Wendy Gattis Stough

Characteristics, Treatments, and Outcomes of Patients With Preserved Systolic Function Hospitalized for Heart Failure. A Report From the OPTIMIZE-HF Registry

OBJECTIVES We sought to evaluate the characteristics, treatments, and outcomes of patients with preserved and reduced systolic function heart failure (HF). BACKGROUND Heart failure with preserved systolic function (PSF) is common but not well understood. METHODS This analysis of the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) registry compared 20,118 patients with left ventricular systolic dysfunction (LVSD) and 21,149 patients with PSF (left ventricular ejection fraction [EF] > or =40%). Sixty- to 90-day follow-up was obtained in a pre-specified 10% sample of patients. Analyses of patients with PSF defined as EF >50% were also performed for comparison. RESULTS Patients with PSF (EF > or =40%) were more likely to be older, female, and Caucasian and to have a nonischemic etiology. Although length of hospital stay was the same in both groups, risk of in-hospital mortality was lower in patients with PSF (EF > or =40%) (2.9% vs. 3.9%; p < 0.0001). During 60- to 90-day post-discharge follow-up, patients with PSF (EF > or =40%) had a similar mortality risk (9.5% vs. 9.8%; p = 0.459) and rehospitalization rates (29.2% vs. 29.9%; p = 0.591) compared with patients with LVSD. Findings were comparable with those with PSF defined as EF >50%. In a risk- and propensity-adjusted model, there were no significant relationships between discharge use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or beta-blocker and 60- to 90-day mortality and rehospitalization rates in patients with PSF. CONCLUSIONS Data from the OPTIMIZE-HF registry reveal a high prevalence of HF with PSF, and these patients have a similar post-discharge mortality risk and equally high rates of rehospitalization as patients with HF and LVSD. Despite the burden to patients and health care systems, data are lacking on effective management strategies for patients with HF and PSF. (Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]); http://www.clinicaltrials.gov/ct/show/NCT00344513?order=1; NCT00344513).

Clinical ResearchHeart FailureCharacteristics, Treatments, and Outcomes of Patients With Preserved Systolic Function Hospitalized for Heart Failure: A Report From the OPTIMIZE-HF Registry

OBJECTIVES We sought to evaluate the characteristics, treatments, and outcomes of patients with preserved and reduced systolic function heart failure (HF). BACKGROUND Heart failure with preserved systolic function (PSF) is common but not well understood. METHODS This analysis of the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) registry compared 20,118 patients with left ventricular systolic dysfunction (LVSD) and 21,149 patients with PSF (left ventricular ejection fraction [EF] > or =40%). Sixty- to 90-day follow-up was obtained in a pre-specified 10% sample of patients. Analyses of patients with PSF defined as EF >50% were also performed for comparison. RESULTS Patients with PSF (EF > or =40%) were more likely to be older, female, and Caucasian and to have a nonischemic etiology. Although length of hospital stay was the same in both groups, risk of in-hospital mortality was lower in patients with PSF (EF > or =40%) (2.9% vs. 3.9%; p < 0.0001). During 60- to 90-day post-discharge follow-up, patients with PSF (EF > or =40%) had a similar mortality risk (9.5% vs. 9.8%; p = 0.459) and rehospitalization rates (29.2% vs. 29.9%; p = 0.591) compared with patients with LVSD. Findings were comparable with those with PSF defined as EF >50%. In a risk- and propensity-adjusted model, there were no significant relationships between discharge use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or beta-blocker and 60- to 90-day mortality and rehospitalization rates in patients with PSF. CONCLUSIONS Data from the OPTIMIZE-HF registry reveal a high prevalence of HF with PSF, and these patients have a similar post-discharge mortality risk and equally high rates of rehospitalization as patients with HF and LVSD. Despite the burden to patients and health care systems, data are lacking on effective management strategies for patients with HF and PSF. (Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]); http://www.clinicaltrials.gov/ct/show/NCT00344513?order=1; NCT00344513).

Predictors of In-Hospital Mortality in Patients Hospitalized for Heart Failure: Insights From the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF)

OBJECTIVES The aim of this study was to develop a clinical model predictive of in-hospital mortality in a broad hospitalized heart failure (HF) patient population. BACKGROUND Heart failure patients experience high rates of hospital stays and poor outcomes. Although predictors of mortality have been identified in HF clinical trials, hospitalized patients might differ greatly from trial populations, and such predictors might underestimate mortality in a real-world population. METHODS The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) is a registry/performance improvement program for patients hospitalized with HF in 259 U.S. hospitals. Forty-five potential predictor variables were used in a stepwise logistic regression model for in-hospital mortality. Continuous variables that did not meet linearity assumptions were transformed. All significant variables (p < 0.05) were entered into multivariate analysis. Generalized estimating equations were used to account for the correlation of data within the same hospital in the adjusted models. RESULTS Of 48,612 patients enrolled, mean age was 73.1 years, 52% were women, 74% were Caucasian, and 46% had ischemic etiology. Mean left ventricular ejection fraction was 0.39 +/- 0.18. In-hospital mortality occurred in 1,834 (3.8%). Multivariable predictors of mortality included age, heart rate, systolic blood pressure (SBP), sodium, creatinine, HF as primary cause of hospitalization, and presence/absence of left ventricular systolic dysfunction. A scoring system was developed to predict mortality. CONCLUSIONS Risk of in-hospital mortality for patients hospitalized with HF remains high and is increased in patients who are older and have low SBP or sodium levels and elevated heart rate or creatinine at admission. Application of this risk-prediction algorithm might help identify patients at high risk for in-hospital mortality who might benefit from aggressive monitoring and intervention.

Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE trial.

We examined the relation of maximal in‐hospital diuretic dose to weight loss, changes in renal function, and mortality in hospitalised heart failure (HF) patients.

Predictors of mortality after discharge in patients hospitalized with heart failure: An analysis from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF)

BACKGROUND Patients with heart failure (HF) are at high risk for mortality and rehospitalization in the early period after hospital discharge. We developed clinical models predictive of short-term clinical outcomes in a broad patient population discharged after hospitalization for HF. METHODS The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry is a comprehensive hospital-based registry and performance-improvement program for patients hospitalized with HF. Follow-up data were scheduled to be prospectively collected at 60 to 90 days postdischarge in a prespecified 10% sample. For the 4,402 patients included in this analysis, 19 prespecified potential predictor variables were used in a stepwise Cox proportional hazards model for all-cause mortality. Logistic regression including 45 potential variables was used to model mortality or rehospitalization. RESULTS The 60- to 90-day postdischarge mortality rate was 8.6% (n = 481), and 29.6% (n = 1,715) were rehospitalized. Factors predicting early postdischarge mortality include age, serum creatinine, reactive airway disease, liver disease, lower systolic blood pressure, lower serum sodium, lower admission weight, and depression. Use of statins and beta-blockers at discharge was associated with significantly decreased mortality. The C-index of the model was 0.74. The most important predictors for the combined end point of death or rehospitalization were admission serum creatinine, systolic blood pressure, admission hemoglobin, discharge use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and pulmonary disease. From this analysis, 8 factors identified to carry significant risk were selected for use in a point scoring system to predict the risk of mortality within 60 days after discharge, with a C-index of 0.72. CONCLUSIONS A substantial risk of mortality and mortality or rehospitalization is present in the first 60 to 90 days after discharge from a hospitalization for HF. Several factors were identified that signal high-risk patients. Application of these findings with a simple algorithm can distinguish patients who are low risk from those at high risk who may benefit from closer monitoring and aggressive evidence-based treatment.

Factors identified as precipitating hospital admissions for heart failure and clinical outcomes: Findings from OPTIMIZE-HF

BACKGROUND Few studies have examined factors identified as contributing to heart failure (HF) hospitalization, and, to our knowledge, none has explored their relationship to length of stay and mortality. This study evaluated the association between precipitating factors identified at the time of HF hospital admission and subsequent clinical outcomes. METHODS During 2003 to 2004, 259 US hospitals in OPTIMIZE-HF submitted data on 48 612 patients, with a prespecified subgroup of at least 10% providing 60- to 90-day follow-up data. Identifiable factors contributing to HF hospitalization were captured at admission and included ischemia, arrhythmia, nonadherence to diet or medications, pneumonia/respiratory process, hypertension, and worsening renal function. Multivariate analyses were performed for length of stay, in-hospital mortality, 60- to 90-day follow-up mortality, and death/rehospitalization. RESULTS Mean patient age was 73.1 years, 52% of patients were female, and mean ejection fraction was 39.0%. Of 48 612 patients, 29 814 (61.3%) had 1 or more precipitating factors identified, with pneumonia/respiratory process (15.3%), ischemia (14.7%), and arrhythmia (13.5%) being most frequent. Pneumonia (odds ratio, 1.60), ischemia (1.20), and worsening renal function (1.48) were independently associated with higher in-hospital mortality, whereas uncontrolled hypertension (0.74) was associated with lower in-hospital mortality. Ischemia (1.52) and worsening renal function (1.46) were associated with a higher risk of follow-up mortality. Uncontrolled hypertension as a precipitating factor was associated with lower postdischarge death/rehospitalization (hazard ratio, 0.71). CONCLUSIONS Precipitating factors are frequently identified in patients hospitalized for HF and are associated with clinical outcomes independent of other predictive variables. Increased attention to these factors, many of which are avoidable, is important in optimizing the management of HF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00344513.

Improving Evidence-Based Care for Heart Failure in Outpatient Cardiology Practices Primary Results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF)

Background— A treatment gap exists between heart failure (HF) guidelines and the clinical care of patients. The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) prospectively tested a multidimensional practice-specific performance improvement intervention on the use of guideline-recommended therapies for HF in outpatient cardiology practices. Methods and Results— Performance data were collected in a random sample of HF patients from 167 US outpatient cardiology practices at baseline, longitudinally after intervention at 12 and 24 months, and in single-point-in-time patient cohorts at 6 and 18 months. Participants included 34 810 patients with reduced left ventricular ejection fraction (≤35%) and chronic HF or previous myocardial infarction. To quantify guideline adherence, 7 quality measures were assessed. Interventions included clinical decision support tools, structured improvement strategies, and chart audits with feedback. The performance improvement intervention resulted in significant improvements in 5 of 7 quality measures at the 24-month assessment compared with baseline: &bgr;-blocker (92.2% versus 86.0%, +6.2%), aldosterone antagonist (60.3% versus 34.5%, +25.1%), cardiac resynchronization therapy (66.3% versus 37.2%, +29.9%), implantable cardioverter-defibrillator (77.5% versus 50.1%, +27.4%), and HF education (72.1% versus 59.5%, +12.6%) (each P<0.001). There were no statistically significant improvements in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use or anticoagulation for atrial fibrillation. Sensitivity analyses at the patient level and limited to patients with both baseline and 24-month quality measure data yielded similar results. Improvements in the single-point-in-time cohorts were smaller, and there were no concurrent control practices. Conclusions— The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting, a defined and scalable practice-specific performance improvement intervention, was associated with substantial improvements in the use of guideline-recommended therapies in eligible patients with HF in outpatient cardiology practices. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00303979.

Safety and Efficacy of Sertraline for Depression in Patients With Heart Failure: Results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) Trial

OBJECTIVES The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo. BACKGROUND Depression is common among HF patients. It is associated with increased hospitalization and mortality. METHODS The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fraction < or =45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks. RESULTS A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean +/- SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was -7.1 +/- 0.5 (sertraline) and -6.8 +/- 0.5 (placebo) (p < 0.001 from baseline, p = 0.89 between groups, mean change between groups -0.4; 95% confidence interval: -1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78). CONCLUSIONS Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; NCT00078286).

Influence of Beta-Blocker Continuation or Withdrawal on Outcomes in Patients Hospitalized With Heart Failure. Findings From the OPTIMIZE-HF Program

OBJECTIVES This study ascertains the relationship between continuation or withdrawal of beta-blocker therapy and clinical outcomes in patients hospitalized with systolic heart failure (HF). BACKGROUND Whether beta-blocker therapy should be continued or withdrawn during hospitalization for decompensated HF has not been well studied in a broad cohort of patients. METHODS The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) program enrolled 5,791 patients admitted with HF in a registry with pre-specified 60- to 90-day follow-up at 91 academic and community hospitals throughout the U.S. Outcomes data were prospectively collected and analyzed according to whether beta-blocker therapy was continued, withdrawn, or not started. RESULTS Among 2,373 patients eligible for beta-blockers at discharge, there were 1,350 (56.9%) who were receiving beta-blockers before admission and continued on therapy, 632 (26.6%) newly started, 79 (3.3%) in which therapy was withdrawn, and 303 (12.8%) eligible but not treated. Continuation of beta-blockers was associated with a significantly lower risk and propensity adjusted post-discharge death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.37 to 0.99, p = 0.044) and death/rehospitalization (odds ratio: 0.69; 95% CI: 0.52 to 0.92, p = 0.012) compared with no beta-blocker. In contrast, withdrawal of beta-blocker was associated with a substantially higher adjusted risk for mortality compared with those continued on beta-blockers (HR: 2.3; 95% CI: 1.2 to 4.6, p = 0.013), but with similar risk as HF patients eligible but not treated with beta-blockers. CONCLUSIONS The continuation of beta-blocker therapy in patients hospitalized with decompensated HF is associated with lower post-discharge mortality risk and improved treatment rates. In contrast, withdrawal of beta-blocker therapy is associated with worse risk and propensity-adjusted mortality. (Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513).

New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.