Spirituality in Patients With Heart Failure.

With advances in heart failure (HF) treatment, patients are living longer, putting further emphasis on quality of life (QOL) and the role of palliative care principles in their care. Spirituality is a core domain of palliative care, best defined as a dynamic, multidimensional aspect of oneself for which 1 dimension is that of finding meaning and purpose. There are substantial data describing the role of spirituality in patients with cancer but a relative paucity of studies in HF. In this review article, we explore the current knowledge of spirituality in patients with HF; describe associations among spirituality, QOL, and HF outcomes; and propose clinical applications and future directions regarding spiritual care in this population. Studies suggest that spirituality serves as a potential target for palliative care interventions to improve QOL, caregiver support, and patient outcomes including rehospitalization and mortality. We suggest the development of a spirituality-screening tool, similar to the Patient Health Questionnaire-2 used to screen for depression, to identify patients with HF at risk for spiritual distress. Novel tools are soon to be validated by members of our group. Given spirituality in HF remains less well studied compared with other patient populations, further controlled trials and uniform measures of spirituality are needed to understand its impact better.

Long-Chain Omega-3 Fatty Acid Supplements in Depressed Heart Failure Patients: Results of the OCEAN Trial.

OBJECTIVES: The goal of this study was to test the effects of long-chain omega-3 fatty acid supplementation on omega-3 levels, depressive symptoms, and other psychosocial factors, as well as other chronic heart failure (CHF)-related functional measures. BACKGROUND: Patients with CHF and depression had low blood omega-3 concentrations that were associated with an elevated risk of mortality. METHODS: This study was a randomized, double-blind, placebo-controlled pilot clinical trial using a 400/200 eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) fish oil at 2 g and an almost pure EPA at 2 g, compared with a matched placebo, daily for 12 weeks for patients with CHF and major depressive disorder. Statistical analyses included the intention-to-treat population and "completers" (defined as participants consuming ≥70% of the capsules and completing the final endpoint evaluation between 10 and 14 weeks). RESULTS: A total of 108 patients with CHF and major depressive disorder and a score ≥18 on the Hamilton Depression Scale who were randomized at 1:1:1 to the 3 interventions at 3 enrolling centers from June 12, 2014, to May 19, 2016; 80 (74.1%) qualified as completers. Intention-to-treat analyses revealed that the levels of all omega-3 variables were significantly elevated in the omega-3 groups, whereas the placebo group showed little change; there were no between-group differences with overall depression measurements. Per-protocol exploratory analyses showed that scores on the social functioning measurement of the 36-item Short Form Health Survey improved notably in the 400/200 EPA/DHA (p = 0.040) and EPA (p = 0.10) groups compared with the placebo group. Spearman correlation analysis indicated that increased omega-3 indices were associated with improved cognitive depressive symptoms. CONCLUSIONS: Omega-3 supplementation resulted in significant increases in omega-3 levels in red blood cell counts, corresponding to a particular compound of omega-3. Changes in cognitive depressive symptoms and social function were in favor of the omega-3 supplementation. Further studies with larger sample sizes are necessary to confirm the benefits of omega-3 supplementation on modifying psychosocial factors for patients with CHF. (Omega-3 Supplementation for Co-Morbid Depression and Heart Failure Treatment [OCEAN]; NCT02057406).

Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury.

BACKGROUND: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, N-acetyl-ß-d-glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation-Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. METHODS: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C. RESULTS: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300-815 mg), which induced a urine output of 8425 mL (interquartile range, 6341-10 528 mL) over the 72-hour intervention period. Levels of N-acetyl-ß-d-glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both P>0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (-8.7 ng/mg; interquartile range, -169 to 35 ng/mg; P<0.001). WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: neutrophil gelatinase-associated lipocalin (P=0.21), N-acetyl-ß-d-glucosaminidase (P=0.46), or kidney injury molecule 1 (P=0.22). Increases in neutrophil gelatinase-associated lipocalin, N-acetyl-ß-d-glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69-0.91; P=0.001). CONCLUSIONS: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

The palliative care in heart failure trial: rationale and design.

BACKGROUND: The progressive nature of heart failure (HF) coupled with high mortality and poor quality of life mandates greater attention to palliative care as a routine component of advanced HF management. Limited evidence exists from randomized, controlled trials supporting the use of interdisciplinary palliative care in HF. METHODS: PAL-HF is a prospective, controlled, unblinded, single-center study of an interdisciplinary palliative care intervention in 200 patients with advanced HF estimated to have a high likelihood of mortality or rehospitalization in the ensuing 6 months. The 6-month PAL-HF intervention focuses on physical and psychosocial symptom relief, attention to spiritual concerns, and advanced care planning. The primary end point is health-related quality of life measured by the Kansas City Cardiomyopathy Questionnaire and the Functional Assessment of Chronic Illness Therapy with Palliative Care Subscale score at 6 months. Secondary end points include changes in anxiety/depression, spiritual well-being, caregiver satisfaction, cost and resource utilization, and a composite of death, HF hospitalization, and quality of life. CONCLUSIONS: PAL-HF is a randomized, controlled clinical trial that will help evaluate the efficacy and cost effectiveness of palliative care in advanced HF using a patient-centered outcome as well as clinical and economic end points.

Diuretic strategies in patients with acute decompensated heart failure.

BACKGROUND: Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use. METHODS: In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours. RESULTS: In the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 µmol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 µmol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 µmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 µmol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function. CONCLUSIONS: Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.).

The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

The following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation" chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with non-ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75-100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75-100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75-100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75-100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A).

Financial implications of a model heart failure disease management program for providers, hospital, healthcare systems, and payer perspectives.

Although heart failure disease management (HFDM) programs improve patient outcomes, the implementation of these programs has been limited because of financial barriers. We undertook the present study to understand the economic incentives and disincentives for adoption of disease management strategies from the perspectives of a physician (group), a hospital, an integrated health system, and a third-party payer. Using the combined results of a group of randomized controlled trials and a set of financial assumptions from a single academic medical center, a financial model was developed to compute the expected costs before and after the implementation of a HFDM program by 3 provider types (physicians, hospitals, and health systems), as well as the costs incurred from a payer perspective. The base-case model showed that implementation of HFDM results in a net financial loss to all potential providers of HFDM. Implementation of HFDM as described in our base-case analysis would create a net loss of US dollars 179,549 in the first year for a physician practice, US dollars 464,132 for an integrated health system, and US dollars 652,643 in the first year for a hospital. Third-party payers would be able to save US dollars 713,661 annually for the care of 350 patients with heart failure in a HFDM program. In conclusion, although HFDM programs may provide patients with improved clinical outcomes and decreased hospitalizations that save third-party payers money, limited financial incentives are currently in place for healthcare providers and hospitals to initiate these programs.

Effects of amino acid supplementation on left ventricular remodeling in patients with chronic heart failure with decreased systolic function and diabetes mellitus: rationale and design of a magnetic resonance imaging study.

A considerable number of patients with reduced systolic function caused by primary or ischemic cardiomyopathy have viable and noncontractile myocardium. This may be related to numerous and perhaps overlapping factors, such as chronic ischemia (stunning/hibernation), neurohormonal abnormalities, oxidative stress, metabolic imbalances, and/or nutritional depletion. Changes in myocardial substrate utilization have adverse effects on the metabolism of the viable but noncontractile myocardium. Shifting the energy substrate preference away from fatty acids and replenishing the tricarboxylic acid cycle components via amino acids rather than via fatty acids would increase adenosine triphosphate production, with positive effects on cellular metabolism. A proposed study design is described and will be piloted through the Effects of Diatrofen on Myocardial Function in Patients with Chronic Heart Failure trial (D-CHF), an evaluation of an oral amino acid supplementation treatment in outpatients with heart failure.