Hybrid-ALPPS followed by Ante Situm with Cardiopulmonary Bypass: Rapid Liver Augmentation and Complex Surgery.

BACKGROUND: Tumors invading the inferior vena cava (IVC) and hepatic veins pose a challenge for surgeons. Hannoun et al.1 were able to show that the resection of these tumors can be done under hypothermia in the Ante-Situm position. Additionally, not only the localization of the tumor but the remaining volume of the remnant liver (FLR) needs to be considered. Schnitzbauer et al.2 were able to induce massive liver hypertrophy in a short period, combining an in-situ split with a portal vein ligation (ALPPS). As this controversial technique has evolved, a safe ALPPS can be performed nowadays.3 To our knowledge, this is the first case that combines a laparoscopic partial ALPPS with an extended resection requiring cardiopulmonary bypass (CPB). METHODS: A 58-year-old female presented with a known chronic hepatitis C suffered from a pulmonary embolism, caused by a large, central hepatocellular carcinoma (HCC) with invasion of the suprahepatic IVC and continuous growth into the right atrium (RA). Due to the small FLR, we performed a laparoscopic hybrid-partial-ALPPS with an embolization of the right portal vein. We were able to remove the mass with an Ante-Situm position and resection of the RA under CPB. RESULTS: The postoperative course was complicated by posthepatic liver failure and bleeding. However, after 28 days the patient was discharged in a good medical condition. CONCLUSIONS: Although tumors invading the suprahepatic IVC and RA pose a surgical challenge, patients can be treated adequately with multidisciplinary management. Advanced HCCs have high recurrence rates; however, a R0 resection might improve overall survival. Wakayma et al. showed in their retrospective study with 13 patients a median survival of 30.8 months when a complete resection was performed.4 Our patient had a disease-free survival of 11 months and is still alive after 24 months. Taking the complexity of the operation and the oncological prospect with a probable recurrence into account, indication for surgery needs to be considered on an individual basis.

Persistent atrial fibrillation ablation concomitant to coronary surgery.

OBJECTIVE: This analysis was undertaken to evaluate the results of persistent atrial fibrillation (pAF) ablation procedures concomitant to coronary surgery and to identify the risk factors for pAF recurrence. METHODS: Since 2001, a total of 126 consecutive patients with pAF (duration: 0.5-33 years) underwent ablation concomitant to coronary surgery (isolated or in combination with valve surgery), whereby two encircling isolation lesions around the left and the right pulmonary veins and a connecting lesion between both was created using radiofrequency ablation. Patients were reevaluated at discharge, 3 months and 3 years after surgery. RESULTS: Survivals at the time of reexamination were 96.8, 95.1 and 94.7 %, respectively. Stable sinus rhythm (SR) could be documented in 66.4, 75.1 and 75.9 % of surviving patients. Long-term pAF before surgery and a larger left atrium (LA) were predictive of postoperative pAF return ( P < 0.01). Statistical analysis demonstrated a cut-off point of 5 years for pAF and 50 mm for LA diameter: 89.1 % of patients with pAF duration of < 5 years and 86.2 % of patients with LA size of ≤ 50 mm were in stable SR at late follow-up. Cardiac rhythm at 3 months was predictive for long-term rhythm prognosis ( P < 0.01). Age, gender and concomitant diseases (e.g. arterial hypertension, diabetes, renal insufficiency), and the underlying cause of heart disease did not significantly influence the postoperative cardiac rhythm. CONCLUSIONS: The duration of pAF and the LA size are the most reliable preoperative variables to predict the success rate of ablation in patients undergoing coronary surgery. The probability of re-establishing stable SR is excellent when pAF duration is short and LA size is small.

Contrast enhanced IR-SSFP examination compared with T1-weighted turbo spin-echo imaging of cardiac tumors and tumorlike lesions.

PURPOSE: To show that the use of an early and delayed contrast enhanced multislice inversion recovery steady state free precession (SS-IR-SSFP) is a valuable substitute for conventional post-contrast fat saturated turbo spin-echo (TSE) T1-weighted images in the assessment of cardiac tumors. MATERIALS AND METHODS: 34 consecutive patients referred for MRI in order to assess cardiac tumors were examined. Shortly after administration of gadopenetate dimeglumine (Gd-DTPA) images were obtained using a SS-IR-SSFP sequence. The inversion time (TI) was set at 350ms to achieve a good demarcation of intracavitary tumor spread. Hereafter 9 slices of a T1w TSE sequence were obtained. Finally a SS-IR-SSFP sequence with an optimized TI to null normal myocardium was employed. Quantitative comparisons were performed by calculating contrast to noise ratios of tumor/myocardium (CNR(tumor/myo)) and CNR of tumor/left ventricular cavity (CNR(tumor/LVC)). Image quality was assessed regarding overall image quality, artifacts and tumor conspicuity. RESULTS: Neither calculation of CNR(tumor/LVC) when comparing the early IR-SSFP and T1w TSE, nor calculation of CNR(tumor/myo) when comparing the late IR-SSFP and T1w TSE sequence resulted in statistically significant differences. However, qualitative assessments revealed significant superior results for the early and the late IR-SSFP images compared to the T1-weighted TSE images (p<0.001). CONCLUSIONS: Image quality and tumor conspicuity were superior and image degradation by artifacts was less on IR-SSFP images compared to TSE images without loss of CNR. Thus the use of IR-SSFP sequences is an attractive alternative imaging method compared to post-contrast T1w TSE imaging in the assessment of cardiac tumors.

[Caspofungin after solid organ transplantation in Germany: observational study on treatment of invasive fungal infections]. / Caspofungin nach Transplantation solider Organe in Deutschland: Beobachtungsstudie zur Behandlung invasiver Pilzinfektion.

BACKGROUND: This study was a pre-planned country-specific secondary analysis of results in Germany from a multinational multicenter observational study to retrospectively evaluate clinical outcomes with caspofungin in patients with probable and proven invasive fungal infection following solid organ transplantation (SOT). METHODS: Data were retrospectively collected on a single episode of invasive fungal infection (IFI) in patients who had a SOT between January 2004 and June 2007. Effectiveness was reported as the proportion of patients who received at least five doses of caspofungin with a favorable (complete or partial) response. Safety was assessed for patients who received at least one dose of caspofungin. Descriptive statistics were employed for all evaluations. RESULTS: A total of 41 SOT patients (27 male, 14 female; median age 56 years, median APACHE II score at start of caspofungin therapy 23) were enrolled from 5 sites in Germany. Organs transplanted were mainly heart (51%) and liver (46%). Prevalent risk factors for IFI at baseline were use of central venous catheter (37 out of 41 patients, 90%), steroid use (37 out of 41 patients, 90%), recent stay in intensive care (36 out of 41 patients, 88%),and duration of SOT procedure >5 hours (21 out of 41 patients, 51%). Candidiasis was diagnosed in 34 patients (83%) and aspergillosis in 10 patients (24%). The lungs were the most common site of IFI (21 out of 41, 51%). Caspofungin as monotherapy was received by 28 patients (68%); 6 patients (15%) received caspofungin as salvage therapy for IFI, in most cases because they were refractory to prior antifungal drugs. Immunosuppressants were administered with caspofungin in 39 out of 41 patients (95%). In subjects with at least 5 doses of caspofungin (modified intention to treat population) the favorable response rate at the end of caspofungin therapy was 88% overall, 29 out of 33 patients; 95% confidence interval (95%-CI) 72-97%), 86% (19 out of 22 patients) with monotherapy and 91% (10 out of 11 patients) with combination therapy. No (serious) adverse events or drug interactions related to treatment with caspofungin were reported. The overall survival rate was 79% (26 out of 33 patients; 95%-CI 61-91%) at 7 days after completion of caspofungin treatment. CONCLUSION: Caspofungin was found to be an effective treatment of probable and proven invasive fungal infections in patients following SOT in Germany.

A beta-adrenergic antagonist reduces traumatic memories and PTSD symptoms in female but not in male patients after cardiac surgery.

BACKGROUND: Epinephrine enhances emotional memory whereas beta-adrenoceptor antagonists (beta-blockers, BBs) impair it. However, the effects of BB administration on memory are sex dependent. Therefore, we predicted differential effects of epinephrine and the BB metoprolol given to male and female patients after cardiac surgery (CS) on traumatic memories and post-traumatic stress disorder (PTSD) symptoms. METHOD: We performed a prospective observational study and determined the number of standardized traumatic memories (NTRM) and PTSD symptom intensity in cardiac surgical patients at 1 day before surgery, and at 1 week and 6 months after the procedure. PTSD symptoms and NTRM were quantified using validated questionnaires. Metoprolol could be administered any time post-operatively. RESULTS: Baseline NTRM was not significantly different between male (n=95) and female patients (n=33). One week after CS, the NTRM in male patients was significantly higher. Metoprolol had no significant effect in either sex. At 6 months, females with metoprolol (n=18) showed a significantly lower NTRM and significantly lower PTSD symptom scores than females without BBs (n=15, p=0.02). By contrast, the totally administered dosage of epinephrine correlated with NTRM in males (r=0.33, p<0.01) but not in females (r=0.21, p=0.29). CONCLUSIONS: beta-Adrenergic stimulation with epinephrine enhances memory for adverse experiences in males but not in females whereas beta-blockade selectively reduces memory for post-operative adverse events and PTSD symptoms in females.

Multidrug-resistant gram-positive infections in patients with ventricular assist devices: the role of daptomycin.

OBJECTIVES: The rate of infection in patients who require ventricular assist devices (VADs) is estimated at more than 35%. Infections with multidrug-resistant (MDR) organisms in VAD recipients present a high mortality rate. Daptomycin (Cubicin, Novartis, Nuremberg, Germany), a new cyclic lipopeptide antibiotic, is useful for MDR gram-positive organisms. We report the successful use of daptomycin in patients presenting with MDR gram-positive infections after VAD implantation. METHODS: We retrospectively studied nine consecutive patients presenting with resistant gram-positive infections after VAD implantation treated with daptomycin. We analyzed type of VAD, type of infection, responsible microorganism, outcome, and adverse events. RESULTS: We studied nine patients (eight males, one female), of overall mean age of 51 +/- 8 years; 78% required a biventricular assist device or a left VAD (Berlin Heart, Berlin, Germany), 22% received other ventricular support. Sixty-six percent presented with catheter-related infections (CRIs). Therapy with daptomycin was empirically initiated in all cases. The initial dose was 6 mg/kg, continued at 4 mg/kg. The mean duration of therapy was 16 +/- 5 days. The reported pathogens were MRSA, 33%; E. faecium, 25%; methicillin-resistant staphylococcus epidermidis, 12.5%; methicillin-sensitive staphylococcus aureus, 12.5%; others, 17%. Successful outcomes were reported in seven subjects (78%), with two patients succumbing due to multiorgan failure related to their heart condition prior completing antibiotic therapy. No adverse events were reported. CONCLUSIONS: Among our VAD patients, daptomycin proved efficient as a therapy for CRI with bacteremia. However, controlled studies are necessary to evaluate this antibiotic in patients presenting with VAD and MDR bacteremia.

Successful ABO-incompatible heart transplantation in a child despite blood-group sensitization after ventricular assist device support.

In the first two yr of life blood-group incompatible (ABO-incompatible) heart transplantation can be performed leading to immune tolerance to donor blood group. Antibody titers should be below 1:4. VAD use is correlated with sensitization toward blood-group antigens. A boy was diagnosed with dilated cardiomyopathy at nine months of age and listed for 0-compatible transplantation. Progressive heart failure required implantation of a left VAD. His listing was extended for ABO-incompatible transplantation despite antibody titers of 1:32 anti-A and 1:8 anti-B. After 26 days on VAD, he was transplanted with a B donor heart. No hyperacute or acute rejection occurred in 12 months post-transplant. Anti-B antibodies rose to a maximum of 1:2. No use of rituximab or plasmapheresis was required. There are no signs of graft vasculopathy. This indicates that inclusion criteria for ABO-incompatible transplantation may be extended to immediate cases. This is the first case with a healthy immune system to show signs of tolerance development after ABO-incompatible heart transplantation with increased prior antibody titers and without specific treatment.

Primary graft failure and Ca2+ sensitizers after heart transplantation.

Primary organ failure after heart transplantation is a severe complication generally related to prolonged ischemia time, poor quality of the organ, or rejection. Ca(2+) sensitisers increase cardiac contractility without altering intracellular Ca(2+) levels. Our aim was to evaluate the influence of levosimendan in the therapy of primary failure after heart transplantation. Five patients presenting with reduced ejection fraction (EF<30%) and high dosed catecholamines after heart transplantation were treated with levosimendan (Simdax, Abbot GesmbH, Vienna, Austria) in a 24-hour continuous infusion (0.10 microg/kg*min) postoperatively. We assessed hemodynamic measurements including MAP, CVP, and PAP as well as heart function. Pharmacologic support with catecholamines could be halved at 24 hours and terminated in four of the patients 72 hours after levosimendan administration. Hemodynamics (MAP 70 +/- 11 vs 85 +/- 6 mm Hg; CI 2.5 +/- 0.4 vs 3.6 +/- 0.4 L/min/m(2)) and EF (28 +/- 10 vs 54 +/- 4%) improved at 48 hours after treatment. Acute graft failure after cardiac transplantation is associated with poor short- and long-term outcomes. Among our patients, levosimendan reduced the need for catecholamine support as well as improved ventricular performance.

Successful reimplantation of a passive-fixation ventricle lead perforating the chest wall.

Delayed perforation of a passive fixed pacemaker lead is a rare complication after pacemaker implantation and is associated with increased morbidity and mortality. We report the case of an 82-year-old patient who presented with a delayed perforation of the right heart wall, the pericardium, and the chest wall by a passive-fixation ventricular lead 14 months after pacemaker implantation. The lead was uneventfully extracted transvenously and repositioned in the right ventricle with good pacing and sensing.

Alternatives to heart transplantation. Symposium of the "Treatment of End-stage Heart and Lung Failure" working group on October 22, 2005 in Munich.

Heart transplantation is currently the treatment of first choice in patients with end-stage refractory heart failure. But already the demand for donor organs cannot be met, and patients face long waiting times for transplantation. In the future waiting times will become even longer as life expectancy increases and the number of heart-failure patients requiring transplantation grows. Consequently, in view of the poor prognosis of the disease in its advanced stages, alternatives to heart transplantation are increasingly gaining importance. In recent years new innovative treatment methods and techniques have been developed which have already proved clinically successful in patients with end-stage heart failure, especially as bridging measures. Some of these techniques appear suitable for long-term use and could therefore serve as an alternative to heart transplantation in some patients. Interesting new avenues of research may even lead to cardiac cell replacement therapies in the future. These approaches are currently undergoing initial clinical trials. This report presents surgical and cardiologic treatments for end-stage heart failure that have already been clinically investigated as well as techniques that are still in the preclinical stage and discusses their potential as alternatives to heart transplantation.

Sirolimus-associated infertility: case report and literature review of possible mechanisms.

The mammalian-target-of-rapamycin/mTOR-inhibitor sirolimus as a component of the immunosuppressive strategy after solid organ transplantation is effective at preventing allograft rejection. However, recent reports indicate that sirolimus is associated with altered sex hormone levels and impaired sperm quality parameters. Herein, we report on a case of sirolimus-associated infertility in a young male heart-lung transplant recipient and provide a detailed synopsis of potential mechanisms by which sirolimus may negatively influence spermatogenesis. Testicular immunohistochemistry, the course of sex hormone and sperm quality parameters of our patient support the hypothesis that mTOR might act as an important key regulator in the reproductive system. Fortunately, due to withdrawal of sirolimus as part of the maintenance, immunosuppression improved sperm quality and sex hormone parameters could be observed. Recently, these improvements even resulted in a spontaneous pregnancy of the patient's wife more than 1 year after the drug was withdrawn. In our view, oligospermia as a possible and at least partly reversible side-effect of mTOR inhibitors has to be taken into consideration, particularly, when administrated to young male patients.

Successful pulmonary thromboendarterectomy for right atrial thrombosis in a heart transplant recipient: a case report.

Acute massive or submassive pulmonary embolism is a life-threatening condition with a poor prognosis. It causes sudden hemodynamic deterioration and warrants immediate surgery. We report the case of a 41-year-old male heart transplant recipient who had not been treated prophylactically for thrombosis, who was referred to our center because of exertional dyspnea after immobilization owing to an injury in one of his legs. Transesophageal echocardiography revealed a large, mobile, right atrial mass originating from a pacemaker lead. Furthermore, contrast-enhanced computed tomography scanning of the chest revealed multiple pulmonary emboli resulting in subtotal occlusion of both pulmonary arteries. Although typically reserved for patients with chronic thromboembolic pulmonary hypertension, surgical thromboendarterectomy was successfully performed. Six months after discharge, the patient is well and has a New York Heart Association class 1 rating. This is the first report of a successful pulmonary thromboendarterectomy in a heart transplant recipient.

[Evaluation of diastolic function in patients with constrictive pericarditis before and after pericardectomy]. / Vergleich prä- und postoperativer MRT-Untersuchungen des Herzens bei Patienten mit Pericarditis constrictiva unter besonderer Berücksichtigung der diastolischen Funktion.

PURPOSE: The aim of the study was to evaluate diastolic function in patients with constrictive pericarditis using velocity-encoded flow measurements before and after pericardectomy. MATERIALS AND METHODS: Velocity-encoded flow measurements were performed at the atrioventricular valves in nine patients with constrictive pericarditis. The resulting flow curves were evaluated. For assessment of diastolic function the amplitudes of the E and A waves were measured and the E to A wave ratios calculated. Appearance of mid-diastolic flow, indicating diastolic dysfunction, was registered. RESULTS: The measurements at the mitral valves prior to pericardectomy revealed diastolic dysfunction grade I in two patients, grade II in three patients, and grade III in three patients. Mid-diastolic flow was detected in two patients. At the tricuspid valves diastolic dysfunction grade I was present in two patients, grade II in four patients, and grade III in three patients. Improvement of diastolic function after pericardectomy was documented in five patients at the mitral valve and in two patients at the tricuspid valve. CONCLUSION: Velocity-encoded flow measurements are feasible and a valuable tool for assessment of diastolic function in patients with constrictive pericarditis prior to and after pericardectomy.

AAV-mediated gene transfer to cardiac cells in a heterotopic rat heart transplantation model.

INTRODUCTION: Adeno-associated virus (AAV) vectors offer the possibility to transfer genes to a wide range of organ and cell types. To determine the efficiency of AAV-mediated gene transfer to cardiac cells, vectors were administered to the heart under various conditions. METHODS: In Sprague-Dawley rats, AAV vectors based on serotype 2 and coding for beta-galactosidase were injected via coronaries into hypothermic nonbeating and normothermic beating hearts before transplantation. In addition, vectors were injected intravenously or into the thigh muscle. After 28 days all animals were humanely killed and organs explanted for analysis. RESULTS: Transgenic DNA was always detectable in the liver and the heart, irrespective of the application mode. However, transgenic mRNA could not be determined in the transplanted hearts. In contrast, direct injection into the thigh muscle resulted in transgenic mRNA production and marker gene expression. After systemic application, transgenic mRNA was detected in the liver but not in the heart. CONCLUSION: The results of our study indicated that AAV-mediated gene transfer to cardiac cells is possible. However, it was impossible to detect transgenic mRNA or marker gene expression in the transplanted hearts after intracoronary perfusion or systemic injection.

Transgenic animals in experimental xenotransplantation models: orthotopic heart transplantation in the pig-to-baboon model.

Pig organs are at risk for hyperacute and acute vascular rejection mediated by anti-pig antibodies, mainly binding to the Galalpha(1,3)Gal epitope. Acute cellular rejection is characterized by progressive infiltration of mononuclear cells. There is an ongoing search for immunosuppressive regimens that provide adequate protection against all patterns of xenograft rejection, but have no severe impact on the condition of xenograft recipients. Herein orthotopic heart transplantations were performed from hDAF or hCD46 piglets to nonsplenectomized baboons. Basic immunosuppression consisted of tacrolimus, sirolimus, GAS914, steroids, and ATG. Group 1 received basic immunosuppression. Group 2 was additionally treated with rituximab and group 3 with half-dose cyclophosphamide. Group 4 received cyclophosphamide and an anti-HLA-DR antibody. Three baboons received GAS914 and TPC. Monitoring included the regular assessment of anti-porcine antibodies, blood counts, therapeutic drug monitoring, and graft histology. Two grafts failed due to technical mistakes. In group 1, baboons died after 1 and 9 days. In group 2, maximum survival was 30 hours. In group 3, baboons lived 20 hours, 25 days, and 14 days. Group 4 survival times were 9.5 hours, 5.5 hours, 4 days, 34 hours, and 3 days. An increase of non-Galalpha(1,3)Gal antibodies was observed. Depositions of immunoglobulins and complement revealed a humoral rejection process. No cellular infiltration could be observed. In conclusion, suppressing cellular rejection with half-dose cyclophosphamide together with tacrolimus and sirolimus produced longer graft survival with a good general condition. Prevention of acute xenograft rejection further needs inhibition of non-Galalpha(1,3)Gal cytotoxicity by sufficient depression of B-cell activation.

Fluorescent microspheres reveal different regional blood flow in hyperacutely rejected nontransgenic and hDAF pig hearts.

Classic features of hyperacute rejection show differential severity in the inner compared to the outer myocardium. In the present study, regional blood flow (RBF) measured by fluorescent microspheres served as a marker of the extent of hyperacute rejection. Using a working heart model, hearts of nontransgenic and hDAF transgenic pigs were perfused with human blood. Additionally, hDAF transgenic pig hearts were perfused with human blood containing GAS914 or the GPIIb/IIIa inhibitor tirofiban. Injections of fluorescent microspheres into the donor heart were performed in situ and during perfusion. Reference arterial blood samples were collected from the inferior aorta and the afterload line. Perfusion was terminated before hyperacutely rejected hearts failed to pump against the afterload column. RBF was determined in tissue samples of standardized areas of the left atrium and ventricle. Each specimen was divided into subepicardial and subendocardial tissue samples. Fluorescence intensity was measured using an automated luminescence spectrometer. At the end of perfusion with human blood, hyperacutely rejected nontransgenic pig hearts showed a higher RBF in the subendocardium. In hDAF-transgenic pig hearts perfused with unmodified human blood the subendocardial/subepicardial blood flow ratio changed in favor of the subepicardium. This ratio was not further improved by GAS914. In contrast, tirofiban was able to assimilate subepicardial and subendocardial blood flow. In conclusion, RBF of hyperacutely rejected pig hearts was inhomogeneous. Inhibition of complement activation improved the reduced subepicardial RBF, but depletion of antibodies had no positive effect. The ability of tirofiban to further increase subepicardial RBF affirms thrombosis of subepicardial veins as the defining characteristic of hyperacute rejection.

Mean xenograft survival of 14.6 days in a small group of hDAF-transgenic pig hearts transplanted orthotopically into baboons.

INTRODUCTION: In a discordant orthotopic xenotransplantation model (pig-to-baboon) donor pigs expressing human decay accelerating factor (hDAF) as a regulator of complement activity were used to prevent hyperacute xenograft rejection (HXR). We investigated a modified immunosuppressive therapy consisting of ERL080 (Novartis Pharma AG, Base, Switzerland), cyclosporin A (Neoral), steroids, and a cyclophosphamide (CyP) induction protocol with several reduced doses to prevent acute vascular rejection (AVR). METHODS: Donor hearts were harvested from hDAF-transgenic pigs (18.8 +/- 2.6 kg, Imutran Ltd., a Novartis Pharma AG Company). Four adult baboons (25.6 +/- 2.7 kg) with high titers of xenoreactive antibodies (XAb) served as recipients. Serological and hemodynamic parameters were measured. Finally, myocardial tissue was sampled for histological and immunohistochemical examinations. RESULTS: In the first baboon, an acute graft failure occurred after 1 hour due to preservation injury. The second succumbed after 11.1 day due to an acute renal failure. The third died after 13.1 days of an ileus. The fourth baboon had continuously excellent cardiac function (mean echocardiographic ejection fraction, 69.2%), but succumbed on day 20 due to anemia. Corrected mean xenograft survival (excluding the first baboon because of a technical failure) was 14.6 +/- 2.6 days. XAb decreased after day 3 to constantly low levels (<1:64 titer) after CyP induction. White blood cell count decreased from 10.3 +/- 0.8 to 0.9 +/- 0.3 G/L after day 3. Macroscopically and histologically no typical signs of HXR or severe AVR could be detected. CONCLUSIONS: These results confirm that hDAF transgen blocks HXR in this life-supporting model. AVR was prevented by using a modified quadruple immunosuppressive drug combination (Neoral, ERL080, steroids, and several small single doses of CyP). An optimum "fine-tuning" of immunosuppression is required to achieve the best risk-benefit ratio.