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1.
J Artif Organs ; 26(2): 156-159, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35951178

RESUMO

The optimal surgical approach in patients with pectus excavatum (PEx) who need cardiac surgery remains uncertain. The challenge is even greater, if it is already foreseeable that the patient will be needed further procedure in the next future. We describe a novel sternotomy-sparing approach for minimal-invasive biventricular assist device (BiVAD) implantation in a patient with an acute heart failure (HF) due to dilated cardiomyopathy and severe PEx. Moreover, alternative approaches for ventricular assist device (VAD) implantation and timing of the repair of PEx will be discussed.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Tórax em Funil , Insuficiência Cardíaca , Coração Auxiliar , Humanos , Tórax em Funil/complicações , Tórax em Funil/cirurgia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Esternotomia/métodos , Estudos Retrospectivos , Resultado do Tratamento
2.
Heart Fail Rev ; 27(5): 1795-1805, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35315505

RESUMO

Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by left or biventricular systolic impairment. Historically, most of the clinical attention has been devoted to the evaluation of left ventricular function and morphology, while right ventricle (RV) has been for many years the forgotten chamber. Recently, progresses in cardiac imaging gave clinicians precious tools for the evaluation of RV, raising the awareness of the importance of biventricular assessment in DCM. Indeed, RV involvement is far from being uncommon in DCM, and the presence of right ventricular dysfunction (RVD) is one of the major negative prognostic determinants in DCM patients. However, some aspects such as the possible role of specific genetic mutations in determining the biventricular phenotype in DCM, or the lack of specific treatments able to primarily counteract RVD, still need research. In this review, we summarized the current knowledge on RV involvement in DCM, giving an overview on the epidemiology and pathogenetic mechanisms implicated in determining RVD. Furthermore, we discussed the imaging techniques to evaluate RV function and the role of RV failure in advanced heart failure.


Assuntos
Cardiomiopatia Dilatada , Insuficiência Cardíaca , Disfunção Ventricular Direita , Cardiomiopatia Dilatada/epidemiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Prevalência , Prognóstico , Disfunção Ventricular Direita/epidemiologia , Função Ventricular Direita/fisiologia
3.
Int J Mol Sci ; 23(12)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35743126

RESUMO

Fukutin encoded by FKTN is a ribitol 5-phosphate transferase involved in glycosylation of α-dystroglycan. It is known that mutations in FKTN affect the glycosylation of α-dystroglycan, leading to a dystroglycanopathy. Dystroglycanopathies are a group of syndromes with a broad clinical spectrum including dilated cardiomyopathy and muscular dystrophy. In this study, we reported the case of a patient with muscular dystrophy, early onset dilated cardiomyopathy, and elevated creatine kinase levels who was a carrier of the compound heterozygous variants p.Ser299Arg and p.Asn442Ser in FKTN. Our work showed that compound heterozygous mutations in FKTN lead to a loss of fully glycosylated α-dystroglycan and result in cardiomyopathy and end-stage heart failure at a young age.


Assuntos
Cardiomiopatia Dilatada , Distrofias Musculares , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/metabolismo , Distroglicanas/genética , Distroglicanas/metabolismo , Glicosilação , Humanos , Proteínas de Membrana/metabolismo , Músculo Esquelético/metabolismo , Distrofias Musculares/genética , Distrofias Musculares/metabolismo , Mutação
4.
Hum Mutat ; 41(11): 1931-1943, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32840935

RESUMO

Mutations in RBM20 encoding the RNA-binding motif protein 20 (RBM20) are associated with an early onset and clinically severe forms of cardiomyopathies. Transcriptome analyses revealed RBM20 as an important regulator of cardiac alternative splicing. RBM20 mutations are especially localized in exons 9 and 11 including the highly conserved arginine and serine-rich domain (RS domain). Here, we investigated in several cardiomyopathy patients, the previously described RBM20-mutation p.Pro638Leu localized within the RS domain. In addition, we identified in a patient the novel mutation p.Val914Ala localized in the (glutamate-rich) Glu-rich domain of RBM20 encoded by exon 11. Its impact on the disease was investigated with a novel TTN- and RYR2-splicing assay based on the patients' cardiac messenger RNA. Furthermore, we showed in cell culture and in human cardiac tissue that mutant RBM20-p.Pro638Leu is not localized in the nuclei but causes an abnormal cytoplasmic localization of the protein. In contrast the splicing deficient RBM20-p.Val914Ala has no influence on the intracellular localization. These results indicate that disease-associated variants in RBM20 lead to aberrant splicing through different pathomechanisms dependent on the localization of the mutation. This might have an impact on the future development of therapeutic strategies for the treatment of RBM20-induced cardiomyopathies.


Assuntos
Cardiomiopatias/genética , Mutação , Proteínas de Ligação a RNA/genética , Adulto , Processamento Alternativo , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem
5.
Environ Manage ; 65(5): 618-629, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32130463

RESUMO

Changes in landscape composition caused by conversion of natural habitats into human-altered ecosystems can directly influence the physical characteristics of stream networks. Such impacts can modify the functional structure of fish communities, although the exact consequences of anthropic land-use changes can be context-dependent. This study investigated the influence of different land-use classes on the functional structure of fish communities in 32 headwater streams from southern Brazil. Trait composition and indices of functional diversity of the fish community were related to four land-use classes: native forest vegetation, silviculture, agriculture, and urban areas. Streams surrounded by larger areas of native forest were characterized by the predominance of foraging specialist species like grazers. However, as native vegetation is replaced by agriculture and urban areas, specialist species are replaced by species with generalist diet like detritivores. In streams surrounded by larger areas of agriculture, functional richness and divergence increased, while functional evenness decreased. Most likely, these changes were induced by alterations in the water quality, indicated by increased electrical conductivity and water temperature in streams with more agriculture areas. In conclusion, the conservation of the native forest vegetation is essential to maintain habitat characteristics and ecological processes in streams and to avoid the loss of specialist species in fish communities.


Assuntos
Ecossistema , Rios , Agricultura , Animais , Biodiversidade , Brasil , Peixes , Humanos
6.
Am J Transplant ; 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30884079

RESUMO

In the 12-month, open-label MANDELA study, patients were randomized at month 6 after heart transplantation to (i) convert to calcineurin inhibitor (CNI)-free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI-free, n=71), or to (ii) continue reduced-exposure CNI, with EVR and steroids (EVR/redCNI, n=74). Tacrolimus was administered in 48.8% of EVR/redCNI patients and 52.6% of CNI-free patients at radomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFR at month 18 post-transplant post-randomization) with superiority of the CNI-free group versus EVR/redCNI : mean 64.1mL/min/1.73m2 versus 52.9mL/min/1.73m2 ; difference +11.3mL/min/1.73m2 (p<0.001). By month 18, estimated GFR had increased by ≥10mL/min/1.732 in 31.8% and 55.2% of EVR/redCNI and CNI-free patients, respectively, and by ≥25 mL/min/1.73m2 in 4.5% and 20.9%. Rates of biopsy-proven acute rejection (BPAR) were 6.8% and 21.1%; all cases were without hemodynamic compromise. BPAR was less frequent with EVR/redCNI versus the CNI-free regimen (p=0.015); 6/15 episodes in CNI-free patients occurred with EVR concentration <5ng/mL. Rates of adverse events and associated discontinuations were comparable EVR/redCNI from month 6 achieved stable renal function with infrequent BPAR. One-year renal function can be improved by early conversion to EVR-based CNI-free therapy but requires close EVR monitoring. This article is protected by copyright. All rights reserved.

7.
Transpl Int ; 31(11): 1223-1232, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29885002

RESUMO

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation.


Assuntos
Rejeição de Enxerto/epidemiologia , Cardiopatias/cirurgia , Insuficiência Cardíaca/cirurgia , Transplante de Coração/estatística & dados numéricos , Disfunção Primária do Enxerto/epidemiologia , Reoperação/estatística & dados numéricos , Adulto , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Doadores de Tecidos , Adulto Jovem
8.
Eur Heart J ; 38(29): 2279-2286, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28498942

RESUMO

AIMS: Circulating 25-hydroxyvitamin D (25OHD) levels <75 nmol/L are associated with a nonlinear increase in mortality risk. Such 25OHD levels are common in heart failure (HF). We therefore examined whether oral vitamin D supplementation reduces mortality in patients with advanced HF. METHODS AND RESULTS: Four hundred HF patients with 25OHD levels <75 nmol/L were randomized to receive 4000 IU vitamin D daily or matching placebo for 3 years. Primary endpoint was all-cause mortality. Key secondary outcome measures included hospitalization, resuscitation, mechanical circulatory support (MCS) implant, high urgent listing for heart transplantation, heart transplantation, and hypercalcaemia. Initial 25OHD levels were on average <40 nmol/L, remained around 40 nmol/L in patients assigned to placebo and plateaued around 100 nmol/L in patients assigned to vitamin D. Mortality was not different in patients receiving vitamin D (19.6%; n = 39) or placebo (17.9%; n = 36) with a hazard ratio (HR) of 1.09 [95% confidence interval (CI): 0.69-1.71; P = 0.726]. The need for MCS implant was however greater in patients assigned to vitamin D (15.4%, n = 28) vs. placebo [9.0%, n = 15; HR: 1.96 (95% CI: 1.04-3.66); P = 0.031]. Other secondary clinical endpoints were similar between groups. The incidence of hypercalcaemia was 6.2% (n = 10) and 3.1% (n = 5) in patients receiving vitamin D or placebo (P = 0.192). CONCLUSION: A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants. Data indicate caution regarding long-term supplementation with moderately high vitamin D doses. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov Idenitfier: NCT01326650.


Assuntos
Insuficiência Cardíaca/dietoterapia , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/mortalidade , Causas de Morte , Suplementos Nutricionais , Feminino , Insuficiência Cardíaca/mortalidade , Transplante de Coração/mortalidade , Transplante de Coração/estatística & dados numéricos , Coração Auxiliar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/dietoterapia
9.
Hum Mutat ; 38(8): 947-952, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28493373

RESUMO

Restrictive cardiomyopathy (RCM) is a rare heart disease characterized by diastolic dysfunction and atrial enlargement. The genetic etiology of RCM is not completely known. We identified by a next-generation sequencing panel the novel CRYAB missense mutation c.326A>G, p.D109G in a small family with RCM in combination with skeletal myopathy with an early onset of the disease. CRYAB encodes αB-crystallin, a member of the small heat shock protein family, which is highly expressed in cardiac and skeletal muscle. In addition to in silico prediction analysis, our structural analysis of explanted myocardial tissue of a mutation carrier as well as in vitro cell transfection experiments revealed abnormal protein aggregation of mutant αB-crystallin and desmin, supporting the deleterious effect of this novel mutation. In conclusion, CRYAB appears to be a novel RCM gene, which might have relevance for the molecular diagnosis and the genetic counseling of further affected families in the future.


Assuntos
Cardiomiopatia Restritiva/diagnóstico , Cardiomiopatia Restritiva/genética , Cadeia B de alfa-Cristalina/genética , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação de Sentido Incorreto/genética , Linhagem , Adulto Jovem
10.
Eur Heart J ; 37(33): 2591-601, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26746629

RESUMO

AIMS: A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance. METHODS AND RESULTS: Blood samples for GEP testing (AlloMap(®), CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0-39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2-6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively. CONCLUSION: For ≥2-6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.


Assuntos
Transplante de Coração , Biópsia , Perfilação da Expressão Gênica , Rejeição de Enxerto , Humanos , Análise em Microsséries , Miocárdio , Transcriptoma
11.
J Mol Cell Cardiol ; 91: 207-14, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26724190

RESUMO

BACKGROUND: Dilated cardiomyopathy (DCM) could be caused by mutations in more than 40 different genes. However, the pathogenic impact of specific mutations is in most cases unknown complicating the genetic counseling of affected families. Therefore, functional studies could contribute to distinguish pathogenic mutations and benign variants. Here, we present a novel heterozygous DES missense variant (c.407C>T; p.L136P) identified by next generation sequencing in a DCM patient. DES encodes the cardiac intermediate filament protein desmin, which has important functions in mechanical stabilization and linkage of the cell structures in cardiomyocytes. METHODS AND RESULTS: Cell transfection experiments and assembly assays of recombinant desmin in combination with atomic force microscopy were used to investigate the impact of this novel DES variant on filament formation. Desmin-p.L136P forms cytoplasmic aggregates indicating a severe intrinsic filament assembly defect of this mutant. Co-transfection experiments of wild-type and mutant desmin conjugated to different fluorescence proteins revealed a dominant affect of this mutant on filament assembly. These experiments were complemented by apertureless scanning near-field optical microscopy. CONCLUSION: In vitro analysis demonstrated that desmin-p.L136P is unable to form regular filaments and accumulate instead within the cytoplasm. Therefore, we classified DES-p.L136P as a likely pathogenic mutation. In conclusion, the functional characterization of DES-p.L136P might have relevance for the genetic counseling of affected families with similar DES mutations and could contribute to distinguish pathogenic mutations from benign rare variants.


Assuntos
Cardiomiopatia Dilatada/genética , Desmina/genética , Filamentos Intermediários/metabolismo , Mutação de Sentido Incorreto , Proteínas Recombinantes de Fusão/genética , Sequência de Aminoácidos , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/patologia , Desmina/química , Desmina/metabolismo , Desmossomos/metabolismo , Desmossomos/ultraestrutura , Feminino , Expressão Gênica , Genes Dominantes , Aconselhamento Genético , Células HEK293 , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Filamentos Intermediários/ultraestrutura , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Dados de Sequência Molecular , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Linhagem , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de Sequência
12.
Circulation ; 129(1): 57-65, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24081973

RESUMO

BACKGROUND: For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). METHODS AND RESULTS: We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival (P=0.006) in patients on anticoagulation compared with patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant (P=0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95% confidence interval, 0.66-0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. CONCLUSIONS: The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01347216.


Assuntos
Anticoagulantes/administração & dosagem , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/mortalidade , Trombose/mortalidade , Trombose/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Hipertensão Pulmonar Primária Familiar , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Sistema de Registros
14.
Transpl Int ; 28(3): 259-69, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25363471

RESUMO

Clinical data relating to rabbit antithymocyte globulin (rATG) induction in heart transplantation are far less extensive than for other immunosuppressants, or indeed for rATG in other indications. This was highlighted by the low grade of evidence and the lack of detailed recommendations for prescribing rATG in the International Society for Heart and Lung Transplantation (ISHLT) guidelines. The heart transplant population includes an increasing frequency of patients on mechanical circulatory support (MCS), often with ongoing infection and/or presensitization, who are at high immunological risk but also vulnerable to infectious complications. The number of patients with renal impairment is also growing due to lengthening waiting times, intensifying the need for strategies that minimize calcineurin inhibitor (CNI) toxicity. Additionally, the importance of donor-specific antibodies (DSA) in predicting graft failure is influencing immunosuppressive regimens. In light of these developments, and in view of the lack of evidence-based prescribing criteria, experts from Germany, Austria, and Switzerland convened to identify indications for rATG induction in heart transplantation and to develop an algorithm for its use based on patient characteristics.


Assuntos
Soro Antilinfocitário/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração , Tolerância Imunológica , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Animais , Humanos , Coelhos
15.
BMC Cardiovasc Disord ; 15: 120, 2015 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-26452346

RESUMO

BACKGROUND: A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0-40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. METHODS: We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. RESULTS: The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). CONCLUSION: In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00761787.


Assuntos
Perfilação da Expressão Gênica , Rejeição de Enxerto , Transplante de Coração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reoperação , Fatores de Risco
16.
Thorac Cardiovasc Surg ; 63(8): 647-52, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26177226

RESUMO

BACKGROUND: Heart transplantation (HTx) is still considered the therapeutic gold standard in end-stage heart failure. METHODS: In "high urgent" (HU)-listed patients for HTx (n = 274) and patients receiving left ventricular assist device (LVAD) implants (n = 332), we compared 1-year overall survival (primary endpoint) and 1-year probability of HTx and therapy failure (the need for LVAD implantation in HU-listed patients or the need for HU listing in LVAD patients) (secondary endpoints). RESULTS: In the HU and LVAD group, 1-year survival was 86.8 and 64.7%, respectively (p < 0.001). The propensity score (PS)-adjusted hazard ratio of mortality did not differ between the groups and for the LVAD group (reference = HU group) was = 1.36 (95% confidence interval [CI]: 0.85-2.19; p = 0.198). The PS-adjusted hazard ratio for the failure to receive HTx for the LVAD group (reference = HU group) was = 9.77 (95% CI: 6.00-15.89; p < 0.001). The corresponding hazard ratio for therapy failure for the LVAD group was = 0.16, 95% CI: 0.10-0.27; p < 0.001). CONCLUSION: Despite considerable differences in the probability of HTx and therapy failure, 1-year overall survival was similar in HU and LVAD patients.


Assuntos
Insuficiência Cardíaca/terapia , Transplante de Coração , Coração Auxiliar , Função Ventricular Esquerda , Listas de Espera , Adulto , Idoso , Distribuição de Qui-Quadrado , Progressão da Doença , Intervalo Livre de Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pontuação de Propensão , Modelos de Riscos Proporcionais , Desenho de Prótese , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Listas de Espera/mortalidade
17.
Thorac Cardiovasc Surg ; 63(8): 663-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25938270

RESUMO

BACKGROUND: Left ventricular assist device (LVAD) implants bear the risk of driveline/device infections and technical failures. METHODS: We assessed clinical outcome in LVAD patients with device-related complications. Group 1 (n = 12) received device exchange (DEx) as destination therapy (DT), group 2 (n = 15) received DEx as a bridge to transplant (BTT), group 3 (n = 34) was allocated to receive high-urgency (HU) heart transplantation (HTx), and group 4 (n = 27) had device-related complications that could only be solved by HTx. Primary endpoint was 1-year overall survival. RESULTS: Age and Simplified Acute Physiology Score II differed significantly between groups and were highest in group 1, lowest in group 3. One-year survival in groups 1 to 4 was 66.7, 60.0, 82.4, and 70.4% (p = 0.30). Covariate-adjusted odds ratio of 1-year survival (reference: group 1) was for group 2 = 1.52 (95% confidence interval [CI]: 0.42-5.57), for group 3 = 1.13 (95% CI: 0.28-4.56), and for group 4 = 1.89 (95% CI: 0.51-7.04; p for trend 0.70). Clinical complications (need of mechanical ventilator support, extracorporeal circulatory membrane oxygenation (ECMO) implants, kidney/liver dialysis) were comparable between groups. CONCLUSION: Data indicate similar 1-year clinical outcomes in LVAD patients with device-related complications receiving DEx or HTx.


Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Falha de Prótese , Função Ventricular Esquerda , APACHE , Adulto , Idoso , Distribuição de Qui-Quadrado , Remoção de Dispositivo , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Humanos , Estimativa de Kaplan-Meier , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Listas de Espera
18.
Heart Surg Forum ; 18(6): E250-2, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26726715

RESUMO

Nocardia has emerged as an important opportunistic pathogen, especially in organ transplant recipients. Heart transplant (HT) recipients initially had an especially high rate of Nocardia infection, but this could be reduced by the routine use of cyclosporine. Our objective was to clarify the prevalence and presentation of Nocardiosis in HT recipients in a retrospective cross-sectional analysis.


Assuntos
Transplante de Coração/efeitos adversos , Nocardiose/diagnóstico , Infecções Oportunistas/diagnóstico , Antibacterianos/uso terapêutico , Azatioprina/uso terapêutico , Pré-Escolar , Estudos Transversais , Ciclosporina/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nocardiose/tratamento farmacológico , Infecções Oportunistas/tratamento farmacológico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Estudos Retrospectivos
19.
J Biol Chem ; 288(45): 32138-32148, 2013 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-24064210

RESUMO

Endothelin receptor A (ETA), a G protein-coupled receptor, mediates endothelin signaling, which is regulated by GRK2. Three Ser and seven Thr residues recently proven to be phosphoacceptor sites are located in the C-terminal extremity (CTE) of the receptor following its palmitoylation site. We created various phosphorylation-deficient ETA mutants. The phospholipase C activity of mutant receptors in HEK-293 cells was analyzed during continuous endothelin stimulation to investigate the impact of phosphorylation sites on ETA desensitization. Total deletion of phosphoacceptor sites in the CTE affected proper receptor regulation. However, proximal and distal phosphoacceptor sites both turned out to be sufficient to induce WT-like desensitization. Overexpression of the Gαq coupling-deficient mutant GRK2-D110A suppressed ETA-WT signaling but failed to decrease phospholipase C activity mediated by the phosphorylation-deficient mutant ETA-6PD. In contrast, GRK2-WT acted on both receptors, whereas the kinase-inactive mutant GRK2-D110A/K220R failed to inhibit signaling of ETA-WT and ETA-6PD. This demonstrates that ETA desensitization involves at least two autonomous GRK2-mediated components: 1) a phosphorylation-independent signal decrease mediated by blocking of Gαq and 2) a mechanism involving phosphorylation of Ser and Thr residues in the CTE of the receptor in a redundant fashion, able to incorporate either proximal or distal phosphoacceptor sites. High level transfection of GRK2 variants influenced signaling of ETA-WT and ETA-6PD and hints at an additional phosphorylation-independent regulatory mechanism. Furthermore, internalization of mRuby-tagged receptors was observed with ETA-WT and the phosphorylation-deficient mutant ETA-14PD (lacking 14 phosphoacceptor sites) and turned out to be based on a phosphorylation-independent mechanism.


Assuntos
Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Receptores de Endotelina/metabolismo , Substituição de Aminoácidos , Quinase 2 de Receptor Acoplado a Proteína G/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Mutação de Sentido Incorreto , Fosforilação/fisiologia , Transporte Proteico/fisiologia , Receptores de Endotelina/genética , Fosfolipases Tipo C/genética , Fosfolipases Tipo C/metabolismo
20.
Zoolog Sci ; 31(8): 501-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25088590

RESUMO

Differences in nest attendance between genders in seabirds may be related to morphological differences. Southern giant petrel is a dimorphic species with gender-specific foraging behavior. The objective of this study was to investigate sex-related differences in nest attendance during the breeding period of southern giant petrels by presence/absence patterns of both sexes during incubation and compare use of the colony after nest failure. Fourteen birds were tagged with digitally coded radio-transmitters in a colony at Elephant Island, Antarctica, in the beginning of 2009/2010 breeding season. Females were present during 18 periods (min. 3 days, max. 9 days) and males only in five periods (min. 2 days, max. 13 days). The difference in mean number of radio signals per day between females (4330; s.e. 313.5) and males (2691; s.e. 248.6) was highly significant (t = 4.3; d.f. = 199; P < 0.001; Fig. 4 ). As consequence of the severe weather conditions that year, all tagged birds failed to reproduce. After abandonment of the nests, the presence of both genders decreased drastically, although the tagged individuals stayed in the area. Under severe weather conditions female Southern Giant Petrels continue breeding while males abandon the nest earlier.


Assuntos
Aves/fisiologia , Comportamento de Nidação/fisiologia , Tempo (Meteorologia) , Sistemas de Identificação Animal , Animais , Feminino , Masculino , Telemetria
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