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LDL receptor-null mice on a Western diet (WD) have inflammation in large arteries and endothelial dysfunction in small arteries, which are improved with the apolipoprotein A-I mimetic D-4F. The role of hyperlipidemia in causing inflammation of very small vessels such as brain arterioles has not previously been studied. A WD caused a marked increase in the percent of brain arterioles with associated macrophages (microglia) (P < 0.01), which was reduced by oral D-4F but not by scrambled D-4F (ScD-4F; P < 0.01). D-4F (but not ScD-4F) reduced the percent of brain arterioles associated with CCL3/macrophage inflammatory protein-1alpha (P < 0.01) and CCL2/monocyte chemoattractant protein-1 (P < 0.001). A WD increased (P < 0.001) brain arteriole wall thickness and smooth muscle alpha-actin, which was reduced by D-4F but not by ScD-4F (P < 0.0001). There was no difference in plasma lipid levels, blood pressure, or arteriole lumen diameter with D-4F treatment. Cognitive performance in the T-maze continuous alternation task and in the Morris Water Maze was impaired by a WD and was significantly improved with D-4F but not ScD-4F (P < 0.05). We conclude that a WD induces brain arteriole inflammation and cognitive impairment that is ameliorated by oral D-4F without altering plasma lipids, blood pressure, or arteriole lumen size.

Objectives: The study aimed to evaluate the role of obesity in the prognosis of patients with heart failure (HF)., Background: Previous reports link obesity to the development of HF. However, the impact of obesity in patients with established HF has not been studied., Methods: We analyzed 1,203 patients with advanced HF followed in a comprehensive HF management program. The patients were subclassified into categories of body mass index (BMI) defined as: underweight BMI <20.7 (n = 164), recommended BMI 20.7 to 27.7 (n = 692), overweight BMI 27.8 to 31 (n = 168) and obese BMI >31 (n = 179). This sample size allows the detection of small effects (0.02), with a power of 0.80 and an alpha level of 0.05 for comparing one-year survival between BMI groups., Results: The four BMI groups had similar profiles in terms of ejection fraction (mean 0.22), sodium, creatinine and smoking. The obese and overweight groups had significantly higher rates of hypertension and diabetes, as well as higher levels of cholesterol, triglycerides and low density lipoprotein cholesterol. The four BMI groups had similar survival rates. Ejection fraction, HF etiology and angiotensin-converting enzyme inhibitor use predicted survival on univariate analysis (p < 0.01), although BMI did not. On multivariate analysis, cardiopulmonary exercise tests, pulmonary capillary wedge pressure and serum sodium were strong predictors of survival (p < 0.05). Higher BMI was not a risk factor for increased mortality, but was associated with a trend toward improved survival., Conclusions: In a large cohort of patients with advanced HF of multiple etiologies, obesity is not associated with increased mortality and may confer a more favorable prognosis. Further studies need to delineate whether weight loss promotion in medically optimized patients with HF is a worthwhile therapeutic goal.

Despite scientific evidence that secondary prevention medical therapies reduce mortality in patients with established coronary artery disease, these therapies continue to be underutilized in patients receiving conventional care. To address this issue, a Cardiac Hospital Atherosclerosis Management Program (CHAMP) focused on initiation of aspirin, cholesterol-lowering medication (hydroxymethylglutaryl coenzyme A [HMG CoA] reductase inhibitor titrated to achieve low-density lipoprotein [LDL] cholesterol < or =100 mg/dl), beta blocker, and angiotensin-converting enzyme (ACE) inhibitor therapy in conjunction with diet and exercise counseling before hospital discharge in patients with established coronary artery disease. Treatment rates and clinical outcome were compared in patients discharged after myocardial infarction in the 2-year period before (1992 to 1993) and the 2-year period after (1994 to 1995) CHAMP was implemented. In the pre- and post-CHAMP patient groups, aspirin use at discharge improved from 68% to 92% (p <0.01), beta blocker use improved from 12% to 62% (p <0.01), ACE inhibitor use increased from 6% to 58% (p <0.01), and statin use increased from 6% to 86% (p <0.01). This increased use of treatment persisted during subsequent follow-up. There was also a significant increase in patients achieving a LDL cholesterol < or =100 mg/dl (6% vs 58%, p <0.001) and a reduction in recurrent myocardial infarction and 1-year mortality. Compared with conventional guidelines and care, CHAMP was associated with a significant increase in use of medications that have been previously demonstrated to reduce mortality; more patients achieved an LDL cholesterol < or =100 mg/dl, and there were improved clinical outcomes in patients after hospitalization for acute myocardial infarction.

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.

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.

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.

Objectives: This study determined the frequency of improvement in peak oxygen uptake and its role in reevaluation of candidates awaiting heart transplantation., Background: Ambulatory candidates for transplantation usually wait > 6 months to undergo the procedure, and during this period symptoms may lessen, and peak oxygen uptake may improve. Whereas initial transplant candidacy is based increasingly on objective criteria, there are no established guidelines for reevaluation to determine who can leave the active waiting list., Methods: All ambulatory transplant candidates with initial peak oxygen uptake < 14 ml/kg per min were identified. Of 107 such patients listed, 68 survived without early deterioration or transplantation to undergo repeat exercise. A strategy of reevaluation using specific clinical criteria and exercise performance was tested to determine whether patients with improved oxygen uptake could safely be followed without transplantation., Results: In 38 of the 68 patients, peak oxygen uptake increased by > or = 2 ml/kg per min to a level > or = 12 ml/kg per min after 6 +/- 5 months, together with an increase in anaerobic threshold, peak oxygen pulse and exercise heart rate reserve and a decrease in heart rate at rest. Increased peak oxygen uptake was accompanied by stable clinical status without congestion in 31 of 38 patients, and these 31 were taken off the active waiting list. At 2 years, their actuarial survival rate was 100%, and the survival rate without relisting for transplantation was 85%., Conclusion: Reevaluation of exercise capacity and clinical status allowed removal of 31 (29%) of 107 ambulatory transplant candidates from the waiting list with excellent early survival despite low peak oxygen uptake on initial testing. The ability to increase peak oxygen uptake, particularly with increased peak oxygen pulse, may indicate improved prognosis as well as functional capacity and, in combination with stable clinical status, may be an indication to defer transplantation in favor of more compromised candidates.

Background: Each month, the number of transplant candidates added to the waiting list exceeds the number of transplantations performed, and many outpatients deteriorate to require transplantation urgently. The current list of 2400 candidates and the average wait of 8 months continue to increase., Methods and Results: To determine the size at which the outpatient and critical candidate pools will stabilize, population models were constructed using current statistics for donor hearts, candidate listing, sudden death, and outpatient decline to urgent status and revised to predict the impact of alterations in policies of candidate listing. If current practices continue, within 48 months the predicted list will stabilize as the sum of an estimated 270 hospitalized candidates, among whom, together with newly listed urgent candidates, all hearts will be distributed and 3700 outpatient candidates with virtually no chance of transplantation unless they deteriorate to an urgent status. Decreasing the upper age limit now to 55 years would reduce the number listed each month by 30% and result within 48 months in a list of only 1490. The list could also be decreased by 30%, however, if it were possible to list only a candidate group with an 80% chance (compared with 52% estimated currently) of sudden death or deterioration during the next year. With this strategy, the waiting list would equilibrate within 48 months to one-third the current size, with 50% of hearts for outpatient candidates, who would then have an 11% chance each month of receiving a heart compared with 0% if recent policies prevail. Total deaths, with and without transplantation, would be minimized by this rigorous selection of outpatient candidates., Conclusions: This study implies that immediate provisions should be made to limit candidate listing and revise expectations to reflect the diminishing likelihood of transplantation for outpatient candidates. Future emphasis should be on improved selection of candidates at highest risk without transplantation.

To compare the benefit of angiotensin-converting enzyme inhibition and direct vasodilation on the prognosis of advanced heart failure, 117 patients evaluated for cardiac transplantation who had severe symptoms and abnormal hemodynamic status at rest were randomized to treatment with either captopril or hydralazine plus isosorbide dinitrate (Hy-C Trial). Comparable hemodynamic effects of the two regimens were sought by titrating vasodilator doses to match the hemodynamic status achieved with nitroprusside and diuretic agents, attempting to achieve a pulmonary capillary wedge pressure of 15 mm Hg and a systemic vascular resistance of 1,200 dynes.s.cm-5. Treatment with the alternate vasodilator was started because of poor hemodynamic response or side effects (40% of patients in the captopril group and 22% in the hydralazine group). Adequate hemodynamic response in patients with a serum sodium level less than 135 mg/dl was more likely with hydralazine than with captopril (71% vs. 33%, p = 0.04). Isosorbide dinitrate was prescribed in 88% of the hydralazine-treated patients and 84% of the captopril-treated patients. The hemodynamic improvements from each regimen were equivalent. After 8 +/- 7 months of follow-up, the actuarial 1-year survival rate was 81% in the captopril-treated patients and 51% in the hydralazine-treated patients (p = 0.05). The improved survival with captopril resulted from a lower rate of sudden death, which occurred in only 3 of 44 captopril-treated patients compared with 17 of 60 hydralazine-treated patients (p = 0.01). In the subset of patients who continued treatment with the initial vasodilator, results were similar to those for the entire treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)

During the first year after myocardial infarction, 5% to 15% of patients die, and the majority of deaths occur suddenly. Highly efficacious therapy, such as the implantable cardioverter-defibrillator, may reduce the chance of sudden death, but broad application is limited by associated risks. Hence, attempts to identify patients at high risk so they can receive therapy are desirable. Subgroups with high or low sudden death risks can be identified based on left ventricular function. Further risk stratification using programmed electrical stimulation and the signal-averaged ECG has been advocated, but the best strategy is unknown. Using a decision analysis model, we compared the 1-year survival rates in survivors of myocardial infarction treated with the implantable cardioverter-defibrillator either empirically or based on screening with the signal-averaged ECG and programmed electrical stimulation. The best strategy for selecting patients for therapy depended on the pre-therapy sudden death risk. For patients at low risk, such as those with well-preserved ventricular function, antiarrhythmic therapy selected with screening tests or given empirically increased both the mortality rate resulting from the adverse effects of therapy and the excellent survival rate without therapy. In the moderate-risk population, both empiric and stratified approaches reduced mortality, but stratification substantially limited the number of patients receiving unnecessary therapy. In the high-risk population, empiric treatment achieved the best survival rate, and screening resulted in only a small reduction in the number of patients treated unnecessarily.(ABSTRACT TRUNCATED AT 250 WORDS)

To identify patients with left ventricular ejection fractions less than 20% who are likely to survive on tailored medical therapy after referral to transplantation, this study of 152 patients addressed the hypotheses that (1) severely elevated filling pressures initially measured at referral would not necessarily predict poor outcome, (2) survival would be best when low pulmonary wedge pressures could be achieved with therapy tailored for hemodynamic goals, and (3) coronary artery disease would be an independent risk factor for early mortality. Despite an average initial ejection fraction of 0.15, cardiac index of 2.0 liters/min/m2 and pulmonary artery wedge pressure of 28 mm Hg, the actuarial survival with tailored therapy was 63% at 1 year, with 34 of 41 (83%) deaths occurring suddenly. Survival was not related to initial filling pressure elevation, but was best predicted by the pulmonary artery wedge pressures during therapy; patients achieving pressure of less than or equal to 16 mm Hg had 1-year survival of 83 vs 38% (p = 0.0001). The other independent predictors were serum sodium and coronary artery disease. Patients with high filling pressures during therapy and coronary artery disease had 21% survival at 1 year. Survival after referral to transplantation with an ejection fraction less than or equal to 20% is better than previously described. Patients in whom left ventricular filling pressures cannot be adequately reduced by tailored therapy, particularly if coronary artery disease is present, should be considered for early transplantation.

In advanced heart failure, mitral regurgitation increases the burden of the failing ventricle and decreases effective stroke volume. Although tailored afterload reduction decreases mitral regurgitation at rest, it is not known if this benefit is maintained during upright exercise. Simultaneous radionuclide ventriculography and thermodilution stroke volumes were compared to measure the forward ejection fraction in 10 patients during upright bicycle exercise before and after therapy with vasodilators and diuretics tailored to decrease pulmonary capillary wedge pressure and systemic vascular resistance. Ventricular volumes, total ejection fraction and the forward ejection fraction did not change during exercise at baseline. At rest, tailored therapy decreased average pulmonary capillary wedge pressure from 36 to 19 mm Hg (p less than 0.01), systemic vascular resistance from 1,570 to 1,210 dynes.s.cm-5 (p less than 0.05), and left ventricular volume index from 251 to 177 ml/m2 (p less than 0.01), while increasing the forward ejection fraction from 0.53 to 0.85 (p less than 0.01) without change in total ejection fraction (0.18 from 0.17). During steady state exercise at low work load, tailored therapy decreased left ventricular volume index from 279 to 213 (p less than 0.05) and increased forward ejection fraction from 0.52 to 0.79 (p less than 0.01) without change in total ejection fraction (0.20 from 0.19). The total stroke volume during exercise was not increased after therapy; the increase in forward stroke volume after therapy appeared to result instead from the decrease in mitral regurgitant flow. The benefits of tailored afterload reduction are maintained throughout upright exercise.

Antiarrhythmic drugs occasionally facilitate, rather than prevent, ventricular tachycardia. The purpose of this study was to assess the incidence of procainamide facilitation of ventricular tachycardia initiation during programmed electrical stimulation in patients with no history of spontaneous sustained ventricular tachycardia but who are at high risk. Twenty patients with advanced heart failure (mean left ventricular ejection fraction 0.19 +/- 0.09) and nonsustained ventricular tachycardia and in whom sustained ventricular tachycardia was not inducible by programmed electrical stimulation in the basal state were studied. Six patients had coronary artery disease, 13 had idiopathic dilated cardiomyopathy, and 1 had valvular heart disease. All patients received programmed stimulation from the right ventricular apex with one to three extra-stimuli before and after the intravenous infusion of 10 mg/kg of procainamide (serum level 6.6 +/- 2.4 mcg/l). In two patients (10%) sustained monomorphic ventricular tachycardia was initiated only after the administration of procainamide. One of these patients later died in ventricular tachycardia during hyperkalemia. Of the noninducible patients, during a follow-up period of 6 +/- 5 months, two died suddenly and one developed symptomatic ventricular tachycardia. Thus, procainamide can unmask potential reentry circuits in some patients who have not had spontaneous sustained ventricular tachycardia. In patients with heart failure, this risk, as assessed by programmed stimulation after a single dose of procainamide, appears to be low.

Cardiac transplantation is predicted to improve survival for patients with severe symptoms of heart failure and ejection fraction of 20% or less, but the exercise capacity after cardiac transplantation is less than normal. Patients responding to vasodilators and diuretics have progressive improvement in exercise capacity despite low ejection fraction. We hypothesized that among patients currently considered appropriate for transplantation who could nonetheless subsequently be stabilized on medical therapy tailored to hemodynamic goals, survivors after 6 months of sustained medical therapy would demonstrate exercise capacity comparable to that of survivors of transplantation. Of 146 patients referred, 118 (81%) were discharged on tailored therapy without transplantation, and 88 (60%) were stable for at least 1 month. Stability after discharge was more likely in patients with lower right atrial pressures and better renal function on therapy. Of the 88 stable patients, 45 patients were listed for transplant, and 43 were ineligible or unwilling. From these patients, 42 survivors for more than 6 months follow-up after cardiac transplantation or tailoring of medical therapy underwent exercise testing. Baseline functional and hemodynamic status and left ventricular ejection fraction (15 +/- 4%) were not different between the transplant and sustained medical survivor groups at the time of initial evaluation. After 14 +/- 6 months, left ventricular ejection fraction had increased to 62 +/- 7% after transplantation (p less than 0.01) and only 22 +/- 9% after sustained medical therapy (p less than 0.05). However, there were no significant differences in the maximum workload, oxygen uptake, anaerobic threshold, or maximum oxygen pulse between survivors of cardiac transplantation and survivors on sustained medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Sudden death is common in patients with severe heart failure, but antiarrhythmic drug therapy has potential risks as well as benefits. Programmed electrical stimulation may offer a means of identifying lower risk patients who are less likely to benefit from antiarrhythmic therapy and who could potentially be spared the risk of adverse drug effects. Therefore 72 consecutive patients referred for management of severe heart failure (left ventricular ejection fraction 0.18 +/- 0.06) were studied. The mean age was 47 +/- 12 years; 45 (61%) patients had idiopathic dilated cardiomyopathy and 24 (33%) had coronary artery disease. Fifty-eight (82%) patients had nonsustained ventricular tachycardia. Following adjustment of vasodilators and diuretics, programmed stimulation was performed from the right ventricular apex with one, two, and three extrastimuli. Sustained ventricular tachycardia was initiated in nine (13%) patients and all received chronic antiarrhythmic drug therapy. During follow-up of 176 +/- 187 days, 1 of 13 patients treated for inducible ventricular tachycardia and 13 of 63 noninducible patients died suddenly (p = 0.20). The actuarial risk of sudden death in the noninducible patients was 13% at 6 weeks and 30% at 6 months. The only independent predictors of sudden death were pulmonary artery systolic pressure greater than 55% mm Hg and a pulmonary capillary wedge pressure with vasodilator therapy greater than 16 mm Hg. Of the 63 noninducible patients, 11 (17%) received long-term antiarrhythmic agents due to atrial fibrillation or referring physician preference, and antiarrhythmic therapy was not associated with a lower risk of sudden death in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary prevention of death from ischemic heart disease requires further understanding of the pathogenesis of this disorder. Cellular defects of cholesterol metabolism may be more significant markers that serum lipid levels for the identification and treatment of atherosclerotic risk. Coronary spasm has been shown to be an important cause of ischemia in the presence and absence of atherosclerotic lesions. Careful manipulation of physiologic variables with vasodilator agents during cardiopulmonary bypass can substantially alter the myocardial oxygen supply-demand relation, thereby minimizing ischemic injury. The cellular basis for loss of mechanical function during ischemia and the factors that determine irreversible injury are yet unknown.

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Professor of Medicine.

Therapy of elevated ventricular filling pressures in patients with dilated heart failure may be limited by concern that cardiac output will be further compromised. Twenty-five patients with severe symptoms and ejection fractions of 25% or less were studied to determine the lowest ventricular filling pressures that could be achieved with vasodilator and diuretic therapy while maintaining cardiac output. In 20 of 25 patients normal pulmonary capillary wedge pressures (PCWs) were achieved (mean 10 mm Hg compared with 30 mm Hg at baseline). Stroke volume was 60 vs 39 ml at baseline. Stroke work index was 30 vs 19 g-m/m2. For each patient, over the range of PCWs, stroke volume and stroke work index were maintained and were often maximal at the lowest PCW achieved. The upright position was well tolerated in patients with normal supine PCW. Normal filling pressures can be achieved in patients with congestive heart failure without compromise of cardiac output. While congestive symptoms should be improved, the feasibility and benefit of maintaining normal filling pressures over a long term must be established.

The mechanism by which afterload reduction increases left ventricular stroke volume while decreasing left ventricular filling pressure has not previously been established. In 15 patients with severe congestive heart failure due to ischemic or idiopathic dilated cardiomyopathy, absolute ventricular volume, ejection fraction and total stroke volume from radionuclide ventriculography were compared with thermodilution stroke volume before and after intensive afterload reduction with vasodilators and diuretics titrated to hemodynamic goals. After 48 to 72 hours, pulmonary artery wedge pressure decreased from 32 +/- 8 to 16 +/- 4 mm Hg and systemic vascular resistance from 1,960 +/- 700 to 1,200 +/- 400 dynes s cm-5. End-diastolic volume decreased from 390 +/- 138 to 301 +/- 126 ml (p less than 0.01) and end-systolic volume from 316 +/- 127 to 241 +/- 111 (p less than 0.01). Ejection fraction did not change and total stroke volume decreased from 74 +/- 22 to 59 +/- 20 ml (p less than 0.01). Simultaneous forward stroke volume by thermodilution increased from 37 +/- 14 to 52 +/- 14 ml (p less than 0.01), and forward fraction increased from 0.55 +/- 0.40 to 0.96 +/- 0.42. Intensive reduction of ventricular filling pressure and systemic vascular resistance decreased total ventricular stroke volume by 20% but increased forward stroke volume by 40%. The major effect of intensive afterload reduction for severe congestive heart failure may be the reduction of ventricular volume and mitral regurgitation.

The effects of chronic oral vasodilator therapy were studied in a group of patients with refractory congestive heart failure. Fifteen patients were treated acutely with intravenous sodium nitroprusside and sublingual isosorbide dinitrate. After continuous therapy with nitroprusside and isosorbide dinitrate for up to 72 hours the patients were then placed on isosorbide dinitrate and oral phenoxybenzamine. Hemodynamic responses to nitroprusside, isosorbide dinitrate, and phenoxybenzamine with isosorbide dinitrate were determined. After a mean follow-up of seven months, nine patients who were receiving isosorbide dinitrate and phenoxybenzamine underwent repeat hemodynamic studies. Beneficial effects of acute vasodilator therapy included a significant reduction in pulmonary capillary wedge pressure and systemic vascular resistance, and significant increases in cardiac index and stroke work index. Mean arterial blood pressure and heart rate were unchanged. During the period of chronic vasodilator administration, no other change in basic therapy with isosorbide dinitrate and phenoxybenzamine (3-21 months), the favorable effects observed acutely were maintained. All patients demonstrated symptomatic improvement with minimal side effects. The beneficial hemodynamic responses that are noted with acute vasodilator therapy in patients in advanced congestive heart failure are maintained with oral therapy on a chronic basis.

Variant angina presents as an atypical form of angina caused by coronary artery spasm. Due to the sudden disruption of blood and oxygen supply to the myocardium, a number of severe hemodynamic changes may occur, including life-threatening dysrhythmias, and left ventricular dysfunction. Rapid intervention can alleviate the symptoms caused by the arterial spasm and prevent catastrophic results. The critical care nurse plays a vital role in the diagnosis of variant angina and rapid treatment of the patient.

The success of heart transplantation has created longer waiting lists of candidates, some of whom require transplantation urgently. Decisions must be made regarding which patients require urgent transplantation and how many donor hearts should be committed to urgent transplantation. To determine whether some patients who are considered refractory to medical therapy may be stabilized for elective transplantation, 40 patients transferred for urgent transplantation underwent intensive vasodilator and diuretic therapy, and outcomes were determined. To examine the impact of urgent transplantation on survival, we then determined the survival for urgent priority candidates in the western region. Discharge of the patients who were receiving oral dosages of vasodilators and diuretics was possible for 32 of 40 patients (80%), with a 6-month actuarial survival of 75% on medical therapy, despite an initial ejection fraction of 0.15 +/- 0.04, a cardiac index of 1.9 +/- 0.6 L/min/m2, and a pulmonary wedge pressure of 30 +/- 8 mm Hg. Of 11 patients discharged to await regular priority transplantation, one died suddenly, one died postoperatively, and the others went home 14 +/- 4 days after transplantation. The eight patients unable to be discharged after transfer had lower initial mean arterial pressures and serum sodium levels. Of 59 urgent priority patients from the five western region programs, 50 patients underwent transplantation after 33 +/- 41 days. Subsequent 1-month survival was 88% and overall survival 80%, compared with 97% and 90% in 137 regular priority patients, with a 4.5 times greater risk of early mortality in the urgent group (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

To improve the accuracy of scintigraphic ventricular volume determination, which is limited by photon attenuation between the heart and the gamma camera, a method was developed for directly measuring the photon attenuation of radioactivity delivered as a bolus through a Swan-Ganz catheter into the right atrium. Comparison of the count rate recovered from this bolus with the total ex vivo measured activity determined by imaging an aliquot of the administered activity allowed calculation of the attenuation factor. Left ventricular stroke volumes determined scintigraphically by the count method in gated blood pool studies and then corrected with this attenuation factor correlated well with stroke volumes determined from thermodilution cardiac output and heart rate (r = 0.92; SEE, 6.1 ml). The agreement between the two measurements was markedly less when an average attenuation factor was employed for correction of scintigraphic volumes (r = 0.52; SEE, 14.8 ml). The results indicate that correction for photon attenuation is needed for accurate measurement of left ventricular volumes. Correction of left ventricular counts based on body weight or body surface area improves the accuracy of volume estimates.

Studies have shown that the extraction of glucose per unit flow is increased in moderately ischemic myocardium primarily due to anaerobic glucose metabolism manifested as lactate production, whereas myocardial infarction is characterized by the loss of metabolically active myocardium. To determine the feasibility of demonstrating these metabolic abnormalities reflecting both ischemia and infarction, we used positron computed tomography (PCT) to evaluate relative regional myocardial exogenous glucose utilization and perfusion in 15 patients with recent myocardial infarction. The positron-emitting tracers of glucose metabolism and perfusion, 18F-2-fluoro-2-deoxyglucose (FDG) and N-13 ammonia, respectively, were used. Fourteen of 19 documented infarctions were demonstrated by PCT to have concordantly decreased glucose utilization and perfusion. However, in an additional 11 regions, glucose utilization was disproportionately increased relative to perfusion, consistent with ischemic glucose consumption. These findings correlated with the presence of postinfarction angina, the site of ischemic electrocardiographic changes during chest pain, and the presence of regional left ventricular dysfunction and severe coronary artery disease. Because three ECG infarct zones not detected by PCT demonstrated ischemic glucose utilization, only two of 19 electrocardiographically defined infarctions had no detectable metabolic abnormality. We conclude that the changes in regional FDG and N-13 ammonia concentrations detected with PCT in patients who had had a recent myocardial infarction are consistent with regional exogenous glucose utilization and perfusion in moderately ischemic and irreversibly infarcted myocardium. This approach has the potential to identify and differentiate resting myocardial ischemia from infarction and to assess tissue viability after an ischemic event.

Positron emission tomography has been shown to distinguish between reversible and irreversible ischemic tissue injury. Using this technique, 13 patients with acute myocardial infarction were studied within 72 hours of onset of symptoms to evaluate regional blood flow and glucose metabolism with nitrogen (N)-13 ammonia and fluorine (F)-18 deoxyglucose, respectively. Serial noninvasive assessment of wall motion was performed to determine the prognostic value of metabolic indexes for functional tissue recovery. Segmental blood flow and glucose utilization were evaluated using a circumferential profile technique and compared with previously established semiquantitative criteria. Relative N-13 ammonia uptake was depressed in 32 left ventricular segments. Sixteen segments demonstrated a concordant decrease in flow and glucose metabolism. Regional function did not change over time in these segments. In contrast, 16 other segments with reduced blood flow revealed maintained F-18 deoxyglucose uptake consistent with remaining viable tissue. The average wall motion score improved significantly in these segments (p less than 0.01), yet the degree of recovery varied considerably among patients. Coronary anatomy was defined in 9 of 13 patients: patent infarct vessels supplied 8 of 10 segments with F-18 deoxyglucose uptake, while 10 of 13 segments in the territory of an occluded vessel showed concordant decreases in flow and metabolism (p less than 0.01). Thus, positron emission tomography reveals a high incidence of residual tissue viability in ventricular segments with reduced flow and impaired function during the subacute phase of myocardial infarction. Absence of residual tissue metabolism is associated with irreversible injury, while preservation of metabolic activity identifies segments with a variable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of brief periods of ischemia on vascular space size, vascular permeability to albumin, tissue water and extracellular space size, and vascular resistance were studied in the perfused isolated rabbit interventricular septum. Vascular space size increased 264% over control after 30 min ischemia and 52% after 60 min ischemia, but vascular resistance increased. Total tissue water did not change after ischemia and extracellular space size did not increase after 30 min ischemia and decreased slightly after 60 min ischemia. These results demonstrate that the initial increase in vascular resistance after ischemia is not initiated by interstitial edema or cellular edema. These events appear to be later phenomena. The initiating cause of the increased vascular resistance appears to be a combination of increased vascular tone and conversion of a portion of vascular flow from low resistance large vessel flow to higher resistance small vessel flow (capillary recruitment).

With the advent of therapeutic interventions to restore blood flow in patients with acute infarction, early identification of salvageable myocardium has gained clinical importance. It was the purpose of this study to define regional blood flow and glucose metabolism in patients with acute myocardial infarction as assessed by positron emission tomography (PET) and to correlate these findings with coronary anatomy. In 15 patients blood flow as determined by N-13 ammonia was reduced in 37 left ventricular segments. In 20 segments there was a similar decrease in FDG uptake, consistent with tissue necrosis. In contrast, 17 segments with reduced blood flow revealed maintained FDG uptake suggesting residual viability in the electrocardiographically defined 'infarct segment'. PET viability and necrosis was significantly associated with presence or absence of anterograde flow in the infarct artery. Evaluation of regional wall motion did not distinguish segments with PET criteria for viability from segments with necrosis. Thus, in patients without thrombolytic therapy during evolving myocardial infarction, spontaneous reperfusion appears to be beneficial for tissue survival. PET offers the unique possibility to assess tissue viability early after the ischaemic injury where evaluation of wall motion fails to identify salvageable myocardium.

Shock is a state of systemic imbalance between supply and demand for oxygenated blood. We discuss here management of shock states not primarily of cardiac origin. Inadequacy or maldistribution of blood volume is important in the pathogenesis of most forms of shock. The Military Anti-Shock Trouser (MAST) suit assists the redistribution of blood from the periphery to the central circulation. Normal saline and Ringer's lactate solution may be used interchangeably for acute volume replacement. Colloid replacement requires smaller volumes but carries a higher risk of pulmonary edema, whereas crystalloid replacement requires larger volumes and leads to more systemic edema. Myocardial injury may contribute notably to the transition from reversible to irreversible shock. Naloxone, lidocaine, and indomethacin have improved survival in animal models of endotoxin shock, but proof of efficacy in humans is lacking. A role for corticosteroid administration in shock remains to be defined. Effective antibiotic therapy is the best treatment for septic shock; antisera against endotoxic antigens may develop as important adjunctive therapy.

Cardiac transplantation can only be performed in a few patients with severe congestive heart failure (CHF), due to the shortage of donor hearts. The efficacy of current medical therapy tailored for severe CHF, which has not previously been determined for transplant candidates, is of particular importance in patients considered for urgent cardiac transplantation. In this study, 50 consecutive in-patients transferred from other hospitals for urgent transplantation underwent intensive afterload reduction therapy, initially with intravenous and subsequently with oral vasodilators and diuretics tailored to hemodynamic goals. Oral regimens allowed hospital discharge without surgery for 40 of 50 patients. Nineteen of these patients had arrived on inotropic infusions and 32 had received oral vasodilators in the previous month. Cardiac index increased from 1.9 +/- 0.6 to 2.8 +/- 0.7 liters/min/m2, while pulmonary capillary wedge pressure decreased from 30 +/- 8 to 15 +/- 4 mm Hg and systemic vascular resistance decreased from 1,800 +/- 800 to 1,100 +/- 200 dynes-s-cm-5. Despite poor initial hemodynamics, ejection fraction 16 +/- 4%, serum sodium 131 +/- 6 mEq/liter, and apparent failure of previous medical therapy, actuarial survival for 24 discharged patients receiving sustained medical therapy alone was 67% at 1 year, with 67% of survivors employed full- or part-time, and 14 of 16 (88%) discharged transplant candidates survived until transplantation. By decreasing the need for transplantation to be performed urgently, increased emphasis on the design of medical therapy may allow more effective distribution of limited donor hearts.