High inter-individual variability in tacrolimus clearance is attributed to genetic polymorphisms of CYP3A enzymes. However, due to CYP3A phenoconversion induced by non-genetic factors, continuous changes in tacrolimus-metabolizing capacity entail frequent dose-refinement for optimal immunosuppression. In heart transplant recipients, the contribution of patients’ CYP3A-status (CYP3A5 genotype and CYP3A4 expression) to tacrolimus blood concentration and dose-requirement was evaluated in the early and late post-operative period. In low CYP3A4 expressers carrying CYP3A5*3/*3, the dose-corrected tacrolimus level was significantly higher than in normal CYP3A4 expressers or in those with CYP3A5*1. Modification of the initial tacrolimus dose was required for all patients: dose reduction by 20% for low CYP3A4 expressers, a 40% increase for normal expressers and a 2.4-fold increase for CYP3A5*1 carriers. The perioperative high-dose corticosteroid therapy was assumed to ameliorate the low initial tacrolimus-metabolizing capacity during the first month. The fluctuation of CYP3A4 expression and tacrolimus blood concentration (C0/D) was found to be associated with tapering and cessation of corticosteroid in CYP3A5 non-expressers, but not in those carrying CYP3A5*1. Although monitoring of tacrolimus blood concentration cannot be omitted, assaying recipients’ CYP3A-status can guide optimization of the initial tacrolimus dose, and can facilitate personalized tacrolimus therapy during steroid withdrawal in the late post-operative period.
Since the establishment of highly active antiretroviral therapy, survival rates have improved among patients with human immunodeficiency virus infection giving them the possibility to become transplant candidates. Recent publications revealed that human immunodeficiency virus-positive heart transplant recipients' survival is similar to non-infected patients. We present the case of a 40-year-old human immunodeficiency virus infected patient, who was hospitalized due to severely decreased left ventricular function with a possible aetiology of acute myocarditis, that has later been confirmed by histological investigation of myocardial biopsy. Due to rapid progression to refractory cardiogenic shock, extracorporeal membrane oxygenation implantation had been initiated, which was upgraded to biventricular assist device later. On the 35th day of upgraded support, the patient underwent heart transplantation uneventfully. Our clinical experience confirms that implementation of temporary mechanical circulatory support and subsequent cardiac transplantation might be successful in human immunodeficiency virus-positive patients even in case of new onset, irreversible acute heart failure.
IntroductionDespite the significant contribution of circumferential shortening to the global ventricular function, data are scarce concerning its prognostic value on long-term mortality. Accordingly, our study aimed to assess both left (LV) and right ventricular (RV) global longitudinal (GLS) and global circumferential strain (GCS) using three-dimensional echocardiography (3DE) to determine their prognostic importance.MethodsThree hundred fifty-seven patients with a wide variety of left-sided cardiac diseases were retrospectively identified (64 ± 15 years, 70% males) who underwent clinically indicated 3DE. LV and RV GLS, and GCS were quantified. To determine the prognostic power of the different patterns of biventricular mechanics, we divided the patient population into four groups. Group 1 consisted of patients with both LV GLS and RV GCS above the respective median values; Group 2 was defined as patients with LV GLS below the median while RV GCS above the median, whereas in Group 3, patients had LV GLS values above the median, while RV GCS was below median. Group 4 was defined as patients with both LV GLS and RV GCS below the median. Patients were followed up for a median of 41 months. The primary endpoint was all-cause mortality.ResultsFifty-five patients (15%) met the primary endpoint. Impaired values of both LV GCS (HR, 1.056 [95% CI, 1.027–1.085], p < 0.001) and RV GCS (1.115 [1.068–1.164], p < 0.001) were associated with increased risk of death by univariable Cox regression. Patients with both LV GLS and RV GCS below the median (Group 4) had a more than 5-fold increased risk of death compared with those in Group 1 (5.089 [2.399–10.793], p < 0.001) and more than 3.5-fold compared with those in Group 2 (3.565 [1.256–10.122], p = 0.017). Interestingly, there was no significant difference in mortality between Group 3 (with LV GLS above the median) and Group 4, but being categorized into Group 3 versus Group 1 still held a more than 3-fold risk (3.099 [1.284–7.484], p = 0.012).DiscussionThe impaired values of both LV and RV GCS are associated with long-term all-cause mortality, emphasizing the importance of assessing biventricular circumferential mechanics. Reduced RV GCS is associated with significantly increased risk of mortality even if LV GLS is preserved.
The authors give a short introduction of the Hungarian and the international history of adult heart transplantation, and highlight the similarities in the evolution of the two programs. Their aim was to show how the Hungarian post-transplant survival changed in the last five years. They wanted to investigate how all the changes they had made in the program affected the post-transplant results. They investigated 496 heart transplantation data and compared to international data. Orv Hetil. 2018; 159(46): 1869–1875.
Background Mycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient. Case presentation Our 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers. Conclusions Donor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.
The occurrence of tricuspid insufficiency (TI) is common after orthotropic heart transplantation (OHT). Sometimes it can be serious and lead to mortality. We investigated possible variables influencing TI after OHT and identified possible risk factors responsible for clinical significant TI development and progression. Methods: We identified an incidence of tricuspid insufficiency in 857 from 1515 patients who underwent OHT between years 1986-2010, survived at least 12 months and had echocardiographic assessments available. The variables that can influence tricuspid insufficiency statistically analysed on representative group of 152 patients. The patients of representative group, according to severity of TI divided into two groups, patients with TI≤ 2 grade and with TI > 2 grade. Results: We found no significant difference among the groups in terms of recipient gender, basic disease, recipient weight, recipient's BMI, BSA, preoperative pulmonary arterial pressure, donor organ ischemia time, donor gender, age, height, weight, BMI, BSA, chest X-Ray thorax width, chest X-ray heart width, chest X-Ray thorax/heart ratio, highest rejection grade on biopsy and vascular reaction. In univariate analysis study variables such as age of recipient (p= 0.027), donor to recipient right atrium anterior wall ratio (p< 0.001), tricuspid annulus anterior to septal leaflet excursion ratio (p= 0.001), dialysis (p= 0.026), total biopsy number (p= 0.003) showed significance and variables height of recipient (p= 0.080), BMI donor to BMI recipient ratio (p= 0.080) and number of biopsies with more than moderate grade (p= 0.067) showed trend to significance for developing severe TI after OHT. In multivariate analysis we found that, there is an independent significant association between TI after OHT and donor to recipient right atrium anterior wall ratio, number of biopsies and dialysis. Moderate to severe and severe TI have no significance for mortality after OHT. Conclusion: Donor to recipient right atrium front wall ratio, number of biopsy, and dialysis act as major risk factor for TI after OHT. Which shows that preserving annular geometry, decreasing biopsy number and preventing functional tricuspid insufficiency is essential for freedom from respectively further progression of tricuspid insufficiency after cardiac transplantation.
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