Alterations of myocardial amino acid metabolism in chronic ischemic heart disease.

Arteriovenous differences (A-V) of all naturally occurring amino acids, lactate, and oxygen were measured simultaneously with coronary sinus blood flow (CSBF) in 8 normal subjects and 11 patients with coronary artery disease at rest and during pacing stress. Mean values for CSBF and myocardial oxygen consumptions (MVO2) for the two groups were similar at rest and during pacing, although mean CSBF and MVO2 increased significantly in both groups in the paced as compared to the rest state. Alanine (ala) was the only amino acid released by the myocardium, while only glutamic acid(glu) demonstrated uptake. Mean A-V ala was negative at rest in the control and coronary disease groups (-4.8+/-3.8 vs. -22.0+/-3.0 nmol/ml, respectively), but was significantly more negative in the coronary group (P less than 0.001) and not statistically different than zero in the normals. A-V ala became significantly negative with pacing in the normals (-10.0+/-4.3 nmol/ml), remained unchanged in the coronary group (-23.0+/-2.9 nmol/ml), and was significantly more negative in the coronary group (P less than 0.05). Calculation of data on the basis of net ala flux ([A-V] X [CSBF X hematocrit]) yielded similar results as that obtained with A-V differences. A-V glu was significantly positive in normals (27.7 +/- 8.9 nmol/ml, P less than 0.01) and coronary patients (59.9 +/- 8.9 nmol/ml, P less than 0.01) at rest but significantly greater in the latter group (P less than 0.001). With pacing, A-V glu remained significantly greater than zero in coronary patients (35.3 +/- 6.3 nmol/ml) and decreased to zero in the normals (4.3 +/- 11.8 nmol/ml). Calculation of net glu flux (nmol/min) at rest yielded data similar to that based on A-V difference. With pacing, net glu flux in the coronary patients did not decrease due to the augmentation of CSBF. No relation between A-V glu or ala and CSBF, MVO2 or A-V lactate was noted. The data demonstrate that specific alterations of myocardial amino acid metabolism characterize patients with chronic ischemic heart disease.

Bradycardia after heart transplantation: reversal with theophylline.

OBJECTIVES: We attempted to demonstrate that theophylline, an adenosine receptor antagonist, can reverse bradyarrhythmias after orthotopic heart transplantation. BACKGROUND: Sinus node dysfunction, primarily sinus bradycardia, frequently occurs after orthotopic heart transplantation and may lead to permanent pacemaker implantation. Endogenous adenosine has been implicated as a cause of such posttransplantation bradyarrhythmia. METHODS: Twenty-nine transplant recipients (group 1) were given theophylline after bradyarrhythmias developed after transplantation. Data in these patients were compared with those in a control group of 18 patients without bradyarrhythmias (group 2) who were not given theophylline. RESULTS: The mean heart rate in group 1 increased from 62 +/- 7 to 89 +/- 10 beats/min after administration of theophylline (p < 0.0001); the mean heart rate in group 2 was 88 +/- 12 beats/min. Patients in group 1 required more days of temporary atrial pacing (3.5 +/- 1 vs. 1.5 +/- 3, p < 0.04) before the administration of theophylline than did patients in group 2. The length of hospital stay after transplantation did not differ significantly between groups 1 and 2 (17 +/- 7.5 vs. 20 +/- 16 days, p = NS). Age, gender, underlying disease, preoperative use of amiodarone, graft ischemia time or the incidence of moderate to severe rejection were not different between patient groups. CONCLUSIONS: The use of theophylline for posttransplantation bradyarrhythmias increased heart rate and facilitated the withdrawal of chronotropic support. We conclude that theophylline offers effective and specific therapy for heart transplant patients with early bradyarrhythmias, reducing the need for implantation of a permanent pacemaker.

Resistance exercise training restores bone mineral density in heart transplant recipients.

OBJECTIVES: This was a prospective, randomized, controlled study designed to determine the effect of resistance exercise training on bone metabolism in heart transplant recipients. BACKGROUND: Osteoporosis frequently complicates heart transplantation. No preventative strategy is generally accepted for glucocorticoid-induced bone loss. METHODS: Sixteen male heart transplant recipients were randomly assigned to a resistance exercise group that trained for 6 months (mean [+/- SD] age 56 +/- 6 years) or a control group (mean age 52 +/- 10 years) that did not perform resistance exercise. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L2 to L3) was measured by dual-energy X-ray absorptiometry before and 2 months after transplantation and after 3 and 6 months of resistance exercise or a control period. The exercise regimen consisted of lumbar extension exercise (MedX) performed 1 day/week and variable resistance exercises (Nautilus) performed 2 days/week. Each exercise consisted of one set of 10 to 15 repetitions performed to volitional fatigue. RESULTS: Pretransplantation baseline values for regional BMD did not differ in the control and training groups. Bone mineral density of the total body, femur neck and lumbar vertebra (L2 to L3) were significantly decreased below baseline at 2 months after transplantation in both the control (-3.3 +/- 1.3%, -4.5 +/- 2.8%, -12.7 +/- 3.2%, -14.8 +/- 3.1%, respectively). Six months of resistance exercise restored BMD of the whole body, femur neck and lumbar vertebra to within 1%, 1.9% and 3.6% of pretransplantation levels, respectively. Bone mineral density of the control group remained unchanged from the 2-month posttransplantation levels. CONCLUSIONS: Within 2 months after heart transplantation, approximately 3% of whole-body BMD is lost, mostly due to decreases in trabecular bone (-12% to -15% of lumbar vertebra). Six months of resistance exercise, consisting of low back exercise that isolates the lumbar spine and a regimen of variable resistance exercises, restores BMD toward pretransplantation levels. Our results suggest that resistance exercise is osteogenic and should be initiated early after heart transplantation.

Breakdown of blood pressure and body fluid homeostasis in heart transplant recipients.

OBJECTIVES: This study was designed to investigate disturbances in arterial blood pressure and body fluid homeostasis in stable heart transplant recipients. BACKGROUND: Hypertension and fluid retention frequently complicate heart transplantation. METHODS: Blood pressure, renal and endocrine responses to acute volume expansion were compared in 10 heart transplant recipients (57 +/- 9 years old [mean +/- SD]) 20 +/- 5 months after transplantation, 6 liver transplant recipients receiving similar doses of cyclosporine (cyclosporine control group) and 7 normal volunteers (normal control subjects). After 3 days of a constant diet containing 87 mEq/24 h of sodium, 0.154 mol/liter saline was infused at 8 ml/kg per h for 4 h. Blood pressure and plasma vasopressin, angiotensin II, aldosterone, atrial natiuretic peptide and renin activity levels were determined before and at 30, 60, 120 and 240 min during the infusion. Urine was collected at 2 and 4 h. Blood pressure, fluid balance hormones and renal function were monitored for 48 h after the infusion. RESULTS: Blood pressure did not change in the two control groups but increased in the heart transplant recipients (+15 +/- 8/8 +/- 5 mm Hg) and remained elevated for 48 h (p < or = 0.05). Urine flow and urinary sodium excretion increased abruptly in the control groups sufficient to account for elimination of 86 +/- 9% of the sodium load by 48 h; the increases were blunted (p < or = 0.05) and delayed in the heart transplant recipients, resulting in elimination of only 51 +/- 13% of the sodium load. Saline infusion suppressed vasopressin, renin activity, angiotensin II and aldosterone in the two control groups (p < or = 0.05) but not in the heart transplant recipients. Heart transplant recipients had elevated atrial natriuretic peptide levels at baseline (p < or = 0.05), but relative increases during the infusion were similar to those in both control groups. CONCLUSIONS: Blood pressure in heart transplant recipients is salt sensitive. These patients have a blunted diuretic and natriuretic response to volume expansion that may be mediated by a failure to reflexly suppress fluid regulatory hormones. These defects in blood pressure and fluid homeostasis were not seen in liver transplant recipients receiving cyclosporine and therefore cannot be attributed to cyclosporine alone. Abnormal cardiorenal neuroendocrine reflexes, secondary to cardiac denervation, may contribute to salt-sensitive hypertension and fluid retention in heart transplant recipients.

Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group.

OBJECTIVES: The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 microg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo. BACKGROUND: Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied. METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction < or =35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion. RESULTS: One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion. CONCLUSIONS: The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.

High dose angiotensin-converting enzyme inhibition prevents fluid volume expansion in heart transplant recipients.

OBJECTIVES: We sought to test the hypothesis that plasma volume (PV) expansion in heart transplant recipients (HTRs) is caused by failure to reflexively suppress the renin-angiotensin-aldosterone (RAA) axis. BACKGROUND: Extracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs. METHODS: Plasma volume and fluid regulatory hormones were measured in eight HTRs (57+/-6 years old) both before and after treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na+, PV was measured by using the modified Evans blue dye dilution technique. After approximately four months (16+/-5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was repeated. RESULTS: Captopril pharmacologically suppressed (p<0.05) supine rest levels of angiotensin II (-65%) and aldosterone (-75%). The reductions in vasopressin and atrial natriuretic peptide levels after captopril did not reach statistical significance. The PV, normalized for body weight (ml/kg), was significantly reduced by 12% when the HTRs received captopril. CONCLUSIONS: Extracellular fluid volume is expanded (12%) in clinically stable HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that fluid retention is partly engendered by a failure to reflexively suppress the RAA axis when HTRs become hypervolemic.

Exercise-induced hypoxemia in heart transplant recipients.

OBJECTIVES: The purpose of this study was to determine whether heart transplantation has an adverse effect on pulmonary diffusion and to investigate the potentially deleterious effects of impaired pulmonary diffusion on arterial blood gas dynamics during exercise in heart transplant recipients. BACKGROUND: Abnormal pulmonary diffusing capacity is reported in patients after orthotopic heart transplantation. Abnormal diffusion may be caused by cyclosporine or by the persistence of preexisting conditions known to adversely affect diffusion, such as congestive heart failure and chronic obstructive pulmonary disease. METHODS: Eleven patients (mean age 50 +/- 14 years) performed pulmonary function tests 3 +/- 1 months before and 18 +/- 12 (mean +/- SD) months after heart transplantation. Transplant patients were assigned to groups with diffusion > 70% (n = 5) or diffusion < 70% of predicted values (n = 5). The control group and both subsets of patients performed 10 min of cycle exercise at 40% and 70% of peak power output. Arterial blood gases were drawn every 30 s during the 1st 5 min and at 6, 8 and 10 min. RESULTS: Significant improvements in forced vital capacity (17.4%), forced expiratory volume in 1 s (11.7%) and diffusion capacity (6.6%) occurred in the patients; however, posttransplantation vital capacity, forced expiratory volume and diffusion were lower (p < or = 0.05) compared with values in 11 matched control subjects. Changes in blood gases were similar among groups at 40% of peak power output. At 70% of peak power output, arterial blood gases and pH were significantly (p < or = 0.05) lower in transplant patients with low diffusion (arterial oxygen pressure 15 to 38 mm Hg below baseline) than in patients with normal diffusion and control subjects. Cardiac index did not differ (p > or = 0.05) between transplant patients with normal and low diffusion at rest or during exercise. Posttransplantation mean pulmonary artery pressure was significantly related to exercise-induced hypoxemia (r = 0.71; p = 0.03). CONCLUSIONS: Abnormal pulmonary diffusion observed in patients before heart transplantation persists after transplantation with or without restrictive or obstructive ventilatory defects. Heart transplant recipients experience exercise-induced hypoxemia when diffusion at rest is < 70% of predicted. Our data also suggest that abnormal pulmonary gas exchange possibly contributes to diminished peak oxygen consumption in some heart transplant recipients; however, direct testing of this hypothesis was beyond the scope of the present study. This possibility needs to be investigated further.

Effectiveness and safety of diltiazem or lisinopril in treatment of hypertension after heart transplantation. Results of a prospective, randomized multicenter trail.

OBJECTIVES: The purpose of this study was to determine the effectiveness and safety of diltiazem or lisinopril for treatment of hypertension after heart transplantation. BACKGROUND: Systemic hypertension is common after heart transplantation, and to date there are no randomized, prospective multicenter treatment trials. METHODS: Members of the Cardiac Transplant Research Database Group developed and implemented a prospective, randomized multicenter trial of the effectiveness and safety of diltiazem or lisinopril in the treatment of hypertension in cyclosporine-treated patients after heart transplantation. RESULTS: One hundred sixteen patients with hypertension (blood pressure > or = 140/90 mm Hg) after heart transplantation were randomized for > or = 3 months of treatment. Of 55 diltiazem-treated patients, 21 (38%) were responders (diastolic blood pressure < 90 mm Hg), 23 (42%) were nonresponders (diastolic blood pressure > or = 90 mm Hg), and 11 (20%) were withdrawn from the study. Of 61 lisinopril-treated patients, 28 (46%) were responders, 22 (36%) were nonresponders, and 11 (18%) were withdrawn. There was no difference in baseline characteristics or percent responders between the two groups. Systolic pressure decreased from 157 +/- 2.3 to 130 +/- 2.0 mm Hg (mean +/- 1 SEM) in the diltiazem-treated responders and from 153 +/- 2.1 to 127 +/- 2.7 mm Hg in the lisinopril-treated responders (p < 0.0001). Diastolic pressure decreased from 100 +/- 0.9 to 85 +/- 1.6 mm Hg in the diltiazem-treated responders and from 100 +/- 1.0 to 84 +/- 2.0 mm Hg in the lisinopril-treated responders (p < 0.0001). There were a total of 35 reported adverse events, 22 of which led to withdrawal of the patient from the study. All drug-related side effects were considered minor and resolved with discontinuation of the drug. CONCLUSIONS: These results indicate that both diltiazem and lisinopril are safe for treatment of hypertension after heart transplantation, although titrated monotherapy with either drug controlled the condition in < 50% of patients.

Long-term hemodynamic responses to vasodilator therapy in patients with severe left ventricular dysfunction.

Maximal oral vasodilator therapy resulted in long-term reduction of initially elevated pulmonary vascular resistance in 10 of 13 patients with severe heart failure who tolerated inotrope-supported uptitration of afterload reduction. Eleven patients were unable to tolerate vasodilator therapy and required inotropic support for successful cardiac transplantation.

Cardiac output responses during exercise in volume-expanded heart transplant recipients.

The mechanisms responsible for immediate adjustments in cardiac output at onset of exercise, in the absence of neural drive, are not well defined in heart transplant (HT) recipients. Seven male HT recipients (mean +/- SD 57 +/- 6 years) and 7 age-matched sedentary normal control subjects (mean age 57 +/- 5 years) performed constant load cycle exercise at 40% of peak power output (Watts). Cardiac output and plasma norepinephrine were determined at rest and every 30 seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All subjects were admitted to the General Clinical Research Center for determination of plasma volume. After 3 days of equilibration to a controlled and standardized diet, plasma volume was measured using a modified Evans Blue Dye (T-1824) dilution technique. Heart rate at rest was higher in the HT group (105 +/- 12 vs 74 +/- 6 beats/min), but during submaximum exercise, heart rates in the control group increased more rapidly (p < or = 0.05) and to a greater magnitude (54 +/- 7% vs 17 +/- 4% above rest). Stroke volume at rest was lower in HT recipients (45 +/- 4 vs 68 +/- 9 ml) but was significantly augmented immediately after onset of exercise (30 seconds) and the relative increase was greater than controls at peak exercise (61% vs 38% greater than baseline). Cardiac output at rest was within the normal range in both groups (4.58 +/- 0.27 vs 4.94 +/- 0.40 L/min). Relative increases in cardiac output were similar (p > or = 0.05) for the HT (106 +/- 12%) and control groups (97 +/- 10%). Plasma norepinephrine did not become significantly greater than resting values until approximately 4 minutes after onset of exercise in both groups. Blood volume, normalized for body weight, was 12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%) augment stroke volume immediately after the onset of exercise. Plasma norepinephrine levels contribute negligibly to the rapid adjustment in cardiac output. Rather, we speculate that abrupt on-transit increases in stroke volume are due to augmented venous return, secondary to expanded blood volume.

Natural history of S-T segment elevation after acute myocardial infarction.

Clinical, electrocardiographic and cineventriculographic data in two patient groups were analyzed to define the natural history of S-T segment elevation after myocardial infarction. In sixteen of 22 patients (73 percent) with acute inferior myocardial infarction, S-T segment elevation was present on hospital admission, persisting in 1 (5 percent) by the 2nd week. S-T segment elevation was present on admission in 18 of 23 patients (78 per cent) with acute anterior myocardial infarction and persisted in 13 after 1 week and in 9 of 14 (64 percent) during a follow-up period of 1 to 6 months. S-T segment elevation lasting more than 2 weeks after myocardial infarction did not resolve. Compared with patients with inferior myocardial infarction or anterior infarction without persistent S-T segment elevation, patients with anterior infarction and persistent S-T segment elevation had a higher level of mean maximal serum creatine phosphokinase (CPK), more severe left ventricular decompensation and a greater frequency of death in the early follow-up period. In a separate series of 95 patients with cineangiographically documented coronary artery disease, 40 of 65 patients (62 percent) with advanced anterior and apical asynergy had persistent S-T segment elevation. By contrast, only 1 of 30 (3 percent) with coronary disease and normal ventriculograms had persistent S-T segment elevation. We concluded that (1) the natural history of S-T segment elevation after myocardial infarction is resolution within 2 weeks in 95 percent of inferior but in only 40 percent of anterior infarctions; (2) S-T segment elevation persisting more than 2 weeks after myocardial infarction does not resolve; (3) persistent S-T segment elevation is associated with clinically more severe myocardial infarction; and (4) in patients with coronary artery disease, persistent S-T segment elevation after myocardial infarction is a specific but insensitive index of advanced asynergy.

Clinical improvement after atrioventricular nodal ablation for atrial fibrillation does not correlate with improved ejection fraction.

A retrospective review of 15 patients with atrial fibrillation and class III to IV congestive heart failure who underwent atrioventricular nodal ablation demonstrated a marked improvement in their functional abilities. This improvement, however, could not be explained by the improvement in ejection fraction alone.

QT dispersion is a marker for life-threatening ventricular arrhythmias after atrioventricular nodal ablation using radiofrequency energy.

QT dispersion has been cited as a measure of nonuniform myocardial repolarization and a predictor of sudden cardiac death. We describe 38 patients who underwent atrioventricular nodal ablation, 3 of whom had an increase in measured QT dispersion and experienced potentially fatal, pulseless, polymorphic ventricular tachycardia after the procedure.

Sustained effect of orally administered isosorbide dinitrate on exercise performance of patients with angina pectoris.

The efficacy of oral isosorbide dinitrate was evaluated in nine hospitalized patients with chronic angina pectoris and positive maximal bicycle exercise tests. Patients were randomized double-blind to receive either 20 mg of isosorbide dinitrate or placebo on successive days after a control maximal upright bicycle exercise test. On each day hourly exercise tests were performed for 4 hours after drug administration to an end point of fatigue or angina pectoris. Mean systolic blood pressure 4 hours after the administration of isosorbide dinitrate was 25 mm Hg less than the control value (P less than 0.001). The values for resting heart rate and exercise-attained heart rate-blood pressure product were not significantly different from the values after placebo. The duration of exercise was prolonged (P less than 0.025) for at least 3 hours, and less ST depression (P less than 0.01) was observed up to 3 hours after the administration of isosorbide dinitrate compared with control values. The demonstration of sustained imporved exercise performance and previously described hemodynamic effects with the use of higher doses suggests that adequate blood levels of isosorbide dinitrate or mononitrate metabolites may be important for the efficacy of oral organic nitrates.

Outcome after major dissection during coronary angioplasty using the perfusion balloon catheter.

Coronary artery dissection is an infrequent but serious complication of coronary angioplasty that can lead to periprocedural vessel occlusion, emergency bypass surgery, myocardial infarction or death. Recently, a perfusion balloon catheter was developed that permits passive perfusion of blood through the central lumen of the catheter. It enables prolonged balloon inflations to be performed and has been used to provide distal blood flow after coronary occlusion. To evaluate the effectiveness of the perfusion balloon catheter in patients with major coronary dissections, 36 consecutive patients treated with the perfusion balloon catheter were compared with 46 consecutive patients treated before its availability. The 2 groups were similar in terms of clinical, angiographic and initial procedural characteristics. Use of the perfusion balloon catheter permitted a significantly longer inflation than standard balloon inflation (average 18 +/- 5 min). Angiographic success was significantly greater with the perfusion balloon catheter (84 vs 62% for conventional therapy), whereas complications were markedly reduced (48 vs 78%). With the perfusion balloon catheter there were fewer deaths (2 vs 6%), myocardial infarctions (14 vs 40%) and emergency bypass operations (11 vs 25%). The findings of this retrospective comparison demonstrate that the perfusion balloon catheter is effective for the management of major dissections after coronary angioplasty. The use of the perfusion balloon catheter should be considered when a major coronary dissection occurs and when emergency bypass surgery is contemplated.

Prior restenosis predicts restenosis after coronary angioplasty of a new significant narrowing.

To determine the influence of a history of restenosis on subsequent restenosis after percutaneous transluminal coronary angioplasty (PTCA) of a new significant narrowing, the records of 100 patients who underwent successful PTCA at another site ("new narrowing PTCA") greater than or equal to 2 months after successful initial PTCA were retrospectively reviewed. Patients were grouped according to whether initial PTCA resulted in restenosis, which was determined by angiographic follow-up greater than or equal to 3 months after initial PTCA. Patients in group 1 did not have restenosis after initial PTCA (n = 50), whereas patients in group 2 did (n = 40). All patients were followed for recurrent symptoms, with serial exercise tests, for greater than or equal to 6 months after new narrowing PTCA. Clinically suspected and angiographically confirmed restenosis occurred in 11 of 50 (22%) patients and 12 of 63 (19%) narrowings in group 1, and in 20 of 40 (50%) patients and 22 of 48 (46%) narrowings in group 2 (p less than 0.01 for patients, p less than 0.002 for narrowings). Multivariate analysis identified that prior restenosis (p less than 0.02, odds ratio 3.4), left anterior descending artery location of stenosis (p less than 0.04, odds ratio 3.0), and severity of stenosis before PTCA (p less than 0.02, odds ratio 1.8) were independently associated with restenosis after new narrowing PTCA. In conclusion, prior restenosis is an independent risk factor for subsequent restenosis after new narrowing PTCA.

An update on nesiritide for treatment of decompensated heart failure.

In the July 1999 issue of this publication, we described the chemical properties, pharmacology and clinical trials involving nesiritide as a therapeutic agent for patients with decompensated heart failure (Exp. Opin. Invest. Drugs) (1999) 8(7):1063--1072). At the time of publication, the US Food and Drug Administration reviewed the clinical experience with the compound and did not approve the drug for clinical use. More data were requested regarding safety issues, comparison with nitroglycerine, onset of effects, need for invasive haemodynamic monitoring and symptomatic improvement. The VMAC Study was designed to address these issues. A dosing regimen, 0.2 microgram/kg bolus followed by 0.01 microg/kg/min continuous infusion, was chosen to provide rapid onset of actions and haemodynamic improvement without a high incidence of symptomatic hypotension. Nesiritide was superior to iv. nitroglycerine in its haemodynamic effects, easier to administer without the need for dose titration and better tolerated overall. The drug could be administered safely without the need for invasive haemodynamic monitoring. Symptomatic hypotension occurred in 4% of patients. Beneficial haemodynamic effects correlated with symptomatic improvement in heart failure patients. Nesiritide appears to be an ideal first-line agent for treatment of patients with acutely decompensated heart failure.

Surgical management of carcinoid heart disease.

Two female patients with carcinoid heart disease, ages 56 and 32 years, underwent pulmonic valve resection surgery and tricuspid valve replacement with a porcine bioprosthesis. Preoperatively, both patients were in function class 4 with severe right-side congestive failure and signs of tricuspid regurgitation and pulmonic stenosis. Both underwent surgery for porcine tricuspid valve replacement (33 and 31 mm valves) and pulmonic valve resection. Postoperatively, both patients had only minimal symptoms, including trace ankle edema and soft pulmonic murmurs, despite persistence of the systemic symptoms of carcinoid syndrome. Pre- and postoperative catheterization data documented hemodynamic improvements. One patient eventually died of hepatic failure due to metastatic disease. At autopsy, her bioprosthesis was free of carcinoid valvular changes.

Intracoronary anastomosis in the absence of obstructive lesions of the coronary arteries.

The patient had collateral flow from the right coronary to left circumflex coronary artery in the absence of proximal obstructive disease. This supports the hypothesis that the intercoronary collaterals seen in coronary atherosclerotic disease are present in the normal heart.

Prolonged survival of a patient with left ventricular pseudoaneurysm following myocardial infarction and mitral valve replacement.

We present the case of a patient with left ventricular pseudoaneurysm following acute myocardial infarction. Survival for 2 years following diagnosis, despite the large size of the aneurysm, and subsequent management with cardiac transplantation represent unusual and interesting aspects of this complication of myocardial infarction.