Intracranial bleed during bridge to transplant may not preclude a successful result.

We report the case of a 29-year-old man who suffered sub-arachnoid bleeding while stabilized on a biventricular assist device as a bridge to cardiac transplantation. We adjusted his anti-coagulation therapy to control the bleeding and to concurrently minimize thrombosis while on support. He underwent 2 craniotomy operations to evacuate sub-arachnoid hematomas, and he underwent a subsequent operation to debride and close the dura. Eighteen days later, he underwent successful orthotopic heart transplant and was discharged to home 3 weeks post-transplant.

Ventricular assist device use with mechanical heart valves: an outcome series and literature review.

BACKGROUND: Management of postcardiotomy cardiogenic shock with a ventricular assist device (VAD) is a common and accepted therapeutic option. However, VAD use in patients with mechanical heart valves (MHVs) is thought to carry an increased risk of thromboembolus. We report a series of 7 patients with combined VAD-MHV and review the literature. METHODS: A retrospective review was performed on all patients who were supported with a ventricular assist device with a mechanical heart valve in place. A literature review was also performed from 1966 to 2000. RESULTS: Seven patients were identified from April 1988 to June 2000 as having VAD support with a MHV. One thromboembolic event was documented in the 7 patients (14%). Five of the 7 patients (71%) underwent VAD explantation. Overall survival rate was 3 of 7 (43%). Causes of death included heart failure, renal failure, multisystem organ failure, adult respiratory distress syndrome, and cerebral hypoxia. All patients who died had support withdrawn at the request of the family. All patients discharged are currently alive with length of survival of 3, 26, and 84 months. CONCLUSIONS: This study suggests that this population's rate of survival to discharge and risk of thromboembolus compare favorably to that of the general VAD population. We believe that anticoagulation can be managed as with any MHV patient and that flow rates can be kept slightly lower, which may encourage valve washing.

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.

Hemodynamic effects of supplemental oxygen administration in congestive heart failure.

OBJECTIVES: This study sought to determine the hemodynamic effects of oxygen therapy in heart failure. BACKGROUND: High dose oxygen has detrimental hemodynamic effects in normal subjects, yet oxygen is a common therapy for heart failure. Whether oxygen alters hemodynamic variables in heart failure is unknown. METHODS: We studied 10 patients with New York Heart Association functional class III and IV congestive heart failure who inhaled room air and 100% oxygen for 20 min. Variables measured included cardiac output, stroke volume, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance, mean arterial pressure and heart rate. Graded oxygen concentrations were also studied (room air, 24%, 40% and 100% oxygen, respectively; n = 7). In five separate patients, muscle sympathetic nerve activity and ventilation were measured during 100% oxygen. RESULTS: The 100% oxygen reduced cardiac output (from 3.7 +/- 0.3 to 3.1 +/- 0.4 liters/min [mean +/- SE], p < 0.01) and stroke volume (from 46 +/- 4 to 38 +/- 5 ml/beat per min, p < 0.01) and increased pulmonary capillary wedge pressure (from 25 +/- 2 to 29 +/- 3 mm Hg, p < 0.05) and systemic vascular resistance (from 1,628 +/- 154 to 2,203 +/- 199 dynes.s/cm5, p < 0.01). Graded oxygen led to a progressive decline in cardiac output (one-way analysis of variance, p < 0.0001) and stroke volume (p < 0.017) and an increase in systemic vascular resistance (p < 0.005). The 100% oxygen did not alter sympathetic activity or ventilation. CONCLUSIONS: In heart failure, oxygen has a detrimental effect on cardiac output, stroke volume, pulmonary capillary wedge pressure and systemic vascular resistance. These changes are independent of sympathetic activity and ventilation.

Neuropeptide Y infusion decreases plasma renin activity in postmyocardial infarction rats.

We wished to determine if chronic neuropeptide Y (NPY) infusion (1 ng/min for 1 week by Alzet minipump) could decrease plasma renin activity (PRA) and norepinephrine (NE) in a rat myocardial infarction (MI) model of moderate compensated congestive heart failure (CHF). CHF was produced by prior (6-8 weeks) ligation of the left coronary artery; control rats were sham-operated. Carotid arterial blood was drawn for PRA and NE in conscious unrestrained rats that had been instrumented 24 h earlier. MI rats had increased PRA as compared with sham-operated rats [8.73 +/- 1.27 vs. 5.10 +/- 0.91 ng angiotensin (AI) I/ml.h, mean +/- SE]. During chronic NPY infusion, PRA was reduced to normal in the MI group (4.78 +/- 0.91) but was not affected in the sham group (5.65 +/- 0.51). Plasma NE was altered similarly, but the changes did not reach statistical significance. These data suggest that NPY has the capacity to restrain renin release in moderate compensated CHF.

Matching the heart donor and heart transplant recipient. Clues for successful expansion of the donor pool: a multivariable, multiinstitutional report. The Cardiac Transplant Research Database Group.

Little information is available regarding donor-specific parameters that predict success or failure after heart transplantation. Furthermore, with increasing numbers of patients awaiting heart transplantation, there is tremendous pressure to expand the donor pool by stretching the margins of donor acceptability. To gain insight into donor-related and donor-recipient interrelated predictors of death after transplantation, 1719 consecutive primary transplantations performed at 27 institutions between Jan. 1, 1990, and June 30, 1992, were analyzed. Mean follow-up of survivors was 13.9 months, and actuarial survival was 85% at 1 year. By multivariable analysis, risk factors for death included younger recipient age (p = 0.006), older recipient age (p = 0.0005), ventilator support at time of transplantation (p = 0.0006), higher pulmonary vascular resistance (p = 0.02), older donor age (p < 0.0001), smaller donor body surface area (female donor heart placed into larger male patient) (p = 0.003), greater donor inotropic support (p = 0.01), donor diabetes mellitus (p = 0.01), longer ischemic time (p = 0.0003), diffuse donor heart wall motion abnormalities by echocardiography (p = 0.06), and, for pediatric donors, death from causes other than closed head trauma (p = 0.02). The overall 30-day mortality rate was 7% but increased to 11% when donor age exceeded 50 years and was 12% when inotropic support exceeded 20 micrograms/kg/min dopamine plus dobutamine and 22% with diffuse echocardiographic wall motion abnormalities. The interaction of donor risk factors was such that the heart of a smaller female donor given high-dose inotropes placed into a larger male recipient produced a predicted 30-day mortality rate of 26% and the heart of a 25-year-old male donor given high-dose inotropes with diffuse echocardiographic wall motion abnormalities transplanted into a 50-year-old male recipient led to a predicted 30-day mortality rate of 17%. This analysis supports cautious extension of criteria for donor acceptance but with an anticipated greater risk in the presence of diffuse echocardiographic wall motion abnormalities and long anticipated ischemic time, particularly in older donors given inotropic support.

Prejunctional angiotensin II receptors. Facilitation of norepinephrine release in the human forearm.

To determine if peripheral angiotensin II (Ang II) prejunctional receptors facilitating NE release exist in humans, we used [3H]NE kinetic methodology to measure forearm NE spillover during intrabrachial arterial Ang II infusions in eight normal male subjects. We used the following protocol to optimize conditions for demonstrating these receptors: (a) lower body negative pressure (-15 mmHg) to increase sympathetic nerve activity to skeletal muscle; and (b) intraarterial nitroprusside to maintain a high constant forearm blood flow (approximately 10 ml/min.100 ml) to maximize the proportion of neuronally released NE that spills over into the circulation. During lower body negative pressure, the following were infused intraarterially for three consecutive 20-min periods: saline, Ang II (4 ng/min), and Ang II (16 ng/min). During the Ang II infusions, forearm venous NE increased significantly from 173 to 189 and 224 pg/ml (P < 0.01), and forearm NE spillover increased from 384 to 439 and 560 ng/min.100 ml (P < 0.05 for high Ang II). Forearm NE clearance was unchanged. During low and high dose Ang II, the plasma venous Ang II concentrations were 25 and 97 pM, respectively. Since normal subjects increase plasma Ang II from 4 to 20-22 pM with exercise, standing, or diuretic administration, and patients with severe congestive heart failure can have a plasma Ang II of approximately 25 pM at rest, we suggest that Ang II might facilitate NE release in severe congestive heart failure, especially under conditions of stress.

Heart transplantation for tumor.

Unresectable cardiac tumors, although unusual, are often rapidly fatal. A 31-year-old woman presented with a large tumor arising from the left ventricle and causing symptoms of a constrictive cardiomyopathy. After evaluation with echocardiography, angiography, and computed tomography, an exploration was carried out to confirm the extent of disease. Orthotopic heart transplantation was subsequently performed when a donor organ became available. She is now alive and disease-free 12 months after transplantation.

Regulation of tissue noradrenaline in the rat myocardial infarction model of chronic heart failure.

OBJECTIVE: The aim was to evaluate mechanisms regulating tissue noradrenaline in congestive heart failure. METHODS: Tissue noradrenaline was measured in the conscious post myocardial infarction rat model of congestive heart failure and in sham operated rats (1) under control conditions, (2) 6 h after inhibition of tyrosine hydroxylase by the intraperitoneal administration of alpha-methyl-para-tyrosine (AMPT) (100 mg.kg-1 every 2 h), (3) 6 h after AMPT with desipramine pretreatment (0.3 mg.kg-1), and (4) following exhaustive exercise after AMPT. Tissue noradrenaline was extracted with perchloric acid and measured by high performance liquid chromatography with electrochemical detection. RESULTS: In control animals without drug, tissue noradrenaline concentration was lower in the following tissues in the rats with myocardial infarction compared with the sham operated group: left and right ventricles, spleen, soleus and white gastrocnemius muscles, kidney cortex, and tail artery. After AMPT, tissue noradrenaline concentration in the sham operated group was significantly lower than control; in the myocardial infarction group the fall in noradrenaline was only significant in the kidney, and group differences were no longer present. In the sham operated animals, coadministration of desipramine with AMPT attenuated the fall in tissue noradrenaline caused by AMPT in the heart and spleen. With exercise to exhaustion, cardiac noradrenaline was lower in rats with myocardial infarction than in sham operated rats, but higher in the soleus muscle. CONCLUSIONS: These data suggest that tissue noradrenaline depletion in congestive heart failure is not isolated to the heart, and it occurs despite activation of mechanisms that might be operating to conserve neuronal noradrenaline. One mechanism may be reduced organ blood flow to retard diffusion of noradrenaline into the circulation. If this increases interstitial noradrenaline concentration, it would facilitate prejunctional alpha 2 receptor restraint on noradrenaline release. Metabolic coronary vasodilatation during exercise reverses this process, and makes the heart most susceptible to noradrenaline depletion in congestive heart failure.

Comparison of norepinephrine and isoproterenol clearance in congestive heart failure.

Congestive heart failure (CHF) is accompanied by increased sympathetic nervous activity. Previous studies have demonstrated that plasma norepinephrine (NE), a marker of sympathetic nervous activity, is elevated in CHF due to increased NE spillover into the circulation and decreased NE clearance. In this study we compared the clearance of NE and isoproterenol (ISO) in eight CHF subjects (plasma NE 601 +/- 133 pg/ml), and in nine controls (plasma NE 285 +/- 53 pg/ml) by using steady-state infusions of tritiated NE ([3H]NE) and tritiated ISO ([3H]ISO). Because ISO is not a substrate of neuronal reuptake but is removed from the circulation in a way that is similar to NE after neuronal reuptake blockade with desipramine, ISO clearance may permit a gross estimation of non-neuronal uptake of circulating NE. The NE clearance was lower in CHF than in the control group (CHF 1.25 +/- 0.13, controls 2.04 +/- 0.22 l.min-1.m-2; P = 0.009). The ISO clearance was reduced similarly in CHF (CHF 0.90 +/- 0.09, controls 1.59 +/- 0.12 l.min-1.m-2; P less than 0.001). Because the ratio of ISO to NE clearance was similar in both groups, our findings suggest that a low cardiac output in CHF decreases the availability of circulating catecholamines to tissue elimination sites.

Acute myocarditis in fulminant systemic sclerosis.

Myositis and myocarditis have been reported in progressive systemic sclerosis, and these patients have had favorable therapeutic responses to intravenous pulse methylprednisolone. Thus far, premortem biopsy documentation of myocarditis and myocardial fibrosis has not been reported in such patients. We report the case of a patient with subacute congestive heart failure six months after she developed Raynaud's phenomenon. Clinical examination was typical of scleroderma but there was no proximal muscle weakness. She had elevated creatine kinase and MB-creatine kinase and laboratory evidence of hypothyroidism. Echocardiogram demonstrated four-chamber dilatation and severe left ventricular dysfunction. Cardiac catheterization revealed normal epicardial coronary arteries and severely decreased cardiac index. A skin biopsy specimen of the forearm was consistent with diffuse systemic sclerosis, and an endomyocardial biopsy specimen demonstrated mild fibrosis and lymphocytic infiltrate. Her heart failure initially improved with digoxin, furosemide, and enalapril. She also received L-thyroxine and intravenous methylprednisolone. The heart failure progressed over the next six weeks and she died. Patients with scleroderma and new-onset heart failure may have acute myocarditis.

Orthotopic heart transplantation with preoperative unsuspected left superior vena cava and absence of right superior vena cava.

We report the case history of a 47-year-old man who underwent orthotopic heart transplantation for ischemic cardiomyopathy. At the time of cardiectomy, the patient was found to have a persistent left superior vena cava draining into the coronary sinus and complete absence of his right superior vena cava. The donor heart had been removed without knowledge of this venous anomaly; consequently, the donor's superior vena cava and innominate vein were not harvested. The persistent left superior vena cava was cannulated for cardiopulmonary bypass. The recipient's heart was excised along the atrial ventricular groove, preserving the persistent left superior vena cava and coronary sinus. The atrial cuffs of the recipient and donor were fashioned for atrial-to-atrial anastomoses. Successful endomyocardial biopsies have been performed through the femoral veins after transplantation.

Time-constant adaptations in heart failure.

The circulatory compensatory mechanisms designed to cope quickly with physiological stress (e.g. sympathetic nervous system and the Frank-Starling mechanism) are less effective when there is chronic pathological stress, such as congestive heart failure (CHF). Other mechanisms come into play that operate over a longer time (e.g. activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and physiological deconditioning). Changes in blood vessels and skeletal muscle metabolism that result from inadequate delivery of oxygenated blood to working muscles belong to the group of mechanisms that develop slowly. When CHF therapy is successful, the abnormalities produced by this latter group of mechanisms will improve, but slowly. The concept that compensatory mechanisms have either short or long time constants for activation and reversal may explain why exercise tolerance improves much later than haemodynamics, which can be reversed acutely with vasodilator therapy.

Angioplasty of occluded coronary arteries: use of thin shaft balloon over-the-wire system without pre-dilatation.

A retrospective review was done on 13 consecutive patients who underwent PTCA of totally occluded coronary arteries using a recently released thin shaft balloon over-the-wire angioplasty system. Balloon size was determined by the closest fit to the arterial size and used without predilatation techniques. This technique was initially successful in 12 patients with only 2 clinically insignificant episodes of distal embolization and one probable early reclosure. Using thin shaft angioplasty systems, balloon dilatation of totally occluded coronary arteries can be done safely with a single balloon in many cases resulting in simplified procedures and economic benefits.

Effects of desipramine on norepinephrine clearance in congestive heart failure.

Elevated plasma norepinephrine (NE) in congestive heart failure (CHF) is caused by increased NE spillover and decreased NE clearance. To evaluate the effects of neuronal uptake blockade on NE clearance, we studied NE kinetics during steady-state infusions of [3H]NE, before and after oral desipramine (DMI, 50 mg) in 11 patients with CHF and 8 normal volunteers. Baseline plasma NE was greater in the CHF group (637 +/- 56 vs. 271 +/- 32 pg/ml; P less than 0.001), NE clearance was lower in CHF (1.31 +/- 0.21 vs. 1.94 +/- 0.17 l.min-1.m-2; P = 0.026), and NE spillover was greater in CHF (4.71 +/- 0.78 vs. 3.04 +/- 0.35 nmol.min-1.m-2, P = 0.054). After DMI, plasma NE rose significantly in CHF (778 +/- 67; P = 0.008), and NE clearance decreased further in CHF (0.97 +/- 0.16; P = 0.024), but neither changed in normal subjects. NE spillover did not change in either group. There appears to be an enhanced effect of DMI on NE clearance in CHF patients. Two general mechanisms may be responsible for this finding, an increased concentration of drug, possibly caused by a decreased volume of distribution, and an increased sensitivity of neuronal amine pumps to DMI. Both mechanisms may reflect a more general abnormality of clearance of drugs and hormones related to abnormalities of tissue perfusion in CHF.