Michael S. Cuffe

Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study.

OBJECTIVES The goal of this study was to assess the interaction between heart failure (HF) etiology and response to milrinone in decompensated HF. BACKGROUND Etiology has prognostic and therapeutic implications in HF, but its relationship to response to inotropic therapy is unknown. METHODS The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic dysfunction and decompensated HF to receive 48 to 72 h of intravenous milrinone or placebo. The primary end point was days hospitalized from cardiovascular causes within 60 days. In a post-hoc analysis, we evaluated the interaction between response to milrinone and etiology of HF. RESULTS The primary end point was 13.0 days for ischemic patients and 11.7 days for nonischemic patients (p = 0.2). Sixty-day mortality was 11.6% for the ischemic group and 7.5% for the nonischemic group (p = 0.03). After adjustment for baseline differences, there was a significant interaction between etiology and the effect of milrinone. Milrinone-treated patients with ischemic etiology tended to have worse outcomes than those treated with placebo in terms of the primary end point (13.6 days for milrinone vs. 12.4 days for placebo, p = 0.055 for interaction) and the composite of death or rehospitalization (42% vs. 36% for placebo, p = 0.01 for interaction). In contrast, outcomes in nonischemic patients treated with milrinone tended to be improved in terms of the primary end point (10.9 vs. 12.6 days placebo) and the composite of death or rehospitalization (28% vs. 35% placebo). CONCLUSIONS Milrinone may have a bidirectional effect based on etiology in decompensated HF. Milrinone may be deleterious in ischemic HF, but neutral to beneficial in nonischemic cardiomyopathy.

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).

Prognostic Value of Anxiety and Depression in Patients With Chronic Heart Failure

Background—Anxiety is often present with depression and may be one of its manifestations. Although the adverse effects of depression in patients with chronic heart failure (CHF) have been well studied, the relation between anxiety and CHF prognosis has not been addressed. In a secondary analysis of data collected for a published study of depression and prognosis in patients with CHF, we examined the relations among anxiety, depression, and prognosis. Methods and Results—We measured symptoms of anxiety with the Spielberger State-Trait Anxiety Inventory (STAI) scale and symptoms of depression with the Beck Depression Inventory (BDI) scale in 291 patients with CHF hospitalized as a result of cardiac events. We followed up these patients for all-cause mortality over 1 year. The mean scores for state anxiety (State-A) and trait anxiety (Trait-A) were identical at 33.5; the mean BDI score was 8.7±7.6. State-A and Trait-A scores correlated highly with each other (r=0.85; P<0.01) and with BDI score (State-A, r=0.52; Trait-A, r=0.59; P<0.01). Cox proportional-hazards model with and without confounding variables showed no relation between State-A or Trait-A and 1-year mortality. BDI scores, however, significantly predicted increased mortality during 1-year follow-up (hazard ratio, 1.04 for each 1-unit increase; P<0.01). Conclusions—Although anxiety and depression are highly correlated in CHF patients, depression alone predicts a significantly worse prognosis for these patients.

Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure

We investigated the prevalence of anemia and its relation to clinical events in patients with decompensated heart failure enrolled in the OPTIME-CHF study. Our data demonstrate that anemia is common in patients hospitalized with decompensated heart failure and is associated with a greater number of co-morbid conditions. Lower baseline hemoglobin is associated with risk of short-term adverse clinical outcomes in this population, even after controlling for other baseline differences.

Music, imagery, touch, and prayer as adjuncts to interventional cardiac care: the Monitoring and Actualisation of Noetic Trainings (MANTRA) II randomised study

BACKGROUND Data from a pilot study suggested that noetic therapies-healing practices that are not mediated by tangible elements-can reduce preprocedural distress and might affect outcomes in patients undergoing percutaneous coronary intervention. We undertook a multicentre, prospective trial of two such practices: intercessory prayer and music, imagery, and touch (MIT) therapy. METHODS 748 patients undergoing percutaneous coronary intervention or elective catheterisation in nine USA centres were assigned in a 2x2 factorial randomisation either off-site prayer by established congregations of various religions or no off-site prayer (double-blinded) and MIT therapy or none (unmasked). The primary endpoint was combined in-hospital major adverse cardiovascular events and 6-month readmission or death. Prespecified secondary endpoints were 6-month major adverse cardiovascular events, 6 month death or readmission, and 6-month mortality. FINDINGS 371 patients were assigned prayer and 377 no prayer; 374 were assigned MIT therapy and 374 no MIT therapy. The factorial distribution was: standard care only, 192; prayer only, 182; MIT therapy only, 185; and both prayer and MIT therapy, 189. No significant difference was found for the primary composite endpoint in any treatment comparison. Mortality at 6 months was lower with MIT therapy than with no MIT therapy (hazard ratio 0.35 (95% CI 0.15-0.82, p=0.016). INTERPRETATION Neither masked prayer nor MIT therapy significantly improved clinical outcome after elective catheterisation or percutaneous coronary intervention.

The Support, Education, and Research in Chronic Heart Failure Study (SEARCH): A mindfulness-based psychoeducational intervention improves depression and clinical symptoms in patients with chronic heart failure

BACKGROUND The Support, Education, and Research in Chronic Heart Failure (SEARCH) study was designed to assess the impact of a mindfulness-based psychoeducational intervention on clinical outcomes, depression, and quality of life in patients with chronic heart failure (CHF). Although research has shown that psychosocial factors including depression are important risk factors for adverse events in patients with CHF, no large clinical trials have investigated the efficacy of psychosocial interventions to reduce these factors in this population. METHODS This was a prospective cohort study of 208 adults with left ventricular ejection fraction < or =40% and CHF geographically assigned to treatment or control groups with follow-up at 3, 6, and 12 months. Treatment groups met weekly for 8 consecutive weeks for training in mindfulness meditation, coping skills, and support group discussion. RESULTS Subjects had a mean age of 61 years, left ventricular ejection fraction 26%, and median New York Heart Association class II. The majority were treated with angiotensin-converting enzyme inhibitors (80%) and beta-blockers (86%). At baseline, patients in the treatment group had more severe CHF with higher New York Heart Association class (P = .0209) and more severe psychological distress (Center of Epidemiology - Depression, Profile of Mood States; P < .05). When compared with controls, treatment resulted in lower anxiety (Profile of Mood States, P = .003), depression (Center of Epidemiology - Depression, P = .05), improved symptoms (Kansas City Cardiomyopathy Questionnaire symptom scale, P = .033) and clinical scores (Kansas City Cardiomyopathy Questionnaire clinical score, P = .024) over time. There were no treatment effects on death/rehospitalization at 1 year. CONCLUSIONS An 8-week mindfulness-based psychoeducational intervention reduced anxiety and depression; this effect was attenuated at 1 year. Importantly, the intervention led to significantly better symptoms of CHF at 12 months compared to control subjects. Our results suggest that interventions of this type might have a role in optimal therapy for CHF.

Antidepressant Use, Depression, and Survival in Patients With Heart Failure

BACKGROUND Recent studies suggest that the use of antidepressants may be associated with increased mortality in patients with cardiac disease. Because depression has also been shown to be associated with increased mortality in these patients, it remains unclear if this association is attributable to the use of antidepressants or to depression. METHODS To evaluate the association of long-term mortality with antidepressant use and depression, we studied 1006 patients aged 18 years or older with clinical heart failure and an ejection fraction of 35% or less (62% with ischemic disease) between March 1997 and June 2003. The patients were followed up for vital status annually thereafter. Depression status, which was assessed by the Beck Depression Inventory (BDI) scale and use of antidepressants, was prospectively collected. The main outcome of interest was long-term mortality. RESULTS Of the study patients, 30.0% were depressed (defined by a BDI score > or =10) and 24.2% were taking antidepressants (79.6% of these patients were taking selective serotonin reuptake inhibitors [SSRIs] only). The vital status was obtained from all participants at an average follow-up of 972 (731) (mean [SD]) days. During this period, 42.7% of the participants died. Overall, the use of antidepressants (unadjusted hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.03-1.69) or SSRIs only (unadjusted HR, 1.32; 95% CI, 0.99-1.74) was associated with increased mortality. However, the association between antidepressant use (HR, 1.24; 95% CI, 0.94-1.64) and increased mortality no longer existed after depression and other confounders were controlled for. Nonetheless, depression remained associated with increased mortality (HR, 1.33; 95% CI, 1.07-1.66). Similarly, depression (HR, 1.34; 95% CI, 1.08-1.68) rather than SSRI use (HR, 1.10; 95% CI, 0.81-1.50) was independently associated with increased mortality after adjustment. CONCLUSION Our findings suggest that depression (defined by a BDI score > or =10), but not antidepressant use, is associated with increased mortality in patients with heart failure.

Clinical characteristics and long-term outcomes of patients with heart failure and preserved systolic function

Although the syndrome of heart failure with preserved systolic function may occur in up to 40% of all heart failure patients, the clinical, angiographic characteristics, and long-term outcomes of these patients are poorly understood. We prospectively evaluated 2,498 consecutive patients with New York Heart Association class II to IV symptoms and ejection fractions of >40%, who underwent cardiac catheterization between January 1984 and December 1996 at Duke University Medical Center. The median age for the entire cohort was 63 years; 25% of the population was >71 years old. In addition, 55% of the patients were women, 65% had ischemic heart disease, 28% had a history of diabetes, and 62% had a history of hypertension. The median ejection fraction was 58%. One third of the patients had multivessel disease by coronary angiography. The overall 5-year mortality of the total population was 28%. The independent predictors of mortality (p <0.05) using a multivariable Cox proportional hazard model were age, class IV symptoms, ejection fraction, coronary artery disease index, diabetes, peripheral vascular disease, and minority ethnic group. Heart failure with preserved systolic function is characterized by unique clinical and angiographic characteristics associated with a 5-year mortality rate of 28%. Furthermore, several clinical and angiographic characteristics are predictive of long-term survival.

Characteristics of depression remission and its relation with cardiovascular outcome among patients with chronic heart failure (from the SADHART-CHF Study).

Depression is prevalent in patients with heart failure and is associated with a significant increase in hospitalizations and death. Primary results of the Sertraline Against Depression and Heart Disease in Chronic Heart Failure (SADHART-CHF) trial revealed that sertraline and placebo had comparable effects on depression and cardiovascular outcomes. In this study, we explored whether remission from depression was associated with better survival and aimed to characterize participants who remitted during the trial. Based on depression response during the 12-week treatment phase, SADHART-CHF participants were divided into 2 groups: (1) remission, defined as participants whose last measured Hamilton Depression Rating Scale (HDRS) score was <8, and (2) nonremission, defined as participants whose last measured HDRS score was ≥8. Patients who dropped out before having any repeat HDRS were not included. Baseline characteristics and survival differences up to 5 years were evaluated between the remission and nonremission groups. Of the 469 SADHART-CHF participants, 208 (44.3%) achieved remission, 194 (41.4%) remained depressed, and 67 (14.3%) dropped out or died without any repeat HDRS assessment. Patients in the remission group had significantly fewer cardiovascular events than those in the nonremission group (1.34 ± 1.86 vs 1.93 ± 2.71, adjusted p = 0.01). Men patients were more likely to remit than women patients (56.5 vs 44.8%, p = 0.02). The remission group had milder depressive symptoms at baseline compared to the nonremission group (HDRS 17.0 ± 5.4 vs 19.6 ± 5.5, Beck Depression Inventory scale 17.9 ± 6.5 vs 20.3 ± 7.2, p <0.001 for the 2 comparisons). In conclusion, this study indicates that remission from depression may improve the cardiovascular outcome of patients with heart failure.

Safety and efficacy of sertraline for depression in patients with CHF (SADHART-CHF): a randomized, double-blind, placebo-controlled trial of sertraline for major depression with congestive heart failure.

BACKGROUND Sertraline, a selective serotonin-reuptake inhibitor, has demonstrated substantial mood improvement in patients with post myocardial infarction or with unstable angina. The impact of sertraline on the prognosis and depression of patients with chronic heart failure (HF) and comorbid major depressive disorder (MDD) is unknown. METHOD This is a prospective, randomized, double-blind, placebo-controlled study designed to assess the safety and efficacy of sertraline in the treatment of MDD in patients with HF. The study is designed also to examine the effects of treating depression on cardiac events and morbidity/mortality in patients with HF. Approximately 500 men and women who are >or=45 years of age with current MDD and chronic systolic HF, characterized by left ventricular ejection fraction <or=45% and New York Heart Association class >or=II, comprise the study population. Eligible participants are randomized to either sertraline or placebo for a 12-week acute treatment phase. All patients, regardless of acute treatment phase completion, are followed routinely until the last subject completes 6-month follow-up. Quality of life and certain physiologic parameters, as well as pro-inflammatory and HF biomarkers, that may reflect the impact of sertraline in this particular population are measured at baseline and at the end of the acute treatment phase. CONCLUSION Because of the high prevalence of depression and its significant adverse impact on prognosis of patients with ischemic heart disease (IHD) and HF, the Safety and Efficacy of Sertraline for Depression in Patients with Chronic Heart Failure (SADHART-CHF) trial aims to assess the effects of sertraline on response of depression as well as on the cardiac prognosis of patients with HF.