Long-term results after transcatheter aortic valve implantation: what do we know today?

Transcatheter aortic valve implantation (TAVI) is evolving rapidly as a therapeutic option in patients deemed to be at high risk for surgical aortic valve replacement. Early outcome and survival of controlled feasibility trials and single- center experience with TAVI have been previously reported. Valve performance and hemodynamics seem to improve significantly after TAVI. Long-term outcome up to 3 years have been demonstrated in recent studies. Admittedly, the results are encouraging with a survival rate at 2 and 3 years ranging from 62 to 74% and from 56 to 61% respectively. The improvement in hemodynamical and clinical status sustained beyond the 3 years follows up. However, paravalvular leakage after TAVI remains an important issue in this rapidely evolving field.

Which way in? The necessity of multiple approaches to transcatheter valve therapy.

TAVI (transcatheter aortic valve implantation) is a less invasive treatment of the stenotic aortic valve while avoiding midline sternotomy and cardiopulmonary bypass. A crimped biological valve on a self-expanding or balloonexpandable stent is inserted antegradely or retrogradely under fluoroscopy, and deployed on the beating heart. Among the worldwide TAVI programs, many different concepts have been established for the choice of the access site. Whether retrograde or antegrade TAVI should be considered the superior approach is matter of an ongoing debate. The published literature demonstrates safety of all techniques if performed within a dedicated multidisciplinary team. Since there is no data providing evidence if one approach is superior to another, we conclude that an individualized patient-centered decision making process is most beneficial, taking advantage of the complementarity of the different access options. The aim of this article is to give an overview of the current practice of access techniques for transcatheter based valve treatment and to outline the respective special characteristics.

Combined spontaneous contralateral pneumothorax and post-pneumonectomy mediastinal shift-associated dextrocardia.

We report here on an unusual late postoperative presentation of extreme post-pneumonectomy dextrocardia and spontaneous contralateral pneumothorax presenting as late complications occurring approximately 2 years after right-sided pneumonectomy. Computed tomography is the diagnostic modality of choice to obtain information on anatomical changes within the post-pneumonectomy space. Knowledge of the spectrum of cardiopulmonary, pleural, and other complications after lung resection is important to properly manage complications in post-pneumonectomy patients.

Proton pump inhibitors reduce mycophenolate exposure in heart transplant recipients-a prospective case-controlled study.

This prospective study investigates the impact of proton pump inhibitors (PPI) on mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus. MPA plasma concentrations at baseline (C(0 h)), 30 min (C(0.5 h)), 1(C(1 h)) and 2 h (C(2 h)) were obtained by high-performance liquid chromatography (HPLC) in 22 patients treated with pantoprazole 40 mg and MMF 2000 mg. Measurements were repeated 1 month after pantoprazole withdrawal. A four-point limited-sampling strategy was applied to calculate the MPA area under the curve (MPA-AUC). Predose MPA concentrations with PPI were 2.6 +/- 1.6 mg/L versus 3.4 +/- 2.7 mg/L without PPI (p = ns). Postdose MPA concentrations were lower with PPI at C(0.5 h) (8.3 +/- 5.7 mg/L vs. 18.3 +/- 11.3 mg/L, p = 0.001) and C(1 h) (10.0 +/- 5.6 mg/L vs. 15.8 +/- 8.4 mg/L, p = 0.004), without significant differences at C(2 h) (8.3 +/- 6.5 mg/L vs. 7.6 +/- 3.9 mg/L). The MPA-AUC was significantly lower with PPI medication (51.2 +/- 26.6 mg x h/L vs. 68.7 +/- 30.3 mg x h/L; p = 0.003). The maximum concentration of MPA (MPA-C(max)) was lower (12.2 +/- 7.5 mg/L vs. 20.6 +/- 9.3 mg/L; p = 0.001) and the time to reach MPA-C(max) (t(max)) was longer with PPI (60.0 +/- 27.8 min vs. 46.4 +/- 22.2 min; p = 0.05). This is the first study to document an important drug interaction between a widely used immunosuppressive agent and a class of drugs frequently used in transplant patients. This interaction results in a decreased MMF drug exposure which may lead to patients having a higher risk for acute rejection and transplant vasculopathy.

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.

Cardiac transplantation in a 14-yr-old patient with mitochondrial encephalomyopathy.

We report a rare case of a successful cardiac transplantation in a patient suffering from cardiomyopathy and complex mitochondrial disease. The patient presented with severe heart failure and malignant ventricular arrhythmias requiring implantation of a defibrillator and advanced medical treatment. The patient was listed for urgent heart transplantation and received a donor heart after 36 days. One yr post-operatively, the patient has completely recovered.

Successful single lung fontan operation in 2 children: case reports.

We report on 2 children, aged 3 and 4 years, with single ventricle physiology who underwent Fontan operation in the presence of a single right lung successfully with good midterm outcome. Therefore, the absence of one lung is not a contraindication for a Fontan palliation in selected patients with optimal hemodynamics.

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.

Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer.

The present study was undertaken in order to determine the feasibility and efficacy of induction chemotherapy with carboplatin and etoposide, followed by weekly carboplatin and full-course radiotherapy as pre-operative therapy for marginally resectable non-small cell lung cancer (NSCLC). Twenty-eight patients with good Eastern Cooperative Oncology Group (ECOG) performance status ratings and stage IIIA NSCLC received induction chemotherapy with carboplatin (dose computed with the Egorin formula, days 1 and 29) and etoposide (100 mg/m2/day, days 1 through 3 and 29 through 31). This was followed by 100 mg/m2 weekly carboplatin given over 6 weeks, concurrently with 60 Gy radiotherapy. Patients with either responsive or stable disease underwent thoracotomy 4 weeks after the completion of combined-modality therapy. All 28 patients received the first chemotherapy cycle (average carboplatin dose, 407 mg/m2; range, 195 to 586 mg/m2). World Health Organization (WHO) grade 3/4 neutropenia and thrombocytopenia were observed in 53 and 34% of patients, respectively. There were three febrile neutropenic episodes, but no septic deaths. Five patients (18%) required dose reductions prior to the second chemotherapy cycle, but the dose intensity of carboplatin was maintained (average dose, 390 mg/m2; range, 195 to 586 mg/m2). In all, 82% of patients received full-dose radiotherapy, and 73% received at least five of six planned concurrent weekly carboplatin doses. Carboplatin doses were most frequently delayed for thrombocytopenia and/or leukopenia. Carboplatin did not increase the incidence of radiation-induced esophagitis. Only three patients required interruption of radiotherapy, for esophagitis (two patients) and persistent thrombocytopenia (one patient). The response rate to pre-operative therapy was 64%. In this study, we demonstrated the ability to deliver escalated doses of carboplatin with standard-dose etoposide as induction chemotherapy with reasonable myelotoxicity. The combined-modality therapy was well tolerated, and the addition of weekly carboplatin did not result in increased radiation-related toxicity. This neoadjuvant regimen is active in the treatment of locally advanced NSCLC, and compares favorably to other cisplatin-based regimens.

Sensitive and specific detection of the 4B5 antigen in bronchial lavage specimens from patients with primary bronchogenic carcinoma.

The monoclonal antibody 4B5 binds to a mucin-like antigen elaborated by respiratory epithelium of patients with non-small cell bronchogenic carcinoma. Several immunoassay formats were used to determine the presence of the antigen in lavage specimens. A qualitative immunodrop binding assay showed immunoreactivity in 37 (64%) of 58 specimens from patients with non-small cell lung cancer. In contrast, only 11 (12%) of 93 specimens from patients with either metastatic carcinoma or benign pulmonary diseases exhibited 4B5 immunoreactivity. A quantitative radioimmunoassay using standardized amounts of mucin exhibited similar sensitivity and specificity. Positive immunoreactivity was associated significantly with tobacco use and the cytopathologic diagnoses of squamous metaplasia, atypia, or dysplasia. Conversely, no significant association was found between 4B5 immunoreactivity and age, gender, race, benign cytologic findings, frankly malignant cytologic findings, or stage of disease. The expression of 4B5 antigen in bronchial secretions from patients with bronchogenic carcinoma deserves additional evaluation as a potential marker of pulmonary carcinogenesis.

Detection of a novel marker in the bronchial secretions of patients with non-small cell lung cancer using the 4B5 monoclonal antibody.

A murine monoclonal antibody designated 4B5 was raised against the high molecular weight fraction of pooled sputum from patients with non-small cell lung cancer (NSCLC). Immunohistochemical staining indicated that 4B5 binds to histologically normal bronchial epithelium distant from tumor in 72% (39 of 54) of patients with NSCLC, but it binds to the primary cancer in only 13% (7 of 54) of the same patients. The antibody reacted less intensely with the bronchial epithelium in 16.6% (3 of 18) of autopsied patients without significant lung disease. The antigen recognized by 4B5 is a high molecular weight glycoprotein of more than 400 kilodaltons, judged by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis. Antigenic activity persisted after heating and resisted treatment with neuraminidase, but it was destroyed using protease and periodate. Multiple epitopes were present on each molecule recognized by 4B5. The determinants recognized by this antibody deserve additional study as possible markers of premalignant change in patients with NSCLC.