infarction (n=482) treated with any P2Y12 inhibitor to understand cangrelor use by hospital. In phase 2, data were collected in a 2:1 (cangrelor-: non-cangrelor-treated) ratio of patients with myocardial infarction (n=873). In phase 1, cangrelor use varied across hospitals (overall, 50.4% [range, 6.0%-100%]). Of patients receiving cangrelor in both phases (n=819), 3.3% received either the bolus or infusion only. Cangrelor was infused for a median of 121 (76-196) minutes; and 38.3% received an infusion for <2 hours. Most patients transitioned from cangrelor to ticagrelor (ticagrelor, 85.3%; clopidogrel, 9.5%; prasugrel, 5.2%). Many patients (16.4%) had a >1-hour gap between cangrelor cessation and oral P2Y12 inhibitor initiation; this was highest among those transitioned to clopidogrel (56.6% versus 34.5% prasugrel versus 10.8% ticagrelor; P<0.001). Only 27.3% were dosed with cangrelor and transitioned to an oral P2Y12 inhibitor in a fashion consistent with the pivotal trials and US Food and Drug Administration label. Conclusions This multicenter registry demonstrated interhospital variability in how cangrelor was administered and transitioned to an oral P2Y12 inhibitor. These findings highlight opportunities for optimization of cangrelor dosing, infusion duration, and transition of care from the catheterization laboratory to the ward setting.

Effect of pulmonary hypertension on clinical outcomes in advanced heart failure: analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) database.

BACKGROUND: Pulmonary hypertension has been shown to predict hospitalizations and mortality in patients with heart failure. We aimed to define the prevalence of mixed pulmonary hypertension (MPH; mean pulmonary artery pressure > or = 25 mm Hg, pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance > or = 3 Wood units), identify clinical predictors of MPH, and determine whether MPH predicts adverse outcomes in patients hospitalized with severe heart failure. METHODS: This is a subgroup analysis of patients assigned to pulmonary artery catheter placement in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Patients with and without MPH were compared with respect to baseline characteristics and clinical outcomes, including NYHA class, 6-minute walk distance, quality of life, days hospitalized, and 6-month mortality. RESULTS: Of the 171 patients studied, 80 (47%) had MPH. Older age was the only significant predictor of MPH. MPH patients had lower cardiac index (1.8 +/- 0.5 L/min vs 2.1 +/- 0.5 L/min, P = .001) and higher systemic vascular resistance index (3,179 +/- 1,454 vs 2,550 +/- 927 dynes x s/cm5 x m2, P < .001) compared to those without MPH. Importantly, right ventricular function was relatively preserved (median RVSWI 8.7 gm-m/m2/beat) in MPH patients. There were no significant differences in clinical outcomes between the two groups. CONCLUSIONS: Mixed pulmonary hypertension is common in patients hospitalized with advanced heart failure and is not associated with adverse short-term clinical outcomes over and above the poor prognosis of ADHF patients without MPH.

Correlation of impedance cardiography with invasive hemodynamic measurements in patients with advanced heart failure: the BioImpedance CardioGraphy (BIG) substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) Trial.

BACKGROUND: Impedance cardiography (ICG) is a noninvasive modality that uses changes in impedance across the thorax to assess hemodynamic parameters, including cardiac output (CO). The utility of ICG in patients hospitalized with heart failure is uncertain. METHODS: The BioImpedance CardioGraphy in Advanced Heart Failure study was a prospective substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness. A total of 170 subjects underwent blinded ICG measurements using BioZ (CardioDynamics, San Diego, CA); of these, 82 underwent right heart catheterization. We compared ICG with invasively measured hemodynamics by simple correlation and compared overall ICG hemodynamic profiles ("wet" [thoracic fluid content > or =47/kOhm in men and > or =37/kOhm in women] and "cold" [cardiac index < or =2.2 L min(-1)m(-2)) versus those determined by invasive measurements (wet [pulmonary capillary wedge pressure > or =22 mm Hg] and cold [cardiac index < or =2.2 L min(-1)m(-2)). We also determined whether ICG measurements were associated with subsequent death or hospitalization within 6 months. RESULTS: There was modest correlation between ICG and invasively measured CO (r = 0.4 to 0.6 on serial measurement). Thoracic fluid content measured by ICG was not a reliable measure of pulmonary capillary wedge pressure. There was poor agreement between ICG and invasively measured hemodynamic profiles (kappa < or =0.1). No ICG variable alone or in combination was associated with outcome. CONCLUSIONS: In hospitalized patients with advanced heart failure, ICG provides some information about CO but not left-sided filling pressures. Impedance cardiography did not have prognostic utility in this patient population.

Adaptive servo-ventilation reduces atrial fibrillation burden in patients with heart failure and sleep apnea.

BACKGROUND: Patients with heart failure and sleep apnea are at increased risk for developing arrhythmias. Whether treatment of sleep apnea reduces arrhythmias is unknown. OBJECTIVE: The purpose of this study was to determine whether adaptive servo-ventilation (ASV) with optimal medical therapy (OMT) reduces atrial fibrillation (AF) and/or ventricular tachycardia/ventricular fibrillation (VT/VF) burden compared to OMT alone. METHODS: We conducted a prospective substudy of patients with pacemakers/defibrillators in the Cardiovascular Improvements with Minute Ventilation-Targeted ASV Therapy in Heart Failure (CAT-HF) trial. Change in arrhythmia burden was compared using a mixed model analysis to account for multiple measurements per patient. RESULTS: Among 35 randomized patients eligible and analyzed (19 ASV, 16 OMT only) in the AF cohort, mean age was 64 ± 12 years, 23% were women (n = 8), 49% had previous AF (n = 17), 89% had reduced ejection fraction (n = 31), and mean apnea hypopnea index was 41 ± 17 events per hour. Baseline characteristics were similar between groups. Change in AF burden from baseline to follow-up was -15.8% ± 36.5% with ASV vs +23.7% ± 36.2% with OMT (P = .034). There was no significant change in the AF cohort in the mean number of VT/VF events: +3.3 ± 14.9 events with ASV vs -0.3 ± 7.3 events with OMT (P = .58). Five subjects had appropriate therapies for VT/VF in the ASV arm vs 6 subjects in the OMT arm. CONCLUSION: This study provides proof of concept that treatment of sleep apnea with ASV leads to reduction in AF burden compared with OMT alone, without an increase in VT/VF events. This hypothesis should be tested in a large outcomes trial.

High mortality without ESCAPE: the registry of heart failure patients receiving pulmonary artery catheters without randomization.

BACKGROUND: In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), there was no difference in days alive and out of the hospital for patients with decompensated heart failure randomly assigned to therapy guided by pulmonary artery catheter (PAC) plus clinical assessment versus clinical assessment alone. The external validity of these findings is debated. METHODS AND RESULTS: ESCAPE sites enrolled 439 patients receiving PAC without randomization in a prospective registry. Baseline characteristics, pertinent trial exclusion criteria, reasons for PAC use, hemodynamics, and complications were collected. Survival was determined from the National Death Index and the Alberta Registry. On average, registry patients had lower blood pressure, worse renal function, less neurohormonal antagonist therapy, and higher use of intravenous inotropes compared with trial patients. Although clinical assessment anticipated less volume overload and greater hypoperfusion among the registry population, measured filling pressures were similarly elevated in the registry and trial patients, whereas measured perfusion was slightly higher among registry patients. Registry patients had longer hospitalization (13 vs 6 days, P < .001) and higher 6-month mortality (34% vs 20%, P < .001) than trial patients. CONCLUSIONS: The decision to use PAC without randomization identified a population with higher disease severity and risk of mortality. This prospective registry highlights the complex context of patient selection for randomized trials.

Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure.

BACKGROUND: Treatment of decompensated heart failure often includes the use of intravenous vasoactive medications, but the effect on outcome has not been clearly defined. METHODS: Data from 433 patients enrolled in the ESCAPE trial were analyzed to determine 6-month risks of all-cause mortality and all-cause mortality plus rehospitalization associated with the use of vasodilators, inotropes, and their combination. Patients had a mean left ventricular ejection fraction of 19%, 6-minute walk distance of 414 ft, and systolic blood pressure of 106 mm Hg. The main outcome measure was multivariable risk-adjusted 6-month hazard ratios (HRs). RESULTS: Overall 6-month mortality was 19%. Risk-adjusted HRs were not statistically significant for vasodilators (1.39, 95% CI 0.64-3.00), but were significant for inotropes (2.14, 95% CI 1.10-4.15) and the combination (4.81, 95% CI 2.34-9.90). Risk-adjusted 6-month mortality plus rehospitalization HRs were not significant for vasodilators (1.20, 95% CI 0.81-1.78, P = .37), but were significant for inotropes (1.96, 95% CI 1.37-2.82, P < .001) and their combination (2.90, 95% CI 1.88-4.48, P = .001). The decision to use vasodilators or inotropes was determined by hemodynamic parameters and renal function, but the main factor was treatment site. CONCLUSIONS: In ESCAPE, the choice of medications was mainly determined by the treatment site. Use of inotropic agents was associated with adverse outcomes, whereas the use of vasodilators was not. Inotropes in combination with vasodilators identified a group with the highest mortality. Prospective studies are needed to establish the appropriate use of vasoactive medications in this population.

Rapid assay brain natriuretic peptide and troponin I in patients hospitalized with decompensated heart failure (from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness Trial).

Rapid-assay biomarkers may predict outcomes in patients with decompensated heart failure (HF). This study assessed whether rapid-assay B-type natriuretic peptide (BNP) and troponin I predicts length of stay and mortality and correlates with pulmonary artery catheter (PAC)-derived hemodynamics in patients hospitalized with acute HF. There were 141 nonconsecutive patients in this prospective cohort study of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), a randomized trial testing PACs in 433 patients with severe decompensated HF. Biomarkers were drawn at baseline and discharge and when the first, second, and final hemodynamics were obtained in 69 patients randomly assigned to PACs. Cox analysis was used to model mortality, length of stay, and rehospitalization, and Pearson's correlations were used to describe the relation among BNP, troponin I, and PAC-derived hemodynamics. The median (25th percentile, 75th percentile) BNP levels were 783 pg/ml (329, 1,565) at baseline and 468 pg/ml (240, 946) at discharge. After treatment for HF, the median BNP level decreased by 144 pg/ml (-653, 55; p = 0.004). Patients with baseline BNP levels >1,500 pg/ml had greater mortality at 6 months and almost twice the length of stay as patients with BNP levels <500 pg/ml (10.1 vs 5.7 days, p = 0.002). Troponin I did not predict these outcomes. First BNP correlated modestly with first right atrial pressure (r = 0.47, p = 0.005) and first pulmonary capillary wedge pressure (r = 0.54, p = 0.001). Final BNP correlated modestly with final right atrial pressure (r = 0.63, p = 0.001). In conclusion, patients with BNP >1,500 pg/ml had greater mortality and longer length of stay than patients with BNP <500 pg/ml. BNP decreased after hospitalization, but correlated modestly with PAC-derived hemodynamics. Rapid-assay BNP may provide information that helps physicians decide when to pursue more aggressive and invasive therapies.

Cardiovascular Outcomes With Minute Ventilation-Targeted Adaptive Servo-Ventilation Therapy in Heart Failure: The CAT-HF Trial.

BACKGROUND: Sleep apnea is common in hospitalized heart failure (HF) patients and is associated with increased morbidity and mortality. OBJECTIVES: The CAT-HF (Cardiovascular Improvements With MV-ASV Therapy in Heart Failure) trial investigated whether minute ventilation (MV) adaptive servo-ventilation (ASV) improved cardiovascular outcomes in hospitalized HF patients with moderate-to-severe sleep apnea. METHODS: Eligible patients hospitalized with HF and moderate-to-severe sleep apnea were randomized to ASV plus optimized medical therapy (OMT) or OMT alone (control). The primary endpoint was a composite global rank score (hierarchy of death, cardiovascular hospitalizations, and percent changes in 6-min walk distance) at 6 months. RESULTS: 126 of 215 planned patients were randomized; enrollment was stopped early following release of the SERVE-HF (Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure) trial results. Average device usage was 2.7 h/night. Mean number of events measured by the apnea-hypopnea index decreased from 35.7/h to 2.1/h at 6 months in the ASV group versus 35.1/h to 19.0/h in the control group (p < 0.0001). The primary endpoint did not differ significantly between the ASV and control groups (p = 0.92 Wilcoxon). Changes in composite endpoint components were not significantly different between ASV and control. There was no significant interaction between treatment and ejection fraction (p = 0.10 Cox model); however, pre-specified subgroup analysis suggested a positive effect of ASV in patients with HF with preserved ejection fraction (p = 0.036). CONCLUSIONS: In hospitalized HF patients with moderate-to-severe sleep apnea, adding ASV to OMT did not improve 6-month cardiovascular outcomes. Study power was limited for detection of safety signals and identifying differential effects of ASV in patients with HF with preserved ejection fraction, but additional studies are warranted in this population. (Cardiovascular Improvements With MV ASV Therapy in Heart Failure [CAT-HF]; NCT01953874).

Prognostic usefulness of white blood cell count and temperature in acute myocardial infarction (from the CARDINAL Trial).

White blood cell (WBC) count and temperature are 2 global measures of inflammation that are systematically gathered and easily identifiable in a clinical setting, unlike many other markers of inflammation being investigated in patients with coronary artery disease. The prognostic usefulness of the WBC count and temperature were evaluated in a large acute myocardial infarction trial, the Complement And ReDuction of INfarct size after Angioplasty or Lytics program. Baseline and serial measurements of WBC counts and temperature were correlated with infarct size and clinical outcome.

Implications of elevated cardiac troponin T in ambulatory patients with heart failure: a prospective analysis.

BACKGROUND: Elevated concentrations of cardiac troponin T (TnT) have been reported in patients hospitalized for decompensated heart failure (HF). We assessed whether elevated TnT levels are associated with the severity, etiology, and prognosis of HF in stable, ambulatory patients. METHODS: From 1998-1999, we prospectively collected data from 136 ambulatory patients with HF, New York Heart Association functional class II to IV, ejection fraction < or =35%, and no recent unstable angina, myocardial infarction, surgery, or coronary revascularization. Blood was obtained and analyzed by immunoassay for TnT, and patients were followed for 14.0 +/- 4.3 months for death or HF hospitalization (primary end point) and other adverse cardiovascular outcomes. RESULTS: Thirty-three patients (24%) had an elevated TnT level (> or =0.02 ng/mL). Mean TnT concentration did not differ by etiology of HF (0.002 +/- 0.03 ng/mL vs 0.02 +/- 0.04 ng/mL for ischemic and nonischemic etiologies, P =.25). Compared with patients with normal (undetectable) levels of TnT, patients with elevated TnT were significantly older, had worse functional class, and had poorer renal function. Elevated TnT concentrations were associated with increased relative risks (RR) of death or HF hospitalization (RR 2.7, 95% CI 1.7-4.3, P =.001) and death alone (RR 4.2, 95% CI 1.8-9.5, P =.001) during follow-up. Elevated TnT and New York Heart Association class were significant, independent predictors of death or HF hospitalization. Increased age and serum creatinine concentrations were significant independent predictors of death alone. CONCLUSIONS: Nearly one fourth of ambulatory patients with chronic HF have ongoing myocardial necrosis as shown by abnormal TnT values, which are associated with increased mortality and morbidity.

Incidence and characteristics of stroke during 90-day follow-up in patients stabilized after an acute coronary syndrome.

BACKGROUND: Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes (ACS). The type, outcome, and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported. METHODS: We evaluated stroke incidence, subtypes, and outcomes, in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. RESULTS: Of 15,904 stabilized patients with ACS, 113 (0.71%) had a stroke over a median follow-up of 90 days. The majority of strokes occurred within 30 days of presentation, and the time course for stroke occurrence paralleled that of myocardial (re)infarction. Most strokes were ischemic (78%), and 52% resulted in moderate or severe disability or death. Patients with stroke were older and more often had hypertension, diabetes, peripheral vascular disease, and atrial fibrillation. Among patients with stroke who had cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass grafting, stroke occurred predominantly after the procedure. No difference in occurrence or type of stroke was observed in the assigned treatment groups. In multivariable modeling age, heart failure, prior stroke, left bundle branch block, and systolic blood pressure predicted the occurrence of stroke. CONCLUSIONS: In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and/or aspirin, stroke occurred in fewer than 1% within 90 days but carried a significant mortality and morbidity risk.

Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: a randomized trial.

BACKGROUND: Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants. METHODS: This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified. RESULTS: Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants. CONCLUSIONS: This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury.

Triage after hospitalization with advanced heart failure: the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) risk model and discharge score.

OBJECTIVES: Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective triage to management strategies. BACKGROUND: Heart failure severity at presentation predicts outcomes, but the prognostic importance of clinical status changes due to interventions is less well described. METHODS: Predictive models using variables obtained during hospitalization were created using data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial and internally validated by the bootstrapping method. Model coefficients were converted to an additive risk score. Additionally, data from FIRST (Flolan International Randomized Survival Trial) was used to externally validate this model. RESULTS: Patients discharged with complete data (n = 423) had 6-month mortality and death and rehospitalization rates of 18.7% and 64%, respectively. Discharge risk factors for mortality included BNP, per doubling (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.15 to 1.75), cardiopulmonary resuscitation or mechanical ventilation during hospitalization (HR: 2.54, 95% CI: 1.12 to 5.78), blood urea nitrogen, per 20-U increase (HR: 1.22, 95% CI: 0.96 to 1.55), serum sodium, per unit increase (HR: 0.93, 95% CI: 0.87 to 0.99), age >70 years (HR: 1.05, 95% CI: 0.51 to 2.17), daily loop diuretic, furosemide equivalents >240 mg (HR: 1.49, 95% CI: 0.68 to 3.26), lack of beta-blocker (HR: 1.28, 95% CI: 0.68 to 2.41), and 6-min walk, per 100-foot increase (HR: 0.955, 95% CI: 0.99 to 1.00; c-index 0.76). A simplified discharge score discriminated mortality risk from 5% (score = 0) to 94% (score = 8). Bootstrap validation demonstrated good internal validation of the model (c-index 0.78, 95% CI: 0.68 to 0.83). CONCLUSIONS: The ESCAPE study discharge risk model and score refine risk assessment after in-hospital therapy for advanced decompensated systolic HF, allowing clinicians to focus surveillance and triage for early life-saving interventions in this high-risk population. (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE]; NCT00000619).

Association of weight change with subsequent outcomes in patients hospitalized with acute decompensated heart failure.

The association of weight loss achieved through various decongestive strategies with clinical outcomes in patients with acute decompensated heart failure (HF) is not well described. The aim of this study was to determine the relation between weight change during hospitalization and subsequent clinical events in patients with decompensated HF. Data from 433 patients hospitalized with advanced HF enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial were evaluated. The influence of change in weight during hospitalization to clinical outcomes (days alive out of the hospital in the first 6 months; death; death or rehospitalization; and death, rehospitalization, or cardiac transplantation) was evaluated. On average, patients lost approximately 3.6 kg during hospitalization. When categorized into 3 weight loss tertiles, those in the highest tertile were more likely to be older, women, and smokers, with higher body weights, previous percutaneous coronary interventions, baseline heart rates, and brain natriuretic peptide and blood urea nitrogen values but lower ejection fractions and peak oxygen consumption. No significant differences were observed between weight change and any in-hospital or follow-up events (days well: hazard ratio 0.995, 95% confidence interval 0.975 to 1.016; 180-day death: hazard ratio 1.012, 95% confidence interval 0.969 to 1.057; death or rehospitalization at 180 days: hazard ratio 1.014, 95% confidence interval 0.990 to 1.038). In conclusion, weight loss in patients with acute decompensated HF during hospitalization was not related to clinical end points. These data challenge the merit of using weight as a surrogate end point for more important clinical events (i.e., death and/or rehospitalization) in patients with HF in the design of treatment strategies for novel therapeutic agents in randomized controlled clinical trials.

Reduction in mitral regurgitation during therapy guided by measured filling pressures in the ESCAPE trial.

BACKGROUND: Dynamic mitral regurgitation (MR) contributes to decompensation in chronic dilated heart failure. Reduction of MR was the primary physiological end point in the ESCAPE trial, which compared acute therapy guided by jugular venous pressure, edema, and weight (CLIN) with therapy guided additionally by pulmonary artery catheters (PAC) toward pulmonary wedge pressure