Changing Strategy Between Bridge to Transplant and Destination LVAD Therapy After the First 3 Months: Analysis of the STS-INTERMACS Database.

BACKGROUND: Left ventricular assist devices (LVADs) have been implanted as bridge to transplantation (BTT), bridge to candidacy (BTC) or destination therapy (DT) on the basis of relative and absolute contraindications to transplantation. Multiple factors may lead to changes in the strategy of support after LVAD implantation. METHODS: Based on INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) 2012-2020 data, 11,262 patients survived to 3 months on continuous-flow LVADs with intent of BTT or DT. Preimplant characteristics and early events post-LVAD were analyzed in relation to changes in BTT or DT strategy during the next 12 months. RESULTS: Among 3216 BTT patients at 3 months, later transplant delisting or death without transplant occurred in 536 (16.7%) and was more common with age, profiles 1-2, renal dysfunction, and independently for prior cardiac surgery (HR 1.25, 95% CI 1.04-1.51; P = 0.02). Post-LVAD events of infections, gastrointestinal bleeding, stroke, and right heart failure as defined by inotropic therapy, predicted delisting and death, as did in-hospital location at 3 months (HR 1.67, 95% CI 1.20-2.33; P = 0.0024). Of 8046 patients surviving to 3 months with the intent of destination therapy, 750 (9.3%) subsequently underwent listing or transplantation, often with initial histories of acute HF (HR 1.70, 95% CI 1.27-2.27; P = 0.0012) or malnutrition-cachexia (1.73, 95% CI 1.14-2.63; P = 0.0099). Multiple gastrointestinal bleeding events (≥ 4) with LVAD increased transition from BTT to DT (HR 4.22, 95% CI 1.46-12.275; P = 0.0078) but also from DT to BTT (HR 5.17, 95% CI 1.92-13.9; P = 0.0011). CONCLUSIONS: Implant strategies change over time in relation to preimplant characteristics and adverse events post implant. Preimplant recognition of factors predicting later change in implant strategy will refine initial triage, whereas further reduction of post-LVAD complications will expand options, including eventual consideration of heart transplantation.

Arrhythmias as Presentation of Genetic Cardiomyopathy.

There is increasing evidence regarding the prevalence of genetic cardiomyopathies, for which arrhythmias may be the first presentation. Ventricular and atrial arrhythmias presenting in the absence of known myocardial disease are often labelled as idiopathic, or lone. While ventricular arrhythmias are well-recognized as presentation for arrhythmogenic cardiomyopathy in the right ventricle, the scope of arrhythmogenic cardiomyopathy has broadened to include those with dominant left ventricular involvement, usually with a phenotype of dilated cardiomyopathy. In addition, careful evaluation for genetic cardiomyopathy is also warranted for patients presenting with frequent premature ventricular contractions, conduction system disease, and early onset atrial fibrillation, in which most detected genes are in the cardiomyopathy panels. Sudden death can occur early in the course of these genetic cardiomyopathies, for which risk is not adequately tracked by left ventricular ejection fraction. Only a few of the cardiomyopathy genotypes implicated in early sudden death are recognized in current indications for implantable cardioverter defibrillators which otherwise rely upon a left ventricular ejection fraction ≤0.35 in dilated cardiomyopathy. The genetic diagnoses impact other aspects of clinical management such as exercise prescription and pharmacological therapy of arrhythmias, and new therapies are coming into clinical investigation for specific genetic cardiomyopathies. The expansion of available genetic information and implications raises new challenges for genetic counseling, particularly with the family member who has no evidence of a cardiomyopathy phenotype and may face a potentially negative impact of a genetic diagnosis. Discussions of risk for both probands and relatives need to be tailored to their numeric literacy during shared decision-making. For patients presenting with arrhythmias or cardiomyopathy, extension of genetic testing and its implications will enable cascade screening, intervention to change the trajectory for specific genotype-phenotype profiles, and enable further development and evaluation of emerging targeted therapies.

Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. CLINICAL TRIAL REGISTRATION: NCT04481919.

Sustained Reduction in Pulmonary Artery Pressures and Hospitalizations During 2 Years of Ambulatory Monitoring.

BACKGROUND: Therapy guided by pulmonary artery (PA) pressure monitoring reduces PA pressures and heart failure hospitalizations (HFH) during the first year, but the durability of efficacy and safety through 2 years is not known. METHODS AND RESULTS: The CardioMEMS Post-Approval Study investigated whether benefit and safety were generalized and sustained. Enrollment at 104 centers in the United States included 1200 patients with NYHA Class III symptoms on recommended HF therapies with prior HFH. Therapy was adjusted toward PA diastolic pressure 8-20 mmHg. Intervention frequency and PA pressure reduction were most intense during first 90 days, with sustained reduction of PA diastolic pressure from baseline 24.7 mmHg to 21.0 at 1 year and 20.8 at 2 years for all patients. Patients completing two year follow-up (n = 710) showed similar 2-year reduction (23.9 to 20.8 mmHg), with reduction in PA mean pressure (33.7 to 29.4 mmHg) in patients with reduced left ventricular ejection. The HFH rate was 1.25 events/patient/year prior to sensor implant, 0.54 at 1 year, and 0.37 at 2 years, with 59% of patients free of HFH during follow-up. CONCLUSIONS: Reduction in PA pressures and hospitalizations were early and sustained during 2 years of PA pressure-guided management, with no signal of safety concerns regarding the implanted sensor.

Current Emergency Department Disposition of Patients With Acute Heart Failure: An Opportunity for Improvement.

Emergency department (ED) providers play a critical role in the stabilization and diagnostic evaluation of patients presenting with acute heart failure (AHF), and EDs are key areas for establishing current best practices and future considerations for the disposition of and decision making for patients with AHF. These elements include accurate risk assessment; response to initial treatment and shared decision making concerning optimal venue of care; reframing of physicians' risk perceptions for patients presenting with AHF; exploration of alternative venues of care beyond hospitalization; population-level changes in demographics, management and outcomes of HF patients; development and testing of data-driven pathways to assist with disposition decisions in the ED; and suggested outcomes for measuring success.

Frailty Measures of Patient-reported Activity and Fatigue May Predict 1-year Outcomes in Ambulatory Advanced Heart Failure: A Report From the REVIVAL Registry.

BACKGROUND: The Fried Frailty Phenotype predicts adverse outcomes in geriatric populations, but has not been well-studied in advanced heart failure (HF). The Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life (REVIVAL) study prospectively collected frailty measures in patients with advanced HF to determine relevant assessments and their impact on clinical outcomes. METHODS AND RESULTS: HF-Fried Frailty was defined by 5 baseline components (1 point each): (1) weakness: hand grip strength less than 25% of body weight; (2) slowness based on time to walk 15 feet; (3) weight loss of more than 10 lbs in the past year; (4) inactivity; and (5) exhaustion, both assessed by the Kansas City Cardiomyopathy Questionnaire. A score of 0 or 1 was deemed nonfrail, 2 prefrail, and 3 or greater was considered frail. The primary composite outcome was durable mechanical circulatory support implantation, cardiac transplant or death at 1 year. Event-free survival for each group was determined by the Kaplan-Meier method and the hazard of prefrailty and frailty were compared with nonfrailty with proportional hazards modeling. Among 345 patients with all 5 frailty domains assessed, frailty was present in 17%, prefrailty in 40%, and 43% were nonfrail, with 67% (n = 232) meeting the criteria based on inactivity and 54% (n = 186) for exhaustion. Frail patients had an increased risk of the primary composite outcome (unadjusted hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.52-5.24; adjusted HR 3.41, 95% CI 1.79-6.52), as did prefrail patients (unadjusted HR 1.97, 95% CI 1.14-3.41; adjusted HR 2.11, 95% CI 1.21-3.66) compared with nonfrail patients, however, the predictive value of HF-Fried Frailty criteria was modest (Harrel's C-statistic of 0.603, P = .004). CONCLUSIONS: The HF-Fried Frailty criteria had only modest predictive power in identifying ambulatory patients with advanced HF at high risk for durable mechanical circulatory support, transplant, or death within 1 year, driven primarily by assessments of inactivity and exhaustion. Focus on these patient-reported measures may better inform clinical trajectories in this population.

Active B-Type Natriuretic Peptide Measured by Mass Spectrometry and Response to Sacubitril/Valsartan.

BACKGROUND: B-type natriuretic peptide (BNP) immunoassays (BNPia) do not differentiate active and inactive forms. Inactive NT-proBNP is used to track heart failure (HF) during treatment with sacubitril/valsartan, which inhibits BNP degradation. Mass spectrometry (MS) may better assess effects of HF treatment on biologically active BNP1-32. METHODS AND RESULTS: We developed a MS assay with immediate protease inhibition to quantify BNP1-32 over a linear range, using labeled recombinant BNP standard. In 4 healthy volunteers, BNP1-32 by MS (BNPMS) increased from below the 5 pg/mL detection limit to 228 pg/mL after nesiritide. In patients with HF, BNPMS was measured in parallel with BNP and NT-proBNP immunoassays before and during sacubitril/valsartan treatment. BNPMS was 4.4-fold lower than BNPia in patients with HF. Among patients not taking sacubitril/valsartan and without end-stage renal disease, BNPMS correlated with BNPia (rs = 0.77, P < .001) and NT-proBNP (rs = 0.74, P < .001). After a median of 8 weeks on sacubitril/valsartan, active BNPMS levels decreased by 50% (interquartile range -98.3% to 41.7%, n = 22, P = .048) and correlated with NT-proBNP (rs = 0.64, P < .001), but not with BNPia (rs = 0.46, P = .057). CONCLUSIONS: Active BNP measured by MS accounts for only a small amount of BNP measured by immunoassays. Although decreased BNP production was anticipated to be masked by inhibition of degradation, levels of active BNP decreased during chronic sacubitril/valsartan treatment.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

Characterization of the Progression From Ambulatory to Hospitalized Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Some patients develop elevated filling pressures exclusively during exercise and never require hospitalization, whereas others periodically develop congestion that requires inpatient treatment. The features differentiating these cohorts are unclear. METHODS: We performed a secondary analysis of 7 National Institutes of Health-sponsored multicenter trials of HFpEF (EF ≥ 50%, N = 727). Patients were stratified by history of hospitalization because of HF, comparing patients never hospitalized (HFpEFNH) to those with a prior hospitalization (HFpEFPH). Currently hospitalized (HFpEFCH) patients were included to fill the spectrum. Clinical characteristics, cardiac structure, biomarkers, quality of life, functional capacity, activity levels, and outcomes were compared. RESULTS: As expected, HFpEFCH (n = 338) displayed the greatest severity of congestion, as assessed by N-terminal pro B-type natriuretic peptide levels, edema and orthopnea. As compared to HFpEFNH (n = 109), HFpEFPH (n = 280) displayed greater comorbidity burden, with more lung disease, renal dysfunction and anemia, along with lower activity levels (accelerometry), poorer exercise capacity (6-minute walk distance and peak exercise capacity), and more orthopnea. Patients with current or prior hospitalization displayed higher rates of future HF hospitalization, but quality of life was similarly impaired in all patients with HFpEF, regardless of hospitalization history. CONCLUSIONS: A greater burden of noncardiac organ dysfunction, sedentariness, functional impairment, and higher event rates distinguish patients with HFpEF and prior HF hospitalization from those never hospitalized. Despite lower event rates, quality of life is severely and similarly limited in patients with no history of hospitalization. These data suggest that the 2 clinical profiles of HFpEF may require different treatment strategies.

Adverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity display a number of pathophysiologic features that may render them more or less vulnerable to negative effects of decongestion on renal function, including greater right ventricular remodeling, plasma volume expansion and pericardial restraint. We aimed to contrast the renal response to decongestion in obese compared to nonobese patients with HFpEF METHODS AND RESULTS: National Institutes of Health heart failure network studies that enrolled patients with acute decompensated HFpEF (EF ≥ 50%) were included (DOSE, CARRESS, ROSE, and ATHENA). Obese HFpEF was defined as a body mass index ≥ 30 kg/m2. Compared to nonobese HFpEF (n = 118), patients with obese HFpEF (n = 214) were an average of 9 years younger (71 vs 80 years,< 0.001), were more likely to have diabetes (64% vs 31%, P< 0.001) but had less atrial fibrillation (56% vs 75%, P< 0.001). Renal dysfunction (glomerular filtration rate < 60 mL/min/1.73m2) was present in 82% of patients, and there was no difference at baseline between obese and nonobese patients. Despite similar weight loss through decongestive therapies, obese patients with HFpEF demonstrated greater rise in creatinine (Cr) and decline in glomerular filtration rate, with a 2-fold higher incidence of mild worsening renal function (rise in Cr ≥ 0.3 mg/dL) (28 vs 14%, P = 0.008) and a substantially greater increase in severe worsening of renal function (rise in Cr > 0.5 mg/dL) (9 vs 0%, P = 0.002). CONCLUSIONS: Despite being nearly a decade younger, obese patients with HFpEF experience greater deterioration in renal function during decongestion than do nonobese patients with HFpEF. Further study to elucidate the complex relationships between volume distribution, cardiorenal hemodynamics and adiposity in HFpEF is needed.

Trends in Utilization and Outcomes of Pulmonary Artery Catheterization in Heart Failure With and Without Cardiogenic Shock.

BACKGROUND: The pulmonary artery catheter (PAC) has been used in a wide range of critically ill patients. It is not indicated for routine care of heart failure (HF), but its role in cardiogenic shock (CS) has not been clarified. METHODS AND RESULTS: We conducted a retrospective cohort study with the use of the National Inpatient Sample and identified a total of 9,431,944 adult patients admitted from 2004 to 2014 with the primary diagnosis of HF (n = 8,516,528) or who developed CS (n = 915,416) during the index hospitalization. Overall, patients with PAC had increased hospital costs, length of stay, and mechanical circulatory support use. In patients with HF, PAC use was associated with higher mortality (9.9% vs 3.3%, OR 3.96; P < .001) but the excess of mortality declined over time. In those with CS, PAC was associated with lower mortality (35.1% vs 39.2%, OR 0.91; P < .001) and in-hospital cardiac arrest (14.9% vs 18.3%, OR 0.77; P < .001); this paradox persisted after propensity score matching. CONCLUSIONS: The use of PAC in CS has decreased from 2004 to 2014, although its use is now associated with improved outcomes, which may reflect better selection of patients or better use of the information to guide therapies. Our data provide reassurance that PAC use in this population is an appropriate strategy.

Impact of Practice-Based Management of Pulmonary Artery Pressures in 2000 Patients Implanted With the CardioMEMS Sensor.

BACKGROUND: Elevated pulmonary artery (PA) pressures in patients with heart failure are associated with a high risk for hospitalization and mortality. Recent clinical trial evidence demonstrated a direct relationship between lowering remotely monitored PA pressures and heart failure hospitalization risk reduction with a novel implantable PA pressure monitoring system (CardioMEMS HF System, St. Jude Medical). This study examines PA pressure changes in the first 2000 US patients implanted in general practice use. METHODS: Deidentified data from the remote monitoring Merlin.net (St. Jude Medical) database were used to examine PA pressure trends from the first consecutive 2000 patients with at least 6 months of follow-up. Changes in PA pressures were evaluated with an area under the curve methodology to estimate the total sum increase or decrease in pressures (mm Hg-day) during the follow-up period relative to the baseline pressure. As a reference, the PA pressure trends were compared with the historic CHAMPION clinical trial (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association [NYHA] Functional Class III Heart Failure Patients). The area under the curve results are presented as mean±2 SE, and P values comparing the area under the curve of the general-use cohort with outcomes in the CHAMPION trial were computed by the t test with equal variance. RESULTS: Patients were on average 70±12 years old; 60% were male; 34% had preserved ejection fraction; and patients were followed up for an average of 333±125 days. At implantation, the mean PA pressure for the general-use patients was 34.9±10.2 mm Hg compared with 31.3±10.9 mm Hg for CHAMPION treatment and 32.0±10.5 mm Hg for CHAMPION control groups. The general-use patients had an area under the curve of -32.8 mm Hg-day at the 1-month time mark, -156.2 mm Hg-day at the 3-month time mark, and -434.0 mm Hg-day after 6 months of hemodynamic guided care, which was significantly lower than the treatment group in the CHAMPION trial. Patients consistently transmitted pressure information with a median of 1.27 days between transmissions after 6 months. CONCLUSIONS: The first 2000 general-use patients managed with hemodynamic-guided heart failure care had higher PA pressures at baseline and experienced greater reduction in PA pressure over time compared with the pivotal CHAMPION clinical trial. These data demonstrate that general use of implantable hemodynamic technology in a nontrial setting leads to significant lowering of PA pressures.

Spot Urine Sodium as Triage for Effective Diuretic Infusion in an Ambulatory Heart Failure Unit.

BACKGROUND: Admission for diuresis remains a common and costly event in patients with advanced heart failure (HF). We tested whether spot urine sodium could identify patients likely to respond to ambulatory diuretic infusion without hospitalization. METHODS AND RESULTS: We prospectively followed 176 consecutive patients with advanced heart failure receiving intravenous furosemide for congestion in an ambulatory clinic. Spot urine sodium was measured in 1st voided urine after diuretic infusion and compared with 3-hour urine output and subsequent risk of 30-day hospitalization or emergency department (ED) visit. Spot urine sodium was significantly associated with urine output in a model adjusted for age, renal function, and blood urea nitrogen (P = .02). Higher urine sodium was associated with lower risk of hospitalization or ED visit within 30 days (odds ratio [OR] 0.82 [95% confidence interval 0.72-0.94] per 10 mmol/L increase; P < .001), in a model adjusted for hemoglobin (OR 0.80 [0.66-0.97]; P = .02) and systolic blood pressure (OR 0.82 [0.67-1.0]; P = .05). Spot urine sodium ≥65 mmol/L and urine output ≥1200 mL identified a lower-risk group for outpatient management. CONCLUSION: High spot urine sodium after diuretic administration identifies HF patients likely to respond to an ambulatory diuretic infusion with lower rates of hospitalization or ED visits at 30 days.

Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial.

BACKGROUND: In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group. METHODS: The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. FINDINGS: Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55-0·80]; p<0·0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0·52 [95% CI 0·40-0·69]; p<0·0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported. INTERPRETATION: Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure. FUNDING: St Jude Medical Inc.

Unanswered Questions in Contemporary Heart Failure.

OBJECTIVE: The epidemiology of heart failure (HF) is changing. This study aimed to describe questions that arise during the routine care of HF patients that are unanswered by the current literature and describe how the type and focus of these questions has changed over time. METHODS: Investigators from the National Heart, Lung, and Blood Institute-sponsored Heart Failure Apprentice Network collected and categorized questions from 5 academic hospitals over 12 months. A total of 174 unanswered questions were collected and analyzed. RESULTS: Compared with 2004, there were more unanswered questions about "whether" to use therapies and fewer about "how" to use therapies. There were fewer questions about what therapeutic targets, therapy adjustment, and combination therapies. There were more questions about whether or how to stop therapies and how to add therapies back. Newly prominent topics, not observed in 2004, including novel therapeutics, refractory ventricular tachycardia, right heart failure, and nutrition/frailty, accounted for 24% of questions. CONCLUSIONS: Compared with 2004, there are fewer unanswered questions about how to use, adjust, and combine therapies. There were more unanswered questions about whether and how to stop therapies. Almost 25% of unanswered questions dealt with topics indicative of more advanced disease which were not observed in 2004.

Hemodynamic Predictors of Heart Failure Morbidity and Mortality: Fluid or Flow?

BACKGROUND: Patients with advanced heart failure may continue for prolonged times with persistent hemodynamic abnormalities; intermediate- and long-term outcomes of these patients are unknown. METHODS AND RESULTS: We used ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial data to examine characteristics and outcomes of patients with invasive hemodynamic monitoring during an acute heart failure hospitalization. Patients were stratified by final measurement of cardiac index (CI; L/min/m2) and pulmonary capillary wedge pressure (PCWP; mmHg) before catheter removal. The study groups were CI ≥ 2/PCWP < 20 (n = 74), CI ≥ 2/PCWP ≥ 20 (n = 37), CI < 2/PCWP < 20 (n = 23), and CI < 2/PCWP ≥ 20 (n = 17). Final CI was not associated with the combined risk of death, cardiovascular hospitalization, and transplantation (hazard ratio [HR]1.03, 95% confidence interval 0.96-1.11 per 0.2 L/min/m2 decrease, P = .39), but final PCWP ≥ 20 mmHg was associated with increased risk of these events (HR 2.03, 95% confidence interval 1.31-3.15, P < .01), as was higher final right atrial pressure (HR 1.09, 95% confidence interval 1.06-1.12 per mmHg increase, P < .01). CONCLUSION: Final PCWP and final right atrial pressure were stronger predictors of postdischarge outcomes than CI in patients with advanced heart failure. The ability to lower filling pressures appears to be more prognostically important than improving CI in the management of patients with advanced heart failure. ClinicalTrials.govIdentifier: NCT00000619.

Ultrafiltration in decompensated heart failure with cardiorenal syndrome.

BACKGROUND: Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function. METHODS: We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Patients were followed for 60 days. RESULTS: Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96 hours after enrollment (P=0.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96 hours, the mean change in the creatinine level was -0.04±0.53 mg per deciliter (-3.5±46.9 µmol per liter) in the pharmacologic-therapy group, as compared with +0.23±0.70 mg per deciliter (20.3±61.9 µmol per liter) in the ultrafiltration group (P=0.003). There was no significant difference in weight loss 96 hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5±5.1 kg [12.1±11.3 lb] and 5.7±3.9 kg [12.6±8.5 lb], respectively; P=0.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P=0.03). CONCLUSIONS: In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491.).