Amir K. Bigdeli

Three-dimensional printing of models for preoperative planning and simulation of transcatheter valve replacement.

In this study, we show the use of three-dimensional printing models for preoperative planning of transcatheter valve replacement in a patient with an extreme porcelain aorta. A 70-year-old man with severe aortic stenosis and a porcelain aorta was referred to our center for transcatheter aortic valve replacement. Unfortunately, the patient died after the procedure because of a potential ischemic event. Therefore, we decided to fabricate three-dimensional models to evaluate the potential effects of these constructs for previous surgical planning and simulation of the transcatheter valve replacement.

3-Dimensional Printing of Models to Create Custom-Made Devices for Coil Embolization of an Anastomotic Leak After Aortic Arch Replacement

PURPOSE The objective of this study was to show the use of 3-dimensional printing models to fabricate a custom-made occluder for device embolization of an anastomotic leak after replacement of the ascending aorta and the aortic arch in a human immunodeficiency virus (HIV)-infected patient. DESCRIPTION We present a 50-year-old HIV-infected patient who underwent ascending aorta and aortic arch replacement for a type A dissection, and who had an aortic arch pseudoaneurysm (sized 5 x 5 x 4 cm) with a slit-shaped entrance hole located anteriorly to the implanted supra-aortic vessels. The patients 128-slice computed tomography data were visualized and reconstructed. Afterward we fabricated a life-like replica of the complex pathology of the ascending aorta and the aortic arch using a rapid prototyping machine. After careful examination of the model, we fabricated a custom-made occluder device for interventional closure of the leakage. EVALUATION Using data derived from 128-slid computed tomography linked to proprietary software, we were able to create models of the ascending aorta, the aortic arch end, especially the pseudoaneurysm with its slit-shaped opening between the aortic lumen and the aneurysm. This was very helpful to build a perfectly fitting custom-made occluder device to plan and simulate the interventional closure. Moreover, the models were helpful for intra-interventional orientation. CONCLUSIONS The stereolithographic replicas were extremely useful for choosing the treatment option and for planning and simulating the occlusion of the pseudoaneurysm. Furthermore, the models were necessary for our engineers who were building the custom-made occluder device.

Effects of Donor Pre-Treatment With Dopamine on Survival After Heart Transplantation A Cohort Study of Heart Transplant Recipients Nested in a Randomized Controlled Multicenter Trial

OBJECTIVES We determined the outcome of cardiac allografts from multiorgan donors enrolled in a randomized trial of donor pre-treatment with dopamine. BACKGROUND Treatment of the brain-dead donor with low-dose dopamine improves immediate graft function after kidney transplantation. METHODS A cohort study of 93 heart transplants from 21 European centers was undertaken between March 2004 and August 2007. We assessed post-transplant left ventricular function (LVF), requirement of a left ventricular assist device (LVAD) or biventricular assist device (BVAD), need for hemofiltration, acute rejection, and survival of recipients of a dopamine-treated versus untreated graft. RESULTS Donor dopamine was associated with improved survival 3 years after transplantation (87.0% vs. 67.8%, p = 0.03). Fewer recipients of a pre-treated graft required hemofiltration after transplant (21.7% vs. 40.4%, p = 0.05). Impaired LVF (15.2% vs. 21.3%, p = 0.59), requirement of a LVAD (4.4% vs. 10.6%, p = 0.44), and biopsy-proven acute rejection (19.6% vs. 14.9%, p = 0.59) were not statistically different between groups. Post-transplant impaired LVF (hazard ratio [HR]: 4.95; 95% confidence interval [CI]: 2.08 to 11.79; p < 0.001), requirement of LVAD (HR: 6.65; 95% CI: 2.40 to 18.45; p < 0.001), and hemofiltration (HR: 2.83; 95% CI: 1.20 to 6.69; p = 0.02) were predictive of death. The survival benefit remained (HR: 0.33; 95% CI: 0.12 to 0.89; p = 0.03) after adjustment for various risks affecting mortality, including pre-transplant LVAD/BVAD, inotropic support, and impaired kidney function. CONCLUSIONS Treatment of brain-dead donors with dopamine of 4 μg/kg/min will not harm cardiac allografts but appears to improve the clinical course of the heart allograft recipient. (Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation; NCT00115115).

Proton Pump Inhibitor Co-medication Reduces Mycophenolate Acid Drug Exposure in Heart Transplant Recipients

BACKGROUND Proton pump inhibitors (PPIs) are often prescribed for gastrointestinal discomfort after heart transplantation (HTx). This study investigates the impact of PPI use on mycophenolate acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus (Tac). METHODS MPA post-dose plasma concentrations at 0 to 2 hours were obtained by high-performance liquid chromatography (HPLC) in 21 patients on pantoprazole 40 mg/day (PPI group) and 12 patients not on pantoprazole (control group). In a subgroup, MPA plasma concentrations at 0 to 12 hours were measured to evaluate full MPA area-under-the-curve (AUC) measurements. RESULTS In the PPI group, the mean daily MMF dose was 1,912 +/- 1,023 mg with mean pre-dose serum concentrations (C(0)) of 1.9 +/- 1.4 mg/liter, without a significant difference from controls. Mean post-dose MPA concentrations at 30 minutes (C(0.5h)) were significantly higher in the control group (control, 17.9 +/- 11.5 mg/liter; PPI, 6.7 +/- 4.6 mg/liter; p < 0.001). One- and 2-hour (C(1h, 2h)) MPA concentrations were persistently higher in the control group (1 hour: control, 13.8 +/- 9.1 mg/liter; PPI, 7.7 +/- 4.1 mg/liter; 2 hours: control, 7.6 +/- 4.2; PPI, 5.0 +/- 2.8 mg/liter; p < 0.05). In the subgroup with full AUC measurements, the control group had higher MPA levels 12 hours after dosing (C(12h): control, 3.3 +/- 2.4 mg/liter; PPI, 1.6 +/- 1.3 mg/liter; p < 0.05) and a significantly higher dose-adjusted AUC C(0-3h) (control, 59.5 +/- 20.7 mg/liter; PPI, 41.7 +/- 23.4 mg/liter; p < 0.05). In the subgroup, the maximum plasma concentration of mycophenolic acid (MPA C(max)) in the PPI group was significantly lower (10.1 +/- 4.7 mg/liter) than in the control group (45.5 +/- 53.5 mg/liter, p < 0.0001), whereas t(max) revealed no differences (control: 1.1 +/- 0.77 hours; PPI: 1.1 +/- 0.97 hours). Furthermore, a clear trend for more acute rejection episodes (AREs) and more transplant vasculopathy (TVP) was found in the PPI group. CONCLUSIONS Patients with PPI co-medication show significantly lower MPA plasma concentrations, possibly due to decreased absorption. Therapeutic drug monitoring allows identification of patients with decreased MMF drug exposure who might be at risk for acute rejection.

Long-term outcomes after 1000 heart transplantations in six different eras of innovation in a single center.

The objective of this study was to evaluate long‐term outcomes of cardiac transplantation (HTx) in different eras of innovation at a single center during a period of 27 years. We performed a retrospective analysis of 960 cardiac allograft recipients (40 re‐HTx) between 1981 and 2008. The results of six different eras based on milestones in HTx were analysed: Era 1: the early years (n = 222, 1981–1992); era 2: introduction of inhalative nitric oxide, prostanoids, University of Wisconsin solution (UW) replacing Bretschneider’s solution (HTK, n = 118, 1992–1994); era 3: statins (n = 102, 1994–1995); era 4: tacrolimus (n = 115, 1995–1996); era 5: mycophenolate mofetil (MMF, n = 143, 1997–2000) and era 6: sirolimus (n = 300, 2000–2008). Outcome variables were survival, freedom from cardiac allograft vasculopathy (CAV) and from acute rejection episodes (AREs). Differences in survival was found comparing era 1 and era 2 with era 4 and era 6 (P < 0.001). Organ preservation through UW demonstrated a significantly better survival as compared with HTK (P < 0.001). Less AREs occurred in patients receiving tacrolimus‐sirolimus or tacrolimus‐MMF (P < 0.001). Patients receiving tacrolimus‐MMF showed less CAV than when treated with cyclosporine‐MMF (P < 0.005). There were more ventricular assist device implantations and more re‐HTx in era 6 (P < 0.0001) than when compared with other eras. Although the causes for improvement in survival over time are multifactorial, we believe that changes in immunosuppressive therapy have had a major impact on survival.

Defining algorithms for efficient therapeutic drug monitoring of mycophenolate mofetil in heart transplant recipients.

Pharmacokinetics of mycophenolate mofetil (MMF) show large interindividual variability. Concentration-controlled dosing of MMF based on routine therapeutic drug monitoring, which requires area under the concentration-time curve (mycophenolic acid [MPA]-AUC0-12h) determinations, is uncommon. Dose adjustments are based on predose concentrations (C0h) or side effects. The aim of this study was to compare C0h with postdose concentrations (C0.5h-C12h) and to develop practical methods for estimation of MPA-AUCs on the basis of a limited sampling strategy (LSS) in heart transplant recipients under MMF and tacrolimus maintenance immunosuppression. Full MPA-AUC0-12h profiles were generated by high-performance liquid chromatography in 28 patients. Statistical analysis for MPA-AUC0-12h was performed by a case resampling bootstrap method. Bland and Altmann analysis was performed to test agreement between “predicted AUC” and “measured AUC.” C1h provided the highest coefficient of determination (r2 = 0.57) among the concentrations determined during the 12-hour interval, which were correlated with AUC. All other MPA levels were better surrogates of the MPA-AUC0-12h when compared with C0h (r2 = 0.14). The best estimation of MPA-AUC0-12h was achieved with four sampling points with the algorithm AUC = 1.25*C1h + 5.29*C4h + 2.90*C8h + 3.61*C10h (r2 = 0.95). Since LSS with four time points appeared unpractical, the authors prefer models with three or two points. To optimize practicability, LSS with sample points within the first 2 hours were evaluated resulting in the algorithms: AUC = 1.09*C0.5h + 1.19*C1h + 3.60*C2h (r2 = 0.84) and AUC = 1.65*C0.5h + 4.74*C2h (r2 = 0.75) for three and two sample points, respectively. The results provide strong evidence for the use of either LSS or the use of time points other than C0h for therapeutic drug monitoring of MMF. Using the algorithms for the estimation of MPA-AUC0-12h based on LSS within the first 2 hours after MMF dosing may help to optimize treatment with MMF by individualization of dosing.

Successful management of late right ventricular perforation after pacemaker implantation

Complications of pacemaker implantation include myocardial perforation, venous thrombosis, vegetations of the tricuspid valve or pacing lead, and tricuspid regurgitation. We report a patient presenting with a case of delayed ventricular lead perforation through the right ventricle. The lead was uneventfully extracted under transesophageal echocardiographic observation in the operating room with cardiac surgery backup.

Use of Methylene Blue in the Treatment of Refractory Vasodilatory Shock After Cardiac Assist Device Implantation: Report of Four Consecutive Cases

Vasodilatory shock frequently occurs after cardiac surgery, particularly after cardiac assist device implantation. This complication is often associated with high mortality, especially if refractory to conventional vasoconstrictor treatment. Methylene blue, a guanylate cyclase inhibitor, has been successfully used in the management of vasodilatory shock associated with cardiopulmonary bypass. We present four successive cases after implantation of cardiac assist devices suffering from norepinephrine and vasopressin refractory severe vasodilatory shock. In all patients, administration of a single dose of methylene blue (2 mg/kg body weight) resulted in an immediate and persistent decrease in vasoconstrictor dosages and serum lactate concentrations. Despite of this benefit, all patients deceased during hospital stay, however, this was not related to the methylene blue treatment. Methylene blue seems to be a promising therapeutical option in patients with otherwise resistant vasodilatory shock after cardiac assist device implantation. However, controlled clinical trials are necessary to substantiate safety and efficacy.

Combined Aortic Valve Replacement and Extra-Anatomic Aorta Ascending-Descending Bypass for Recurrent Aortic Coarctation

Aortic recoarctation may be difficult to manage, especially in patients with the need for additional surgical interventions. We describe the case of a 45-year-old man with grown-up congenital heart disease, presenting with recoarctation after initial anatomic repair with a prosthetic graft at the age of 16 years. Further examination revealed heart failure and left ventricular dilation because of severe aortic regurgitation, owing to a bicuspid aortic valve. Through a median sternotomy and CPB, an aortic valve replacement and extra-anatomic ascending-to-descending aortic-bypass-grafting was performed with a posterior pericardial approach. Off-pump coronary artery bypass techniques were applied to reach the descending aorta.

Luminex‐based virtual crossmatching facilitates combined third‐time cardiac and de novo renal transplantation in a sensitized patient with sustained antibody‐mediated cardiac allograft rejection

Deutsch M‐André, Kauke T, Sadoni S, Kofler S, Schmauss D, Bigdeli AK, Weiss M, Reichart B, Kaczmarek I. Luminex‐based virtual crossmatching facilitates combined third‐time cardiac and de novo renal transplantation in a sensitized patient with sustained antibody‐mediated cardiac allograft rejection.
Pediatr Transplantation 2010: 14:E96–E100.