Homografts: a review.

Since their introduction into clinical practice in 1965 homografts have become established in clinical routine. The storing and sterilization procedures have been improved over time. Long-term results showed that homografts had a superior durability compared to xenogenic biological prostheses. Approximately 40% were still in place 20 years after implantation in aortic position. Their low rate of thromboembolic events made a life-time anticoagulative therapy unnecessary and their hemodynamics were superior to all other heart valve prostheses. There exist two implantation techniques, subcoronary or mini-root, both technically more demanding compared with implantation of stented valve prostheses. When using the subcoronary technique, the valve is suspended into the aortic root leaving the coronary arteries untouched. The success of this technique, however, depends on the relation of the recipients aortic root and the implanted valve. The mini-root technique requires reimplantation of the coronary arteries but left the morphology of the valve and its root unchanged. Especially in patients with endocarditis, the mini-root technique offered the advantage of allowing for excision of all affected tissue with subsequent replacement by the homograft. The Ross-procedure uses the patient's own pulmonary valve as aortic valve substitute with implantation of a homograft in pulmonary position. This proved to be advantageous in children, since in these patients the degeneration of an aortic homograft was faster compared to an older population. This was explained by the recipient's immunologic response to the graft which was more pronounced in younger patients. The advantages of homografts with regards to hemodynamics and thromboembolic risk make them a good alternative to mechanical prostheses in younger, active patients. In very young patients, a Ross-procedure was shown to be superior to aortic homografts due to slower degeneration of the autograft. The decision to use a homograft must be made individually according to the patients demands.

Five years of experience with mitral valve homografts.

INTRODUCTION: The main advantages of mitral homografts are preservation of the subvalvular apparatus and avoidance of life-long anticoagulation. In this communication, we will present our five-year experience using mitral homografts in mitral valve surgery. PATIENTS AND METHODS: Since 1996, 14 patients (mean age 46 +/- 8 years, range 27 - 65 years have had mitral homografts implanted. Thirteen patients had mitral valve replacement; the septal leaflet of the tricuspid valve was replaced in one case. The indications were mitral (n = 6) or tricuspid endocarditis (n = 1), mitral valve stenosis (n = 3), and combined mitral valve disease (n = 4). Complete mitral homografts were implanted in eight patients; partial homografts were used in six cases. Preoperatively, the dimensions of the left ventricle and the mitral valve were measured by transoesophageal echocardiography (TOE). The mean left ventricular ejection fraction was 56 +/- 9%, the mean end-diastolic diameter 58 +/- 6 mm. The technique described by Acar/Carpentier was adapted for implantation; a Carpentier ring was implanted in all cases for annular stabilization. The patients had anticoagulative therapy which was discontinued when stable sinus rhythm was present after three months postoperatively. Follow-up included clinical examination, ECG, and echocardiography, and was initiated six months postoperatively and continued on a yearly basis. The following parameters were determined by echocardiography--left atrial size, left ventricular end-diastolic and end-systolic diameter, pressure gradient across the mitral valve (c/w Doppler, Bernoulli's equation), and mitral regurgitation. RESULTS: All patients survived surgery; the mean operation-time was 281 +/- 37 minutes. Intraoperative TOE revealed a first degree insufficiency in 7 patients. Follow-up was completed in all patients, with a mean period of 30 months (6 - 60 months). Two patients had an acute endocarditis two years postoperatively, requiring repeat valve replacement with a mechanical prosthesis. An additional patient had to be reoperated due to chordal rupture three years postoperatively. All three patients had mitral valve stenosis as the initial indication for surgery and had received a complete homograft. In the remaining eleven patients, the morphological and functional state of the implanted grafts remained unchanged during follow-up. The freedom from valve-related events was 93% after one year, 86% after two years, and 79% after three years. At six-month follow-up, ECG and echocardiography revealed sinus rhythm and sufficient atrial contractions in 13 cases. At the last follow-up, the pressure gradients were 3.4 +/- 0.6 mmHg for complete homografts and 2.8 +/- 0.6 mmHg for partial homografts. In five cases, a mild insufficiency was documented, while six patients presented with competent grafts. CONCLUSIONS: Mitral homografts can be used with acceptable mid-term results in selected cases with good left ventricular function and only slightly dilated left ventricles. Partial mitral homografts represent an additional technique, especially for mitral valve repair in patients with acute endocarditis. The susceptibility to bacterial infections of a homograft makes strict prophylaxis against endocarditis mandatory.

Consistent lowering of clotting factors for the treatment of acute cardiovascular syndromes and hypercoagulability: a different pathophysiological approach.

Hypercoagulability is a key contributor to acute cardiovascular syndromes and to various microcirculatory disorders. The use of heparin-mediated extracorporeal low-density lipoprotein/fibrinogen precipitation (HELP) apheresis makes a controlled, immediately effective reduction of clotting factors possible, and induces subsequent positive effects on plasma viscosity, erythrocyte aggregation, and microcirculation. Oxygen supply to an ischemic artery can thus be increased without hemodilution, qualifying the HELP system as a possible therapeutic tool in the treatment of acute cardiovascular syndromes and microcirculatory disorders.

Preliminary experience with steroidal ovarian suppression for prevention of severe ovarian hyperstimulation syndrome in IVF patients.

The purpose of the study was to evaluate the efficiency of administration of high dose progesterone in combination with oestradiol during the luteal phase for the prevention of ovarian hyperstimulation syndrome in a high-risk population of patients undergoing in vitro fertilization. An observational study was carried out involving 21 women (mean age 28.6 years) undergoing controlled ovarian stimulation for in vitro fertilization. The women were identified as at risk of ovarian hyperstimulation syndrome as they had suffered from the condition when hCG was used for luteal phase support in previous cycles. Steroidal suppression of the stimulated ovary on days 2, 6, 10 and 14 after embryo transfer was achieved by intramuscular injections of 500 mg hydroxyprogesterone caproate and 10 mg oestradiol valerate. The incidence of moderate and severe ovarian hyperstimulation syndrome under steroidal ovarian suppression, serum progesterone concentration and pregnancy rates were compared with those in cycles in which human chorionic gonadotrophin was used for luteal phase support. No cases of moderate or severe ovarian hyperstimulation syndrome occurred under steroidal ovarian suppression. Despite low progesterone concentrations (mean 10.7 nmol l(-1), range 2.6-24.5), indicating almost complete ovarian suppression, the pregnancy rate was not impaired. These preliminary results indicate that steroidal ovarian suppression during the luteal phase is a promising tool for reducing the incidence and severity of ovarian hyperstimulation syndrome in a high-risk population, without compromising the pregnancy rate.

Homografts in patients with combined disease of the aortic valve and the ascending aorta: an alternative to the classical Bentall procedure.

BACKGROUND AND AIM OF THE STUDY: In patients with aneurysms or dissections of the ascending aorta and additional aortic valve disease, valve-containing composite grafts are used in clinical routine. The study aim was to present our experience with homografts for aortic valve replacement extended by a vascular prosthesis as an alternative to the classical Bentall procedure. METHODS: Thirty consecutive patients (mean age 46+/-14 years) were included in this study. Indications for valve replacement were aortic stenosis (n = 15), aortic insufficiency (n = 6), combined aortic valve disease (n = 6), endocarditis of the native valve (n = 1), and endocarditis of a previously placed bioprosthesis (n = 2). The mean diameter of the ascending aorta was 5.6+/-0.5 cm; one patient had an acute dissection (diameter 4.4 cm). For valve replacement, cryopreserved homografts (mean size 24+/-2 mm) were used in a mini-root technique, and the ascending aorta was replaced by collagen-coated vascular prostheses (mean diameter 28+/-3 mm). The size of the vascular prosthesis was adjusted to the diameter of the sinutubular junction of the implanted homograft. Follow up included annual clinical examinations, transthoracic echocardiography and ultrafast computed tomography (CT) scans. RESULTS: All patients survived surgery, and no deaths occurred during follow up. None of the patients had postoperative anticoagulation, and no thromboembolic events were noted. Follow up was complete, with an average 48 months (range: 6 to 84 months). Doppler echocardiography revealed trivial to mild aortic regurgitation in nine patients postoperatively, with no deterioration during follow up. No pathologic pressure gradients over the aortic valves were measured at Doppler echocardiography; the mean valvular orifice area was 2.5+/-0.3 cm2. At ultrafast CT, normal homograft anatomy including the sinotubular junction, no calcifications, and no signs of annular dilatation were seen. In the patient who had surgery for acute endocarditis of the native valve, ultrafast CT revealed a small pseudoaneurysm below the left coronary artery, without need for reoperation. CONCLUSION: Short- and mid-term results show that cryopreserved homografts extended by small-sized vascular prostheses can be used safely for Bentall procedures in selected cases where the diameter of the aortic valve annulus is moderately dilated.

[Endocrinologic aspects of habitual abortion]. / Endokrinologische Aspekte des habituellen Abortes.

Disorders of the luteoplacental progesterone shift in the first and second trimester lead to a insufficient progesterone secretion, thus constituting an important cause of early and late abortions. The endocrinological disorders caused by ovarian malfunction normally occur between the 5th and 10th weeks of pregnancy. We can distinguish early and late disorders of the corpus luteum graviditatis from a relative luteal deficiency owing to ovarian hyperstimulation. The delayed shift, however, is caused by trophoblast disorders and disturbances of placentation, thus leading to low blood levels of progesterone. Progesterone replacement therapy for the duration of insufficiency leads to significantly reduced rates of abortion. An increase in the rate of malformations is not to be expected.

Interferon-gamma modifies cytokine release in vitro by monocytes from surgical patients.

BACKGROUND: Treatment with interferon-gamma (IFN-gamma), a key mediator for adequate forward-regulatory monocyte immune capability, has been advocated to overcome posttraumatic mononuclear leukocyte paralysis. Conversely, IFN-gamma also is a potent proinflammatory mediator contributing to capillary leakage in sepsis-driven organ failure. The objective of this investigation was to further define the potential of IFN-gamma as a modifier of monocyte activity before and after injury. METHODS: Whole blood samples from 19 patients (7 female and 12 male patients; age, 68 +/- 5 years) before and after cardiac surgery with extracorporeal circulation were incubated under continuous rotation with lipopolysaccharide for 12 hours in the presence or absence of human recombinant IFN-gamma. Pro- and anti-inflammatory cytokines were determined in the plasma. RESULTS: Lipopolysaccharide-induced release of tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-1Ra, and prostaglandin E2 was clearly augmented with IFN-gamma most strikingly postoperatively (p < 0.05). There was no effect on IL-1beta, neopterin, and soluble tumor necrosis factor-R release. CONCLUSION: Thus there is a wide spectrum of IFN-gamma activity on monocyte activation including anti-inflammatory properties. Since cellular preactivation facilitates monocyte reactivity toward IFN-gamma, we conclude that exogenous administration should be effective but must be carried out with great caution in patients with profound inflammation.

Pseudoaneurysm complicating homograft aortic valve replacement--two different--courses and strategies.

The courses of two patients with pseudoaneurysm formation following aortic valve replacement using homografts are reported. Both patients had aortic valve replacement due to acute infective endocarditis with paravalvular abscess formation. The first case had an uneventful postoperative course; but on routine echocardiography, a pseudoaneurysm located at the left coronary commissure was found at one year follow-up. As the pseudoaneurysm was completely asymptomatic, the patient was followed up carefully at six months intervals. The second patient also had pseudoaneurysm formation postoperatively, but he presented one year after surgery with fever and elevated leucocyte count. He had surgical revision of the pseudoaneurysm because no other reason for an infection could be found. Four months later he presented again with infection signs and pseudoaneurysm formation. This time, the homograft was completely excised and another homograft was implanted. One year after the final operation, he is now free from re-infection. The two presented courses show that pseudoaneurysms complicating aortic valve replacement should be managed according to attendant circumstances and symptoms.

Health-related quality of life and post-traumatic stress disorder in patients after cardiac surgery and intensive care treatment.

OBJECTIVES: Health-related quality of life and patient satisfaction have become important end points in cardiac surgery. Post-traumatic stress disorder has been described in patients with life-threatening heart disease. In this study, we investigated the occurrence of post-traumatic stress disorder in a sample of patients after cardiac surgery and compared health-related quality of life and patient satisfaction between patients with and without evidence of post-traumatic stress disorder. METHODS: We studied 80 patients serially admitted to the intensive care unit after cardiac surgery (bypass grafting, n = 51; aortic valve replacement, n = 29). Health-related quality of life was assessed with the use of the SF-36 Health Status Questionnaire. Post-traumatic stress disorder was measured with a previously validated instrument (the Post-Traumatic Stress Syndrome 10-Questions Inventory), and 20 different aspects of life satisfaction were quantified on a scale ranging from 0 to 10. For measurements of health-related quality of life and post-traumatic stress disorder, age- and gender-comparable healthy individuals, as well as patients with cardiovascular diseases, served as control groups. RESULTS: Patients who had cardiac surgery described high life satisfaction summary scores (156 of a maximum of 200 points) and only small impairments in physical and mental SF-36 summary scores when compared with healthy control groups (median reduction 7.15, P <.05). Patients with evidence of post-traumatic stress disorder (n = 15) reported the lowest SF-36 mental health summary scores when compared with patients without stress disorder (38.3 vs 48.4, P =.004) and rated their life satisfaction lower (121.5 vs 162.0, P =.002). CONCLUSIONS: Patients who have had cardiac surgery demonstrate a high life satisfaction with an acceptable degree of physical and mental health-related quality of life. Impairments in psychosocial function and life satisfaction were found in a subgroup of patients with evidence of post-traumatic stress disorder.

Mitral valve surgery utilizing homografts: early results.

BACKGROUND AND AIM OF THE STUDY: Mitral valve repair is superior to prosthetic valve replacement due to preservation of the subvalvular apparatus. We used cryopreserved homografts for mitral valve replacement in selected cases, in whom valve repair would not have been successful. METHODS: Cryopreserved homografts were used in 10 patients (four males, six females; mean age 47 +/- 8 years; range: 27-65 years), for either complete (n = 7) or partial (n = 3) mitral valve replacement. Surgery was indicated due to acute endocarditis (n = 3), stenosis (n = 4) or combined mitral valve disease (n = 3). Transesophageal echocardiography (TEE) was performed to determine correct homograft size; these values were compared with intraoperative measurements of valvular dimensions. The function of the implanted grafts was examined intraoperatively by TEE. Follow up included clinical examination, electrocardiography and echocardiography. RESULTS: All patients survived surgery. Intraoperative TEE revealed mild insufficiency (grade I) in six cases and no insufficiency in four. The papillary muscle-mitral annulus distance was the most reliable preoperative echocardiographic parameter to determine the required homograft. Mean pressure gradients were 3.2 +/- 0.7 mmHg for complete and 2.4 +/- 0.5 mmHg for partial homograft replacement. Sinus rhythm was present in all cases at discharge. Mean follow up was 24 months (range: 6-36 months). At six-month and one-year follow up, the pressure gradients had risen slightly to 3.4 +/- 0.6 mmHg (complete) and 2.8 +/- 0.6 mmHg (partial). To date, four patients had competent grafts, and six presented with an insufficiency (grade I). All patients had normal left ventricular function (EF 65 +/- 6%) at their last follow up; there were no signs of endocarditis during the follow up period. CONCLUSION: Mitral homografts for valve replacement or repair are recommended in selected cases in whom conservative reconstruction techniques are not possible. The avoidance of long-term anticoagulation therapy and preservation of left ventricular geometry are clear advantages to other mitral valve prostheses.

Improved outcome of APACHE II score-defined escalating systemic inflammatory response syndrome in patients post cardiac surgery in 1996 compared to 1988-1990: the ESSICS-study pilot project.

OBJECTIVE: Cardiac surgery using extracorporeal circulation leads to the release of cytokines and subsequently to a systemic inflammatory response syndrome, which is thought to be a negative prognostic factor for patients' outcome. A stratification for the risk of an escalating systemic inflammatory response syndrome had been achieved in a monocenter study carried out in 1988-1990, using APACHE II scoring on the morning of the 1st postoperative day. We now re-evaluated this concept prospectively in three independent centers. METHODS: The APACHE II based risk stratification was put to test in three independent heart surgery centers in the period from June to December 1996. Nine hundred and forty-five patients after elective cardiac surgery (excluding heart transplantation) with the assistance of the cardiopulmonary bypass were prospectively monitored. RESULTS: We found an increase in mortality with higher APACHE II score values determined on the 1st postoperative day. The mortality rose to nearly 50% with an APACHE II score of > or = 28. Patients at high risk for the development of a systemic inflammatory response syndrome (APACHE II score > or = 24) significantly differed from patients at lower risk (APACHE II score < 19) in the duration of mechanical ventilation and extracorporeal circulation, age and New York Heart Association (NYHA) classification (P < 0.05). CONCLUSION: The APACHE II score determined on the morning of the 1st postoperative day helps identifying the subgroup of patients with escalating systemic inflammatory response syndrome. Comparison with the data obtained in the years 1988-1990, suggests a better prognosis in the current trial for patients at high risk with a similar degree of escalating systemic inflammatory response syndrome.

Leaflet escape in Omnicarbon monoleaflet valve.

In almost every type of artificial valve, mechanical disruption has been described. We present the first case of leaflet fracture with aortic embolization in an Omnicarbon monoleaflet valve 42 months after implantation. The 22-year-old male patient suffered of acute respiratory insufficiency and was referred to our hospital as an emergency case. Until a few days before presentation, he was in good condition without clinical complaints. By means of transesophageal echocardiography (TEE) and abdominal sonography the diagnosis of leaflet fracture with embolization to the abdominal aorta could be made. The patient underwent consecutive operative valve replacement and foreign body extraction that resulted in a complete recovery.

Coronary risk factor management for the prevention and treatment of graft vessel disease in heart transplant patients.

There is increasing evidence that atherogenic risk factors largely contribute to the pathogenesis of graft vessel disease (GVD) after heart transplantation. Initial endothelial damage of the transplant heart derives from reperfusion ischemia during operation, repeated infections, and rejection episodes. Immunosuppressive medication considerably increases low density lipoprotein (LDL) cholesterol, lipoprotein(a), and fibrinogen blood levels, which in turn further damage the endothelium of the graft coronaries. Probably, this interplay of immunological and atherogenic factors accounts for the rapid development of GVD and its poor prognosis. The rapidity of the disease process makes it necessary to eliminate important risk factors as early and as efficiently as possible. Therefore, we studied whether heart transplant patients could benefit from a combined treatment of statins and apheresis heparin extracorporeal LDL/fibrinogen precipitation (HELP), which has already been shown to be beneficial for the treatment of advanced coronary artery disease. Such a combined treatment allows simultaneous and drastic reduction of LDL, lipoprotein(a), and fibrinogen blood levels and significantly prevented GVD. Moreover, it did not affect the prevention of rejections and infections, respectively.

[Homografts for mitral valve replacement in florid endocarditis--an alternative to prosthetic replacement]. / Homografts für den Mitralklappenersatz bei florider Endokarditis--eine Alternative zum prothetischen Ersatz.

INTRODUCTION: Homografts for valve replacement are indicated in acute valve endocarditis. It is assumed that they possess anti-infective properties. Homografts are an established indication in aortic valve replacement. We present our early results with homografts for mitral valve replacement in acute endocarditis. PATIENTS AND METHODS: Between July 1996 and March 1998 we used cryopreserved homografts for mitral valve replacement in seven patients. In three cases (age 24, 42, and 34 years) the indication was an acute endocarditis with subsequent severe mitral valve insufficiency. The size of the required homograft was measured preoperatively using transesophageal echocardiography. For implantation the technique described by A. Carpentier was used; for stabilization of the mitral anulus a valvular ring (Physio) was implanted. Follow-up was done every six months including clinical and echocardiographical examinations. After the first postoperative year an Ultrafast-CT was done in addition. RESULTS: One patient had complete mitral valve replacement, in the other two cases the diseased parts of the valve were completely excised and the valve was repaired using a partial homograft. There were no perioperative deaths. In the follow-ups, up to 24 months of uneventful homograft function was documented by echocardiography; no insufficiency > degree I was seen on color Doppler echocardiography. At the last follow-up (mean follow-up 16 months, range 12 to 24 months) the average mitral valve orifice was 2.5 +/- 0.5 cm2, the mean pressure gradient 2.8 +/- 0.8 mm Hg. In Ultrafast-CT no morphological abnormalities of the mitral valves and no dilatation of the left ventricle were seen. There were no signs of a recurrence of the endocarditis in any patient during the follow-up period. CONCLUSION: Homografts for mitral valve replacement are an interesting alternative to prosthetic valve replacement, especially in younger patients. In cases with acute endocarditis, in which mechanical prosthesis should not be used, a reconstruction or repair of the mitral valve with preservation of the ventricular geometry is possible even if large parts of the mitral valve are infected.

Detection of coronary artery bypass graft patency by contrast enhanced magnetic resonance angiography.

OBJECTIVE: The subject and purpose of the prospective study was to delineate coronary artery bypass graft (CABG) course and to determine patency of aortocoronary venous bypass grafts (ACVB) compared with internal mammary artery bypass grafts (IMA) in the early postoperative follow-up, by contrast enhanced magnetic resonance angiography (MRA). For control, patients were examined with X-ray angiography and spiral-computed tomography (CT). METHODS: Eighty-five patients (74 male/11 female) with a mean age of 63.7 years underwent MRA examination, applying contrast enhanced gradient-echo sequence after an average distance of 7 days from CABG surgery. A 1.5 Tesla magnetom vision (Siemens, Erlangen, Germany) with phased array coil technology was used. Overall, 247 bypass grafts (160 ACVB/87 IMA) were studied with a 3D (three dimensional) ultrashort TE gradient-echo sequence (TR/TE/a:5 ms/2 ms/40 degrees) with 512*512 matrix and 500 mm FoV in single breath-hold technique after Gd-DTPA bolus injection. CABGs were judged in three different parts, including the course of CABG and both anastomoses. CABGs were controlled by angiography and spiral-CT to examine sensitivity, specificity and efficiency of MRA examination. Additional measurement of bypass graft flow velocity of arterial and venous grafts was performed with 2D phase contrast technique in breath-hold technique with ECG triggering. RESULTS: One hundred and thirty-nine of 160 (86.9%) ACVB grafts and 83 of 87 (95.4%) IMA grafts could be visualized. Suspected occlusions of 10 CABGs were confirmed in 80% with a second modality. Five CABGs were false positive in MRA. MRA proved a high specificity (93.8%), sensitivity (89.9%) and efficiency (1.73), especially in detection of IMA to LAD and ACVB to LAD and RCA (Table 1). 3D maximum intensity projection (MIP) reconstruction was helpful in delineating CABG course and in several cases in detecting stenosis of coronary arteries. Results of flow velocity showed a significant higher mean systolic velocity in arterial bypasses than in venous grafts with a higher maximum velocity in systole than in diastole in both grafts. Bypass stenosis in distal anastomosis could not be verified with MRA and flow method. CONCLUSION: Contrast enhanced 3D ultrashort TE gradient-echo magnetic resonance angiography has the potential for being a reliable method for CABG visualization and CABG patency determination in the early postoperative period. MR flow measurement was not qualified for detection of a bypass stenosis.

Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation: importance of mycophenolic acid therapeutic drug monitoring.

BACKGROUND: Interest has recently been expressed in tacrolimus and mycophenolate mofetil (MMF), two potent immunosuppressants, for a variety of transplant indications. The efficacy of this combination was assessed as primary therapy following cardiac transplantation. METHODS: Forty-five patients were enrolled; 15 into Phase I and 30 to Phase II of the study. Intravenous tacrolimus was administered for 2-3 days to all patients prior to conversion to oral therapy; target blood concentrations were 10-15 ng/mL. Treatment also consisted of steroids and MMF. During Phase I, a fixed 2 g/day dose of MMF was given whilst doses were adjusted according to mycophenolic acid (MPA) plasma levels during Phase II (target range 2.5-4.5 microg/mL). Mean follow-up was 696 +/- 62 days and 436 +/- 88 days for Phases I and II, respectively. RESULTS: Phase I: Patient survival was 100%. Rejection was diagnosed in 66.7% of patients (mean number of episodes per patient 1.33 +/- 1.18). Retrospective analyses indicated that whereas mean MPA plasma levels >3.0 microg/mL were not associated with rejection, no correlation was found with tacrolimus blood concentrations. Phase II: A survival rate of 96.7% was evident, one patient having died from aspergillosis. Diagnoses of rejection were made in 10.0% of patients (0.10 +/- 0.31 episodes per patient) and confounding factors were present in all 3 cases. MPA trough levels were 1.0 +/- 0.3 microg/mL at this time. Resolution was apparent following pulse steroid therapy. Steroids were successfully withdrawn from all patients who completed 6 months' treatment. CONCLUSIONS: Combination therapy with tacrolimus and MMF is associated with suppression of acute myocardial rejection; however, this is dependent upon routine therapeutic drug monitoring.