Biomedical subjects

G C Fonarow

Publications and source records attributed to G C Fonarow.

At least 37 records · Page 2Linked to original sources

PubMed2000

The hemodynamic effects of isotonic exercise using hand-held weights in patients with heart failure.

BACKGROUND: Controversy surrounds the use of resistance exercise in patients with heart failure because of concerns that increases in rate-pressure product and systemic vascular resistance might lead to increased afterload and decreased cardiac output. METHODS: Following pharmacologic left ventricular unloading therapy using a pulmonary artery catheter, 34 patients with advanced heart failure performed isotonic weightlifting exercise at 50%, 65%, and 80% of the calculated one repetition maximum. Measurements were made of hemodynamics, ST segment, rate-pressure product, serum norepinephrine, rating of perceived exertion, and dysrhythmias following each exercise set. RESULTS: Repeated analysis of variance showed significant increases in systolic blood pressure (p = 0.0005), diastolic blood pressure (p = 0.01), rate-pressure product (p = 0.005); serum norepinephrine (p = 0.004), and rating of perceived exertion (p = 0.0005). However, systemic vascular resistance and cardiac output did not change significantly (p>0.05). Pulmonary capillary wedge pressures, the incidence of dysrhythmias, and ST segments did not significantly differ from baseline. No patients experienced angina or dyspnea during the study. CONCLUSIONS: Isotonic exercise using hand-held weights was well tolerated hemodynamically and clinically, and no patients experienced adverse outcomes during exercise.

Adrenergic alpha-Agonists↗

PubMed2000

Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure.

BACKGROUND: This study determined whether evidence of congestion after 4 to 6 weeks of heart failure management predicted outcome for patients hospitalized with chronic New York Heart Association class IV symptoms. Class IV symptoms predict high mortality rates, but outcome is not known for patients who improve to establish freedom from congestion. Revised estimates at 1 month could facilitate decisions regarding transplantation and other high-risk interventions. METHODS: At 4 to 6 weeks after hospital discharge, 146 patients were evaluated for congestion by 5 criteria (orthopnea, jugular venous distention, edema, weight gain, and new increase in baseline diuretics). Heart failure management included inpatient therapy tailored to relieve congestion, followed by adjustments to maintain fluid balance during the next 4 weeks. RESULTS: Freedom from congestion was demonstrated at 4 to 6 weeks in 80 (54%) patients, who had 87% subsequent 2-year survival compared with 67% in 40 patients with 1 or 2 criteria of congestion and 41% in 26 patients with 3 to 5 criteria. The Cox proportional hazards model identified left ventricular dimension, pulmonary wedge pressure on therapy, and freedom from congestion as independent predictors of survival. Persistence of orthopnea itself predicted 38% 2-year survival (without urgent transplantation) versus 77% in 113 without orthopnea. Serum sodium was lower and blood urea nitrogen and heart rate higher when orthopnea persisted. CONCLUSIONS: The ability to maintain freedom from congestion identifies a population with good survival despite previous class IV symptoms. At 4 to 6 weeks, patients with persistent congestion may be considered for high-risk intervention.

Disease Progression↗

PubMed2000

How old is too old for heart transplantation?

Heart transplantation is considered the treatment of choice for patients with advanced heart failure. Given the excellent results with transplantation, there has been growing pressure to liberalize eligibility criteria, especially with regard to age. Registry data and early reports have indicated that there may be increased posttransplantation mortality in older patients. A number of single-center reports have shown that survival of older patients may be similar to that of younger patients. The limited supply of donor hearts makes it imperative that careful consideration be given to transplantation results in older recipients and to the overall impact that expanding eligibility criteria for transplantation will have. The limited supply of donor hearts has also led to increased interest in the use of hearts from older donors. This review presents a current perspective on outcomes after heart transplantation in older recipients, use of older donor hearts, and the matching of donor and recipient risk.

Age Factors↗

PubMed2000

Impaired endothelium-mediated vasodilation is not the principal cause of vasoconstriction in heart failure.

The extent to which abnormal endothelium-dependent vasodilator mechanisms contribute to abnormal resting vasoconstriction and blunted reflex vasodilation seen in heart failure is unknown. The purpose of this study was to test the hypothesis that the resting and reflex abnormalities in vascular tone that characterize heart failure are mediated by abnormal endothelium-mediated mechanisms. Thirteen advanced heart-failure patients (New York Heart Association III-IV) and 13 age-matched normal controls were studied. Saline, acetylcholine (20 microg/min), or L-arginine (10 mg/min) was infused into the brachial artery, and forearm blood flow was measured by venous plethysmography at rest and during mental stress. At rest, acetylcholine decreased forearm vascular resistance in normal subjects, but this response was blunted in heart failure. During mental stress with intra-arterial acetylcholine or L-arginine, the decrease in forearm vascular resistance was not greater than during saline control in heart failure [saline control vs. acetylcholine (7 +/- 3 vs. 6 +/- 3, P = NS) or vs. L-arginine (9 +/- 2 units, P = NS)]. The increase in forearm blood flow was not greater than during saline control in heart failure [saline control vs. acetylcholine (1. 2 +/- 0.3 vs. 1.3 +/- 0.3, P = NS), or vs. L-arginine (1.2 +/- 0.2 ml x min(-1) x 100 ml(-1), P = NS)]. Furthermore, during mental stress with nitroprusside, the decrease in forearm vascular resistance was not greater than during saline control [saline control vs. nitroprusside (7 +/- 3 vs. 5 +/- 4 ml x min(-1) x 100 g(-1), P = NS)], and the increase in forearm blood flow was not greater than during saline control [saline control vs. nitroprusside (1.2 +/- 0.3 vs. 1.3 +/- 0.5 ml x min(-1) x 100 g(-1), P = NS)]. Because the endothelial-independent agent nitroprusside was unable to restore resting and reflex vasodilation to normal in heart failure, we conclude that impaired endothelium-mediated vasodilation with acetylholine-nitric oxide cannot be the principal cause of the attenuated resting- or reflex-mediated vasodilation in heart failure.

Acetylcholine↗

PubMed2000

Differences in mechanisms of SR dysfunction in ischemic vs. idiopathic dilated cardiomyopathy.

We examined 1) contractile properties and the intracellular Ca(2+) concentration ([Ca(2+)](i)) transient in cardiac myocytes and 2) sarcoplasmic reticulum (SR) Ca(2+) uptake and release function in myocardium from patients with end-stage heart failure caused by ischemic (ICM) vs. idiopathic dilated cardiomyopathy (DCM). The amplitude of cell motion was decreased 43 +/- 6% in ICM and 68 +/- 7% in DCM compared with that in normal organ donors (DN). Time to peak of shortening was increased 43 +/- 15% in DCM, but not in ICM. Prolongation of the relaxation time was more predominant in ICM. In DCM the systolic [Ca(2+)](i) was decreased 27 +/- 9% and diastolic [Ca(2+)](i) was increased 36 +/- 11%. In ICM the diastolic [Ca(2+)](i) was increased 59 +/- 12% but the systolic [Ca(2+)](i) was unchanged. A significant decrease of the ATP-dependent SR Ca(2+) uptake rate associated with the reduction of the SR Ca(2+)-ATPase protein level was found in ICM. In contrast, the significant decrease in SR Ca(2+) release rate was distinct in DCM. The large amount of Ca(2+) retained in the SR associated with a significant decrease in the maximum reaction velocity and increase in the Michaelis-Menten constant in the caffeine concentration-response curve suggests a fundamental abnormality in the SR Ca(2+) release channel gating property in DCM. We conclude that potentially important differences exist in the intracellular Ca(2+) homeostasis and excitation-contraction coupling in ICM vs. DCM. The SR Ca(2+) release dysfunction may play an important pathogenetic role in the abnormal Ca(2+) homeostasis in DCM, and the SR Ca(2+) uptake dysfunction may be responsible for the contractile dysfunction in ICM.

Adult↗

PubMed2000

Interscan variation in coronary artery calcium quantification in a large asymptomatic patient population.

OBJECTIVE: We evaluated interscan variation in coronary artery calcium scores in a large screening population as determined by electron beam CT. MATERIALS AND METHODS: One thousand patients (average age, 53 years; age range, 18-85 years) who were asymptomatic for coronary artery disease underwent two consecutive scans of the heart on an electron beam CT scanner. Scans were performed with ECG gating, breath-hold, 3-mm collimation, and 100-msec exposure. Two contiguous pixels with density values greater than 130 H were used as the minimum criterion for a calcific lesion. The calcium score was determined on a vessel-by-vessel basis for both scans of each patient. Interscan variation in calcium and vessels involved with calcification was evaluated on the basis of age, sex, and average calcium score. RESULTS: The percentage of difference between calcium scores in scans was 28.4% and 43.0% for women and men, respectively. For the individual epicardial arteries (left main, left anterior descending, circumflex, and right coronary), the percentage of difference for calcium scores was 20.2-24.2% for women and 30.5-44.9% for men. A difference between the two scans in at least one vessel of the total coronary arteries identified with calcium was noted in 31% of patients. CONCLUSION: Interscan variability in calcium scores may be important in the determination of risk stratification. Subjects with a nonzero calcium score may benefit from undergoing two scans at the time of initial imaging.

Adolescent↗

PubMed2000

Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3.

Treatment of human artery wall cells with apolipoprotein A-I (apoA-I), but not apoA-II, with an apoA-I peptide mimetic, or with high density lipoprotein (HDL), or paraoxonase, rendered the cells unable to oxidize low density lipoprotein (LDL). Human aortic wall cells were found to contain 12-lipoxygenase (12-LO) protein. Transfection of the cells with antisense to 12-LO (but not sense) eliminated the 12-LO protein and prevented LDL-induced monocyte chemotactic activity. Addition of 13(S)-hydroperoxyoctadecadienoic acid [13(S)-HPODE] and 15(S)-hydroperoxyeicosatetraenoic acid [15(S)-HPETE] dramatically enhanced the nonenzymatic oxidation of both 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and cholesteryl linoleate. On a molar basis 13(S)-HPODE and 15(S)-HPETE were approximately two orders of magnitude greater in potency than hydrogen peroxide in causing the formation of biologically active oxidized phospholipids (m/z 594, 610, and 828) from PAPC. Purified paraoxonase inhibited the biologic activity of these oxidized phospholipids. HDL from 10 of 10 normolipidemic patients with coronary artery disease, who were neither diabetic nor receiving hypolipidemic medications, failed to inhibit LDL oxidation by artery wall cells and failed to inhibit the biologic activity of oxidized PAPC, whereas HDL from 10 of 10 age- and sex-matched control subjects did. We conclude that a) mildly oxidized LDL is formed in three steps, one of which involves 12-LO and each of which can be inhibited by normal HDL, and b) HDL from at least some coronary artery disease patients with normal blood lipid levels is defective both in its ability to prevent LDL oxidation by artery wall cells and in its ability to inhibit the biologic activity of oxidized PAPC.

Aorta↗

PubMed2000

Sixteen-year experience with 1,000 heart transplants at UCLA.

1. The consecutive pre- and post-1994 eras have demonstrated improved survival for all age groups. This is linked to improved preservation methods, surgical technique and immunosuppression agents. 2. The use of marginal donor hearts for Status I and alternate elderly patients has followed the model of matching donor and recipient risk without affecting patient outcome and minimized the use of implantable assist devices. 3. A donor history of systemic gram-negative infection, hypertension, or traumatic intracranial bleeds was an important marker for risk. Younger age and shorter ischemia time could compensate for other hazards. 4. Heart transplantation in carefully selected elderly recipients yielded clinical results similar to those of younger patients with less rejection. 5. An adult alternate recipient list proved useful to prevent diversion of standard donors away from younger recipients. 6. Retransplantation for TCAD is acceptable but much less satisfactory for acute graft failure. 7. Trends show an increase in the use of implantable devices; refinement in technology for mechanical assist and replacement is forthcoming.

Adolescent↗

PubMed2000

Heart failure: recent advances in prevention and treatment.

The most important advance in heart failure during the past decade has been the recognition that medications inhibiting neurohormonal activation relieve symptoms, reduce hospitalizations, and prolong survival in patients with heart failure from left ventricular systolic dysfunction. Recent trials with angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, aldosterone antagonists, and beta blockers have provided valuable information regarding the uses, dosing, and extent of therapeutic benefits of neurohormonal inhibition.

Adrenergic beta-Antagonists↗

PubMed1998

Skin test anergy in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

Skin tests to recall antigens are performed as indicators of clinical outcomes in heart failure (HF). A diminution in the response to recall antigens, termed "anergy," is regarded as an indication of poorer clinical prognosis, although little analysis has been done to support that conclusion. Patients with advanced HF (n=222) in New York Heart Association classes III and IV, with complete datasets for all of the variables, were studied. The sample was 77% men, mean age 52+/-12 years, and left ventricular ejection fraction, 21+/-7. Patients with ischemic (n=113) and idiopathic (n=109) disease were analyzed separately. The relation of anergy to 1-year mortality and selected hemodynamic factors, blood chemistries, medications, and nutritional status markers was analyzed. Anergy was present in 45% (47% idiopathic and 42% ischemic) of patients. Anergy was related to 1-year mortality (univariate p=0.038) in patients with ischemic, but not idiopathic, HF. Anergic patients with ischemic HF had shorter survival times (p=0.035). Lower cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were predictors (p <0.001) of mortality in idiopathic HF. In ischemic HF, lower cholesterol, LDL, and triglycerides were univariate predictors (p <0.001, p=0.004, and p=0.005, respectively) of skin test anergy, but not mortality. Thus, there were distinct differences in clinical correlates of skin test anergy in patients with idiopathic and ischemic HF. This study supports evaluation of anergy to skin tests as one of the markers of mortality in patients with ischemic HF.

Adult↗

PubMed1998

Safety and hemodynamic effects of intravenous triiodothyronine in advanced congestive heart failure.

Most patients with advanced congestive heart failure have altered thyroid hormone metabolism. A low triiodothyronine level is associated with impaired hemodynamics and is an independent predictor of poor survival. This study sought to evaluate safety and hemodynamic effects of short-term intravenous administration of triiodothyronine in patients with advanced heart failure. An intravenous bolus dose of triiodothyronine, with or without a 6- to 12-hour infusion (cumulative dose 0. 1 5 to 2.7 microg/kg), was administered to 23 patients with advanced heart failure (mean left ventricular ejection fraction 0.22 +/- 0.01). Cardiac rhythm and hemodynamic status were monitored for 12 hours, and basal metabolic rate by indirect calorimetry, echocardiographic parameters of systolic function and valvular regurgitation, thyroid hormone, and catecholamine levels were measured at baseline and at 4 to 6 hours. Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect. Acute intravenous administration of triiodothyronine is well tolerated in patients with advanced heart failure, establishing the basis for further investigation into the safety and potential hemodynamic benefits of longer infusions, combined infusion with inotropic agents, oral triiodothyronine replacement therapy, and new triiodothyronine analogs.

Female↗

PubMed1998

Paraoxonase and coronary heart disease.

Paraoxonase (PON1) hydrolyses organophosphate insecticides and nerve gases and is responsible for determining the selective toxicity of these compounds in mammals. Human PON1 has two genetic polymorphisms giving rise to amino-acid substitutions at positions 55 and 192. The 192 polymorphism is the major determinant of the PON1 activity polymorphism towards organophosphates. However, the 55 polymorphism also modulates activity. Ex vivo, the PON1 polymorphisms are important in determining the capacity of HDL to protect LDL against oxidative modification in vitro and this may explain the relationship between the PON1 alleles and coronary heart disease in case-control studies. In recent case-control studies serum PON1 concentration and activity were also found to be decreased in coronary heart disease (CHD) independent of the PON1 polymorphism, and in diabetes serum PON1 specific activity decrease is also independent of the PON1 genetic polymorphism. HDL from transgenic mice lacking PON1 fails to protect LDL against oxidative modification. Thus PON1 may be a determinant of resistance to the development of atherosclerosis by protecting lipoproteins against oxidative modification, perhaps by hydrolysing phospholipid and cholesteryl-ester hydroperoxides.

Animals↗

PubMed1998

High density associated enzymes: their role in vascular biology.

Enzymes associated with circulating HDL include lecithin: cholesterol acyl transferase, phospholipid transfer protein, cholesterol ester transfer protein, paraoxonase 1 and platelet activating factor acetylhydrolase. Together with lipoprotein lipase and hepatic lipase these enzymes produce important lipoprotein remodeling and modulate their structure and function and therefore their role in artery wall metabolism.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1997

Impact of acute mental stress on sympathetic nerve activity and regional blood flow in advanced heart failure: implications for 'triggering' adverse cardiac events.

BACKGROUND: Evidence is accumulating that specific "triggers," such as intense psychological stress, may precipitate myocardial infarction and sudden death. Patients with advanced heart failure have increased resting sympathoexcitation, which has been directly related to increased mortality. The impact of triggers on sympathetic nerve activity and regional blood flow in heart failure has not been examined in patients with heart failure. METHODS AND RESULTS: Twenty-seven patients with heart failure (NYHA functional class III or IV) and 26 age-matched normal control subjects were studied. Muscle sympathetic nerve activity, heart rate, mean arterial pressure, forearm blood flow, and renal blood flow were measured during mental stress testing with mental arithmetic and Stroop color word test. Patients with heart failure had elevated levels of resting muscle sympathetic nerve activity and heart rate. Mental stress significantly increased muscle sympathetic nerve activity and heart rate in both patients with heart failure and control subjects, although the magnitude of increases tended to be blunted in patients with heart failure. Nevertheless, absolute levels of sympathetic activity in patients with heart failure remained significantly higher than levels in control subjects during mental stress. The decrease in renal blood flow in patients with heart failure was similar to that of control subjects, despite greater resting renal vasoconstriction. The increase in forearm blood flow during mental stress testing in patients with heart failure was blunted compared with that of control subjects. CONCLUSIONS: Patients with heart failure do not have augmented muscle sympathetic nerve activity responses to mental stress, despite elevated resting levels of sympathetic activity, but they do have markedly higher absolute levels of sympathetic nerve activity during mental stress as well as at rest.

Adult↗

PubMed1997

Sustained hemodynamic efficacy of therapy tailored to reduce filling pressures in survivors with advanced heart failure.

BACKGROUND: During therapy to relieve congestion in advanced heart failure, cardiac filling pressures can frequently be reduced to near-normal levels with improved cardiac output. It is not known whether the early hemodynamic improvement and drug response can be maintained long term. METHODS AND RESULTS: After referral for cardiac transplantation with initially severe hemodynamic decompensation, 25 patients survived without transplantation to undergo hemodynamic reassessment after 8+/-6 months of treatment tailored to early hemodynamic response. Initial changes included net diuresis, increased ACE inhibitor doses, and frequent addition of nitrates. After 8 months of therapy, early reductions were sustained for pulmonary wedge pressure (24+/-9 to 15+/-5 mm Hg early; 12+/-6 mm Hg late) and systemic vascular resistance (1651+/-369 to 1207+/-281 dynes x s(-1) x cm(-5) early; 1003+/-193 dynes x s(-1) x cm(-5) late). Acute response to doses persisted at reevaluation. Sustained reduction in filling pressures was accompanied by a progressive increase in stroke volume (42+/-10 to 56+/-13 mL early; 79+/-20 mL late), improved functional class, and freedom from resting symptoms. Study design did not control for amiodarone, which was initiated for arrhythmias in 12 patients and associated with greater improvement in cardiac index (1.8 to 3.2 L min(-1) x m(-2) late on amiodarone versus 2.0 to 2.6 L x min(-1) x m(-2), P<.05). CONCLUSIONS: During chronic therapy tailored to early hemodynamic response in advanced heart failure, acute vasodilator response persists, and near-normal filling pressures can be maintained in patients who survive without transplantation. Stroke volumes at low filling pressures increase further over time. Chronic hemodynamic improvement was accompanied by symptomatic improvement, but the contributions of the monitored hemodynamic approach, increased vasodilator doses, and comprehensive outpatient management have not yet been established.

Amiodarone↗

PubMed1997

Predictors of natural killer cell-mediated cytotoxicity deficiency in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

The effect of psychologic variables (situational emotional state and psychiatric diagnosis) and physiologic variables (plasma norepinephrine, decreased cardiac exercise capacity, and elevated pulmonary capillary wedge pressure) on natural killer cell activity was evaluated in 19 patients with advanced heart failure of ischemic or idiopathic origin. Only peak exercise capacity was independently predictive of natural killer cell deficiency.

Cardiomyopathy, Dilated↗

PubMed1997

Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio.

We have examined the effects of mildly oxidized LDL and atherosclerosis on the levels of two proteins associated with HDL; apolipoprotein J (apoJ), and paraoxonase (PON). On an atherogenic diet, PON activity decreased by 52%, and apoJ levels increased 2.8-fold in fatty streak susceptible mice, C57BL/6J (BL/6), but not in fatty streak resistant mice, C3H/HeJ (C3H). Plasma PON activity was also significantly decreased, and apoJ levels were markedly increased in apolipoprotein E knockout mice on the chow diet, resulting in a 9.2-fold increase in the apoJ/PON ratio as compared to controls. Furthermore, a dramatic increase in the apoJ/PON ratio (over 100-fold) was observed in LDL receptor knockout mice when they were fed a 0.15%-cholesterol-enriched diet. Injection of mildly oxidized LDL (but not native LDL) into BL/6 mice (but not in C3H mice) on a chow diet resulted in a 59% decrease in PON activity (P < 0.01) and a 3.6-fold increase in apoJ levels (P < 0.01). When an acute phase reaction was induced in rabbits, or the rabbits were placed on an atherogenic diet, hepatic mRNA for apoJ was increased by 2.7-fold and 2.8-fold, respectively. Treatment of HepG2 cells in culture with mildly oxidized LDL (but not native LDL) resulted in reduced mRNA levels for PON (3.0-fold decrease) and increased mRNA levels for apoJ (2.0-fold increase). In normolipidemic patients with angiographically documented coronary artery disease who did not have diabetes and were not on lipid-lowering medication (n = 14), the total cholesterol/HDL cholesterol ratio was 3.1+/-0.9 as compared to 2.9+/-0.4 in the controls (n = 19). This difference was not statistically significant. In contrast, the apoJ/PON ratio was 3.0+/-0.4 in the patients compared to 0.72+/-0.2 in the controls (P < 0.009). In a subset of these normolipidemic patients (n = 5), the PON activity was low (48+/-6.6 versus 98+/-17 U/ml for controls; P < 0.009), despite similar normal HDL levels, and the HDL from these patients failed to protect against LDL oxidation in co-cultures of human artery wall cells. We conclude that: (a) mildly oxidized LDL can induce an increased apoJ/PON ratio, and (b) the apoJ/PON ratio may prove to be a better predictor of atherosclerosis than the total cholesterol/HDL cholesterol ratio.

Animals↗

PubMed1997

Impact of a comprehensive heart failure management program on hospital readmission and functional status of patients with advanced heart failure.

OBJECTIVES: To assess the impact of a comprehensive heart failure management program, functional status, hospital readmission rate and estimated hospital costs were determined and compared for the 6 months before and the 6 months after referral. BACKGROUND: The course of advanced heart failure is characterized by progressive clinical deterioration reflected in frequent hospital admissions, which comprise the major financial cost. METHODS: Over a 3-year period, 214 patients were accepted for heart transplantation and discharged after evaluation, which included adjustments in medical therapy and intensive patient education. Patients were in New York Heart Association functional class III or IV (94 and 120 patients, respectively), with a mean left ventricular ejection fraction of 0.21, peak oxygen consumption of 11 ml/kg per min and a total of 429 hospital admissions in the previous 6 months (average 2.0 per patient). Changes in the medical regimen included a 98% increase in angiotensin-converting enzyme inhibitor dose and a flexible diuretic regimen after 4.2-liter net diuresis, with counseling also regarding diet and progressive exercise. RESULTS: During the 6 months after referral, there were only 63 hospital readmissions (85% reduction), with 0.29/patient (p < 0.0001). Functional status improved as assessed by functional class (p < 0.0001) and peak oxygen consumption (15.2 vs. 11.0 ml/kg per min, p < 0.001). The same results were seen after excluding the 35 patients without full 6-month follow-up (9 deaths, 14 urgent transplant procedures during hospital readmission, 12 elective transplant procedures from home); 34 hospital admissions occurred after referral, compared with 344 before referral. Even when adding in the initial hospital admission after referral for these 179 patients, there was a 35% decrease in total hospital admissions in the 6-month period. The estimated savings in hospital readmission costs after subtracting the initial hospital costs for management was $9,800 per patient. CONCLUSIONS: Comprehensive heart failure management led to improved functional status and an 85% decrease in the hospital admission rate for transplant candidates discharged after evaluation. The potential to reduce both symptoms and costs suggests that referral to a heart failure program may be appropriate not only for potential heart transplantation, but also for medical management of persistent functional class III and IV heart failure.

Comprehensive Health Care↗