Faculty Bibliography

Experimental studies suggest that angiotensin-converting enzyme (ACE) inhibitors with high tissue affinity confer a greater degree of vascular renin-angiotensin system suppression than those with low tissue affinity despite similar suppression of the circulating renin-angiotensin system. To test this hypothesis in a clinical setting, we randomized subjects with chronic heart failure to receive the low tissue affinity ACE inhibitor enalapril or the high tissue affinity ACE inhibitor trandolapril, and assessed the degree of circulating and vascular renin-angiotensin system suppression. Vascular renin-angiotensin system suppression was determined by measuring the pressor response to intravenous injections of angiotensin I. Circulating renin-angiotensin system suppression was determined by measuring plasma angiotensin II. Vascular and circulating renin-angiotensin system suppression, endothelial function (flow-mediated vasodilation), and maximal exercise capacity (peak oxygen uptake) were assessed after a 4-week run-in period on open-label enalapril 40 mg/day and after 8 weeks of randomized double-blind treatment with enalapril 40 mg/day or trandolapril 4 mg/day. Twenty-six men and 4 women (mean age 52 +/- 11 years; mean left ventricular ejection fraction 25 +/- 9%; New York Heart Association class II [n = 16] and III [n = 14]) were studied. After a 2-month randomized treatment period, vascular renin-angiotensin system suppression, circulating renin-angiotensin system suppression, endothelial function, and exercise capacity did not differ between subjects treated with enalapril and those treated with trandolapril. Despite substantial differences in the tissue affinity of enalapril and trandolapril, the degree of vascular renin-angiotensin system suppression achieved with these agents did not differ in subjects with chronic heart failure during long-term therapy

BACKGROUND: Outpatient positive inotropic support combined with implantation of an automatic implantable cardioverter defibrillator (AICD) may be used as a successful bridge to cardiac transplantation in patients with end-stage heart failure. A detailed comparative cost analysis of this outpatient strategy versus in-hospital care has not been previously reported. METHODS AND RESULTS: Twenty-one United Network for Organ Sharing 1B patients awaiting cardiac transplantation received continuous outpatient inotropic therapy for a total of 3070 patient-days. Daily costs for outpatient and in-hospital treatment were calculated. Nonparametric decision analysis was used to determine the strategy with greatest cost savings (immediate hospital discharge after AICD implantation versus in-hospital care). A threshold analysis was performed to test the robustness of the decision analysis model. The outpatient strategy realized an average savings of $71,300 to $120,500 per patient. Decision analysis showed that no fixed period of in-hospital monitoring was more cost-saving than immediate hospital discharge after AICD implantation. Threshold analysis revealed that AICD costs would need to exceed $82,000 (currently $62,000) or that the difference between the outpatient and the in-hospital costs would need to be < or = $475 per day for any other intermediate strategy to be considered cost-saving. CONCLUSION: Outpatient inotropic therapy combined with AICD implantation in selected patients awaiting cardiac transplantation is an effective cost-minimizing strategy

Anemia is highly prevalent in patients with chronic heart failure (HF) and is associated with poor clinical outcomes. Multiple mechanisms contribute to anemia in chronic HF, and subnormal compensatory rise in endogenous erythropoietin levels in response to anemia is one contributory factor. Randomized trials with recombinant human erythropoietin therapy in anemic patients with chronic kidney disease and concomitant heart disease have demonstrated a reduction in left ventricular hypertrophy but variable effects on clinical outcome. Preliminary clinical trials in anemic patients with chronic HF demonstrate that erythropoietin therapy is well tolerated and associated with short-term clinical improvement. The optimum target hemoglobin, erythropoietic agent, and dosing regimen, and the role of iron supplementation in patients with chronic HF, are not known. Additional studies are needed to determine the safety and efficacy of long-term erythropoietic therapy in chronic HF patients

Clinically unrecognized intravascular volume overload may contribute to worsening symptoms and disease progression in patients with chronic heart failure (CHF). The present study was undertaken to prospectively compare measured blood volume status (determined by radiolabeled albumin technique) with clinical and hemodynamic characteristics and patient outcomes in 43 nonedematous ambulatory patients with CHF. Blood volume analysis demonstrated that 2 subjects (5%) were hypovolemic (mean deviation from normal values -20 +/- 6%), 13 subjects (30%) were normovolemic (mean deviation from normal values -1 +/- 1%), and 28 subjects (65%) were hypervolemic (mean deviation from normal values +30 +/- 3%). Physical findings of congestion were infrequent and not associated with blood volume status. Increased blood volume was associated with increased pulmonary capillary wedge pressure (p = 0.01) and greatly increased risk of death or urgent cardiac transplantation during a median follow-up of 719 days (1-year event rate 39% vs 0%, p <0.01 by log-rank test). Systolic blood pressure was significantly lower in hypervolemic patients than in those with normovolemia or hypovolemia (107 +/- 2 vs 119 +/- 2 mm Hg, p = 0.008), and hypotension was independently associated with increased risk of hypervolemia in multivariate analysis (odds ratio 2.64 for a 10-mm Hg decrease in systolic blood pressure, 95% confidence interval 1.13 to 6.19, p = 0.025). These findings demonstrate that clinically unrecognized hypervolemia is frequently present in nonedematous patients with CHF and is associated with increased cardiac filling pressures and worse patient outcomes

OBJECTIVES: We conducted a prospective multicenter registry in a large metropolitan area to define the clinical characteristics, hospital course, treatment, and factors precipitating decompensation in patients hospitalized for heart failure with a normal ejection fraction (HFNEF). BACKGROUND: The clinical profile of patients hospitalized for HFNEF has been characterized by retrospective analyses of hospital records and state data banks, with few prospective single-center studies. METHODS: Patients hospitalized for heart failure (HF) at 24 medical centers in the New York metropolitan area and found to have a left ventricular (LV) ejection fraction of > or 50% within seven days of admission were included in this registry. Patient demographics, signs and symptoms of HF, coexisting and exacerbating cardiovascular and medical conditions, treatment, laboratory tests, procedures, and hospital outcomes data were collected. Analysis by gender and race was prespecified. RESULTS: Of 619 patients, 73% were women, who were on average four years older than men (72.8 +/- 14.1 years vs. 68.6 +/- 13.8 years, p < 0.001). Black non-Hispanic patients comprised 30% of the study population. They were eight years younger than other patients (66.0 +/- 14.2 years vs. 74 +/- 13.5 years p < 0.001). Co-morbid conditions and their prevalence were: hypertension, 78%; increased LV mass, 82%; diabetes, 46%; and obesity, 46%. Before clinical decompensation that precipitated hospitalization, 86% of patients had chronic symptoms compatible with New York Heart Association functional classes II to IV. Factors precipitating clinical decompensation were identified in 53% of patients. In-hospital mortality was 4.2%. CONCLUSIONS: Patients hospitalized for HFNEF are most often chronically incapacitated elderly women with a history of hypertension and increased LV mass. Reasons for clinical decompensation are identified in only one-half of patients

BACKGROUND: The clinical use of positive inotropic therapy at home in patients awaiting cardiac transplantation has not been reported since United Network for Organ Sharing (UNOS) regulations were changed to allow home infusions in Status 1B patients. METHODS: We observed 21 consecutive patients with UNOS 1B status during positive inotropic therapy at home. We used hemodynamic monitoring at the initiation of therapy to optimize dosing. We selected for home therapy patients with stable clinical status and improved functional capacity during inotropic treatment. Implantable cardioverter defibrillators were placed in all but 1 patient before discharge. RESULTS: Initial positive inotropic therapy included dobutamine in 12 patients (mean dose, 4.5 mcg/kg/min; range, 2.5-7.5 mcg/kg/min), milrinone in 8 patients (mean dose, 0.44 mcg/kg/min; range, 0.375-0.55 mcg/kg/min), and dopamine at a dose of 3 mcg/kg/min in 1 patient. Patients had improved functional capacity (New York Heart Association Class 3.7 +/- 0.1 to 2.4 +/- 0.2, p < 0.01), improved renal function (serum creatinine, 1.5 +/- 0.1 to 1.3 +/- 0.1, p < 0.01), improved resting hemodynamics, and decreased number of hospitalizations during positive inotropic infusion therapy when compared with pre-treatment baseline. Implantable cardioverter defibrillator discharges were infrequent (0.19 per 100 patient days of follow-up). Actuarial survival to transplantation at 6 and 12 months was 84%. CONCLUSIONS: Continuous positive inotropic therapy at home was safe and was associated with decreased health care costs in selected patients awaiting cardiac transplantation

The current investigation was undertaken to determine the effects of active versus passive recovery on work performance during repeated bouts of supramaximal exercise. Six healthy sedentary subjects and 9 moderately trained healthy hockey players performed serial 30-second Wingate anaerobic power tests (WAnT) on a bicycle ergometer interposed with 4 minutes of active recovery at a work rate corresponding to 28 % of VO(2)max or passive recovery at rest. Peak power, mean power, total work achieved, and fatigue index were calculated for the serial WAnT. Capillary blood lactate was determined at 5-minute intervals after the last WAnT during 30 minutes of active or passive recovery. Mean power was significantly greater during active recovery in sedentary subjects when compared with passive recovery (388 +/- 42 vs. 303 +/- 37 W, p < 0.05), but did not differ according to recovery mode in moderately trained hockey players (589 +/- 22 W active vs. 563 +/- 26 W passive, p = 0.14). Total work achieved significantly increased during active when compared with passive recovery in sedentary subjects (34 890 +/- 3768 vs. 27 260 +/- 3364 J, p < 0.02) and moderately trained hockey players (86 763 +/- 9151 vs. 75 357 +/- 8281 J, p < 0.05). Capillary blood lactate levels did not differ during active when compared with passive recovery in sedentary subjects but were significantly lower during active when compared with passive recovery in moderately trained hockey players. These data demonstrate that active recovery at a work rate corresponding to 28 % of VO(2)max increases total work achieved during repeated WAnT when compared with passive recovery in sedentary subjects and moderately trained hockey players

Anemia occurs frequently in chronic heart failure (CHF) patients and is associated with increased morbidity and mortality risk. Clinical trials with recombinant human erythropoietin in patients with chronic kidney disease and concomitant structural heart disease have demonstrated beneficial effects on ventricular remodeling but variable effects on clinical outcome. Preliminary clinical trials in patients with CHF demonstrate that erythropoietin therapy is well-tolerated and associated with short-term clinical benefits. The optimum target hemoglobin, erythropoietin dosing regimen, and role of iron supplementation in patients with CHF are not known. Darbepoetin alfa is a glycosylated derivative of erythropoietin with a prolonged half-life that may allow less frequent dosing in CHF populations. Additional studies are needed to determine the safety and efficacy of long-term erythropoietic therapy in CHF patients

BACKGROUND: Cachexia is a common problem in chronic heart failure (CHF) that may be partly mediated by activation of the sympathetic nervous system. The effects of beta-adrenergic receptor blocker (BB) therapy on body weight in cachectic and noncachectic subjects with CHF has not been previously reported. METHODS AND RESULTS: Body weight and plasma norepinephrine, leptin, and insulin levels were measured in 27 subjects with CHF before and after 6 months of beta-adrenergic receptor blockade with carvedilol or long-acting metoprolol. Before BB therapy, baseline weight, plasma leptin, and plasma insulin levels did not differ between cachectic and noncachectic subjects. Baseline plasma norepinephrine levels were increased in cachectic subjects when compared with noncachectic subjects (930+/-248 pg/mL versus 503+/-109 pg/mL, P=.063). After 6 months of BB therapy, subjects with baseline cachexia demonstrated significantly greater weight gain (+5.2+/-9.6 versus +0.8+/-5.0 kg, P=.027), greater increase in plasma leptin levels (+3.7+/-3.9 versus +1.2+/-4.3 ng/mL, P=.030), and greater decrease in plasma norepinephrine levels (-374+/-261 versus -41+/-122 pg/mL, P=.012) when compared with noncachectic subjects. CONCLUSIONS: Six months of BB therapy with carvedilol or long-acting metoprolol is associated with differential effects on body weight and hormonal levels in cachectic and noncachectic subjects with CHF. Further work is needed to determine the role the sympathetic nervous system in the pathogenesis of cachexia in patients with CHF