Treatment Approaches to Congestion Relief in Acute Decompensated HF: Insights After DOSE-AHF and CARRESS-HF.

OPINION STATEMENT: Most patients admitted to the hospital with ADHF do not achieve adequate relief of signs and symptoms of congestion. Patients with inadequate decongestion are known to be at higher risk of readmission for heart failure and mortality, although it is uncertain whether this is a cause or simply a marker of increased risk. Nonetheless, adequate decongestion is critical for improving quality of life. Based on the DOSE-AHF and CARRESS-HF studies, a high-dose diuretic regimen consisting of 2.5 times the daily dose of loop diuretic in furosemide equivalents, administered in twice-daily bolus doses, is reasonable to achieve a goal of 3-5 liters of urine output per day. Transient increases in creatinine in the first 4-5 days of diuresis should not be a limiting factor, but a prolonged progressive increase in creatinine signals a high-risk patient. Current goals for decongestion should be resolution of orthopnea, jugular venous pressure of < 8 cm of water, and trace to no peripheral edema. The hope is that better measures of assessing complete decongestion will reduce the progression to heart failure and mortality. While the best noninvasive method to assess speed of congestion has not been determined, it is clear that hemoconcentration (an increase in hematocrit) reflects a decrease in plasma volume and decongestion. In-line monitoring of hemoconcentration may improve the results of ultrafiltration therapy by preventing too large and/or too rapid a fall in intravascular volume and consequent triggering of neurohormonal activation. Several additional strategies such as serelaxin, high-dose mineralocorticoid receptor antagonists, and new forms and combinations of natriuretic peptides have shown promising results in the relief of congestion in patients with ADHF.

Giving voice to patients' and family caregivers' needs in chronic heart failure: implications for palliative care programs.

BACKGROUND: The American College of Cardiology Foundation/American Heart Association (ACC/AHA) Guidelines for the Management of Heart Failure recommend palliative care in the context of Stage D HF or at the end of life. Previous studies related to heart failure (HF) palliative care provide useful information about patients' experiences, but they do not provide concrete guidance for what palliative care needs are most important and how a palliative care program should be structured. OBJECTIVES: Describe HF patients' and their family caregivers' major concerns and needs. Explore whether, how, and when palliative care would be useful to them. DESIGN AND PARTICIPANTS: Qualitative study using in-depth interviews of 33 adult outpatients with symptomatic HF identified using purposive sampling and 20 of their family caregivers. APPROACH: Interviews were transcribed verbatim and analyzed using the constant comparative method. KEY RESULTS: Overall, patients and caregivers desired early support adjusting to the limitations and future course of illness, relief of a number of diverse symptoms, and the involvement of family caregivers using a team approach. A diverse group of participants desired these elements of palliative care early in illness, concurrent with their disease-specific care, coordinated by a provider who understood their heart condition and knew them well. Some diverging needs and preferences were found based on health status and age. CONCLUSIONS: HF patients and their family caregivers supported early integration of palliative care services, particularly psychosocial support and symptom control, using a collaborative team approach. Future research should test the feasibility and effectiveness of integrating such a program into routine HF care.

Carvedilol for the treatment of benign prostatic hypertrophy in patients with heart failure?

Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only ß-adrenergic blocker approved for HF that also has additional α1-adrenergic blockade. As α1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol was replaced with bisoprolol resulting in acute urinary retention. When carvediolol was reinstituted, the patient's symptoms of BPH resolved. Benign prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after reinstituting the carvediolol, the patient remains free of his BPH symptoms. This case suggests that carvedilol may be considered for the management of HF with systolic dysfunction in patients with concomitant BPH thus eliminating the need for an α1-adrenergic blockers.

Outpatient palliative care for chronic heart failure: a case series.

BACKGROUND/OBJECTIVES: Although the palliative care needs of outpatients with chronic heart failure (HF) are numerous, there is limited published experience in providing outpatient HF palliative care. This article describes the patients seen and the issues addressed in an outpatient palliative care program for patients with HF. METHODS: Case series involving a retrospective medical record review using descriptive quantitative and qualitative analysis. RESULTS: Over a 3 ½ year time period, 50 patients were seen, resulting in 228 total visits. Fifty percent of patients were seen only once. Fifty-eight percent of patients had New York Heart Association (NYHA) Class III-IV HF. Within a year of the initial palliative care visit, 14% of patients died. Depression, anxiety, pain, fatigue, breathlessness, and sleep disturbance were common symptoms addressed during visits. Advance care planning topics were discussed with 48% of patients; hospice and resuscitation status were each discussed with 16% of patients. Fears or concerns about the future arose in 34% of patients. Care coordination was commonly addressed with patients' other health care providers (58%). The most common referrals were to social work (26%) and rehabilitation/physical therapy (20%). CONCLUSIONS: Several findings reflect how outpatient HF palliative care differs from that of inpatient hospital-based palliative care. Many of the issues addressed, including care coordination, advance care planning, and psychosocial issues, imply that palliative HF care is complementary to standard HF care at all stages of the disease process and that future programs should consider dedicating a nurse and/or social worker. Research is needed to test how such a care model affects patient-centered outcomes, utilization, and cost.

Post-pericardial injury syndrome after continuous-flow ventricular assistance.

We present a patient with post-pericardial injury syndrome (PPIS) that occurred after implantation of a continuous-flow left ventricular assistance device. Evidence supporting the diagnosis includes radiographic, electrocardiographic, and serologic markers. Recognition of this syndrome is important in this patient population to appropriately treat the patient as well as prevent unnecessary testing and prolonged hospitalization.

Myocardial protection in sepsis.

Sepsis with myocardial dysfunction is seen commonly. Beta-blockers have been used successfully to treat chronic heart failure based on the premise that chronically elevated adrenergic drive is detrimental to the myocardium. However, recent reports on the acute use of beta-blockers in situations with potential hemodynamic compromise have shown the risks associated with this approach. In critical situations, the main effect of adrenergic activation is to support cardiovascular function. Caution should be exercised in designing studies to assess beta-blockers in septic patients.

Left ventricular assist device as bridge to transplantation does not adversely affect one-year heart transplantation survival.

OBJECTIVE: Left ventricular assist devices are increasingly used as a bridge to transplantation. It remains unclear whether the use of pretransplant left ventricular assist devices adversely affects short-term survival after cardiac transplantation. METHODS: A retrospective review of 317 consecutive patients undergoing cardiac transplantation at an academic center between 1986 and 2006 was undertaken. Left ventricular assist devices were used pretransplant in 23 of these 317 patients, and 294 patients did not require left ventricular assist device support. Patients with a left ventricular assist device were supported with a Heartmate VE or Heartmate XVE (Thoratec Corp, Pleasanton, Calif). Kaplan-Meier survival estimates were compared between the left ventricular assist device group and the non-left ventricular assist device group using the log-rank test. In addition, occurrence of death was analyzed between the 2 groups with a chi-square analysis. The results are expressed as 1-year survival with 95% confidence intervals in parentheses. RESULTS: The 1-year survival for all 317 patients was 0.86 (0.82-0.90). The patient survival for the group without a left ventricular assist device before cardiac transplant was 0.87 (0.83-0.90), and the survival for the group with a left ventricular assist device as bridge to transplantation was 0.83 (0.67-0.98; P = .77). For the deaths that occurred in all 317 patients, 19% of the patients without left ventricular assist devices died within 30 days of transplant, whereas 80% of the patients with left ventricular assist devices died within 30 days of transplant (P < .01). CONCLUSION: When used as a bridge to transplantation, left ventricular assist devices do not compromise 1-year survival after cardiac transplantation. Of the patients who die after transplantation, patients bridged with left ventricular assist devices are at higher risk for death within 30 days of transplant. These data suggest that left ventricular assist devices as a bridge to transplantation should be considered for appropriately selected patients awaiting cardiac transplantation.

Assist devices fail to reverse patterns of fetal gene expression despite beta-blockers.

BACKGROUND: Heart failure is associated with reversal to a fetal gene expression pattern of contractile and metabolic genes. Substantial recovery of ventricular function with assist devices is rare. Our goal was to evaluate the effects of assist devices on fetal gene expression and hypoxia inducible factor-1 alpha (HIF-1 alpha), a transcriptional factor in hypoxic signaling. METHODS: Human heart tissue was obtained from the left ventricular apex at the time of assist device implantation and again from the left ventricular free wall during cardiac transplantation. Non-failing tissue was obtained from unused hearts from human donors. Gene expression was measured with the Affymetrix 133 plus 2 Array. HIF-1 alpha was measured by Western blotting with commercially available antibodies. RESULTS: Heart failure was associated with a decrease in alpha-myosin heavy chain and sarcoplasmic reticulum-Ca(2+) adenosine triphosphatase messenger RNA expression along with an increase in skeletal tropomyosin. This pattern persisted after assist device therapy. Heart failure was also associated with abnormalities in regulatory metabolic genes including glucose transporter 1 (GLUT1). These patterns also persisted after assist device therapy despite a reduction in atrial natriuretic peptide expression and normalization of HIF-1 alpha. CONCLUSIONS: Failure of assist devices to produce sustained recovery of myocardial contractile function may be due in part to persistent fetal transcriptional patterns of contractile and metabolic genes.

Quality of life and prognosis in heart failure: results of the Beta-Blocker Evaluation of Survival Trial (BEST).

BACKGROUND: Quality of life (QOL) was a prespecified secondary end point in the Beta-Blocker Evaluation of Survival Trial. The Beta-Blocker Evaluation of Survival Trial used four QOL questionnaires to evaluate patient health status over time in response to treatment with placebo or bucindolol. The goal of the current study was to determine the relationship between the different questionnaires, assess the effect of treatment on health status, and evaluate the association between changes in health status and prognosis. METHODS: The San Diego Heart Failure (SDHF), Minnesota Living with Heart Failure (MLHF), Patient Global Assessment (PGA), and Physician Global Assessment (PhyGA) questionnaires were measured at baseline through 48 months of follow-up. For SDHF and MLHF, changes from baseline were calculated. Spearman correlation was used to assess relationships, and Cox Proportional Hazards regression was used to predict time to all-cause mortality, and mortality or heart failure hospitalization, bivariately and multivariately. To determine whether beta-blocker treatment affected QOL, the Wilcoxon rank-sum test was used to compare treatment groups. RESULTS: At 12 months, SDHF (r = +0.56, P = .0001), PGA (r = +0.36, P = .0001), and PhyGA (r = +0.37, P = .0001) correlated with MLHF. SDHF (P = .0001), MLHF (P = .0004), PGA (P = .0001), and PhyGA (P = .0001) were all strongly associated with all-cause mortality, with low values of each associated with a lower hazard. For the combined end point of all-cause mortality or heart failure hospitalization, change in QOL with each instrument had a P value of .0001. At 12 months, bucindolol-treated patients had improvement in both PhyGA and PGA compared with placebo; neither the SDHF nor the MLWF instrument distinguished between the two treatment groups unless a worst-rank assignment was used for patients who died. CONCLUSION: The four instruments correlate with each other and predict clinical end points, suggesting that each is a valid measure of health status. According to the PGA and the PhyGA, bucindolol improves QOL.

Low-dose oral enoximone enhances the ability to wean patients with ultra-advanced heart failure from intravenous inotropic support: results of the oral enoximone in intravenous inotrope-dependent subjects trial.

BACKGROUND: We determined whether low-dose oral enoximone could wean patients with ultra-advanced heart failure (UA-HF) from intravenous (i.v.) inotropic support. Chronic parenteral inotropic therapy in UA-HF is costly and requires an indwelling catheter. An effective and safe oral inotrope would have value. METHODS: In this placebo-controlled study, 201 subjects with UA-HF requiring i.v. inotropic therapy were randomized to enoximone or placebo. Subjects receiving intermittent i.v. inotropes were administered study medication of 25 or 50 mg 3 times a day (tid). Subjects receiving continuous i.v. inotropes were administered 50 or 75 mg tid for 1 week, which was reduced to 25 or 50 mg tid. The ability of subjects to remain alive and free of inotropic therapy was assessed for up to 182 days. RESULTS: Thirty days after weaning, 51 (51%) subjects on placebo and 62 (61.4%) subjects in the enoximone group were alive and free of i.v. inotropic therapy (unadjusted primary end point P = 0.14, adjusted for etiology P = .17). At 60 days, the wean rate was 30% in the placebo group and 46.5% in the enoximone group (unadjusted P = .016) Kaplan-Meier curves demonstrated a trend toward a decrease in the time to death or reinitiation of i.v. inotropic therapy over the 182-day study period (hazard ratio 0.76 [95% CI 0.55-1.04]) and a reduction at 60 days (0.62 [95% CI 0.43-0.89], P = .009) and 90 days (0.69 [95% CI 0.49-0.97], P = .031) after weaning in the enoximone group. CONCLUSIONS: Although there was no benefit over placebo in weaning patients from i.v. inotropes from 0 to 30 days, the EMOTE data suggest that low-dose oral enoximone can be used to wean a modest percentage of subjects from i.v. inotropic support for up to 90 days after initiation of therapy.

Rationale and design of the enoximone clinical trials program.

BACKGROUND: Chronic heart failure is a disease syndrome characterized in its advanced stages by a poor quality of life, frequent hospitalizations, and a high risk of mortality. In advanced and ultra-advanced chronic heart failure, many treatment options, such as cardiac transplantation and mechanical devices, are severely limited by availability and cost. Short-term Phase II clinical trials suggest that low-dose oral inotropic therapy with enoximone may improve hemodynamics and exercise capacity, without adversely affecting mortality, in selected subjects with advanced chronic heart failure. Based on these data, the ability of enoximone to deliver safe and efficacious palliative treatment of advanced/ultra-advanced chronic heart failure is being evaluated in Phase III clinical trials. METHODS AND RESULTS: The Enoximone Clinical Trials Program is a series of 4 clinical trials designed to evaluate the safety and efficacy of oral enoximone in advanced chronic heart failure. ESSENTIAL I and II (The Studies of Oral Enoximone Therapy in Advanced Heart Failure) will investigate the effects of oral enoximone on all-cause mortality and cardiovascular hospitalization, submaximal exercise capacity, and quality of life in subjects with New York Heart Association Class III/IV chronic heart failure. EMOTE (Oral Enoximone in Intravenous Inotrope-Dependent Subjects) will evaluate the potential of oral enoximone to wean subjects with ultra-advanced chronic heart failure from chronic intravenous inotropic therapy to which they have been shown to be dependent. EMPOWER (Enoximone Plus Extended-Release Metoprolol Succinate in Subjects with Advanced Chronic Heart Failure) will explore the potential of enoximone to increase the tolerability of continuous release metoprolol in subjects shown previously to be hemodynamically intolerant to beta-blocker treatment. CONCLUSION: These studies are Phase III, multicenter, randomized, double-blinded, placebo-controlled trials designed to test the general hypothesis that chronic oral administration of low doses of enoximone can produce beneficial effects in subjects with advanced or ultra-advanced chronic heart failure.

Peak oxygen consumption and outcome in heart failure patients chronically treated with beta-blockers.

BACKGROUND: Peak oxygen consumption (VO(2)) is an important criterion for listing patients for cardiac transplantation. Beta-blockers improve survival without affecting peak VO(2). We questioned the value of peak VO(2) in predicting outcome in patients treated with beta-blockers. METHODS AND RESULTS: We reviewed the records of 127 patients who had peak VO(2) measured at baseline and were subsequently treated with beta-blockers for at least 3 months. We divided the patients into 2 groups with peak oxygen consumption >14 (VO(2) hi) and < or =14 ml.kg.min (VO(2) lo). VO(2) hi had 109 patients and VO(2) lo had 18 patients. The combined end-point of death or cardiac transplantation was compared between groups. Mean peak VO(2) and left ventricular ejection fraction were lower in VO(2) lo versus VO(2) hi: 12.4+/-1.4 ml.kg.min versus 19.1+/-3.9 ml.kg.min and 17+/-8% versus 21+/-9%, respectively. At 30 months, the percentage of patients who did not reach the combined end-point was 94% in VO(2) lo versus 79% in VO(2) hi (P=.47). In multivariate analysis, only changes in heart rate and LVEF from baseline to follow-up were predictive of survival. CONCLUSIONS: Current peak VO(2) cutoff does not predict survival without transplantation of patients who tolerate chronic treatment with beta-blockers.