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.
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.
Az akut kardiális allograft rejekció a modern immunszuppresszív terápia ellenére jelenleg is az egyik vezető halálok szívtranszplantált betegek körében. Az akut rejekció kimutatásának referenciamódszere az endomiokardiális biopszia, azonban a noninvazív képalkotó diagnosztikus eljárások napjainkban e témában a tudományos kutatások fókuszába kerültek. A szív MR-(CMR) vizsgálat a bal és jobb kamra globális és regionális funkció meghatározásán túl szöveti karakterizációs képessége miatt kiemelkedik ezen modalitások közül. A kevert típusú (celluláris és humorális) rejekció ritka entitás, amelyről csak kevés irodalmi adat áll rendelkezésünkre, diagnosztikája sok esetben kihívást jelenthet. A kevert rejekció okozta CMR-eltérésekről nagyon korlátozottak az ismereteink. Az elmúlt évben három szívtranszplantált betegnél akut kevert típusú rejekciót diagnosztizáltunk, az elvégzett CMR-vizsgálat mindhárom beteg esetében nagyon hasonló eltéréseket mutatott. Egy beteg esetén kontroll CMR-vizsgálatokat is végeztünk, nyomon követve a bal és jobb kamrai ejekciós frakciók, volumenek, valamint az ödéma és késői kontraszthalmozás mintázatának változását a kezelés függvényében. A kutatás az "NVKP_16-1-2016-0017 számú projekt a Nemzeti Kutatási Fejlesztési és Innovációs Alapból biztosított támogatással, az NVKP_16 pályázati program finanszírozásában valósult meg. TheroleofCMRintheevaluationofacutemixedcardiacallograftrejectionDespite of the modern immunosuppressive therapy the acute cardiac allograft rejection is a leading cause of morbidity and mortality in heart transplant patients. Endomyocardial biopsy is considered the current gold standard for the diagnosis of acute cardiac rejection, nevertheless there is an intense research regarding on non-invasive diagnostic methods in this field. Cardiac magnetic resonance imaging (CMR) has an evolving role in the detection of acute rejection among these modalities because of its ability to quantify ventricular function and characterize the complete myocardial tissue. There are only few data of the mixed (cellular and humoral) rejection which is a very rare entity, and the diagnosis remains challenging. Our knowledge about the CMR findings of mixed cardiac rejection is limited as well. In the last year we have made a diagnosis of mixed cardiac rejection in three patients, and the subsequently performed CMR showed very similar features in each patients. We performed serial CMR examinations in one patient to follow-up the changes of left and right ventricular volumes, ejection fractions and the pattern of myocardial oedema and delayed contrast enhancement.
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