Biomedical subjects
Publications and source records attributed to C E Angermann.
Toxoplasmosis may cause serious problems after organ transplantation. For treatment of active infection, pyrimethamine combined with a sulfonamide is recommended. During oral sulfadiazine therapy, a significant decrease in cyclosporine concentrations was observed in three heart transplant recipients. This interaction has not been reported previously.
Transesophageal echocardiography (TEE) is accepted as the procedure of choice for the diagnosis of intracardiac sources of systemic embolism. A case report is presented on a 74-year-old patient with atrial fibrillation referred for TEE evaluation after an acute embolic event. During TEE, atrial fibrillation converted to sinus rhythm. Although TEE is a very safe method, which is performed in increasing numbers of patients, this is the first reported case of conversion of atrial fibrillation to sinus rhythm during the procedure. We suggest that no restriction should be imposed on the use of TEE in patients with atrial fibrillation, as the small risk associated with conversion of atrial fibrillation is outweighed by the potential diagnostic benefits.
The effects of graded supine ergometry on blood pressure, heart rate, and plasma hormones were studied in 14 hypertensive heart transplant recipients before and after 2 weeks and 6 months of enalapril (20 mg/day) plus furosemide (20-80 mg/day) alone or combined with verapamil (120-360 mg/day). Each time, measurements were obtained at rest and at 25 and 50 W exercise. Antihypertensive therapy normalized blood pressure, while heart rate and the blood pressure response to exercise remained unaltered. Pretreatment resting plasma renin activity and catecholamine levels were normal, while atrial natriuretic factor and cyclic guanosine monophosphate concentrations were elevated. All hormones increased significantly with exercise. During treatment, plasma renin activity increased and atrial natriuretic factor and cyclic guanosine monophosphate levels decreased significantly, with a blunted exercise response; concentration of catecholamines increased significantly, with augmented exercise response. Thus, the chosen regimen allowed effective, lasting BP control in hypertensive transplant patients but was associated with significant changes in plasma hormones. Whereas the rise in plasma renin activity may be attributed to converting enzyme inhibition, the decreases in atrial natriuretic factor and cyclic guanosine monophosphate and increases in catecholamine levels seem to indicate marked changes in resting and particularly exercise hemodynamics during antihypertensive therapy.
Detection of acute cardiac allograft rejection (AR) remains an important clinical challenge. The role of Doppler echocardiography for the non-invasive diagnosis of AR is controversial, in particular with regard to milder forms of rejection. This study was designed to evaluate the potential of Doppler echocardiography for the non-invasive diagnosis of mild AR. Serial measurements of left and right ventricular filling parameters were performed in 31 heart transplant recipients and compared with simultaneously obtained endomyocardial biopsies. To account for biological and technical variability, consecutive rejection-free studies were used to calculate 95% confidence limits for mitral and tricuspid maximum early flow velocity and pressure half time. Measurements obtained during mild AR were then compared to these data. The study demonstrated that all parameters varied considerably between consecutive rejection-free examinations. Changes in left and right ventricular filling parameters during mild AR rarely exceeded the calculated 95% confidence limits. Thus Doppler echocardiography appears of little value for the non-invasive diagnosis of mild acute cardiac rejection.
This study was designed to evaluate quality of life and life changes after heart transplantation in long-term survivors, to compare the patients' results with those obtained from healthy subjects of similar age, and to correlate quality of life with psychological and clinical variables. Questionnaires were mailed to all 43 adult German-speaking transplant patients operated between 1982 and 1986. Forty-one (95%) of this patient population completed the questionnaires; 52 controls answered those questions not addressing transplant-specific issues. 83% of the transplant patients versus 88% of the controls rated global quality of life as "good" or "excellent". Psychological affect and well-being were comparable in both groups. 70% of the transplant patients versus only 30% of the controls stated "to be bothered by symptoms". Despite that response, heart transplant recipients perceived postoperative life changes mostly as positive, although sexual function and professional situation had worsened in 34% and 41%, respectively. Global quality of life correlated best with job satisfaction (r = 0.65, p less than 0.01), satisfaction about health (r = 0.64, p less than 0.01), well being (r = 0.53, p less than 0.01), and everyday life function (r = 0.53, p less than 0.01), and correlated negatively with depression (r = -0.40) and physical symptoms (r = -0.36). The study shows that the subjective quality of life of long-term survivors after heart transplantation is similar to that of healthy individuals of the same age group. Thus, survival is certainly not the only indicator of success; aspects of quality of life must also be included in cost effectiveness and/or cost benefit considerations in transplantation policies.
BACKGROUND: This prospective study was designed to examine whether left ventricular (LV) hypertrophy of the denervated transplanted heart may be reversed by medical therapy and, if so, to investigate the time course of this process and its effect on exercise capacity, myocardial function, and cardiac hemodynamics. METHODS AND RESULTS: Ten hypertensive heart transplant recipients with LV hypertrophy were evaluated before therapy with enalapril plus furosemide alone or combined with verapamil, at initial blood pressure (BP) control and after 3, 6, 9, and 12 months, using 24-hour noninvasive ambulatory BP monitoring, M-mode and two-dimensional echocardiography, and supine bicycle ergometry. Average 24-hour systolic and diastolic BP declined from 158 +/- 10 and 104 +/- 7 mm Hg to 129 +/- 9 and 84 +/- 10 mm Hg at initial BP control (p less than 0.005 and p less than 0.025, respectively) and total peripheral resistance from 1,687 +/- 177 to 1,376 +/- 122 dyne.sec.cm-5 (p less than 0.025), remaining normal thereafter. Exercise capacity remained unchanged during the study. LV mass, mass-to-volume ratio, and end-diastolic septal plus posterior wall thickness decreased progressively from 211 +/- 30 g, 2.49 +/- 0.62 g/ml, and 25.7 +/- 2.6 mm to 184 +/- 26 g, 2.22 +/- 0.46 g/ml, and 22.5 +/- 1.9 mm after 3 months (all p less than 0.025) and to 174 +/- 25 g, 2.07 +/- 0.38 g/ml, and 21.5 +/- 1.5 mm after 6 months (all p less than 0.005), remaining unaltered at 9 and 12 months. A correlation was found between the decrease in average 24-hour mean BP and LV mass after 3 months of antihypertensive therapy (r = 0.71, p less than 0.05). Systolic meridional wall stress, LV end-diastolic and stroke volume, ejection fraction, and cardiac output remained unchanged throughout the observation period. CONCLUSIONS: The results indicate that regression of LV hypertrophy is induced by effective antihypertensive therapy in the denervated transplanted heart. The extent of decrease in average 24-hour BP appears to be the main determinant for the extent of reduction in LV mass. LV afterload as characterized by systolic meridional wall stress, LV size and pump function, and physical exercise capacity of the transplant patients are not influenced by the therapeutic regimen chosen in this study.
The aim of this prospective study was to investigate both vasoconstricting and vasodilating plasma hormones and plasma factors regulating the circulatory homeostasis in patients with endstage congestive heart failure before and early after orthotopic heart transplantation and to evaluate factors which may influence their regulation. 19 patients with endstage congestive heart failure were analyzed serially before and 3-4 weeks after orthotopic heart transplantation. A significant decrease in plasma concentrations of noradrenaline (457 +/- 202 vs. 204 +/- 88 pg/ml; p less than 0.001), adrenaline (43 +/- 32 vs. 26 +/- 11 pg/ml), atrial natriuretic peptide (341 +/- 218 vs. 139 +/- 64 pg/ml; p less than 0.005), cyclic guanosine monophosphate (13.8 +/- 7.8 vs. 6.6 +/- 2.2 pmol/ml, p less than 0.05) and in plasma renin activity (16.6 +/- 13.0 vs. 2.0 +/- 2.4 ng AI/ml/h; p less than 0.01) was found after transplantation. The data indicate that the marked increase in plasma catecholamine concentrations and renin activity in endstage congestive heart failure is reversible as early as 3-4 weeks after heart transplantation. This is most likely the consequence of normalization of cardiac function. While elevation of atrial natriuretic peptide and cyclic guanosine monophosphate as well as increased vasoconstrictor activity in heart failure appear to be related to impaired ventricular function, the persistent moderate elevation of both vasodilating agents after transplantation may be compensatory to counteract cyclosporin-induced arterial hypertension after heart transplantation.
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Infection remains a major problem in the early phase after heart transplantation. Immunosuppressive therapy is the most important predisposing factor. It may also reactivate preexisting latent endogenous infections. Unspecific symptoms and a chronic clinical course, as described in this report, may suggest infective endocarditis of the cardiac allograft. From this case, we do not suggest a general antibiotic prophylaxis for heart transplant recipients; however, special precaution should be considered in heart transplant patients with a history of endocarditis.
The de novo hypertension, which develops in most cardiac transplant recipients within the first postoperative months, is multicausal, though toxic side-effects of cyclosporin A seem to play a key role. In order to analyze the circadian behavior of arterial blood pressure and heart rate after cardiac transplantation (HTX) and to evaluate the effect of an antihypertensive regimen on these parameters, 24-h noninvasive ambulatory blood pressure and heart rate monitoring was performed in 10 hypertensive cardiac transplant recipients on cyclosporin A (mean age 42.3 +/- 11.2 years, 14.3 +/- 8.3 months after HTX) before antihypertensive therapy and after introduction of an antihypertensive regimen with the ACE-inhibitor enalapril plus furosemide alone or combined with verapamil. The study demonstrated a complete loss of the usual nocturnal decline in blood pressure in cardiac transplant recipients (mean systolic and diastolic blood pressure 149 +/- 8 and 102 +/- 7 mm Hg during daytime and 152 +/- 8 and 104 +/- 9 mmHg at night). Antihypertensive therapy lowered the blood pressure level effectively, but did not influence the circadian pattern (mean systolic and diastolic blood pressure 121 +/- 8 and 81 +/- 4 mmHg during daytime and 121 +/- 9 and 83 +/- 3 mmHg at night, all p less than or equal to 0.001). Heart rate, in contrast, showed a significant, though in comparison to normal, a blunted decrease at night (mean heart rate 94 +/- 6 beats per min during daytime and 84 +/- 8 beats per min at night, p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Though endomyocardial biopsy has remained the gold standard for diagnosing acute cardiac rejection (AR), this invasive method does not provide adequate means for close monitoring of the rejection process. In order to assess the usefulness of M-Mode- and two-dimensional (2D) echocardiography for the noninvasive diagnosis of AR in heart transplant recipients on cyclosporin, 45 patients (mean age 40.6 +/- 8.8 years, 19.9 +/- 14.4 months postoperatively) were evaluated prospectively. Mean observation time was 9.1 +/- 4.8 months. Echocardiographic examination techniques were strictly standardized; besides measurements of left (LV) and right ventricular (RV) diastolic wall thickness and of the isovolumic relaxation time, computerized frame-by-frame-analysis was applied to LV short axis cross sections for the determination of diastolic cavity cross-sectional area and extent and mean velocity of systolic and diastolic area change. To account for technical and biological variability, 95%-confidence limits were calculated for each parameter from two rejection-free examinations, allowing identification of significant changes during AR. In this study, 36 biopsy-proven AR occurred in 19 patients. Compared to control values, mean heart rate increased from 86.2 +/- 10.2 to 94.6 +/- 15.1 b/min (p less than 0.05), diastolic septal + posterior wall thickness from 21.2 +/- 4.1 to 24.9 +/- 6.2 mm (p less than 0.001) and RV free wall thickness from 6.3 +/- 1.1 to 8.9 +/- 1.8 mm (p less than 0.001). Isovolumic relaxation time decreased from 73.2 +/- 14.4 to 54.8 +/- 16.6 ms (p less than 0.001), diastolic cross-sectional area from 12.8 +/- 2.0 to 11.1 +/- 2.2 cm2 (p less than 0.05), relative area change from 65.8 +/- 9.8 to 49.1 +/- 14.4% (p less than 0.001) and systolic and diastolic area change velocities from 28.1 +/- 7.8 and 41.8 +/- 8.5 cm2/s to 18.9 +/- 5.6 and 28.6 +/- 9.2 cm2/s, respectively (p less than 0.001). Though significant changes occurred during AR, most measurements remained within the normal range. Thus, in individual patients, AR could only be suspected in comparison to the control measurements. None of the examined parameters allowed to establish the diagnosis of AR in all instances. However, when the measurements of all parameters were considered together, 35 of the 36 AR diagnosed by biopsy could also be identified by echocardiography, including all requiring intensified immunosuppressive therapy. Mild AR was not always detected, and the differential diagnosis between LV hypertrophy and AR required an endomyocardial biopsy in some instances.(ABSTRACT TRUNCATED AT 400 WORDS)
Introduction of ciclosporin A into immunosuppressive therapy is considered a major progress in improving results of organ transplantation. Clinical use of ciclosporin, however, is limited by a low therapeutic index and toxic side effects. Therefore, interactions of ciclosporin with other drugs are clinically important. In our study, we used enalapril, furosemide and verapamil for treatment of arterial hypertension in cardiac transplant recipients and investigated the influence of these drugs on ciclosporin whole blood trough levels. The antihypertensive regimen used in this study normalized blood pressure in each of the 25 patients. Enalapril and furosemide did not influence ciclosporin levels. Adding verapamil, however, resulted in a significant increase of ciclosporin levels, whereas cessation of the drug in one patient treated with verapamil only lowered ciclosporin levels. Thus, when verapamil is introduced or discontinued in patients on ciclosporin, close monitoring of ciclosporin levels and dosage adjustment are necessary. Besides its specific effects verapamil allows reduction of ciclosporin dosage necessary to maintain unaltered levels, which is important regarding cost of therapy. In general, use of any drug with unknown influence on ciclosporin levels requires careful monitoring, even if information exists on other substances of the same group of drugs in this respect. This is especially indicated in drugs known to influence the hepatic cytochrome P450 enzyme system.
In orthotopic heart transplantation atrial size and geometry are altered, whereas ventricles and atrioventricular valves remain structurally unchanged. To analyze the anatomy and function of the transplanted heart, 20 heart transplant recipients, with a mean age of 46.0 +/- 11.8 years, were examined with transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE). Both methods showed atrial enlargement and abnormal configurations of the atria. Although valve leaflet structure appeared normal, TEE showed mitral regurgitation in 13 patients (TTE, 11), mitral prolapse in three patients (TTE, two), tricuspid regurgitation in 17 patients (TTE, 17), and tricuspid prolapse in two patients (TTE, one). Only by TEE, "pseudoaneurysms" of the donor part of the interatrial septum were found in six patients and of the receiver part in one patient, possibly as consequence of unequal thickness, asynchronous contraction, and cyclic torsion of both atrial components during the cardiac cycle. Spontaneous atrial echo contrast--again visualized only by TEE--was seen in five patients and a left atrial thrombus in three patients. Spontaneous echo contrast and thrombus formation were associated. One patient with a thrombus had had peripheral arterial embolism. We conclude that, compared with TTE, TEE offers superior imaging of cardiac anatomy, intraatrial abnormalities, and function of the atrioventricular valves. Mitral and tricuspid incompetence are frequent after orthotopic heart transplantation and may be related to abnormal atrial size and function, leading to impaired functional integrity of the valvular apparatus. The high incidence of atrial spontaneous echo contrast and thrombi suggests that antiplatelet or anticoagulant therapy may be advisable in heart transplant recipients with these findings.
The introduction of cyclosporine to immunosuppressive therapy greatly improved the results of organ transplantation. The clinical use of cyclosporine, however, is associated with several serious side effects. Because the drug is primarily eliminated via biliary secretion and thus probably alters bile composition, we investigated the incidence of gallstones in 29 heart transplant recipients receiving immunosuppressive therapy with cyclosporine. Two of three female patients and none of the male patients had gallstones before heart transplantation. After operation, in nine of the 26 male patients cholelithiasis developed during cyclosporine therapy; seven cases of gallstones occurred within the first postoperative year. High cyclosporine blood levels, obesity, and diabetes mellitus in the early postoperative period appeared to be predisposing factors for formation of gallstones. Prevention of biliary calculous disease in heart transplant recipients is especially important because immunosuppressive therapy poses an additional risk on potential complications of cholelithiasis. An immunosuppressive regimen aimed at lower cyclosporine blood levels may help to avoid hepatobiliary complications.