Preoperative haemostasis testing does not predict requirement of blood products in cardiac surgery.

OBJECTIVE: Standard haemostasis screening tests are performed to reveal unknown congenital or acquired disturbances of plasma and/or platelet haemostasis. Since their diagnostic efficacy is often low, routinely performed haemostasis testing has been questioned. We investigated whether preoperatively assessed haemostasis testing can be used to predict the requirement of blood products. METHODS: We retrospectively assessed haemostasis parameters including platelet function testing by PFA 100 as well as the numbers of red blood cell (RBC) concentrates, fresh frozen plasmas (FFPs), and platelet concentrates (PCs) that were given peri-operatively and during the first two postoperative days in 2,831 cardiac surgery patients. Logistic regression analyses were used to select those parameters, which could predict blood product requirement. RESULTS: Of our study cohort, 56.5% needed RBCs, 15% FFPs, and 5% PCs. The need for RBCs was associated with significantly altered pre-operative values of most haemostasis parameters. However, by the use of logistic regression analysis fibrinogen was the only haemostasis parameter that was independently associated with the use of RBCs (odds ratio 1.56; 95% CI: 1.27-1.91; P <0.001). The predictive value of other parameters such as age, body weight, haemoglobin, and haematocrit was however much higher in comparison to fibrinogen (odds ratios: 1.92-3.50; P <0.001). It was not possible to develop a score based on haemostasis parameters to accurately identify patients at risk for RBC use. Moreover, we were unable to estimate the need for FFPs and PCs using preoperative haemostasis testing. CONCLUSIONS: Our data demonstrate that preoperatively performed haemostasis testing is not predictive in estimating the need for blood products in cardiac surgery patients.

Cardiac retransplantation in adults: an evidence-based systematic review.

BACKGROUND: It remains a matter of dispute whether cardiac retransplantation should be performed. We aimed to systematically review the available evidence regarding cardiac retransplantation in adults. MATERIAL AND METHODS: In PubMed, we searched for original reports on cardiac retransplantation in adults. The evidence level of individual studies was assessed. RESULTS: Twenty-two studies met our selection criteria. The cumulative incidence was 3% (range: 1% to 15%). The incidence rate was 164/10,000 person-years (range: 145 to 318/10,000 person-years). The main indications for retransplantation were cardiac allograft vasculopathy (55%), acute rejection (19%), and primary graft failure (17%). The early mortality rate was 16% (range: 5% to 38%). Refractory acute rejection and primary graft failure, female donor, shorter transplant interval, initial diagnosis of ischemic cardiomyopathy, need for mechanical circulatory support, a center volume of less than 9 transplantations/year, older recipient age, requirement of pretransplant ventilator and intensive care, and ischemic time were associated with poorer outcomes, while cardiac allograft vasculopathy as the cause of allograft failure, employment, and later transplant period were associated with improved survival. CONCLUSION: This systematic review shows that the results of cardiac retransplantation in adults are inconclusive. Retransplantation for cardiac allograft vasculopathy is associated with satisfactory outcomes.

Cardiac retransplantation: a 15-year single-center clinical experience.

BACKGROUND: Cardiac retransplantation is a controversial therapy because of the shortage of donor hearts. We retrospectively reviewed the short-term and long-term outcomes after cardiac retransplantation. METHODS AND RESULTS: Twenty-eight cases (18 males, 7 females; mean age, 50.3 +/- 13.5 years) underwent cardiac retransplantation: 25 first retransplantations and 3 second retransplantations. The indications for retransplantation were primary graft failure (PGF) in 11 patients (39.3%), intractable acute cardiac rejection (IACR) in 4 patients (14.3%), and coronary allograft vasculopathy (CAV) in 13 patients (46.4%). The patients had been supported as follows: prolonged cardiopulmonary bypass (CPB; n = 3), intra-aortic balloon pumping (IABP; n = 1), intravenous inotropic support (n = 7), extracorporeal membranoxygenator (ECMO; n = 3), ventricular assist device (VAD; n = 4), and no inotropic support (n = 10). There were 8 deaths within 30 days after retransplantation (28.6%). The overall 1-, 5-, 10-, and 15-year survival rates were 46.4%, 40.6%, 32.5%, and 32.5%, respectively. Acute cardiac rejection was the most common cause of death (43.8%). Thirty-day and 1-year survival rates of IACR, PGF, and CAV were 50.0%/0%, 63.6%/45.5%, and 84.6%/68.4%, respectively. CONCLUSIONS: Long-term survival after retransplantation was acceptable for patients with CAV and PGF; however, we must select patients for retransplantation carefully if the indication is IACR, because of the poor outcome.

Heart transplantation at the Heart Center North Rhine-Westfalia.

At the Heart Center North Rhine-Westfalia, Germany, more than 1,500 adult cardiac transplantations and more than 100 pediatric cardiac transplantations have been performed since the transplant program was initiated in 1989. Each year, we take care of 800 cardiac transplant recipients and 1,700 patients with heart failure who are in a long-term program for cardiac transplantation or on the Eurotransplant waiting list for cardiac transplantation. We have experience with ventricular assist device implantation as bridge to transplant in more than 300 patients. In total, our clinical know-how with cardiac transplant recipients is based on 10,800 patient-years of observation. In 2006, we transplanted the first donor heart worldwide with the Organ Care System, a technology capable of maintaining human organs in a functioning state ex-vivo. Usually, our transplant recipients have more preoperative risk factors than cardiac transplant recipients at other German heart centers. Our postoperative patient care is individualized with respect to immunosuppression and the performance of myocardial biopsies and coronary angiography. Since 1989, we have performed 31 cardiac retransplantations.

Combined calcium and vitamin D supplementation is not superior to calcium supplementation alone in improving disturbed bone metabolism in patients with congestive heart failure.

OBJECTIVES: To clarify the potential role of vitamin D supplementation on bone metabolism in congestive heart failure (CHF) patients with low vitamin D status and insufficient dietary calcium intake. SUBJECTS/METHODS: One hundred and two ambulatory male CHF patients were recruited, of whom the majority was treated with loop diuretics. Nine patients died during follow-up. Additional 14 participants dropped out prematurely because their health status worsened markedly. Five patients had to be excluded due to lack of compliance. A daily vitamin D3 supplement plus 500 mg calcium (CaD group) or a placebo plus 500 mg calcium (Ca group) was given for 9 months. Biochemical parameters of vitamin D and bone metabolism were analyzed at baseline and after 9 months. RESULTS: Median 25-hydroxyvitamin D concentrations increased from 41.7 to 103.0 nmol/l (P < 0.001) in the CaD group and remained constant in the Ca group, while median calcium intake increased above 1200 mg/day in both groups. The percentage of patients with elevated parathyroid hormone levels (> 60 pg/ml), as well as the serum concentration of undercarboxylated osteocalcin, an indicator of osteoporotic fracture risk and the bone resorption marker C-telopeptide fell significantly in both study groups (P < 0.025-0.001). At the end of the study period, biomarkers of bone turnover did not differ between groups. CONCLUSIONS: A vitamin D3 supplement of 50 microg/day has no additional beneficial effects on markers of bone metabolism in CHF patients with low initial 25-hydroxyvitamin D concentrations if an adequate daily calcium intake is guaranteed.

Economic evaluation of everolimus and mycophenolate mofetil versus azathioprine in de novo heart transplantation.

UNLABELLED: Both the proliferation signal inhibitor everolimus (1.5 mg/day) and mycophenolate mofetil (MMF) (3 g/day) have shown superior efficacy versus azathioprine in de novo heart transplantation. The cost-effectiveness of everolimus and MMF versus azathioprine was assessed to 6 months posttransplantation. METHODS: The evaluation was performed from the German health insurance payer perspective. The composite efficacy endpoint in the everolimus trial was death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR) grade>or=3A, rejection with hemodynamic compromise, and loss to follow-up. The composite endpoint in the MMF trial included only death, retransplantation, and BPAR with hemodynamic compromise. To mimic the everolimus endpoint, an estimated number of patients with BPAR>or=3A was added to the MMF trial results, using two mapping scenarios. RESULTS: The incremental 6-month cost versus azathioprine was euro2535 for everolimus and euro3007 for MMF. The absolute reduction in efficacy failure versus azathioprine was 10.4% for everolimus and 9.8% and 10.1% for MMF, respectively, using scenarios 1 and 2. The incremental cost per efficacy failure avoided (ie, the incremental cost versus azathioprine divided by the reduction in efficacy failure) was euro24,457 for everolimus, and euro30,628 and euro29,912 for MMF in scenarios 1 and 2. CONCLUSION: This analysis, based on findings from two clinical trials, suggested that everolimus was more cost-effective than MMF versus azathioprine in the first 6 months after heart transplantation. Data from a head-to-head trial are required to confirm these results.

No evidence for an improvement of long-term survival by HLA matching in heart transplant recipients.

It has been assumed that better HLA matching improves midterm survival in cardiac transplantation. However, statistically reliable data on long-term survival according to HLA matching are scanty. We performed a retrospective analysis of all patients who underwent orthotopic heart transplantation at our heart center between 1989 and 2005. HLA typing data (major histocompatability complex [MHC] class I and II) were available in 923 patients and their heart donors. Univariate and multivariate analyses were performed to assess the impact of HLA matching on long-term survival. The average follow-up period was 6.1 +/- 4.3 years (range, 0.0 to 15.0 years). In total, the 923 patients accrued 5625 patient-years of observation. Zero, one, and two mismatches occurred at each locus in between 0.3% (HLA-B) to 6.6% (HLA-C), 16.6% (HLA-B) to 39.4% (HLA-DQ), and 55.4% (HLA-DQ) to 83.3% (HLA-B), respectively. Two hundred eleven patients died during follow-up (22.9%). Survival at 1, 2, 5, and 10 years was 87.7%, 86.2%, 78.4%, and 63.9%, respectively. In the multivariate analysis, age, transplant era, presence of MHC class I and II antibodies, and high urgency status but not HLA mismatches were independent predictors of long-term survival. Moreover, diagnoses other than dilated cardiomyopathy increased long-term mortality risk. In summary, our data demonstrate that HLA matching is not an independent risk factor for longterm survival in heart transplant recipients. However, several pretransplant factors and transplant era were independently associated with mortality risk.

Cardiac surgery after heart transplantation: coronary artery bypass grafting and heart valve replacement.

INTRODUCTION: Due to increasing need for and a shortage of donor organs, therapeutic procedures such as heart valve replacement for valve insufficiency and coronary artery bypass grafting (CABG) for graft vasculopathy (GVP) must be performed to improve allograft function to avoid retransplantation. METHODS: We performed a retrospective analysis of patients who underwent surgical procedures after orthotopic heart transplantation. Since 1989, we have performed more than 1400 heart transplantation procedures. Valve replacement was necessary in 8 patients and CABG was necessary in 3 patients. Five patients received valve prostheses (3 bioprostheses and 2 mechanical valves) at the tricuspid position. Three patients received a Hancock bioprosthesis at the mitral position. One of the 3 received the valve 3 years after heart transplantation while suffering from mitral regurgitation grade IV, and another patient received the valve 1 year following heart transplantation while suffering from mitral insufficiency grade III due to infective endocarditis. Three patients underwent coronary artery revascularization, 2 patients underwent the procedure 1 and 7 years after heart transplantation because of GVP, 1 patient underwent the procedure simultaneously with heart transplantation because of donor coronary artery disease. One patient received concomitant CABG with heart transplantation because of 75% left anterior descending stenoses in the donor organ, and one patient received CABG 1 year after heart transplantation because of rapidly progressive GVP in the left anterior descending artery. The third patient had 3-vessel disease with 95% left stem and 75% ramus circumflex, ramus marginalis, and ramus diagonalis. RESULTS: Two patients who underwent CABG and 4 patients who underwent valve replacement are still alive and maintain good clinical performance. One patient with a graft at the mitral position died 9 years after heart transplantation and 6 years after mitral valve replacement. Two patients with a graft at the tricuspid position died 17 and 4 years after heart transplantation (6 and 3 years after valve replacement, respectively). One patient with a bioprostheses at the tricuspid position had to be retransplanted 2 years following valve replacement while suffering from a paravalvular leakage grade III. CONCLUSION: Cardiac surgical procedures can be safely performed after heart transplantation. To improve graft and patient survival, such procedures must be carefully performed after heart transplantation to avoid retransplantation. The shortage of donor organs will and must lead to an increase in the number of conventional procedures performed to improve allograft function in transplanted hearts.

Implantation of CardioWest total artificial heart for irreversible acute myocardial infarction shock.

Patients who develop cardiogenic shock after acute myocardial infarction have a very high mortality rate despite early reperfusion therapy. Hemodynamic stabilization can often only be achieved by implanting a mechanical circulatory support system. When, in cases representing expansive myocardial impairment without any chance of recovery, pharmacological therapy and the use of percutaneous assist devices have failed, the implantation of a total artificial heart is indicated. We report our first experiences with this extensive and innovative method of managing irreversible cardiogenic shock patients. The CardioWest total artificial heart was implanted in 5 patients (male; mean age, 50 years). All patients were in irreversible cardiogenic shock despite maximum dosages of catecholamines, an intra-aortic balloon pump and/or a femoro-femoral bypass. In all patients early reperfusion therapy was performed. After implantation of the Cardio West system, all dysfunctional organ systems rapidly recovered in all patients. Four of 5 patients underwent successful heart transplantation after a mean support time of 156 days. One patient died because of enterocolic necroses caused by an embolic event after termination of dicumarol therapy. In summary, our first experiences justify this extensive management in young patients who would otherwise have died within a few hours.

IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support.

Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.

Unusual pacemaker implantation through a left sided superior vena cava via anonymous vein after heart transplantion.

We report the case of a 56-year-old male heart transplant recipient, who underwent postoperative pacemaker implantation through a left sided superior vena cava (LSVC) via anonymous vein. We describe our successful management of this case. We suggest that the specific anatomic conditions should be considered in all heart transplant recipients with LSVC if pacemaker implantation is necessary postoperatively.

The controversy of donor serum sodium levels in heart transplantation--a multicenter experience.

BACKGROUND: Elevated donor serum sodium is a phenomenon often encountered in the management of brain dead donors. The clinical relevance on recipient outcome is less examined. We investigated the impact of elevated donor serum sodium levels (DSL) on outcome after heart transplantation in 1800 heart transplantations. METHODS: Data was conducted in a retrospective analysis from 1989 until 2005. The transplantations were performed at three German heart transplant centers. The joined database included DSL at the time of organ procurement, recipient and donor age, ischemia time, primary graft failure and survival data. RESULTS: Mean DSL was 147.7 +/- 10.3 l/l (range 111 - 208 l/l). Recipients were divided into 4 groups with percentiles of 141, 147, and 154 l/l resulting in DSL of A: 135.8 +/- 4.4, B: 143.6 +/- 1.7, C: 149.7 +/- 1.9, and D: 161.3 +/- 7.7 l/l for the four quartiles. Primary graft failure occurred in 2.6 % of the patients with A: 2.8 %, B: 2.8 %, C: 3.7% and D: 1.4 % ( P = n.s.). Mean 5- and 10-year-survival rates were 70.9 % (57.6 %) with A: 71.1 % (53.86 %), B: 69.3 % (53.9 %), C: 72.7 % (61.0 %), D: 71.2 % (62.4 %), respectively ( P = n. s.). In a multivariate analysis a significant impact on postoperative results could be revealed for recipient age ( P = 0.002), ischemia time ( P = 0.002) and donor age ( P = 0.009). DSL were no individual risk factor in the multivariate analysis. CONCLUSION: There was no impact of donor serum sodium levels neither on early postoperative results, nor on long-term outcome indicating that cardiac allografts from donors with elevated sodium levels might be transplanted successfully, achieving favourable results.

Unusual case of an 18-year-old heart transplant recipient with endocardial fibroelastosis.

An 18-year-old female Japanese patient who suffered from heart failure and severe pulmonary hypertension was referred to our clinic. The etiology of her cardiomyopathy was unclear. Inhaled prostacyclin therapy resulted in an improvement of pulmonary arterial pressure and allowed us to avoid lung transplantation. Heart transplantation resulted in a complete remission of her respiratory function. Autopsies of the explanted heart revealed massive endomyocardial fibroelastosis. We concluded that endomyocardial fibroelastosis has to be considered a cause of heart failure in young adults with unclear cardiomyopathy.

Heart transplantation in children after mechanical circulatory support: comparison of heart transplantation with ventricular assist devices and elective heart transplantation.

Heart transplantation (HTx) is an ultimate treatment for children with end-stage heart failure or inoperable congenital heart disease. The supply of hearts is inadequate; therefore, different mechanical support systems must be used as bridge to HTx in pediatric patients with postoperative low output. The use of ventricular assist devices (VADs) as bridge to HTx in children is limited because of size differences. The purpose of this study was to evaluate the overall long-term outcome of pediatric circulatory support before pediatric HTx. From 1989 through 2004, 91 pediatric patients underwent isolated HTx. Seven of them required mechanical support before transplantation. We reviewed retrospectively the course of 91 children (mean age 14.7 years) who underwent HTx. Group A consisted of elective HTx patients who were treated as outpatients before HTx, whereas group B was the VAD-HTx bridging group (n=7; mean age 12.31 +/- 2.8 years). Mean duration of VAD support was 108 +/- 98 days (minimum 1 day, maximum 258 days). Overall survival rate after HTx was 80% at 1 year without significant differences between groups. Five of seven patients survived and could be discharged after successful HTx, for a survival rate of 77%. The mean follow-up period was 16.76 +/- 10.6 months. No differences in posttransplantation long-term survival and rejection episodes occurred between patients transplanted with or without VAD. VAD therapy can keep pediatric patients with end-stage heart failure alive until successful HTx, and bridge to HTx is a safe procedure in pediatric patients. After HTx, survival rates of these children are similar to those of patients awaiting elective HTx.

Frequent detection of hepatitis B core antibodies in heart transplant recipients without preceding hepatitis B infection.

It is unclear whether heart donors positive for hepatitis B core antibodies (anti-HBc) can transfer hepatitis B virus (HBV) infection to immunosuppressed heart recipients, or whether passive transfer of anti-HBc simulates a hepatitis B infection. Therefore, we performed a case-controlled study in 46 heart recipients who all tested negative for hepatitis B antigen (HbsAg), antiHBc, and hepatitis B surface antibodies before heart transplantation. Twenty-three patients (group 1) received hearts from anti-HBc-positive donors, while 23 other patients (group 2) received hearts from anti-HBc-negative donors. After heart transplantation, anti-HBc were present in 65.0% of blood samples among group 1 and 47.8% of the blood samples among group 2 (P > .05). HbsAg was undetectable in blood samples of all patients of both study groups. The immunoglobulin preparation that we regularly use for immune suppression immediately after heart transplantation contained a relatively high concentration of anti-Hbc antibodies. The nearly identical presence of anti-HBc in both study groups indicated that passive transfer via immunoglobulin preparations rather than HBV infection is the cause for the anti-HBc detected in heart recipients. Since only a small volume of blood is transferred with the donor heart, it seems to be rather unlikely that the donor heart might be the source of anti-HBc. In summary, we observed no evidence for HBV infection in those heart recipients who received organs from anti-HBc-positive donors. Moreover, our data demonstrated that the presence of anti-HBc in heart recipients frequently occurs but does not necessarily indicate a preceding HBV infection.

Aortoplasty with a bovine venous xenograft for pseudoaneurysm after heart transplantation.

The case was a 54-year-old man after orthotopic heart transplantation with infected pseudoaneurysm of the ascending aorta. The operation was performed with hypothermic circulatory arrest. Pseudoaneurysm was excised and aortoplasty was performed with a bovine venous xenograft patch. Six months after the operation, and 2 years after transplantation, the patient is doing well.

Organs from donors with primary brain malignancy: the fate of cardiac allograft recipients.

BACKGROUND: The phenomenon of malignancy transmission from donors with primary brain malignancy (PBM) which is relatively well documented in renal or liver transplant recipients, has not been analyzed in cardiac allograft recipients. METHODS: We reviewed the medical records of 32 cardiac allograft recipients who were transplanted with organs from donors suffering from primary brain malignancies from 1989 to 2003. RESULTS: No case of donor-transmitted malignancy has been reported with a mean follow-up of 80.6 months. CONCLUSIONS: In our experience as well as according to a review of the literature, the risk of tumor transmission from donors with primary brain malignancy to cardiac allograft recipients seems to be extremely low. In the context of the increased donor shortage, we recommend to accept all suitable cardiac allografts harvested from donors with primary brain malignancy provided there are no detectable remote metastases.

Coronary vein leads for cardiac pacing in patients with tricuspid valve replacement.

BACKGROUND: Because after tricuspid valve replacement (TVR) the transvenous implantation of endocardial leads is contraindicated, myocardial screw-in leads were used to ventricular pacing. Recently available coronary vein (CV) leads are stimulating the left ventricle epicardially and can be implanted transvenously, too. METHOD AND RESULTS: We implanted these leads in patients (pts) with TVR (n = 7) or after valve repair (n = 1) without complications. In 7 pts we used bended CV leads with a microporous tip and only in one pt a CV lead with a stimulation via metal ring. The stimulation thresholds (ST) were stable in all pts. CONCLUSIONS: The use of CV leads offers a minimal invasive approach for permanent cardiac stimulation after TVR. Low chronic ST are resulting in an energy saving pacemaker mode. CV leads can be used after previous heart surgery as well as for difficult anatomical situations.