Search

Background: Frailty assessment is recommended to evaluate the candidacy of adults referred for orthotopic heart transplantation (OHT). Psoas muscle area (PMA) is an easily measured biomarker for frailty. There has yet to be a study examining the prognostic impact of PMA in OHT patients., Methods: In this retrospective study, preoperative and postoperative computed tomography (CT) scans were retrieved for adults transplanted between 2000 and 2015 at a tertiary care hospital. Psoas muscle area was measured on a single axial image. Outcomes of interest were all-cause mortality over 6 years and a composite of in-hospital mortality or major morbidity (prolonged ventilation, stroke, dialysis, mediastinitis, or reoperation)., Results: Of 161 adult patients transplanted, 82 had at least 1 abdominal CT scan. At baseline, mean PMA was 25.7 ± 5.8 cm in men and 16.0 ± 3.6 cm in women, and decreased by 8% from the first to the last available CT scan. Adjusting for age, sex, body mass index, and cardiomyopathy etiology, every 1-cm increase in PMA was found to be associated with a 9% reduction in long-term mortality (hazard ratio, 0.91; 95% confidence interval [CI], 0.83-0.99; P = 0.031) and a 17% reduction in in-hospital mortality or major morbidity (odds ratio, 0.83; 95% CI, 0.72-0.96; P = 0.014). When PMA was smaller than the sex-specific median, the risk of mortality or major morbidity increased fourfold (odds ratio, 4.29; 95% CI, 1.19-15.46; P = 0.026)., Conclusions: Muscle mass is an independent predictor of mortality and major morbidity after OHT. Further research is needed to determine whether frail OHT patients with low PMA may benefit from muscle-building interventions to improve outcomes.

Background: We investigated cardiac proinflammatory, mitogenic, and apoptotic signaling events, and plasma biomarkers of inflammation and oxidative stress in de novo adult cardiac transplant (CTX) patients receiving tacrolimus (TAC) or cyclosporine A (CsA)., Methods: One hundred CTX recipients were randomized 1:1 to TAC/CsA in a prospective, randomized open-label multicenter study. Biomarkers of inflammation, immunity, oxidative stress, and cardiac signaling underlying growth and inflammation (extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase, mitogen-activated protein kinase kinases [MEK] 1/2 and 3/6, c-Src), and apoptosis and survival (c-Jun NH2-terminal kinases [JNK], Bax/Bcl2, Akt) were assessed at 2, 4, 12, 26, and 52 weeks post-CTX. Plasma from healthy controls (n = 30) and tissue from explanted non-failing hearts (n = 6) were used as controls., Results: Biomarkers of inflammation/immunity (interleukin -6 and -18, soluble intercellular adhesion molecule, E-selectin, monocyte chemoattractant protein-1, osteopontin, fibrinogen, N-terminal prohormone brain natriuretic peptide, high-sensitive C-reactive protein) and oxidative stress (thiobarbituric acid reactive substances, nitrotyrosine) were increased, and antioxidant capacity was (glutathione/glutathione disulfide) decreased in patients vs healthy controls (p < 0.05). Phosphorylation of mitogen-activated protein kinases and Akt was increased, and Bax/Bcl was decreased in transplanted vs non-transplanted hearts. Except for plasma fibrinogen, which was lower in TAC vs. CsA, (p = 0.01), there were no significant differences in parameters studied between TAC vs CsA immunoprophylaxis., Conclusions: De novo CTX recipients exhibit significant sub-clinical inflammation and oxidative stress that persists 12 months after transplantation. Associated with this is activation of myocardial growth and inflammatory signaling and decreased apoptosis. Our findings suggest that CTX is an inflammatory condition associated with oxidative stress and myocardial growth regardless of CsA or TAC immunoprophylaxis and independently of rejection status., (© 2013 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.)

Left ventricular assist devices (LVADs) are used in chronic end-stage heart failure as "bridge to transplantation" (BTT) and, more recently, for transplant-ineligible patients as "destination therapy" (DT). We reviewed the evidence on clinical effects and cost-effectiveness of 2 types of continuous-flow LVADs (HeartMate II [HM II] and HeartWare), for BTT and DT patients. We systematically searched the scientific literature (January 2008-June 2012) and identified 14 clinical studies (approximately 2900 HM II and approximately 200 HeartWare patients), and 3 economic evaluations (HM II) using simulation models. Data were, however, limited to 2-3 studies per outcome. We made policy recommendations on the basis of our systematic review. Although complications after implantation are frequent, LVAD therapy is often highly effective across transplantation eligibility status and device, with 1-year survival reaching 86% for BTT and 78% for DT (compared with 25% for medical therapy). Neither BTT nor DT currently meet traditional cost-effectiveness limits in models using historical data, although BTT is standard practice for a limited number of patients in many regions. We found that BTT and DT as implantation strategies tend to be no longer mutually exclusive. We conclude that evidence is sufficient to support LVAD use, regardless of transplantation eligibility status, as long as patients are carefully selected and program infrastructure and budget are adequate. However, evidence gaps, limitations in economic models, and the lack of Canadian data point to the importance of mandatory, systematic monitoring of LVAD use and outcomes., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Combined heart and liver transplant is a rare procedure to treat end-stage cardiac and liver disease. First performed during cardiopulmonary bypass and anticoagulation, subsequent concerns about increased bleeding changed the strategy to performing liver implantation following separation from cardiopulmonary bypass. Considering the overall decrease in transfusion requirements during liver transplant and the potential benefits to the transplanted heart to remain on cardiopulmonary bypass during liver implantation, we revised the strategy for combined heart and liver transplant. We report the clinical course of four consecutive patients who underwent this procedure in our institution., Clinical Features: Patient 1 was a 53-yr-old male with familial hypertrophic cardiomyopathy and congestive cirrhosis. Patient 2 was a 57-yr-old male with hypertrophic restrictive cardiomyopathy and congestive cirrhosis. Patient 3 was a 48-yr-old male with dilated cardiomyopathy and hepatitis B cirrhosis. Patient 4 was a 57-yr-old male with ischemic cardiomyopathy and congestive cirrhosis. Each patient underwent combined heart and liver transplant, with liver implantation performed during cardiopulmonary bypass and anticoagulation. Estimated blood loss ranged from 1,000 to 3,000 mL. Intraoperative transfusion included 2-5 U of packed red blood cells, 4-12 U of fresh frozen plasma, 0-20 U of cryoprecipitate, and 5-23 U of platelets. All patients remain well 25-38 months after surgery., Conclusion: Combined heart and liver transplant during cardiopulmonary bypass is a viable strategy that may confer benefit to this unique type of patient.

Background: Chronic kidney disease (CKD), a frequent and serious complication after heart transplantation, is associated with increased mortality. Current strategies include dose reduction or conversion from calcineurin inhibitors (CNIs) to either mycophenolate mofetil and/or rapamycin, with variable results and side-effect profiles., Methods: We evaluated the effectiveness of long-term anti-CD25 monoclonal antibody (MAb)-based immunosuppression in 17 adult heart transplant recipients with CKD at 10 +/- 5 years post-transplant. Seven patients had previously been switched to rapamycin but had untreatable side-effects and 10 patients were still on a CNI. The latter were matched with 10 control heart transplant patients whose renal function had remained stable over a similar post-transplant follow-up period, on CNI., Results: Anti-CD25 MAb were given over 13 +/- 10 months and were well tolerated with CD25 saturation monitoring (target <2% expression). Side-effects secondary to rapamycin resolved in 6 patients. The slope change of the creatinine clearance improved in patients in whom CNIs were discontinued (+0.335 ml/min/month vs -0.124 ml/min/month in controls, p = 0.03). Four patients died. Three died after 2, 6 and 7 months of follow-up, respectively, with the following diagnoses: acute renal failure (the patient refused dialysis); acute rejection (the patient had refused protocol endomyocardial biopsy); and perforated diverticulitis. The fourth patient died of pneumonia, 3 months after conversion from anti-CD25 MAb to rapamycin, because of poor venous access., Conclusions: The use of long-term anti-CD25 MAb therapy as a potential replacement for CNI- and rapamycin-based immunosuppression is feasible. It is crucial that rejection surveillance be intensified. A randomized, controlled trial is required to confirm the benefits and safety of this strategy.

Cardiogenic shock resulting from transplant rejection is a serious complication with high mortality and morbidity. Often resistant to maximal medical therapy, this condition frequently requires mechanical circulatory support until recovery or retransplantation. We present a 52-year-old patient with multiorgan failure secondary to acute graft rejection after orthotopic heart transplantation. Maximal medical therapy was not successful, and the patient was bridged to recovery with an Impella LP 5.0 (Abiomed Inc, Danvers, MA) left ventricular assist device (LVAD). The relative merits of this therapeutic approach are outlined and discussed. The patient was discharged 3 weeks after LVAD removal and remains clinically stable.

Renal dysfunction is a well-known complication following heart transplantation. We examined an early decline in kidney function as a predictor of progression to end-stage renal disease and mortality in heart transplant recipients. We performed a retrospective cohort study of 233 patients who received a heart transplant between July 1985 and July 2004, and who survived >1 month. The decline in estimated creatinine clearance (CrCl) was used to predict the outcomes of need for chronic dialysis or mortality >1-year posttransplant. The earliest time to chronic dialysis was 484 days. A 30% decline in CrCl between 1 month and 12 months predicted the need for chronic dialysis (p = 0.01), all-cause mortality (p < 0.0001) and time to first CrCl 1-year posttransplant (p = 0.02). A 30% decline in CrCl between 1 month and 3 months also independently predicted the need for chronic dialysis (p = 0.04) and time to first CrCl 1-year posttransplant (p = 0.01). In conclusion, an early drop in CrCl within the first year is a strong predictor of chronic dialysis and death >1-year postheart transplantation. Future studies should focus on kidney function preservation in those identified at high risk for progression to end-stage kidney disease and mortality.

We report a case of a 13-year old girl with a diagnosis of cardiac fibroma who was followed for a decade. Although she was predominantly asymptomatic over this time period, she eventually developed significant ventricular arrhythmias. The arrhythmias were originally treated with anti-arrhythmic medications along with an automatic internal cardioverter-defibrillator. However, a nearly fatal event prompted a cardiac transplantation. This represents a unique case of a patient with cardiac fibroma who was bridged to transplantation with an internal cardioverter-defibrillator.

Heart transplant (HTx) patients are at risk of developing renal dysfunction. Sirolimus has been used as an alternative for calcineurin inhibitors (CNI) in transplant patients with renal dysfunction. Recent data suggest that the combination of sirolimus with a CNI is associated with a deterioration of renal function in renal transplant patients. The purpose of the present study was to compare the effect on the creatinine clearance (CrCl) of heart transplant (HTx) patients with renal dysfunction (RD) on CNI-based sirolimus-free regimens of conversion to either reduced-dose CNI plus sirolimus or outright substitution of CNI with sirolimus. We retrospectively identified 29 treatment switches for 26 patients with RD defined as a decline in the CrCl > 25% post-HTx. Treatment switches were divided into two groups. Group 1 included 13 switches in 13 patients (four women, nine men, age 62 +/- 10 yr) in whom sirolimus replaced CNI. Group 2 included 16 switches in 15 patients [two women, 13 men (one man underwent two such switches), age 61 +/- 9 yr] in whom CNI dose was reduced and sirolimus was added. Two men appear in both groups. Average follow-up was 10.4 +/- 3.2 months. Overall mortality, rejection, and side-effects rates were comparable between groups. At 12-months post-switch, the mean CrCl had increased from 48 +/- 15 at time of treatment switch to 56 +/- 22 mL/min in group 1 and decreased from 53 +/- 19 to 47 +/- 17 mL/min in group 2 (p = 0.02). In conclusion, substitution of CNI with sirolimus provided improved renal recovery compared with lower-dose CNI plus sirolimus in HTx patients with renal dysfunction.

Background: Tricuspid regurgitation (TR) occurs commonly in transplanted hearts. Although theoretically attractive, tricuspid valve replacement (TVR) has not been widely investigated as a possible therapy in post-transplant patients. The purpose of this study was to determine the safety of TVR in heart transplant patients and its effects on measurable clinical endpoints., Methods: We acquired data by both retrospective chart review and prospective data collection in all patients who underwent TVR after cardiac transplantation., Results: Nine patients were identified and followed for a period of six months. The age of patients at time of TVR was 62 +/- 6.1 yr and their average time since transplantation was 12 +/- 3.2 yr. Most patients demonstrated a reduction in their furosemide dose (105 +/- 63 mg/d pre-TVR vs. 67.5 +/- 65 mg/d post-TVR, p = 0.001) with a reduction in serum creatinine levels (188 +/- 72 micromol/L pre-TVR vs. 143 +/- 42 micromol/L post-TVR, p = 0.06). Additionally, we found a significant improvement in albumin values (32 +/- 5 g/L pre-TVR vs. 42 +/- 3 g/L post-TVR, p = 0.002) as well as an improvement in total bilirubin (35 +/- 18 micromol/L pre-TVR vs. 18 +/- 5 micromol/L post-TVR, p = 0.05). There was only one death in our series, in the only patient with known severe graft atherosclerosis., Conclusions: TVR appears to be a safe procedure in patients without severe graft atherosclerosis with improvements in serum creatinine, albumin and total bilirubin values, in addition to a reduction in furosemide dose. This may reflect improved forward flow, improved symptomatology from TR as well as possible beneficial effects on nutritional status.

Cardiac transplantation is an acceptable therapeutic option for the pediatric age group and for adult patients with congenital heart disease. There are a myriad of clinical diagnoses in these two patient populations. Survival has continued to improve, with graft half-lives of 14 years and greater in pediatric heart transplantation patients. There are issues unique to these patient populations in relation to heart transplantation for which the present document summarizes the relevant literature and presents management guidelines. Donor availability remains a major limiting factor in organ transplantation at present. Efforts need to be made to increase organ donor awareness, identify potential donors and aggressively manage marginal donors. Indications for transplantation and determination of timing of listing continue to be challenging due to a lack of evidence-based guidelines specifically for prognostic indices of outcome and pretransplant survival. The current status system for listing patients for transplantation does not necessarily reflect the typical clinical course of deterioration experienced by these two patient populations; therefore, consideration needs to be given to a parallel listing strategy. Evidence is accumulating pointing to an advantage to performing transplantations in patients in early infancy. ABO-incompatible heart transplantation has lead to a reduction in waiting time and waiting list mortality. Care of children after heart transplantation must take into consideration physical growth and multisystem development; stage of immunological maturation; intellectual, emotional and social maturation; educational activities; and other pediatric quality of life parameters. Post-transplantation issues are somewhat different, including rejection, coronary artery disease, malignancies and infections. Efforts need to be made to support multicentre trials to determine optimal treatment protocols.

Background: The use of C2 levels for therapeutic drug monitoring (TDM) of cyclosporine microemulsion (CsA) has been clinically validated. Routine TDM of tacrolimus and mycophenolate mofetil (MMF) is based on trough (C0) levels and side effects, respectively. The purpose of the present study was to determine the best single time points to assess the area-under-the-curve (AUC(0-12 hours)) in long-term heart transplant patients being treated with MMF in combination with CsA or tacrolimus., Methods: We studied the AUC(0-12 hours) in long-term (>1 year), adult heart transplant patients being treated with CsA and MMF (14 patients) and with tacrolimus and MMF (9 patients)., Results: C2 is the best surrogate (r2 = 0.87) of CsA AUC(0-12 hours). Tacrolimus C1 (r2 = 0.78), C2 (r2 = 0.83), C3 (r2 = 0.89) and C4 (r2 = 0.92) correlate better than C0 (r2 = 0.51) with the AUC(0-12 hours). When MMF is combined with CsA, there is poor correlation (r2) of MPA at all measured time points (C0 = 0.49, C2 = 0.09, C3 = 0.23, C4 = 0.44, and C6 = 0.60). When MMF is combined with tacrolimus, MPA C2 (r2 = 0.72), C4 (r2 = 0.86), C6 (r2 = 0.85), and C8 (r2 = 0.93) are better surrogates of the AUC(0-12 hours) compared with C0 (r2 = 0.69)., Conclusion: Our results suggest that in long-term heart transplant patients, the calcineurin inhibitor used in combination with MMF affects the correlation between MPA single time points and the AUC(0-12 hours). Future studies should determine the clinical benefit of TDM of tacrolimus and MPA with C2 or C4 compared with C0 and determine the therapeutic ranges. As for CsA-treated patients, CsA TDM should be performed with C2, and the TDM of MMF may be clinically irrelevant.

Background: Tricuspid regurgitation (TR) is common in patients after orthotopic cardiac transplantation (OHT). Endomyocardial biopsy (EMB) used to monitor for rejection may be a cause of TR. The purpose of this study was to identify a correlation between the severity of TR and the number of EMBs., Methods: We studied 101 patients with OHT at our institution between May 1987 and August 2001. The number of EMBs performed in each patient was determined. Data on technique of anastomosis, liver and renal function, ejection fraction, and pulmonary artery pressure were also extracted. Echocardiography reports were reviewed to determine the presence and severity of TR. Symptoms of right heart failure were assessed by the amount of diuretic intake., Results: Twenty-five (25%) of 101 patients had evidence of severe TR, whereas 76 (75%) had non-severe TR. Multivariate analysis identified EMB as the only independent predictor of the severity of TR (p < 0.0001). At last follow-up, 60% of patients with more than 31 EMBs had developed severe TR, whereas none of the patients with less than 18 EMBs had severe TR. Of the 25 patients who had severe TR, 15 (61%) needed high doses of daily diuretics, and 4 (16%) required tricuspid valve replacement., Conclusions: The development of TR after OHT is in large part due to EMBs used to monitor for rejection. There is a direct correlation between the number of EMBs and the severity of TR. We suggest a cutoff of less than 31 EMBs to reduce the risk of severe TR.

Background: Daclizumab is a human monoclonal antibody that binds to the interleukin-2 receptor. It has been used as induction therapy in heart transplantation with repeated administrations over several weeks. At our institution, we use a two-dose regimen of daclizumab based on its extended half-life. We sought to determine the incidence of acute rejection with 2-dose daclizumab in cardiac transplantation., Methods: Eighteen consecutive heart transplants performed at a single center were analyzed retrospectively. Patients received daclizumab (2 mg/kg) within 8 h of cardiac transplantation and a second dose (1 mg/kg) 2 wk thereafter. Maintenance immunosupression included mycophenolate mofetil, prednisone and either cyclosporine or tacrolimus, based on side-effect profile. The endpoint was the incidence of acute rejection as defined by a histologic grade >2 according to the classification of the International Society of Heart and Lung Transplantation., Results: Four patients had acute rejections (all were 3A) during the first 3 months post-transplantation. All four patients had rejection at the first biopsy and only two had rejection thereafter. None of the rejections were hemodynamically significant and no patients were hospitalized. All except one rejection was seen in the context of low 2-h cyclosporine levels. The two-dose regimen was easier to administer on an outpatient basis and resulted in lower cost., Conclusions: This preliminary report suggests that induction therapy with a two-dose regimen of daclizumab appears to be safe and well tolerated in patients undergoing cardiac transplantation.

The authors evaluated the efficacy of antithymocyte globulin (ATG) induction and delayed initiation of cyclosporine (CsA) in heart transplant (HTx) patients with postoperative renal dysfunction (RD). The authors compared 15 adult HTx patients with postoperative RD (serum creatinine [SCr] > or =150 microM) to 17 controls without postoperative RD. ATG was given daily (1.5 mg/kg/day for 5 days) in controls and every 2 to 5 days in RD patients (total lymphocyte count <200/mm). All patients received corticosteroids and mycophenolate mofetil. The initiation of CsA was delayed in RD patients until SCr had decreased to less than 150 microM (day 12 +/- 8 vs. 2 +/- 1, P<0.0001). One-year patient survival and acute rejection rates were 87% and 27% in RD patients and 88% and 59% in controls, respectively (P=not significant). SCr improved in RD patients and did not differ from controls after the first month. The authors' results suggest that marked prolongation of the period of ATG induction permits a safe delay in the initiation of CsA in HTx patients with postoperative RD.

There is a very limited published material about experience with long-term pediatric mechanical circulatory support as a bridge to heart transplant. We report on a 2-year-old, 12 kg boy admitted with 2-week history of low-grade fever, ear pain, pulmonary edema, and congestive heart failure. Trans-thoracic echocardiography confirmed severe myocardial dysfunction with a left ventricular ejection fraction of 0.20 and percentage shortening of 13. After 2 days of ventilatory and inotropic support, the patient continued to deteriorate and subsequently required femoro-femoral extracorporeal life support (ECLS). This was later complicated by a progressive coagulopathy and massive bleeding. On day 17, a pulsatile pediatric paracorporeal biventricular assist device (VAD) (Berlin Heart) was implanted. The patient's condition improved significantly with all coagulopathies corrected, and the patient was extubated 21 days later. After 109 days of bi-VAD support, the patient was successfully transplanted and discharged home 45 days post transplant. Our early experience with initial ECLS bridge to VAD and subsequently to transplant was encouraging. It allowed for additional time to select the ideal organ donor and optimize the recipient's comorbid condition and multiorgan failure. VAD provides an additional armamentarium of circulatory support in pediatric patients with severe heart failure.

Background: Cyclosporine (CsA) 2-h post-dose levels (C(2)) correlate better with the area-under-the-curve compared with trough levels. The purpose of this study was to determine the relationship between C(2) and endomyocardial biopsy (EMB) score in heart transplant patients receiving anti-thymocyte globulin (ATG)-induction., Methods: We reviewed 517 EMB performed during the first year in 39 adult heart transplant patients receiving ATG-induction, corticosteroids, mycophenolate mofetil and CsA. C(2) obtained on the day of EMB was related to the International Society for Heart and Lung Transplantation classification (score /=3A). Furthermore, EMB were related to C(2) (ng/mL), sorted according to the lower recommended range in liver (0-3 months: 850; 4-6 months: 700; 7-12 months: 500) or renal transplantation (0-1 month: 1500; 2-3 months: 1200; 4-6 months: 1000; 7-12 months: 800)., Results: Overall, C(2) did not significantly differ in patients with EMB /=3A. However, during the first month, EMB /=3A (750 ng/mL vs. 530 ng/mL). When C(2) were sorted according to the lower recommended range in liver or renal transplantation, no significant difference was observed when EMB was /=3A., Conclusions: In heart transplant patients receiving ATG-induction, C(2) did not significantly differ according to EMB /=3A. No significant relationship was found between EMB score and C(2) based on the lower recommended range in liver or renal transplantation. However, mean C(2) >750 ng/mL appears to be associated with a lower rejection score during the first month.

Therapeutic drug monitoring of CsA has evolved since the introduction of CsA microemulsion. The purpose of the present review is to summarize the history of CsA concentration 2 hours postdose (C2) monitoring in heart and liver transplantation. C2 has been shown to be the best single time point that correlates with the area-under-the-curve, with a correlation coefficient (r2) ranging between .83 and.93. C2 monitoring (300 to 600 ng/mL) has resulted in a significant clinical benefit in long-term heart and liver transplant patients compared to trough level (C0) monitoring. Moreover, a C2 range of 300 to 600 ng/mL resulted in a similar calcineurin inhibition compared to a C2 range of 700 to 1000 ng/mL or a C0 range of 100 to 200 ng/mL while being less injurious to renal function. In de novo liver transplant patients not receiving induction therapy, the achievement of a target C2 of 850 to 1400 ng/mL by postoperative day 3 has resulted in a low acute rejection rate. Furthermore, C2 monitoring has been associated with a lower rejection rate in hepatitis C virus (HCV)-negative patients and with an overall lesser severity of acute rejection compared to C0 monitoring. In de novo heart transplant patients who receive antithymocyte globulin induction, a lower C2 range may be sufficient to prevent rejection and renal dysfunction. Future studies should help to fine-tune the optimal C2 range in heart or liver transplant patients receiving induction therapy and different maintenance immunosuppressive combinations.

Background: Cyclosporine (CsA) 2-h post-dose level (C2) correlates better than trough levels (C0) with the area under the curve. We evaluated the clinical impact of C2 and mycophenolate mofetil (MMF) dose in adult heart transplant patients receiving anti-thymocyte globulin (ATG) induction., Methods: Two immunosuppressive strategies were sequentially evaluated. In Group 1 (13 patients), simultaneous C0/C2 (ng/mL) were analyzed. CsA dose monitoring was initially based on C0 : <3 months: 200-300, 4-6 months: 150-250, 6-9 months: 100-200, and on C2 thereafter (as in Group 2). In Group 2 (nine patients), C2 monitoring was implemented: <3 months: 600-800, 4-6 months: 500-700, >6 months: 400-600. All patients received ATG induction, corticosteroids, and MMF (1.0 g b.i.d. in Group 1 and 1.5 g b.i.d. in Group 2)., Results: Patients in Group 2 received higher MMF doses during the first trimester. C2 at 1, 3, 6, 12, 24, and 36 months was, respectively, 1199 +/- 476, 1202 +/- 587, 999 +/- 467, 664 +/- 203, 593 +/- 208, and 561 +/- 147 in Group 1, and 809 +/- 160 (p = 0.02), 644 +/- 178 (p = 0.003), 664 +/- 169 (p = 0.02), 616 +/- 221, 464 +/- 234, and 451 +/- 165 in Group 2. The incidence of acute rejection (grade > or =3A) at 6, 12, 24, and 36 months was, respectively, 38.5, 38.5, 46, and 54% in Group 1, and 11, 44, 56, and 56% in Group 2 (p = NS). At 3 months, the creatinine clearance was 25% lower in Group 1. Thereafter, renal function remained stable in both groups., Conclusion: Our results suggest that heart transplant patients receiving ATG induction may experience similar outcomes with either a higher C2 and a lower MMF dose or a lower C2 and a higher MMF dose. These results could be considered to design prospective studies to optimize C2 monitoring, to reduce the incidence of acute rejection without increasing the risk of renal dysfunction.

Assessment of glomerular filtration rate (GFR) in heart transplant (HTx) patients is based on serum creatinine (sCr), the endogenous creatinine clearance (C(Cr)) and radionuclide GFR (rGFR); however, the latter is expensive and time consuming. We reviewed the data of 32 adult HTx patients to determine the correlation between sCr, C(Cr), the calculated C(Cr) (Calc.C(Cr); based on gender, age, weight and sCr) and rGFR in long-term (>1 year) HTx patients receiving calcineurin inhibitors. The Calc.C(Cr) was found to have the best correlation with rGFR (r(2) = 0.65), followed by C(Cr) (r(2) = 0.53) and sCr (r(2) = 0.38). The use of Calc.C(Cr) to estimate GFR may be cost-effective in assessing renal function after HTx.

Many among the large and increasing number of patients suffering from heart failure can benefit from surgical interventions. The indications, efficacy and limitations of various surgical procedures currently available are reviewed, and an integrated approach to offer surgical therapy optimal for the particular patients is proposed.