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Biomedical subjects

M A Hamilton

Publications and source records attributed to M A Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Metastatic paraganglioma causing spinal cord compression.

We describe two cases of metastatic retroperitoneal paraganglioma associated with extradural spinal cord compression. Both occurred in young men; one being metastatic at presentation, the other becoming metastatic 19 years after attempted surgical resection. Despite a long, relatively stable natural history after diagnosis (10 and 19 years, respectively) both had an acceleration of their disease once extradural disease was detected. These cases illustrate the potentially aggressive nature of this disease, the need for long-term follow-up and the effectiveness of a variety of therapies for palliation, and also raise the possibility of "prophylactic" treatment to prevent spinal cord compression.

Adolescent↗
PubMed1999

A controlled trial of exercise rehabilitation after heart transplantation.

BACKGROUND: In patients who have received a cardiac transplant, the denervated donor heart responds abnormally to exercise and exercise tolerance is reduced. The role of physical exercise in the treatment of patients who have undergone cardiac transplantation has not been determined. We assessed the effects of training on the capacity for exercise early after cardiac transplantation. METHODS: Twenty-seven patients who were discharged within two weeks after receiving a heart transplant were randomly assigned to participate in a six-month structured cardiac-rehabilitation program (exercise group, 14 patients) or to undergo unstructured therapy at home (control group, 13 patients). Each patient in the exercise group underwent an individualized program of muscular-strength and aerobic training under the guidance of a physical therapist, whereas control patients received no formal exercise training. Cardiopulmonary stress testing was performed at base line (within one month after heart transplantation) and six months later. RESULTS: As compared with the control group, the exercise group had significantly greater increases in peak oxygen consumption (mean increase, 4.4 ml per kilogram of body weight per minute [49 percent] vs. 1.9 ml per kilogram per minute [18 percent]; P=0.01) and workload (mean increase, 35 W [59 percent] vs. 12 W [18 percent]; P=0.01) and a greater reduction in the ventilatory equivalent for carbon dioxide (mean decrease, 13 [20 percent] vs. 6 [11 percent]; P=0.02). The mean dose of prednisone, the number of patients taking antihypertensive medications, the average number of episodes of rejection and of infection during the study period, and weight gain did not differ significantly between the groups. CONCLUSIONS: When initiated early after cardiac transplantation, exercise training increases the capacity for physical work.

Blood Pressure↗
PubMed1999

The 6-min walk and peak oxygen consumption in advanced heart failure: aerobic capacity and survival.

BACKGROUND: This study sought to determine to what extent the 6-min walk (6MW) distance in advanced heart failure predicts aerobic capacity and provides comparable information regarding survival. Peak oxygen uptake ( VO(2)) and the 6MW both describe function and predict outcome over a wide range of heart failure, but their determinants and implications may differ within a narrower clinical spectrum. This study compared 6MW with aerobic capacity both at peak exercise and during low-level cycling. METHODS AND RESULTS: Both the 6MW and symptom-limited cycle ergometry were performed by 307 patients of whom 264 patients additionally performed 6 min of 20-W cycling to estimate aerobic capacity during sustained low-level activity. In the first 198 patients, multivariate analysis of survival was performed with the 6MW and peak VO (2). Patients achieved the 6MW of 393 +/- 104 m and peak VO (2) of 14 +/- 5 mL/kg per minute. Although low peak VO (2) was more likely with the shorter 6MW, the relation was weak within peak VO (2) range of 10 to 20 mL/kg per minute (n = 213, 69% of patients, r = 0.28). During 20-W exercise, VO (2) was 9.2 +/- 2.0 mL/kg per minute, with respiratory exchange ratio poorly correlated with the 6MW. In contrast to peak VO (2), the 6MW in meters did not predict survival. Division into short, medium, and long walks, however, supplemented simple clinical description. CONCLUSIONS: Although helpful in broader populations for identification of patients with obvious clinical compromise, the 6MW distance is not a surrogate for peak VO (2) in assessing aerobic capacity or prognosis for individuals with advanced heart failure.

Exercise Test↗
PubMed1999

Relationship between right and left-sided filling pressures in 1000 patients with advanced heart failure.

BACKGROUND: Elevated left ventricular filling pressures present a major target of therapy for symptomatic heart failure but are difficult to assess directly. Because the relationship of left- and right-sided pressures remains ill defined in chronic heart failure, this study compared 3 right-sided measurements (right atrial [RA] pressure, pulmonary artery systolic [PAS] pressure, and severity of tricuspid regurgitation [TR]) to the pulmonary capillary wedge (PCW) pressure. METHODS: Hemodynamic measurements and echocardiography were available from 1000 patients undergoing transplant evaluation. Right atrial and PAS pressure, and TR severity were compared to PCW pressure. For 754 patients undergoing repeat measurements, changes in RA and PAS pressures were compared to PCW changes. RESULTS: Right atrial pressure correlated with PCW pressure (r = 0.64), regardless of etiology or TR severity. Right atrial pressure changes correlated with PCW changes (r = 0.62). Discordance was defined as either RA > or = 10 mm Hg despite PCW < 22 mm Hg (6%) or RA < 10 mm Hg despite PCW > or = 22 mm Hg (15%). For detection of PCW > or = 22 mm Hg, positive predictive values were 88% for RA > or = 10 mm Hg, 95% for PAS > or = 60 mm Hg, and 79% for > or = moderate TR. Pulmonary artery systolic pressure correlated very closely with PCW (r = 0.79), and could be estimated as 2 x PCW. Reduction in PAS pressure during therapy was strongly determined by PCW pressure reduction (r = 0.67). CONCLUSIONS: Accurate estimation of RA pressure can potentially guide therapy of left ventricular filling pressures in approximately 80% of chronic heart failure patients without obvious non-cardiac disease. In this population, elevated PAS pressures are largely determined by elevated left-sided filling pressures.

Diuretics↗
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

Color measurement as a means of quantifying surface biofouling.

Laboratory reactors fitted with removable ceramic porcelain growth surfaces were inoculated with a consortium of biofilm forming environmental isolates. A Minolta colorimeter CR-200 (Minolta Camera Co., Ltd, Ramsey, NJ) was used in conjunction with a specially designed adapter to evaluate the reflective color of the porcelain disks as biofilm accumulated on them. Areal viable cell counts were monitored over a period of eleven days in two separate experiments and direct color measurements of the untreated, microbially fouled test surfaces were collected. This colorimetric assay was both non-destructive and immediate. A strong linear relationship between log cell density and log color change was observed. The Pearson product moment correlation coefficient for all 45 observations combined was r = 0.95. Separate regression lines for each experiment were not significantly different (P = 0.19). When adjusted for time, the (partial) correlation coefficient between log cell density and log color change was r = 0.87, which suggests that the relationship between the two measures can not be explained by their mutual dependence on time. Reflective color measurement provided a rapid, non-destructive and quantitative measure of biofllm accumulation.

Biofilms↗
PubMed1998

The University of California at Los Angeles experience in heart transplantation.

In the last decade, the number of patients undergoing heart transplant has steadily increased as a result of expanding indications for this procedure. The limitation on the number of transplants performed has been the number of donor organs available. At UCLA, 900 heart transplant procedures have been performed from 1984-1998. Since 1991, the percent of patients free from rejection and infection in the first year after transplant was 70% and 73%, respectively. Actuarial one-, 3-, and 5-year survival rates are 84%, 76%, and 72%, respectively. Survival of patients aged 60 years and over (n = 105) was comparable to that of patients under age 60. We have been pursuing corticosteroid-free immunosuppression, which has led to a decrease in infection complications. Our work with pravastatin early after transplantation has led to a decrease in clinically severe rejection episodes, which has translated into improved survival. Pravastatin also appears to decrease the development of transplant coronary artery disease and appears to have an adjunct immunosuppressive effect in our heart transplant patients on CsA-based immunosuppression. We have also demonstrated benefit of cardiac rehabilitation early after transplant which should therefore be considered as standard postoperative care. Finally, we have participated and led the multicenter mycophenolate study in demonstrating this drug's effectiveness in improved outcomes in primary heart transplant recipients. Future studies include the use of Rapamycin and interleukin-2 receptor blockers which have been demonstrated in kidney transplantation to significantly reduce rejection. Our program is committed to seek better ways to improve outcome and the quality of life of our heart transplant patients.

Adult↗
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

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↗
PubMed1996

Improving survival for patients with atrial fibrillation and advanced heart failure.

OBJECTIVES: We attempted to determine whether changes in heart failure therapy since 1989 have altered the prognostic significance of atrial fibrillation. BACKGROUND: Atrial fibrillation occurs in 15% to 30% of patients with heart failure. Despite the recognized potential for adverse effects, the impact of atrial fibrillation on prognosis is controversial. METHODS: Two-year survival for 750 consecutive patients discharged from a single hospital after evaluation for heart transplantation from 1985 to 1989 (Group I, n = 359) and from 1990 to April 1993 (Group II, n = 391) was analyzed in relation to atrial fibrillation. In Group I, class I antiarrhythmic drugs and hydralazine vasodilator therapy were routinely allowed. In Group II, amiodarone and angiotensin-converting enzyme inhibitors were first-line antiarrhythmic and vasodilating drugs. RESULTS: A history of atrial fibrillation was present in 20% of patients in Group I and 24% of those in Group II. Patients with atrial fibrillation in the two groups had similar clinical and hemodynamic profiles. Among patients with atrial fibrillation, those in Group II had a markedly better 2-year survival (0.66 vs. 0.39, p = 0.001) and sudden death-free survival (0.84 vs. 0.70, p = 0.01) than those in Group I. In each time period, survival was worse for patients with than without atrial fibrillation in Group I (0.39 vs. 0.55, p = 0.002) but not in Group II (0.66 vs. 0.75, p = 0.09). CONCLUSIONS: The prognosis of patients with advanced heart failure and atrial fibrillation is improving. These findings support the practice of avoiding class I antiarrhythmic drugs in this group and may reflect recent beneficial changes in heart failure therapy.

Adult↗
PubMed1996

Pretransplant panel reactive-antibody screens. Are they truly a marker for poor outcome after cardiac transplantation?

BACKGROUND: The effect of pretransplant sensitization on outcome after cardiac transplant has been controversial. Sensitization, defined as a positive panel-reactive antibody (PRA) screen in patients awaiting transplant, represents circulating antibodies to a random panel of donor lymphocytes (usually T lymphocytes). The significance of pretransplant circulating antibodies to B lymphocytes has not been reported, and many centers disregard its use. METHODS AND RESULTS: We retrospectively reviewed the pretransplant PRA screens for 311 patients who underwent cardiac transplant at our institution. The PRA screen was performed by use of the lymphocytotoxic technique treated with dithiothreitol to remove IgM autoantibodies. Patients with PRA > or = 11% against T or B lymphocytes had significantly lower 3-year survival (T lymphocytes, 39%; B lymphocytes, 56%) than those patients with PRA = 0% and PRA = 1% to 10% (T lymphocytes, 76% and 78%; B lymphocytes, 78% and 74%, respectively) (P < .001). For this high-risk group, the rejection episode tended to occur earlier than in those patients with PRA = 0% and PRA = 1% to 10% (T lymphocytes, 2.3 versus 4.0 and 3.8 months; B lymphocytes, 2.1 versus 4.1 and 3.4 months, respectively), and there were more clinically severe rejections that required OKT3 therapy. CONCLUSIONS: Cardiac transplant patients with pretransplant T- and/or B-lymphocyte PRA > or = 11% despite negative donor-specific crossmatch at the time of transplant appear to have earlier and more severe rejection with significantly lower survival after transplant surgery. Modification of immunosuppression in these high-risk patients may be warranted.

Adult↗
PubMed1996

Thyroid hormone abnormalities in heart failure: possibilities for therapy.

Though thyroid hormone abnormalities have been identified in many cardiac conditions, the role of thyroid hormones in congestive heart failure has not been well defined. In a population of patients with advanced heart failure, a reduction in triiodothyronine (T3) with an increase in reverse T3 was identified in many patients, with an abnormally low ratio of T3/reverse T3 being the strongest predictor of mortality. Normalization of thyroid indices appeared to be necessary for prolonged survival to occur. To address the concern of T3 administration possibility exacerbating a hypermetabolic state, basal metabolic rate was measured in a group of advanced heart failure patients and was found to be generally within the normal range. A preliminary safety study of short-term intravenous T3 administration (bolus +/- 6 h infusion, total dose 0.15-2.7 micrograms/kg) was then performed in 23 patients under hemodynamic and electrocardiographic monitoring. There were neither adverse events nor substantial hemodynamic changes, but some patients had an increase in cardiac output, consistent with a peripheral vasodilatory effect. With this foundation, further investigation into the possible role of T3 and its analogs in congestive heart failure therapy may be pursued.

Heart Failure↗
PubMed1996

Dynamics of muscle sympathetic nerve activity in advanced heart failure patients.

Muscle sympathetic nerve activity (MSNA) is increased in patients with heart failure compared with healthy subjects. We applied spectral and correlation techniques to determine if qualitative as well as quantitative differences in MSNA differentiate heart failure patients from healthy subjects. We recorded MSNA, heart rate, and respiration in 11 heart failure patients and 10 healthy humans. Our results are as follows. 1) Statistically significant low-frequency modulation of MSNA at 0.029 +/- 0.002 Hz (mean +/- SE; range 0.026-0.038 Hz) was found in 10 of 11 heart failure patients but in only 2 of 10 healthy controls (differences between groups, P < 0.01; chi 2 test). 2) Heart rate and respiration also demonstrated significant low-frequency modulation in a similar range. 3) Spectral and correlation techniques revealed that low-frequency modulation of MSNA was highly correlated with low-frequency modulation of respiration in heart failure patients, but not in healthy subjects. In contrast, low-frequency modulation of MSNA did not correlate well with low-frequency modulation of heart rate. In summary, low-frequency modulation of respiration is coupled to low-frequency modulation of MSNA in heart failure patients, but not in normal subjects. We speculate that this low-frequency modulation of respiration may represent subclinical Cheyne-Stokes breathing, which has marked qualitative effects on MSNA in patients with heart failure.

Adolescent↗
PubMed1996

Quantitative analysis of a presence/absence microbiological assay: the hard surface carrier test of disinfectant efficacy.

The Hard Surface Carrier Test (HSCT) is a presence/absence assay for determining the extent to which chemical disinfectants kill bacteria. The disinfectants are marketed for cleaning surfaces in hospitals, restaurants, the home, etc. In the HSCT, a presence response (or equivalently, a positive carrier) is recorded if one or more bacteria survive among M bacteria attached to a glass carrier and exposed to the chemical disinfectant; otherwise, the response is absence. The presence or absence response is observed for each of many (usually 60) glass carriers and the disinfectant is considered effective if few (e.g., < or = 5%) of the carriers are positive. It would be more satisfactory to microbiologists if effectiveness were based on the fraction of bacteria that survive exposure; denote the expected survival fraction by phi. An equivalent parameter commonly used in antimicrobial research is the log-reduction, denoted by psi, where psi = -log10(phi). Although the number M of bacteria on each exposed carrier is not known, this paper shows it is possible to estimate psi. The suggested estimator is based on the assumption that M follows a gamma distribution. The gamma parameters are estimated using counts of bacteria on the HSCT nonexposed (control) carriers. This paper provides a formula for the standard error of the estimate, a computer simulation technique for calculating the lower confidence limit, and a computer simulation study of these statistical methods.

Bacteria↗
PubMed1995

Improving survival for patients with advanced heart failure: a study of 737 consecutive patients.

OBJECTIVES: This study sought to determine whether survival and risk of sudden death have improved for patients with advanced heart failure referred for consideration for heart transplantation as advances in medical therapy were systematically implemented over an 8-year period. BACKGROUND: Recent survival trials in patients with mild to moderate heart failure and patients after a myocardial infarction have shown that angiotensin-converting enzyme inhibitors are beneficial, type I antiarrhythmic drugs can be detrimental, and amiodarone may be beneficial in some groups. The impact of advances in therapy may be enhanced or blunted when applied to severe heart failure. METHODS: One-year mortality and sudden death were determined in relation to time, baseline variables and therapeutics for 737 consecutive patients referred for heart transplantation and discharged home on medical therapy from 1986 to 1988, 1989 to 1990 and 1991 to 1993. Medical care was directed by a single team of physicians with policies established by consensus. From 1986 to 1990, the hydralazine/isosorbide dinitrate combination or angiotensin-converting enzyme inhibitors were the initial vasodilators, and class I antiarrhythmic drugs were allowed. After 1990, captopril was the initial vasodilator, given to 86% of patients compared with 46% of patients before 1989. After mid-1989, class I agents were routinely withdrawn, and amiodarone was used for frequent ventricular ectopic beats or atrial fibrillation (53% of patients after 1990 vs. 10% before 1989). RESULTS: The total 1-year mortality rate decreased from 33% before 1989 to 16% after 1990 (p = 0.0001), and sudden death decreased from 20% to 8% (p = 0.0006). Adjusted for clinical and hemodynamic variables in multivariate proportional hazards models, total mortality and sudden death were lower after 1990. CONCLUSIONS: The large reduction in mortality, particularly in sudden death, from advanced heart failure since 1990 may reflect an enhanced impact of therapeutic advances shown in large randomized trials when they are incorporated into a comprehensive approach in this population. This improved survival supports the growing practice of maintaining potential heart transplant candidates on optimal medical therapy until clinical decompensation mandates transplantation.

Adult↗