Electron-beam computed tomography in the assessment of coronary artery disease after heart transplantation.

BACKGROUND: Our aim was to compare the electron-beam CT (EBCT) features of coronary arteries in heart transplant recipients with those of biplane coronary angiography and intracoronary ultrasound (ICUS). METHODS AND RESULTS: We examined 112 heart transplant recipients (25 female; age, 17 to 69 years; median, 52 years) 1 to 153 months (median, 46 months) after surgery by EBCT to detect coronary artery calcifications. Calcifications were quantified by the Agatston scoring system. EBCT scores were compared with coronary angiography in all patients and ICUS of the left anterior descending coronary artery (LAD) in 100 patients. Coronary artery calcifications were found in 84 patients (75%). Angiographically, 16 patients displayed >50% coronary artery stenoses, all of whom had some degree of coronary artery calcification and only 1 of whom had a score of <55 (P<0.0001). With this threshold, EBCT had a sensitivity of 94%, a specificity of 79%, a positive predictive value of 43%, and a negative predictive value of 99% for detecting stenosis. ICUS confirmed the presence of calcified plaques in all patients with an LAD score >9. EBCT total calcium score was associated with the degree of intimal proliferation in that patients without ICUS features of allograft vasculopathy had a median score of 0 (25th percentile, 0; 75th percentile, 0), whereas patients with Stanford class IV vasculopathy had a median score of 41 (9 to 98, P<0.0001). CONCLUSIONS: EBCT is a promising noninvasive test for the detection of coronary heart disease in cardiac transplant recipients.

Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) frequently is a progressive disease without causative therapy options. Following the hypothesis that in certain patients autoantibodies against cardiac structures may induce, maintain, or promote the progression of the disease, we investigated whether the elimination of these autoantibodies through immunoadsorption would improve cardiac function. METHODS AND RESULTS: This prospective case-control study included 34 patients with IDC. Each patient presented with moderate to severe heart failure and evidence of autoantibodies directed against beta(1)-adrenoceptors (beta(1)-AABs). Seventeen patients received standard medical therapy (control group), whereas 17 were also treated with immunoadsorption (treatment group) to eliminate beta(1)-AABs. A 1-year follow-up included echocardiographic assessment of left ventricular ejection fraction and internal diameters, beta(1)-AAB levels, and clinical status every 3 months. Within 1 year, the mean+/-SD left ventricular ejection fraction rose from 22.3+/-3.3% to 37.9+/-7.9% (P=0.0001) in the treatment group, with a relative increase of 69.9%. However, in the control group, no overall increase was seen (from 23.8+/-3.0% to 25.2+/-5.9%, P=0. 3154). Left ventricular diameter in diastole decreased by 14.5% from 74.5+/-7.1 to 63.7+/-6.0 mm in the treatment group (P=0.0001) and by 3.8% (P=0.2342) in the control group. In the treatment group, the NYHA functional rating improved after immunoadsorption (P=0.0001). beta(1)-AABs did not increase anew. CONCLUSIONS: In IDC, the use of immunoadsorption is superior to the use of standard medical therapy. It significantly improves cardiac performance and clinical status.

Radiologic anatomy of ventricular assist devices.

Ventricular assist devices (VAD) allow for long-term circulatory support of patients with end-stage heart failure. With the increasing duration of circulatory support, diagnostic imaging plays an important role in the management of patients on a VAD. The aim of our review was to analyze the radiologic features of different VADs. From 1987 to 1996, 319 patients (mean age 42 years, range 3 to 74 years) were treated with a VAD. A Berlin Heart VAD was implanted in 263 of the patients, the univentricular Baxtor Novacor was implanted in three patients, and the univentricular CI Heartmate was implanted in 19 patients. All patients were studied by serial chest radiographs. In addition, 70 patients underwent computed tomography (CT), and five patients underwent electron beam CT. The Berlin Heart VAD was used as a biventricular support system in 218 patients. In all cases, the position of the wire-directed cannulae was identified on the chest radiographs, while the exact position of the cannula tip could be visualized by CT only. The plastic cannulae of both the Novacor and the Heartmate were not discernible on radiographs, but required CT for evaluation. Computed tomography also resolved the metal components of the pumps. The titanium-made pump housing of the Heartmate caused beam-hardening artefacts that might conceal fluid accumulations in the pump pocket. Computed tomography is the standard of reference for examinations of cannula position, pump position, and pump components of ventricular assist devices.

Cardiac recovery in dilated cardiomyopathy by unloading with a left ventricular assist device.

BACKGROUND: Lasting recovery from intractable end-stage dilated cardiomyopathy, which occurs with ventricular unloading, has recently been demonstrated in 5 patients. Here our extended clinical experience with the "weaning" concept is presented. METHODS: In 19 patients (23 to 65 years) with intractable end-stage dilated cardiomyopathy, ventricular assist devices were explanted after support periods of up to 26 months, when repeat off-pump studies had shown either restoration of cardiac function (left ventricular ejection fraction, > 45%) and dimensions (left ventricular internal diameter in diastole, < 55 mm) or partial recovery (left ventricular ejection fraction between 35% and 40%) with serious complications on the device. At the time of device placement left ventricular ejection fraction was below 20% and left ventricular internal diameter in diastole more than 64 mm and bridge-to-transplantation had been planned. RESULTS: Seven patients with persistently restored cardiac function for more than 8 months and 5 patients for less than 5 months after weaning were studied. Five patients with recurrent heart failure died within 4 to 8 months after explantation. Four patients had to be transplanted and 2 died for reasons unrelated to cardiac function. An individual optimal left ventricular ejection fraction and left ventricular internal diameter in diastole was reached before pump removal was actually conducted in all patients. These parameters gradually deteriorated until pump removal. CONCLUSIONS: Lasting recovery can be reached by ventricular unloading in a subset of patients with intractable end-stage dilated cardiomyopathy. Obviously, there is an individual optimum of recovery that cannot be further improved by prolonged unloading.

Ventilatory and diffusion abnormalities in long-term survivors after orthotopic heart transplantation.

OBJECTIVE: To investigate the long-term development of pulmonary diffusion abnormalities after orthotopic heart transplantation (oHT). DESIGN: Retrospective analysis of pulmonary function test results of different patient groups at different time intervals after oHT was performed. PATIENTS: This investigation included 642 patients who had undergone oHT for chronic heart failure. Patients were grouped according to the time elapsed after transplantation (group 1: n = 164; age, 47 +/- 14 years; days after oHT, 324 +/- 101; group 2: n = 100; age, 48 +/- 15 years; days after oHT, 723 +/- 104; group 3: n = 106; age, 52 +/- 12 years; days after oHT, 1,092 +/- 98; group 4: n = 84; age, 51 +/- 13 years; days after oHT, 1,442 +/- 99; group 5: n = 61; age, 50 +/- 14 years; days after oHT, 1,819 +/- 105; group 6: n = 101; age, 53 +/- 12 years; days after oHT, 2,463 +/- 303; and group 7: n = 26; age, 54 +/- 14 years; days after oHT, 3,478 +/- 246). In 56 (group 8) of the 642 patients, follow-up measurements were performed with tests before and at two time points after oHT (6.5 +/- 1.7 and 12.5 +/- 9.3 months). RESULTS: Of all patients, 39% showed restrictive and obstructive abnormalities with no differences between the groups. No significant differences in lung transfer factor for carbon monoxide (DLCO) were observed (61.2 vs 63.7 vs 65.5 vs 65.6 vs 64.5 vs 65.7 vs 67.6% predicted). Differences in transfer coefficient for carbon monoxide (Kco) were significant between group 1 and 4 (58.7 vs 64.1% predicted), and group 1 and 6 (58.7 vs 63.4% predicted). No differences occurred in the rate with which patients exhibited pathologic abnormalities for DLCO and KCO. After oHT, a marked reduction in diffusion capacity occurred in group 8. On follow-up, these measurements were only slightly restored in terms of the predicted DLCO percentage. No such improvement was observed in KCO or in the rate of pathologic changes for both DLCO and KCO. We conclude, therefore, that the impairment of diffusion does not improve even after a significant period has passed after the oHT. Whether this has any effect on symptoms and/or the prognosis for these patients is extremely unclear.

[Electron-beam computed tomography in heart surgery]. / Elektronenstrahl-Computertomographie in der Herzchirurgie.

PURPOSE: Electron beam CT (EBCT) has been devised to improve the imaging of the heart and the great vessels. Therefore, this method is expected to facilitate the imaging workup of patients referred for cardiothoracic surgery. We set out to review the most important surgical issues that can be addressed with this method. METHODS: From June, 1997 until July, 1998, more than 300 patients were referred from cardiothoracic surgery. In a retrospective analysis, diagnostic results were reviewed and compared with surgical findings and the clinical course. RESULTS: Aortocoronary bypass graft occlusions were detected with a sensitivity of 100% and a specificity of 95%. Calcifications of the aorta, pericardium and intracardiac tumors were surgically confirmed in all instances. There was a significant association of the degree of coronary artery calcification and the progression of cardiac allograft vasculopathy in 50 heart transplant recipients. In EBCT of the aorta, a high degree of diagnostic confidence was found for aortic dissection, aortic wall hematoma or aortic perforation. CONCLUSIONS: We conclude that EBCT represents an important diagnostic tool both for surgical planning and postoperative surveillance in cardiothoracic surgery.

Successful mechanical circulatory support for more than two years with a left ventricular assist device in a patient with dilated cardiomyopathy.

A 36-year-old man with dilated cardiomyopathy was supported with a left ventricular assist device for 795 days. During this support time gradual functional recovery was noted. The patient tolerated the device well, enjoyed a good quality of life, and experienced no technical device-related problems. When a suitable donor heart became available, the device was switched off, and native ventricular function was assessed. This was judged to be acceptable, and the left ventricular assist device was successfully explanted. Postexplantation function remained acceptable and improved over the following days. The patient was discharged on the twentieth postoperative day and remains well.

Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Implantation of mechanical cardiac support systems (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. We report of long-term effects of ventricular unloading on cardiac function, humoral anti-beta1-adrenoceptor autoantibodies (A-beta1-AABs), and myocardial fibrosis. METHODS AND RESULTS: Seventeen patients in New York Heart Association functional class IV with nonischemic IDC received MCSS. All had a cardiac index of < 1.6 L x min(-1) x m(-2) of body surface area, a left ventricular ejection fraction (LVEF) of <16%, and a left ventricular internal diameter in diastole (LVIDd) of >68 mm and tested positive for A-beta1-AABs. Echocardiographic evaluation, serum tests for A-beta1-AABs, and histological assessment of myocardial fibrosis were performed before and after MCSS implantation. The mean support duration was 230+/-201 days. Six patients died, four were transplanted, and two are still on MCSS. Five patients with significant cardiac recovery (mean LVIDd, 54+/-2.3 mm; LVEF, 47+/-3.7%) were weaned after 160 to 794 days and are now device free for 51 to 592 days. A-beta1-AABs disappeared gradually during MCSS without increase after weaning; cardiac function and volume density of fibrosis remained normal. Nine patients' cardiac function hardly improved during ventricular unloading. CONCLUSIONS: Cardiac function can be normalized in selected patients with end-stage IDC by MCSS. The degree of preoperative myocardial fibrosis may be an indicator for outcome; A-beta1-AABs can be used to monitor myocyte recovery. Weaning from MCSS offers an alternative to cardiac transplantation in certain patients.

Long-term mechanical circulatory support as a bridge to transplantation, for recovery from cardiomyopathy, and for permanent replacement.

Since 1988, 295 patients have undergone MCS at the German Heart Institute Berlin; 246 received biventricular support with the extracorporeal pneumatically-driven Berlin Heart Assist Device, 49 received left ventricular support with implantable assist devices (33 Novacor, 16 TCI). Longer waiting periods for heart transplantation has caused the mean duration of MCS to increase from 12 days in 1988 to 76 days in 1994. Of the 24 patients who underwent MCS for more than 90 days, nine were implanted with a biventricular device, 12 with a Novacor device, and 15 with a TCI device. Eight patients with uni-ventricular devices remain on support after 200 days (range 203-600 days). Six of the Novacor patients could be discharged to a nursing home or to their own residences. One patient still on NC support after more than 600 days currently resides at his home and has regained normal physical activity. Minor pocket infections occurred in two TCI and four Novacor patients; one patient died of sepsis. A total of four patients could be weaned from LVAD after 160-347 days of MCS. An initial high level of beta1 receptor antibodies disappeared completely during left ventricular support. This decline in auto-antibodies was paralleled by a dramatic improvement in cardiac function. LVEF remained unchanged up to 6 months after explantation. Long-term mechanical support has become a reality. Heart transplantation after prolonged MCS yields results comparable to primary HTx. Some patients exhibit immunological changes and a dramatic improvement in ventricular function under long-term MCS and can be weaned with extremely satisfying results.

[Temporary mechanical left heart support. Recovery of heart function in patients with end-stage idiopathic dilated cardiomyopathy]. / Temporäre mechanische Linksherzentlastung. Erholung der Herzfunktion bei Patienten mit idiopathischer dilatativer Kardiomyopathie im Endstadium.

BACKGROUND: Implantation of a mechanical cardiac support system (MCSS) in patients with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and allow explantation of the device. Our experience now includes 13 patients who have been "weaned" from MCSS and we report about the overall results of this treatment as well as the effects of ventricular unloading on cardiac function, anti-beta 1-adrenoceptor-autoantibody (A-beta 1-AAB) level and the degree of myocardial fibrosis. METHODS: 13 patients with non-ischemic IDC who had been admitted here in cardiogenic shock (CI < 1.61.min-1.m2, left ventricular ejection fraction [LVEF] < 16% and left ventricular internal diameter in diastole [LVIDd] > 68 mm) and who all tested positive for A-beta 1-AABs were implanted with an uni-(12 patients) or a biventricular (1 patient) mechanical assist device. Echocardiographic evaluation and A-beta 1-AAB-level-monitoring was routinely performed after implantation and explantation of the MCSS and the degree of myocardial fibrosis was assessed at the time of implantation and after explantation. RESULTS: During a mean duration of mechanical support of 236 +/- 201 days (range: 30 to 794 days), LV-EF improved to a mean of 46% and LVIDd decreased to a mean value of 56 mm in these 13 patients. A-beta 1-AABs decreased and disappeared 11.7 weeks after implantation of the device and did not reincrease thereafter. The highly pathologic degree of fibrosis at the time of implantation diminished to normal values about 1 year after explantation. One patient died of anesthesiologic complications and another patient shortly presented with a new episode of cardiac insufficiency 6 months after explantation. He was implanted again with an univentricular assist device was successfully transplanted 3 weeks later. Mean observation period of the remaining 11 patients now amounts to 12.6 +/- 9.77 (range: 3 to 26) months after explantation of the device--as of May, 31, 1997--with a cumulative observation period of 139 patient months. CONCLUSION: Temporary implantation of a MCSS may normalize cardiac function in selected patients with IDC. The striking degree of myocardial fibrosis can reduce to normal values after explantation of the device. A-beta 1-AABs disappear during ventricular unloading and do not increase thereafter. "Weaning" from mechanical device may constitute an alternative treatment to cardiac transplantation in selected patients.

Reliable noninvasive rejection diagnosis after heart transplantation in childhood.

Rejection diagnosis was exclusively handled with noninvasive techniques in 16 children (mean age, 8.6 +/- 5.7 years; range, 0.9 to 15.2 years) over a total follow-up period of 18.3 patient years. No endomyocardial biopsies were performed. Intramyocardial electrogram recordings and echocardiographic investigations were used as two noninvasive techniques for rejection diagnosis. Daily noninvasive telemetric monitoring of the overnight intramyocardial electrogram was the major diagnostic guideline. The intramyocardial electrogram signal of the sleeping child was transmitted to a bedside receiver by an implanted telemetric pacemaker. The QRS amplitude was automatically analyzed and transferred to the in-hospital computer via a telephone modem connection. Rejection was diagnosed when QRS amplitude fell more than 8% below average baseline levels for 3 successive days, which was the indication for hospital admission. Medical antirejection treatment was instituted only if echocardiography showed impaired early diastolic left ventricular relaxation concomitant with a QRS-amplitude loss. The echocardiographic criterion was a prolongation of the parameter Te (Te is defined as the time span between onset of diastole and peak relaxation velocity of left ventricular wall) by more than 10 milliseconds compared to previous intraindividual values. Survival after a mean follow-up time of 13.7 months (range, 2 to 57 months) is 100%. A total of 22 rejection episodes were treated. During the first 6 postoperative months, the incidence of rejection requiring treatment was 1.4 episodes per patient. In patients at home, distant monitoring detected 13 episodes of a significant QRS-amplitude drop, which led to hospital readmission. In eight children, echocardiography was likewise positive, and rejection treatment was instituted. One child with positive intramyocardial electrography received antirejection treatment because of clinical evidence of rejection, although echocardiography was negative. In three instances, systemic infection was associated with the QRS-voltage loss. In one child a reason for QRS-complex reduction could not be identified. One rejection episode was treated on the grounds of clinical signs and positive echocardiography without a significant QRS-voltage drop. We conclude that distant noninvasive rejection monitoring based on meticulous application of the techniques described is a safe procedure. Daily monitoring of QRS amplitude in patients at home is an excellent safeguard against overlooking significant rejection episodes. This is of special importance in infants and children, in whom routine endomyocardial biopsy cannot be performed. Distant overnight monitoring minimizes psychosocial disturbance during follow-up after heart transplantation.

Clinical heart transplantation without routine endomyocardial biopsy.

In a prospective clinical study, routine endomyocardial biopsy (EMB) for early detection of cardiac allograft rejection was replaced by two noninvasive diagnostic techniques. In 32 patients who underwent transplantation during a 6-month period, intramyocardial electrogram (IMEG) amplitude was recorded with the telemetry function of a dual-chamber pacemaker system. An amplitude decrease of more than 8% below the individual range of variability in overnight long-term recordings served as an indicator of rejection. A prolongation of the time interval Te--the time span between maximal posterior wall contraction and peak retraction velocity--of more than 20 msec was used as an additional indicator of rejection-related left ventricular dysfunction. For patient safety, routine EMBs were still performed but remained undisclosed to the transplantation team. The pathologist was asked to intervene in cases of discrepancies between biopsy results and medical decisions, but no such intervention was necessary. Twenty-seven rejection episodes were treated medically, of which 22 were diagnosed noninvasively. In four patients, EMB, ordered because noninvasive parameters remained inconclusive, led to medical treatment. No false negative IMEG results were observed. Retrospective correlation with rejection gave a 100% negative predictive value for IMEG and a 96.9% negative predictive value for echocardiographic diagnosis. We conclude that omission of a schedule of routine biopsies is justified, if the described techniques of IMEG and echocardiography are meticulously applied and indicate normal cardiac function. EMB remains indicated if noninvasive parameters are not conclusive or if false-positive IMEG results, which were observed in the presence of infection or arrhythmias, are suspected. The frequency of EMB can be reduced by 90%, compared to conventional routine biopsy schedules. Diagnostic safety is increased because the additional information gained from IMEG and echocardiography is helpful in the interpretation of EMBs.

[Therapy of terminal heart failure using heart transplantation]. / Therapie der terminalen Herzinsuffizienz durch Herztransplantation.

Heart transplantation (HTx) has now become an accepted treatment modality for end-stage heart disease. The limited supply of suitable donor organs imposes constraints upon the decision of who should be selected for transplantation. Usually patients are candidates for HTx, who remain NYHA functional class III or IV despite maximal medical therapy. Further criteria are low left ventricular ejection fraction (less than 20%) with heart rhythm disturbances class IIIA-V (LOWN), which are associated with poor prognosis. Additionally, the suffering of the patient and also the course of heart failure are essential for judging the urgency of HTx. Contraindications are absolute in patients with untreated infections, fixed pulmonary vascular resistance (PVR) above 8 WOOD-degrees, severe irreversible kidney and liver disease, active ventricular or duodenal ulcers and acute, psychiatric illness. HTx is relatively contraindicated in patients with diabetes mellitus, age over 60 years, PVR above 6 WOOD-degrees and an unstable psychosocial situation. To prevent rejection of the transplant heart, live-long immunosuppressive therapy is needed. Most immunosuppressive regimes consist of Cyclosporine A and Azathioprine (double drug therapy) or in combination (tripple drug therapy) with Prednisolone. For monitoring of this therapy, control of hole blood cyclosporine A level and white blood count is needed. Rejection episodes can be suspected if there is a greater than 20 mmHg decrease of systolic blood pressure, elevated body temperature, malaise, tachycardia or heart rhythm disturbance. The diagnosis of cardiac rejection can be established by endomyocardial biopsy. Measurement of the voltage of either the surface or intramyocardial ECG, echocardiography with special consideration to early left ventricular filling time as well as immunological methods are additionally used tools. Graft sclerosis as the main risk factor of the late transplant period remains an unsolved problem.

[Cytomegalovirus infection and coronary sclerosis after heart transplantation]. / Cytomegalievirus-Infektion und Koronarsklerose nach Herztransplantation.

Serological tests for cytomegalovirus (CMV) after cardiac transplantation were performed at six to eight-week intervals on 26 patients (3 females and 23 males; mean age 46 [15-62] years) with angiographic or ultimately autopsy evidence of coronary atherosclerosis (group 1) and 24 patients (5 females and 19 males; mean age 45 [25-56] years) without coronary disease in the transplanted heart. A positive result meant an at least fourfold increase in CMV IgG titre, demonstration of CMV IgM or direct viral isolation from blood or other body fluid. In 20 patients of group 1 (77%) a CMV infection had occurred after the transplantation, but in only six patients (25%) in the group 2 (P less than 0.0001). These results are interpreted as demonstrating a relationship between CMV infection and rapidly progressive coronary atherosclerosis after cardiac transplantation.