Barry S. Clemson

The effect of age, diagnosis, and previous surgery in children and adults undergoing heart transplantation for congenital heart disease.

OBJECTIVES We sought to evaluate the outcomes and identify risk factors for mortality after heart transplantation (HT) for congenital heart disease (CHD) in infants, children, and adults. BACKGROUND CHD is considered a risk factor for mortality after HT, yet this unique group of patients represents a spectrum of complexity. METHODS There were 488 patients transplanted for CHD from the combined Pediatric Heart Transplant Study (1993 to 2002, n = 367) and the Cardiac Transplant Registry Database (1990 to 2002, n = 121) who were analyzed. RESULTS The median age at HT was 12.4 years. Primary diagnosis included single ventricle (36%), d-transposition of the great arteries (12%), right ventricular outflow tract lesions (10%), l-transposition of the great arteries (8%), ventricular/atrial septal defects (8%), left ventricular outflow obstruction (8%), and other (18%). Ninety-three percent of patients had at least 1 operation before HT. Survival at 3 months post-HT was significantly worse in CHD patients versus children with cardiomyopathy, but not adults with cardiomyopathy (86%, 94%, and 91%, respectively). There was no difference in conditional 3-month survival among the 3 groups. Five-year survival was 80%. Risk factors for early mortality were older recipient age, older donors with longer ischemic times, and pre-HT Fontan operations. Predicted survival in Fontan patients was lower (77% and 70% at 1 and 5 years) versus non-Fontan patients (88% and 81% at 1 and 5 years). Risk factors for constant phase mortality included younger recipient age, higher transpulmonary gradient, cytomegalovirus mismatch at HT, and earlier classical Glenn operation. CONCLUSIONS Patients undergoing transplantation for CHD have a good late survival if they survive the early post-operative period. Risk factors for reduced survival are older age at transplant and a previous Fontan operation.

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.

Coronary Plaque Morphology and Frequency of Ulceration Distant From Culprit Lesions in Patients With Unstable and Stable Presentation

Objective—Intravascular ultrasound studies describe ruptured coronary plaques at sites remote from the culprit lesion in patients with acute myocardial infarction (MI), suggesting multifocal plaque vulnerability. However, the role of intravascular ultrasound in the diagnosis of lesion vulnerability before rupture is unclear. Methods and Results—We compared morphology and frequency of ulceration of additional plaques proximal to the culprit lesion in 105 patients treated with emergent stenting during an evolving, acute MI in the CADILLAC study and 92 patients with stable/subacute presentation who underwent elective stenting. Additional plaques proximal to the culprit lesion were found in 52 (50%) and 54 (59%) patients in the acute MI and stable/subacute group, respectively. The prevalence of ulceration was significantly higher in the acute MI than in the stable/subacute group (19% versus 4%; P =0.014). However, there was no significant difference in other morphological lesion characteristics. Conclusions—Additional plaques are frequently found adjacent to the culprit lesions in patients undergoing percutaneous coronary intervention independent of clinical presentation. The increased prevalence of plaque ulceration but otherwise similar morphology of additional lesions in patients with acute MI versus stable/subacute presentation demonstrates the limitations of imaging in the assessment of plaque vulnerability.

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.

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

Objectives. The purpose of this study was to determine the effectiveness and safety of diltiazera 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 >140/-90 mm Hg after heart transplantation were randomized for ≥ 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 ≥ 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 1.30 ± 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 < 0.000). 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 discontination of the drug. Conclusions. These results indicate that both diltiazem and lisinopril are safe for treatment of hypertersion after heart transplantation, although titrated memotherapy with either drug controlled the condition in <50% of patients.

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.

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 populations 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.

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.

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.

Normalization of the norepinephrine kinetic response to orthostatic stress after cardiac transplantation

Abstract In summary, we have demonstrated through the use of forearm venous NE kinetic methodology that plasma NE and NE spillover increase normally in response to orthostatic stress after cardiac transplantation. These findings suggest that, in the absence of ventricular afferents, systemic arterial baroreflexes respond in a compensatory manner to activate the sympathetic nervous system.