Comparison of hemodynamic responses during dynamic exercise in the upright and supine postures after orthotopic cardiac transplantation.

Abnormal hemodynamic responses during supine exercise have been well documented in orthotopic cardiac transplant recipients. To determine the effect of posture, central hemodynamics were studied in 20 patients during a change from supine to sitting and during graded upright bicycle exercise (group U) and were compared with those of 20 patients matched for age, gender and time from transplantation who were studied after passive leg elevation and during exercise in the supine posture (group S). Passive leg elevation resulted in a 9% increase in stroke index (34 +/- 6 to 37 +/- 6 ml/m2, p less than 0.001) and a 10% increase in cardiac index (3.1 +/- 0.4 to 3.4 +/- 0.5 liters/min per m2, p less than 0.001) in group S patients compared with a 15% reduction in stroke index (34 +/- 7 to 29 +/- 6 ml/m2, p less than 0.001) and a 9% decrease in cardiac index (3.2 +/- 0.6 to 2.9 +/- 0.5 liters/min per m2, p less than 0.001) in group U patients on assuming the sitting posture. Likewise, both the pulmonary capillary wedge pressure and right atrial pressure increased significantly (13 +/- 4 to 17 +/- 8 mm Hg, p less than 0.001 and 5 +/- 3 to 7 +/- 3 mm Hg, p less than 0.001) with passive leg elevation in group S and decreased on sitting (12 +/- 6 to 8 +/- 5 mm Hg, p less than 0.001 and 5 +/- 3 to 3 +/- 2, p less than 0.001) in group U.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac dynamics during supine exercise in cyclosporine-treated orthotopic heart transplant recipients: assessment by radionuclide angiography.

The mechanisms by which the denervated heart responds to supine exercise were assessed by equilibrium gated radionuclide angiography in 18 cardiac transplant recipients 1 to 25 months (mean 11) after surgery. Results were compared with those in 15 normal subjects. Exercise duration among transplant recipients did not differ significantly from that in normal subjects. The heart rate at rest in transplant patients was 30% higher than in normal volunteers. Heart rate increased only 3% between rest and the first stage of exercise in transplant recipients compared with a 37% increase in the normal group (p less than 0.001). Cardiac output at rest was similar in both groups although the rate of rise of cardiac output and peak cardiac output were significantly lower among the transplant recipients. In early exercise, the means by which cardiac output increased in the transplant patients differed significantly from normal. In the transplant recipients, the left ventricular end-diastolic volume index increased 14% compared with a decrease of 2% in normal subjects (p less than 0.001) during the first stage of exercise. At the same time, the end-systolic volume index increased 6% in the transplant group but decreased 11% in normal subjects (p less than 0.001). These changes resulted in an overall increase in stroke volume by 20% in the transplant group compared with only a slight increase (+3%) in normal subjects (p less than 0.001) during the first stage of exercise. Among transplant recipients, the stroke volume index plateaued after the first stage of exercise, which, in combination with the blunted chronotropic response, resulted in a peak cardiac index 25% lower than that in normal subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. The Quinapril Heart Failure Trial Investigators.

OBJECTIVES: This study was performed to assess the efficacy, safety and clinical consequences of abrupt cessation of quinapril therapy in a placebo-controlled, randomized, double-blind withdrawal trial. BACKGROUND: Angiotensin-converting enzyme inhibitor therapy has assumed a pivotal role in the treatment of chronic heart failure. Quinapril hydrochloride, a nonsulfydryl angiotensin-converting enzyme inhibitor, has shown beneficial clinical effects in previous studies. METHODS: After > or = 10 weeks of single-blind quinapril therapy, 224 patients with New York Heart Association class II or III heart failure were randomized in double-blind fashion to continue quinapril (n = 114) or to receive placebo (n = 110) for 16 weeks. Changes in treadmill exercise time, New York Heart Association functional class, quality of life and symptoms of heart failure were assessed. RESULTS: Patients withdrawn to placebo had a significant deterioration in exercise tolerance (median change -16 s with placebo vs. +3 s with quinapril, p = 0.015). New York Heart Association functional class (p = 0.004) and quality of life were improved and signs and symptoms of congestive heart failure were lessened in those remaining on quinapril therapy compared with those receiving placebo. During double-blind treatment, 18 patients were withdrawn from the placebo group because of worsening heart failure compared with 5 patients withdrawn from quinapril treatment (p < 0.001). Rather than a precipitous deterioration of clinical status or early incidence of adverse events, withdrawal from quinapril was associated with steady worsening of heart failure, beginning 4 to 6 weeks after randomization to placebo. CONCLUSIONS: Quinapril is effective and safe for maintaining clinical stability in patients with moderate congestive heart failure. Withdrawal of quinapril from patients with heart failure results in a slow progressive decline in clinical status.

Serial imaging of canine myocardial infarction by in vivo nuclear magnetic resonance.

Anterior infarction was produced in eight dogs to characterize serial changes in nuclear magnetic resonance signal intensity within the infarct zone. Magnetic resonance imaging was done on the day of infarction, on day 4, 5 or 6, on day 13 and day 20 using a 0.15 tesla (6.25 MHz) resistive imager. Electrocardiographically triggered spin echo (30, 45 and 60 ms echo times) and inversion recovery (400 to 500 ms inversion time) pulse sequences were employed to obtain single slice images. On day 20, the excised hearts were sectioned and examined to determine infarct location and extent. In the spin echo images, signal intensity within the ischemic zone was visibly increased in seven of the eight dogs on the day of infarction, and in all dogs by days 4 to 6. Signal intensity remained elevated in all but two dogs at day 20. With inversion recovery imaging, changes in the infarct zone were highly variable; both ill defined increases and decreases in signal intensity were noted. With a 30 ms echo time, signal intensity in the infarct zone was increased on average 29.8 +/- 24.1% above that in normal myocardium on the day of infarction. The relative signal intensity increased to 62.4 +/- 23.5% during the first 2 weeks after infarction (p less than 0.05), then decreased to 12.0 +/- 18.5% by day 20 (p less than 0.05). Similar changes were detected in the images using the 45 and 60 ms echo times. Nuclear magnetic resonance imaging therefore is able to detect regions of myocardial infarction and follow evolutionary changes in signal intensity within the infarct zone with healing.

Etiology of the Austin Flint murmur.

OBJECTIVES: The aim of the study was to determine the mechanism of the Austin Flint murmur. BACKGROUND: More than 100 years after the initial description of the Austin Flint murmur, the etiology of the murmur remains unclear. METHODS: M-mode and two-dimensional echocardiography, conventional and color flow Doppler study, and cine nuclear magnetic resonance (cine NMR) imaging were performed in 24 patients with clinically moderate or severe aortic regurgitation. Mitral valve area was determined by planimetry and pressure half-time measurement. Overlap of the aortic regurgitation and mitral inflow jets was graded 0 (no overlap) to 4 (marked overlap) by Doppler study and cine NMR imaging. The volume of signal loss resulting from turbulent blood flow secondary to the aortic regurgitation jet was determined on cine NMR images, and the extent of contact with the left ventricular endocardium was graded 0 (no contact) to 4 (extensive contact). RESULTS: The presence of an Austin Flint murmur did not correlate with mitral valve area (2.7 +/- 0.8 cm2 with the murmur vs. 2.5 +/- 0.7 cm2 without), overlap of the aortic regurgitation and mitral flow jets (3 +/- 1 vs. 2.3 +/- 1.2), diastolic mitral regurgitation (50% vs. 71%) or fluttering of the anterior mitral valve leaflet (70% vs. 50%). The presence of an Austin Flint murmur correlated best with the volume of signal loss associated with the aortic regurgitation jet on cine NMR imaging (65 +/- 16 ml with the murmur. vs. 38 +/- 11 ml without, p less than 0.001) and the extent of contact of this signal loss with the left ventricular endocardium (2.9 +/- 0.5 vs. 1.5 +/- 0.4, p less than 0.0001). CONCLUSIONS: The Austin Flint murmur is caused by the aortic regurgitation jet abutting the left ventricular endocardium, resulting in the generation of a low-pitched diastolic rumbling.

Increased circulating monocyte activation in patients with unstable coronary syndromes.

OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.

Hemodynamic profiles at rest and during supine exercise after orthotopic cardiac transplantation.

To characterize the spectrum of hemodynamic findings after orthotopic cardiac transplantation, 20 healthy heart transplant recipients with no evidence of cardiac dysfunction by noninvasive testing were studied for 1 to 51 months (mean 15) following surgery. After routine endomyocardial biopsy, right-sided heart pressures and thermodilution cardiac outputs were measured at rest (supine) and during symptom-limited, graded supine exercise. In addition, the effect of respiration on right atrial pressures and waveforms was determined at rest (supine, legs down), and after passive leg raising (volume loading). During exercise, striking increases of pulmonary artery, pulmonary artery wedge and right atrial pressures were seen. The mean pulmonary artery pressure rose 45% during the first stage of exercise (p less than 0.001) and by peak exercise it had increased 87% above resting values. The pulmonary artery wedge pressure increased significantly with passive leg elevation (p less than 0.001) and during the first stage of exercise rose 61% above baseline values. By peak exercise the mean pulmonary artery wedge pressure was more than double the resting value. Similarly, the right atrial mean pressure increased significantly (p less than 0.001) with passive leg elevation and nearly tripled at peak exercise. All values promptly returned to near baseline after exercise. The cardiac output increased 98% during exercise. During early exercise, the rise in cardiac output was mediated primarily by an increase in stroke volume. At rest, there was an abnormal response in right atrial mean pressure during slow deep inspiration in 7 individuals with legs down and in 12 after passive leg elevation (volume loading), including 4 of 10 patients studied beyond 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic applicability of magnetic resonance imaging in assessing human cardiac allograft rejection.

To assess the diagnostic applicability of magnetic resonance imaging (MRI) for diagnosis of cardiac allograft rejection, 25 patients who recently underwent cardiac transplantation were studied on a 0.15-tesla resistive system within 24 hours of endomyocardial biopsy. Ten normal volunteers and 4 patients who had recent (within 2 weeks) nontransplant cardiac surgery were also studied. In the 19 transplant patients imaged within 24 days of graft implantation, only 1 had evidence of graft rejection on biopsy. However, all nonrejecting grafts had increased T1 and T2 values, 501 +/- 22 and 61 +/- 6 ms, respectively (mean +/- standard deviation) and the only rejecting graft had values of 496 and 60 ms, respectively. In the normal volunteers mean T1 was 352 +/- 18 ms and T2 was 35 +/- 6 ms. There was no significant difference in T1 and T2 values between patients who underwent nontransplant surgery and control subjects. In patients with nonrejecting transplants who were imaged more than 25 days after surgery, the T1 and T2 values had normalized to 359 +/- 17 ms and 36 +/- 7 ms, respectively (n = 28 images in 20 patients). However, in those grafts with rejection, T1 and T2 were both elevated to 502 +/- 21 ms and 62 +/- 6 ms, respectively (n = 15 in 13 patients); wall thickness was also increased. Fourteen of 15 late rejection events (more than 25 days after surgery) were correctly identified on the basis of increases in T1 and T2 to more than 2 standard deviations above normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in skeletal muscle morphology and biochemistry after cardiac transplantation.

Skeletal muscle biopsies (vastus lateralis) were performed in 12 patients (mean age 47 +/- 11 years) before and at 3 and 12 months after cardiac transplantation. Fiber type analysis revealed a predominance of type II fibers before cardiac transplantation (66 +/- 10%); the ratio did not change after transplantation. Fiber cross-sectional area increased by 35% to 39% in all fiber types by 12 months after cardiac transplantation. Fiber cross-sectional area, however, remained below the reported normal values. The number of capillaries surrounding each fiber did not change after cardiac transplantation. Skeletal muscle enzyme activity of phosphofructokinase, citrate synthase, and beta-hydroxyacyl coenzyme A dehydrogenase increased by 26%, 47%, and 63%, respectively, after cardiac transplantation (p < 0.05). Peak oxygen uptake also increased significantly after cardiac transplantation (19.5 +/- 8.1 ml/kg/min at 12 months vs 9.8 +/- 1.4 ml/kg/min before transplant, p < 0.01); however, uptake remained 40% below that of predicted. Thus, significant improvement in skeletal muscle morphology and biochemistry occurs in the first year after cardiac transplantation in association with improved exercise capacity. Recovery, however, may be incomplete, which could explain residual impairment of exercise capacity in these patients.

Serial evaluation of lipid profiles and risk factors for development of hyperlipidemia after cardiac transplantation.

To determine the prevalence, time course and factors responsible for hyperlipidemia after heart transplantation, 83 consecutive 1-year survivors were studied. By 1 year, 83% of patients had serum total cholesterol levels greater than 5.2 mmol/liter (200 mg/dl) and 28% of the patients had serum total cholesterol higher than the age- and sex-matched ninety-fifth percentile. At the end of 1-year follow-up, serum total cholesterol correlated with the recipient age (p less than 0.0001), the preoperative cholesterol level (p less than 0.001), the actual dose of maintenance prednisone at 1 year (p less than 0.02) and the cumulative 1-year steroid dose (p less than 0.03). Similarly, the serum triglyceride level at 1 year correlated with the pretransplant level of serum triglycerides (p less than 0.0001), recipient age (p less than 0.03) and cumulative 1-year steroid dose (p less than 0.03). Patients with a pretransplant diagnosis of coronary artery disease had a significantly higher level of serum total cholesterol and triglyceride levels at 1 year (p less than 0.02 and p less than 0.03, respectively). Heart transplant recipients with body mass index greater than or equal to 25 kg/m2 also presented with significantly elevated serum total cholesterol and triglyceride levels at 1 year compared with nonobese patients (p less than 0.01 and p less than 0.002, respectively). Hyperlipidemia occurs frequently and is detected within the first month after heart transplantation. Optimal management of this problem requires further study.

Evolution of heart rate responsiveness after orthotopic cardiac transplantation.

Although anatomic reinnervation of the donor heart is unlikely after transplantation, individual subjects have been noted to show near physiologic heart rate (HR) responses to exercise. To assess development of this phenomenon, we studied HR changes in response to orthostasis and treadmill exercise in 52 orthotopic cardiac transplant recipients grouped according to time after transplantation. In group 1 (2.0 +/- 0.9 months), no significant increase in HR was seen up to 100 cardiac cycles after standing. A maximal acceleration of 4.0 +/- 3.8 beats was seen within 100 cardiac cycles after standing in group 2 (15.8 +/- 5.6 months). Patients in group 3 (42.4 +/- 12.4 months) showed significant cardioacceleration by 5 cardiac cycles after standing to a maximum of 10.7 +/- 5.8 beats/min within the first 100 cardiac cycles. During exercise, HR increased more rapidly during the first minute in group 3 compared with group 1 (p less than 0.01). After exercise, HR continued to increase in group 1 but decreased rapidly in the other groups, most notably group 3 (-26.5 +/- 16.5 by 2 minutes, p less than 0.0001 vs groups 1 and 2). These data indicate development of functional reinnervation after orthotopic heart transplantation. The phenomenon of early acceleration of the HR after orthostasis and rapid deceleration after exercise in transplant recipients implies a local cardiac mechanism rather than response to circulating catecholamines.

Frequency of angiographic detection and quantitative assessment of coronary arterial disease one and three years after cardiac transplantation.

The reported high incidence of coronary atherosclerosis in many transplant series led us to critically review our experience in 83 patients who have had selective coronary angiography at greater than or equal to 1 years after transplantation. Angiograms were reviewed for evidence of coronary vascular disease, and quantitative analysis of multiple coronary artery segments was performed in serial films. Qualitative analysis revealed only 3 of 83 patients with any angiographic abnormality at follow-up, 1 with minimal luminal irregularities in the right coronary artery at 1 year, a second with a 50% diameter stenosis of the proximal left anterior descending artery and minimal irregularity of the proximal circumflex artery at 1 year and a third patient who developed a new 30% diameter eccentric proximal right coronary artery stenosis at 3-year follow-up. The cumulative incidence of graft vascular disease assessed angiographically was therefore 2% at 1 year and 4% at 3 years. Quantitative analysis, however, showed a significant decrease in coronary artery luminal diameter over time. The mean left main coronary artery diameter decreased from 5.4 +/- 0.9 mm at 1 year to 4.7 +/- 0.8 mm at 3 years (p = 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)

Normalization of upright exercise hemodynamics and improved exercise capacity one year after orthotopic cardiac transplantation.

The mechanisms of improved functional capacity over the first year after cardiac transplantation are not well studied. To assess the contribution of cardiac changes to this improvement, the serial evolution of upright rest and exercise hemodynamics during graded upright bicycle exercise was studied in 17 patients at 3 and 12 months after heart transplantation. Heart rate responsiveness, reflected by rapid heart rate acceleration on sitting and rapid deceleration after exercise, developed in the first year. Pulmonary capillary wedge pressure was lower at 1 year, both at rest and at peak exercise (10 +/- 3 vs 13 +/- 5 mm Hg at rest supine and 14 +/- 6 vs 18 +/- 8 mm Hg at peak exercise, p less than 0.05). Similarly, right atrial pressures were also significantly lower at 1 year (4 +/- 2 vs 6 +/- 3 mm Hg at rest supine and 6 +/- 5 vs 11 +/- 5 mm Hg at peak exercise, p less than 0.05). Cardiac index at peak exercise was greater at 12 months (6.4 +/- 1.3 vs 5.8 +/- 0.8 liters/min/m2, p less than 0.05), mediated primarily by higher exercise heart rate (135 +/- 16 vs 125 +/- 12 beats/min, p less than 0.05). In the first year after heart transplantation, improved rest and exercise hemodynamics and heart rate responsiveness contribute significantly to the improved functional capacity observed in these patients.

Comparison of bepridil with nadolol for angina pectoris.

Bepridil hydrochloride is a unique calcium channel-blocking drug with anti-ischemic and type 1 antiarrhythmic properties. With a half-life of more than 40 hours, once-daily therapy is possible. Twenty-four patients (22 men, 2 women), mean age 58 years (range 43 to 72), with stable exertional angina were assigned to therapy with bepridil and nadolol in a randomized, double-blind, crossover trial. Antianginal efficacy was assessed by a diary of angina frequency and nitroglycerin consumption as well as by treadmill exercise testing. The effect of therapy on ventricular function was assessed by symptom-limited equilibrium gated exercise radionuclide angiography. During therapy with both nadolol and bepridil, the number of episodes of angina per week was significantly reduced and nitroglycerin consumption decreased compared with baseline evaluation. Exercise duration was prolonged by both therapies (baseline 281 +/- 122 seconds, nadolol 377 +/- 96 seconds, bepridil 400 +/- 109 seconds; p less than 0.005 for nadolol and bepridil vs baseline). Time to the onset of angina was similarly prolonged, 50% by nadolol and 65% by bepridil (p less than 0.005). Bepridil had no effect on PR and QRS durations, although QTc was significantly prolonged (baseline 0.43 +/- 0.03, nadolol 0.42 +/- 0.03, bepridil 0.45 +/- 0.04; p less than 0.005 for bepridil vs baseline and nadolol). By radionuclide angiography, neither nadolol nor bepridil had an adverse effect on left ventricular function at rest or during exercise. Bepridil therefore provides effective therapy for angina without adverse effects on left ventricular function, comparable to the effects of beta blockade with nadolol.

Reduction in bleeding after heart-lung transplantation. The importance of posterior mediastinal hemostasis.

To reduce perioperative hemorrhage following heart-lung transplantation, several technical modifications were introduced in June 1988 to secure better posterior mediastinal hemostasis. The intraoperative and postoperative use of blood and blood products, as well as the chest tube drainage in the first 24 hours postoperatively, were compared in the seven patients operated on since June 1988 with the nine patients operated on before that date. Significant (p less than 0.05) reductions were demonstrated in the intraoperative and postoperative transfusion of packed cells, in the postoperative administration of fresh frozen plasma, and in the chest tube drainage within the first 24 hours postoperatively. The one-month and total hospital mortality rates were 6 percent and 12.5 percent, respectively. It is concluded that newer techniques to obtain optimal posterior mediastinal hemostasis have significantly reduced blood loss following heart-lung transplantation in our experience and have contributed to our excellent early postoperative results.

The importance of acquired diffuse bronchomalacia in heart-lung transplant recipients with obliterative bronchiolitis.

The results of heart-lung transplantation are improving with increasing experience in postoperative management, but obliterative bronchiolitis may still develop late postoperatively. We have performed 19 heart-lung transplants, with 1-month, 1-year, and 2-year actuarial survival rates of 95% +/- 5%, 84% +/- 8%, and 69% +/- 16%, respectively. Three early recipients died of bronchiolitis, and four patients who were operated on more than 2 years ago are currently being followed up with bronchiolitis. Since August 1988, 13 surviving recipients have undergone serial postoperative bronchoscopies and transbronchial biopsies with topical analgesia. Diffuse bronchomalacia, involving the main bronchi down to the fifth-order bronchi bilaterally, has developed in four patients with bronchiolitis 9 +/- 2 months after the diagnosis of bronchiolitis was confirmed. Pulmonary function tests have revealed a lower ratio of forced expiratory volume in 1 second to forced vital capacity, lower specific airway conductance, and higher airway resistance in heart-lung recipients with bronchomalacia than in patients with bronchiolitis alone. We conclude that diffuse bronchomalacia occurs frequently in heart-lung transplant recipients who have obliterative bronchiolitis. Bronchomalacia worsens the functional airflow obstruction caused by bronchiolitis and may play an important role clinically in the declining respiratory status of heart-lung transplant recipients.

Heart transplantation after cardioverter-defibrillator implantation. A case control study.

A case control study was performed to determine whether previous implantable cardioverter-defibrillator (ICD) insertion adversely affects outcome after heart transplantation. Six male heart transplant recipients who had undergone ICD insertion 12 +/- 5 months before heart transplantation were compared to a cohort of six heart transplant recipients who were matched according to age, preoperative status and hemodynamics, date of transplantation, graft ischemic time, history of a previous cardiac operation, and duration of follow-up. There were no significant differences in operating room time, chest tube drainage, time to extubation, and the duration of intensive care unit or hospital stay between the two groups. Furthermore, there were no significant differences in the number of units of packed cells, fresh frozen plasma, platelets and cryoprecipitate transfused. The number of treated rejection episodes and the number of patients requiring intravenous antibiotics for infection in the first 90 days was identical between groups. It was concluded that heart transplantation after ICD implantation did not appear to carry more risk than heart transplantation after a previous cardiac operation. Our limited experience supports the potential use of the ICD in patients with life-threatening ventricular dysrhythmias who are awaiting transplantation.

Routine surveillance myocardial biopsies are unnecessary beyond one year after heart transplantation.

BACKGROUND: Myocardial rejection is most apt to occur in the first 90 days after heart transplantation. Nevertheless, surveillance endomyocardial biopsies are often performed on a regular basis, indefinitely. The benefit of this approach to patient management is uncertain. Our objective was to determine the frequency of abnormalities and the influence of a routine annual endomyocardial biopsy on patient management. METHODS: In a consecutive series of 235 transplant recipients who survived 1 year or more, the results of 1123 routine endomyocardial biopsies performed 1 year or more after transplantation were reviewed. The incidence of late rejection, presence of Quilty effect (focal endocardial or myocardial lymphocytic aggregates), and therapeutic reaction to the biopsy result were analyzed. RESULTS: Of 1123 biopsy specimens in 235 patients (1 to 12 years after transplantation), 1115 (99.3%) showed no evidence of significant rejection (grade 0 or 1). Only seven (0.6%) had evidence of rejection grade 2 or worse. Of the seven abnormal biopsy specimens in seven patients, two occurred at 1 year, two at 2 years, and one each at 4, 7, and 8 years. Of these, six were treated for rejection with an increase in the immunosuppressive therapy. One patient was identified as having a symptomatic condition at the time of biopsy. A focal endocardial or myocardial accumulation of lymphocytes (Quilty effect) was present in 311 biopsy specimens (27.6%). Beyond 1 year, 33 patients died, 14 because of graft vascular disease with or without rejection and 19 because of other causes. No deaths were predicted on the basis of a routine surveillance biopsy. CONCLUSIONS: Myocardial rejection is rare beyond 1 year after transplantation. The routine endomyocardial biopsy does not significantly impact patient management beyond 1 year. A selective approach to myocardial biopsies, on the basis of a change in clinical status or immunosuppressive medications, is justified.

Cholesterol-lowering therapy after heart transplantation: a 12-month randomized trial.

BACKGROUND: Hypercholesterolemia, a common problem after heart transplantation, may be important in the genesis and progression of allograft coronary artery disease. The current study was performed to compare the efficacy of gemfibrozil, simvastatin, and cholestyramine for cholesterol lowering in heart transplant recipients. METHODS: In this prospective 1-year study, 48 heart transplant recipients with moderate hypercholesterolemia were randomized to therapy with gemfibrozil 600 mg twice daily (n = 17), simvastatin 10 mg daily (n = 13), and cholestyramine 4 gm twice daily (n = 18). Detailed lipoprotein analysis was performed at baseline and after 3, 6, and 12 months of treatment. RESULTS: Total cholesterol and low-density lipoprotein cholesterol were reduced 19% and 29%, respectively, after 3 months of simvastatin therapy (p < 0.0001) with a sustained reduction in total cholesterol (25%) and low-density lipoprotein cholesterol (39%) at 1 year. Gemfibrozil and cholestyramine treatment did not result in a reduction in cholesterol levels. Apolipoprotein B levels were reduced by 29% at the end of 1 year with simvastatin but not with the other treatments. Serum triglyceride levels were reduced significantly by treatment with gemfibrozil (up to 36%, p < 0.01) but not by the other treatments. High-density lipoprotein cholesterol initially rose in patients treated with simvastatin and gemfibrozil; however, this effect did not persist to 12 months. However, the ratio of low-density lipoprotein/high-density lipoprotein was favorably affected by simvastatin, with a 38% reduction by 12 months (p < 0.0001) but not by the other treatments. Over the course of 1 year, 14 patients dropped out of the study: four from the gemfibrozil arm and ten from the cholestyramine arm. Gastrointestinal intolerance was the most common reason for study termination (8 of 14). All patients in the simvastatin treatment arm completed 12 months of therapy. No biochemical abnormalities resulted from any therapy, and no therapy caused significant alteration in cyclosporine blood levels. CONCLUSIONS: Of the three therapies studied, simvastatin was found to be the most efficacious and well tolerated for cholesterol lowering in patients after heart transplantation.

Extending cardiac allograft ischemic time and donor age: effect on survival and long-term cardiac function.

Of 219 heart transplant patients with follow up for at least 3 months after transplantation, cardiac allograft ischemic time was more than 4 hours in 28% and more than 5 hours in 10%. In 1988 and 1989 grafts with ischemic times longer than 4 hours were used in 44% and 45% of cases, respectively. Overall, donor age has been 35 or more years in 22% and 45 or more in 9%. In 1989 donor age was 35 or more years in 39% of cases and 45 or more in 18%. Fifteen of 20 grafts from donors 45 years or older were used for patients aged 50 or older. There was no relationship between donor age or ischemic time and 90-day graft loss. At 3 and 12 months, cardiac function, assessed by treadmill exercise duration, radionuclide angiography, and rest and peak supine exercise hemodynamics, was also unrelated to donor age or ischemic time. Therefore by careful selection of appropriate donors, extending both graft ischemic time and donor age has increased the potential donor pool and has not to date been associated with increased graft loss or adverse effects on cardiac function 3 months and 1 year after heart transplantation.