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1.
Artif Organs ; 46(7): 1221-1226, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35460277

RESUMO

In 1985, the surgical team led by Bjarne Semb implanted the first total artificial heart (TAH) in Europe, and the following year the first successful bridge to transplant in Europe using the Symbion J-7/100 TAH. Together with the clinical experiences of colleagues in the United States, these early cases preceded the subsequent development of scores of mechanical assist devices to treat advanced heart failure. Semb proved to have the pioneering spirit needed to use the early generation of a TAH, but these early implants also generated much controversy in the medical community as well as the general public.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Artificial , Coração Auxiliar , Transplantes , Europa (Continente) , Insuficiência Cardíaca/cirurgia , Humanos , Estados Unidos
2.
Health Qual Life Outcomes ; 18(1): 376, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33256748

RESUMO

BACKGROUND: Marfan syndrome, a rare hereditary connective tissue disorder caused by mutations in fibrillin-1, can affect many organ systems, especially the cardiovascular system. Previous research has paid less attention to health-related quality of life and prospective studies on this topic are needed. The aim of this study was to assess changes in health-related quality of life after 10 years in a Norwegian Marfan syndrome cohort. METHODS: Forty-seven Marfan syndrome patients ≥ 18 years were investigated for all organ manifestations in the 1996 Ghent nosology and completed the self-reported questionnaire, Short-Form-36 Health Survey, at baseline in 2003-2004 and at follow-up in 2014-2015. Paired sample t tests were performed to compare means and multiple regression analyses were performed with age, sex, new cardiovascular and new non-cardiovascular pathology as predictors. RESULTS: At 10-year follow-up: a significant decline was found in the physical domain. The mental domain was unchanged. Older age predicted a larger decline in physical health-related quality of life. None of the chosen Marfan-related variables predicted changes in any of the subscales of the Short-Form 36 Health Survey or in the physical or the mental domain. CONCLUSION: Knowledge of decline in the physical domain, not related to organ affections, may be important in the follow-up of Marfan syndrome patients.


Assuntos
Síndrome de Marfan/psicologia , Qualidade de Vida , Adulto , Fatores Etários , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Síndrome de Marfan/complicações , Pessoa de Meia-Idade , Noruega , Inquéritos e Questionários
3.
Am J Med Genet A ; 182(2): 397-408, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31825148

RESUMO

The age-dependent penetrance of organ manifestations in Marfan syndrome (MFS) is not known. The aims of this follow-up study were to explore how clinical features change over a 10-year period in the same Norwegian MFS cohort. In 2003-2004, we investigated 105 adults for all manifestations in the 1996 Ghent nosology. Ten years later, we performed follow-up investigations of the survivors (n = 48) who consented. Forty-six fulfilled the revised Ghent criteria. Median age: females 51 years, range 32-80 years; males 45 years, range 30-67 years. New aortic root dilatation was detected in patients up to 70 years. Ascending aortic pathology was diagnosed in 93 versus 72% at baseline. Sixty-five percent had undergone aortic surgery compared to 39% at baseline. Pulmonary trunk mean diameter had increased significantly compared to baseline. From inclusion to follow-up, two patients (three eyes) developed ectopia lentis, four developed dural ectasia, four developed scoliosis, three developed incisional or recurrent herniae, and 14 developed hindfoot deformity. No changes were found regarding protrusio acetabuli, spontaneous pneumothorax, or striae atrophicae. The study confirms that knowledge of incidence and progression of organ manifestations throughout life is important for diagnosis, treatment, and follow-up of patients with verified or suspected MFS.


Assuntos
Aorta/fisiopatologia , Hérnia/diagnóstico , Síndrome de Marfan/epidemiologia , Escoliose/diagnóstico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aorta/cirurgia , Dilatação Patológica/diagnóstico , Dilatação Patológica/fisiopatologia , Ectopia do Cristalino/diagnóstico , Ectopia do Cristalino/fisiopatologia , Feminino , Seguimentos , Hérnia/fisiopatologia , Humanos , Masculino , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/fisiopatologia , Pessoa de Meia-Idade , Escoliose/fisiopatologia
4.
Scand Cardiovasc J ; 53(6): 337-341, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476881

RESUMO

Objectives. Coronary revascularisation and intra-aortic balloon pump (IABP) has been considered the gold standard treatment of acute coronary syndrome with cardiogenic shock, recently challenged by the SHOCK II study. The aim of this non-randomised study was to investigate the long term prognosis after immediate IABP supported angiography, in patients with acute chest pain and cardiogenic shock, treated with percutaneous coronary intervention (PCI), cardiac surgery or optimal medical treatment. We assessed data from 281 consecutive patients admitted to our department from 2004 to 2010. Results. Mean (±SD) age was 63.8 ± 11.5 (range 30-84) years with a follow-up of 5.6 ± 4.4 (0-12.7) years. Acute myocardial infarction was the primary diagnosis in 93% of the patients, 4% presented with unstable angina pectoris and 3% cardiomyopathy or arrhythmias of non-ischemic aetiology. Systolic blood pressure at admittance was 85 ± 18 mmHg and diastolic 55 ± 18 mmHg. Thirty day, one- and five-year survival was 71.2%, 67.3% and 57.7%, respectively. PCI was performed immediately in 70%, surgery was done in 17%, and 13% were not eligible for any revascularisation. Independent variables predicting mortality were medical treatment vs revascularisation, out-of-hospital cardiac arrest, and advanced age. Three serious non-fatal complications occurred due to IABP treatment, i.e. 0.001 per treatment day. Conclusions. We report the use of IABP in patients with acute chest pain admitted for angiography. Long-term survival is acceptable and discriminating factors were no revascularisation, out-of-hospital cardiac arrest and age. IABP was safe and feasible and the complication rate was low.


Assuntos
Angina Pectoris/terapia , Fármacos Cardiovasculares/uso terapêutico , Ponte de Artéria Coronária , Balão Intra-Aórtico , Intervenção Coronária Percutânea , Choque Cardiogênico/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/diagnóstico por imagem , Angina Pectoris/mortalidade , Angina Pectoris/fisiopatologia , Fármacos Cardiovasculares/efeitos adversos , Angiografia Coronária , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Feminino , Humanos , Balão Intra-Aórtico/efeitos adversos , Balão Intra-Aórtico/mortalidade , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
5.
Cells ; 8(2)2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30699940

RESUMO

During the development of hypertrophic cardiomyopathy, the heart returns to fetal energy metabolism where cells utilize more glucose instead of fatty acids as a source of energy. Metabolism of glucose can increase synthesis of the extracellular glycosaminoglycan hyaluronan, which has been shown to be involved in the development of cardiac hypertrophy and fibrosis. The aim of this study was to investigate hyaluronan metabolism in cardiac tissue from patients with hypertrophic cardiomyopathy in relation to cardiac growth. NMR and qRT-PCR analysis of human cardiac tissue from hypertrophic cardiomyopathy patients and healthy control hearts showed dysregulated glucose and hyaluronan metabolism in the patients. Gas phase electrophoresis revealed a higher amount of low molecular mass hyaluronan and larger cardiomyocytes in cardiac tissue from patients with hypertrophic cardiomyopathy. Histochemistry showed high concentrations of hyaluronan around individual cardiomyocytes in hearts from hypertrophic cardiomyopathy patients. Experimentally, we could also observe accumulation of low molecular mass hyaluronan in cardiac hypertrophy in a rat model. In conclusion, the development of hypertrophic cardiomyopathy with increased glucose metabolism affected both hyaluronan molecular mass and amount. The process of regulating cardiomyocyte size seems to involve fragmentation of hyaluronan.


Assuntos
Cardiomiopatia Hipertrófica/metabolismo , Ácido Hialurônico/metabolismo , Miocárdio/metabolismo , Animais , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Tamanho Celular , Análise Fatorial , Feminino , Regulação da Expressão Gênica , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Septos Cardíacos/cirurgia , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Peso Molecular , Miocárdio/patologia , Miócitos Cardíacos/patologia , Ratos Wistar
6.
Transplantation ; 103(4): 807-814, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30086099

RESUMO

BACKGROUND: Organs from older donors are increasingly used in lung transplantation, and studies have demonstrated that this could be safe in selected recipients. However, which recipient groups that have the largest benefit of older organs are unclear. This multicenter study reviews all bilateral lung transplantations (BLTx) from donors 55 years or older stratified by recipient diagnosis and compares outcomes with transplantations from younger donors. METHODS: All BLTx recipients (excluding retransplantation) at 5 Scandiatransplant centers between 2000 and 2013 were included (n = 913). Recipients were stratified to diagnosis groups including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and "other." Intensive care unit (ICU) length of stay (LOS) and survival were assessed. RESULTS: Overall, there was no difference in survival among patients transplanted from donors 55 years or older compared with younger donors. However, in CF recipients, donor age 55 years or older was associated with inferior survival (P = 0.014), and this remained significant in a multivariate model (hazard ratio, 5.0; 95% confidence interval, 1.8-14.1; P = 0.002). There was no significant effect of donor age on survival in recipients with COPD, ILD, or in the "other" group in multivariate models. Utilization of older donors was associated with increased ICU LOS for recipients with CF and ILD, but not in the COPD or "other" group. CONCLUSIONS: The BLTx recipients with CF had inferior survival and longer ICU LOS when receiving organs from donors 55 years or older. Recipients with COPD, ILD, or in the "other" group did not have inferior survival in multivariate models.


Assuntos
Transplante de Pulmão/mortalidade , Doadores de Tecidos , Adulto , Fatores Etários , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade
7.
Mol Genet Genomic Med ; 6(6): 1114-1123, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30393980

RESUMO

BACKGROUND: To explore survival, causes of death, and the prevalence of cardiovascular events in a Norwegian Marfan syndrome (MFS) cohort. MFS is a heritable connective tissue disorder associated with reduced life expectancy-primarily due to aortic pathology. METHODS: A follow-up study of 84 MFS adults, initially investigated in 2003-2004. In 2014-2015, 16 were deceased, 47 of 68 survivors consented to new clinical investigations. Analyses of events were performed for 47 survivors and 16 deceased at follow-up. Standardized mortality ratios (SMR), using the mortality rate of the Norwegian population as reference, were calculated for all 84 and calculated for men and women separately. Causes of death and information on cardiovascular events were retrieved from death certificates and medical records. RESULTS: Standardized mortality ratios (95% confidence interval): for the whole cohort: 5.24 (3.00-8.51); for men: 8.20 (3.54-16.16); for women: 3.85 (1.66-7.58). Cardiovascular causes were found in 11 of 16 deceased, eight of these related to aortic pathology. Cancer was the cause of death in three patients. At follow-up, 51% had new cardiovascular events; 59% had undergone aortic surgery. Men experienced aortic events at younger age than women. 32% of the survivors were not followed-up as recommended. CONCLUSION: Life expectancy is reduced in this MFS cohort compared to the Norwegian population. Cardiovascular complications develop throughout life, particularly aortic pathology, the major cause of death in MFS. Death and aortic pathology seem to occur earlier in men. There is a need to improve follow-up according to guidelines.


Assuntos
Síndrome de Marfan/epidemiologia , Adulto , Idoso , Aorta/patologia , Causas de Morte , Feminino , Humanos , Masculino , Síndrome de Marfan/mortalidade , Síndrome de Marfan/patologia , Pessoa de Meia-Idade , Noruega
8.
J Heart Lung Transplant ; 37(12): 1403-1409, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30241891

RESUMO

BACKGROUND: Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill patients, the Scandiatransplant urgent lung allocation system (ScULAS) was introduced in 2009, giving supranational priority to patients considered urgent. There were no pre-defined criteria for listing a patient as urgent, but each center was granted only 3 urgent calls per year. This study aims to explore the characteristics and outcome of patients listed as urgent, assess changes associated with the implementation of ScULAS, and describe how the system was utilized by the member centers. METHODS: All patients listed for lung transplantation at the 5 Scandiatransplant centers 5 years before and after implementation of ScULAS were included. RESULTS: After implementation, 8.3% of all listed patients received urgent status, of whom 81% were transplanted within 4 weeks. Patients listed as urgent were younger, more commonly had suppurative lung disease, and were more often on life support compared with patients without urgent status. For patients listed as urgent, post-transplant graft survival was inferior at 30 and 90 days. Although there were no pre-defined criteria for urgent listing, the system was not utilized at its maximum. CONCLUSIONS: ScULAS rapidly allocated organs to patients considered urgent. These patients were younger and more often had suppurative lung disease. Patients with urgent status had inferior short-term outcome, plausibly due to the higher proportion on life support before transplantation.


Assuntos
Emergências , Transplante de Pulmão/métodos , Alocação de Recursos/organização & administração , Obtenção de Tecidos e Órgãos/organização & administração , Listas de Espera , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Implementação de Plano de Saúde/organização & administração , Humanos , Lactente , Recém-Nascido , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Países Escandinavos e Nórdicos , Taxa de Sobrevida , Doadores de Tecidos/provisão & distribuição , Adulto Jovem
9.
Transplant Direct ; 4(7): e366, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30046656

RESUMO

BACKGROUND: Donation after circulatory death (DCD) can increase the pool of available organs for transplantation. This pilot study evaluates the implementation of a controlled DCD (cDCD) protocol using normothermic regional perfusion in Norway. METHODS: Patients aged 16 to 60 years that are in coma with documented devastating brain injury in need of mechanical ventilation, who would most likely attain cardiac arrest within 60 minutes after extubation, were eligible. With the acceptance from the next of kin and their wish for organ donation, life support was withdrawn and cardiac arrest observed. After a 5-minute no-touch period, extracorporeal membrane oxygenation for post mortem regional normothermic regional perfusion was established. Cerebral and cardiac reperfusion was prevented by an aortic occlusion catheter. Measured glomerular filtration rates 1 year postengraftment were compared between cDCD grafts and age-matched grafts donated after brain death (DBD). RESULTS: Eight cDCD were performed from 2014 to 2015. Circulation ceased median 12 (range, 6-24) minutes after withdrawal of life-sustaining treatment. Fourteen kidneys and 2 livers were retrieved and subsequently transplanted. Functional warm ischemic time was 26 (20-51) minutes. Regional perfusion was applied for 97 minutes (54-106 minutes). Measured glomerular filtration rate 1 year postengraftment was not significantly different between cDCD and donation after brain death organs, 75 (65-76) vs 60 (37-112) mL/min per 1.73 m2 (P = 0.23). No complications have been observed in the 2 cDCD livers. CONCLUSION: A protocol for cDCD is successfully established in Norway. Excellent transplant outcomes have encouraged us to continue this work addressing the shortage of organs for transplantation.

11.
Eur J Cardiothorac Surg ; 52(6): 1125-1131, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28541520

RESUMO

OBJECTIVES: The first publication of Loeys-Dietz syndrome (LDS) described aortic rupture at young ages. Experience with new LDS types showed that the clinical course varies, and thresholds for prophylactic surgery are discussed. As this is an uncommon disease, experience needs to be shared. METHODS: Retrospective review of patients with LDS types 1-4 undergoing cardiovascular surgery during the years 1991-2016. RESULTS: Thirty-five patients (including 6 children with LDS2) underwent 57 operations. LDS 1, 2, 3 and 4 included 4, 17, 11 and 3 patients, respectively. Mean age at first surgery was 36 years, with a non-significant trend that LDS2 patients were younger. Of the 9 emergency surgeries, 7 were type A dissections, with 1 postoperative death. Twenty-two patients had prophylactic aortic root surgery (17 valve-sparing root replacements), with 1 postoperative death, 1 reoperation with valve replacement and 1 late death. Freedom from root reintervention and death was 92% at 13 years. Of the 11 patients with LDS3, 5 needed mitral valve surgery. Mitral valve disease was not found in the other LDS types. Ten patients needed >1 operation. Of the 57 operations, 33 were in the ascending aorta, 20 in the aorta distal to the arch including branches and 4 were isolated heart surgeries. Of the 20 vascular operations, 16 were in LDS2. Cumulative survival 20 years after first surgery (all patients) was 94.3%. CONCLUSIONS: Clinical course seems to be more aggressive in LDS2, with index operation at a younger age, and higher risk of needing several operations. Vascular disease distal to the arch is not uncommon. LDS3 seems to be associated with mitral valve disease. Prophylactic aortic root surgery is safe and durable.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Síndrome de Loeys-Dietz/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Síndrome de Loeys-Dietz/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Scand Cardiovasc J ; 51(1): 1-7, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27248460

RESUMO

OBJECTIVES: Growing number of patients with terminal heart failure and a shortage of heart donors have increased use of short- and long-term mechanical circulatory support (MCS). Few studies have analyzed survival rates and healthcare costs for heart transplantation (HTx), with or without extracorporeal membrane oxygenation (ECMO) and left ventricular assist device (LVAD). DESIGN: In a retrospective, single-center study, data were analyzed from patients listed for HTx who died on the waiting list (DWL, n = 12), underwent HTx (n = 206), had ECMO as bridge to HTx (ECHTx, n = 15), or received LVAD treatment, either isolated (LVAD, n = 19) or bridging to HTx (LVADHTx, n = 26) during 2005-2012. Survival and hospital costs were assessed. RESULTS: One- and five-year survival rates were 96% and 83% for the LVADHTx group, 92% and 81% for HTx, 70% and 70% for ECHTx, 48% and 36% for LVAD and 0% for the DWL group (overall survival, p < 0.001). Total hospital cost at one year was $102,101 ± 202,604 for DWL, $151,685 ± 86,892 for HTx, $292,078 ± 101,915 for ECHTx, $427,337 ± 365,154 for LVAD, and $600,897 ± 198,109 for LVADHTx. CONCLUSION: The LVADHTx and HTx groups showed excellent one- and five-year survival. The combined group of DWL and HTx patients had similar survival to the combined groups of MCS, but use of LVAD pre-transplant quadrupled the cost.


Assuntos
Oxigenação por Membrana Extracorpórea/economia , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/terapia , Transplante de Coração/economia , Coração Auxiliar/economia , Custos Hospitalares , Avaliação de Processos em Cuidados de Saúde/economia , Adolescente , Adulto , Idoso , Terapia Combinada , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Coração Auxiliar/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Noruega , Desenho de Prótese , Recuperação de Função Fisiológica , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda , Adulto Jovem
13.
Ann Thorac Surg ; 102(5): 1756-1761, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27772574

RESUMO

In 1977, Karl Viktor Hall implanted a novel tilting disc heart valve prosthesis at Rikshospitalet in Oslo, Norway. The Medtronic-Hall valve was known for its excellent durability and low thrombogenicity. Hall popularized the use of the great saphenous vein in situ as an arterial shunt in the 1960s, made a metal stripper to lyse vein valves, and introduced electromagnetic flowmeters in vascular surgery. He performed the first coronary artery bypass graft in Scandinavia in 1969. Under his leadership the first heart transplantation and the first heart-lung transplantation were performed in Scandinavia by his successor Tor Frøysaker in 1983 and 1986, respectively.


Assuntos
Arteriopatias Oclusivas/história , Cardiologia/história , Doenças das Valvas Cardíacas/história , Próteses Valvulares Cardíacas/história , Veia Safena/transplante , Arteriopatias Oclusivas/cirurgia , Doenças das Valvas Cardíacas/cirurgia , História do Século XX , História do Século XXI , Humanos , Noruega
14.
BMC Med Genet ; 16: 113, 2015 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-26684006

RESUMO

BACKGROUND: Pathogenic mutations in FBN1, encoding the glycoprotein, fibrillin-1, cause Marfan syndrome (MFS) and related connective tissue disorders. In the present study, qualitative and quantitative effects of 16 mutations, identified in FBN1 in MFS patients with systematically described phenotypes, were investigated in vitro. METHODS: Qualitative analysis was performed with reverse transcription-PCR (RT-PCR) and gel electrophoresis, and quantitative analysis to determine the FBN1 mRNA levels in fibroblasts from the 16 patients with MFS was performed with real-time PCR. RESULTS: Qualitative analysis documented that the mutations c.4817-2delA and c.A4925G led to aberrant FBN1 mRNA splicing leading to in frame deletion of exon 39 and in exon 39, respectively. No difference in the mean FBN1 mRNA level was observed between the entire group of cases and controls, nor between the group of patients with missense mutations and controls. The mean expression levels associated with premature termination codon (PTC) and splice site mutations were significantly lower than the levels in patients with missense mutations. A high level of FBN1 mRNA in the patient with the missense mutation c.G2447T did not segregate with the mutation in three of his first degree relatives. No association was indicated between the FBN1 transcript level and specific phenotypic manifestations. CONCLUSIONS: Abnormal FBN1 transcripts were indicated in fibroblasts from patients with the splice site mutation c.4817-2delA and the missense mutation c.A4925G. While the mean FBN1 mRNA expression level in fibroblasts from patients with splice site and PTC mutations were lower than the mean level in patients with missense mutations and controls, inter-individual variability was high. The observation that high level of FBN1 mRNA in the patient with the missense mutation c.G2447T did not segregate with the mutation in the family suggests that variable expression of the normal FBN1 allele may contribute to explain the variability in FBN1 mRNA level.


Assuntos
Fibroblastos/metabolismo , Síndrome de Marfan/genética , Proteínas dos Microfilamentos/genética , RNA Mensageiro/genética , Sequência de Bases , Células Cultivadas , Análise Mutacional de DNA , Fibrilina-1 , Fibrilinas , Predisposição Genética para Doença/genética , Genótipo , Humanos , Síndrome de Marfan/metabolismo , Síndrome de Marfan/patologia , Mutação , Mutação de Sentido Incorreto , Sítios de Splice de RNA/genética , Splicing de RNA/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Deleção de Sequência
15.
J Card Fail ; 21(11): 916-23, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26231517

RESUMO

BACKGROUND: Adipose tissue has endocrine properties, secreting a wide range of mediators into the circulation, including factors involved in cardiovascular disease. However, little is known about the potential role of adipose tissue in heart failure (HF), and the aim of this study was to investigate epicardial (EAT) and subcutaneous (SAT) adipose tissue in HF patients. METHODS AND RESULTS: Thirty patients with systolic HF and 30 patients with normal systolic function undergoing thoracic surgery were included in the study. Plasma was sampled and examined with the use of enzyme-linked immunosorbent assays, whereas SAT and EAT biopsies were collected and examined by means of reverse-transcription polymerase chain reaction and gas chromatography. Significantly higher expressions of mRNA encoding interleukin-6, adrenomedullin, peroxisome proliferator-activated receptor α, and fatty acid (FA)-binding protein 3, as well as higher levels of monounsaturated FA and palmitoleic acid, were seen in the EAT of HF patients, whereas the levels of docosahexaenoic acid were lower. Palmitoleic acid levels in EAT were correlated with 2 parameters of cardiac remodeling: increasing left ventricular end-diastolic diameter and N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: Our results demonstrate adipose tissue depot-specific alterations of synthesis of FA and inflammatory and metabolic mediators in systolic HF patients. EAT may be a source of increased circulatory and myocardial levels of these mediators through endocrine actions.


Assuntos
Proteína C-Reativa/metabolismo , Ácidos Graxos/metabolismo , Insuficiência Cardíaca Sistólica/metabolismo , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Tecido Adiposo/metabolismo , Adulto , Idoso , Biomarcadores/análise , Procedimentos Cirúrgicos Cardíacos/métodos , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Procedimentos Cirúrgicos Eletivos , Ensaio de Imunoadsorção Enzimática , Feminino , Insuficiência Cardíaca Sistólica/diagnóstico por imagem , Insuficiência Cardíaca Sistólica/cirurgia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pericárdio/metabolismo , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estatísticas não Paramétricas , Gordura Subcutânea/metabolismo , Ultrassonografia
16.
Acta Ophthalmol ; 93(1): 46-53, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24853997

RESUMO

PURPOSE: To study ocular characteristics in 87 patients with verified Marfan syndrome (MFS) based on the Ghent criteria from 1996 (Ghent-1). METHODS: The position of the lens was noted by observing the eye in different gaze directions in maximal mydriasis during slit lamp examination. Ectopia lentis (EL) was classified as subluxated (dislocation slightly backwards) or luxated (vertical or horizontal displacement). Corneal curvature, axial length (AL), corneal diameter, central corneal thickness, anterior chamber depth, lens thickness, condition of the iris, intraocular pressure, spherical equivalent and visual acuity were also investigated. RESULTS: EL was found in 108 eyes (62.1%). Of the 68 phakic eyes with EL, 43 (63.2%) had subluxation. Mean AL was 24.80 ± 2.57 mm, and the AL was above 23.5 mm in 65.3%. Mean keratometry (K) in phakic eyes was 41.79 ± 1.70 diopters (D), and the K value was <41.5D in 46.8%. Iris hypoplasia was found in 3.4%. Myopia above 3D occurred in 38.4% of the phakic eyes. Mean binocular logMAR was 0.10 ± 0.32. Only five patients (5.7%) had a logMAR more than 0.5. These 5 patients had EL, and 4 of them were amblyopic. CONCLUSION: In this strictly defined MFS group fulfilling the Ghent-1 criteria, the prevalence of EL was 62.1%. In many cases, the dislocation of the lens was subtle. On average, the corneas were flattened and the globe length was increased. Only a few patients were visually impaired. Children with MFS should have a thorough follow up to avoid amblyopia.


Assuntos
Comprimento Axial do Olho/patologia , Ectopia do Cristalino/diagnóstico , Síndrome de Marfan/diagnóstico , Miopia/diagnóstico , Adulto , Idoso , Ectopia do Cristalino/epidemiologia , Ectopia do Cristalino/cirurgia , Feminino , Glaucoma/diagnóstico , Glaucoma/epidemiologia , Glaucoma/terapia , Humanos , Iris/anormalidades , Masculino , Síndrome de Marfan/epidemiologia , Pessoa de Meia-Idade , Miopia/epidemiologia , Miopia/cirurgia , Noruega/epidemiologia , Refração Ocular/fisiologia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/cirurgia , Acuidade Visual/fisiologia , Adulto Jovem
18.
Heart ; 100(8): 631-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24368281

RESUMO

OBJECTIVE: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the reference standard for non-invasive assessment of fibrosis. In hypertrophic cardiomyopathy (HCM) patients the histological substrate for LGE is still unknown. The aim of this study was to assess the ability of LGE and strain echocardiography to detect type and extent of myocardial fibrosis in obstructive HCM patients undergoing septal myectomy. METHODS: Thirty-two HCM patients (age 60±10) were included in this cross-sectional study and preoperatively examined by speckle-tracking strain echocardiography and LGE-CMR (n=21). Histological fibrosis was classified as interstitial, replacement and total. RESULTS: Histological fibrosis was present in 31 patients. The percentage of total, interstitial and replacement fibrosis was 15(7, 31)%, 11(5, 24)% and 3(1, 6)%, respectively. Reduced longitudinal septal strain correlated with total (r=0.50, p=0.01) and interstitial (r=0.40, p=0.03), but not with replacement fibrosis (r=0.28, p=0.14). Septal LGE was detected in 13/21 (62%), but percentage LGE did not correlate with total fibrosis (r=0.25, p=0.28). Extent of fibrosis did not differ between patients with and without septal LGE (20(9, 58)% versus 14(5, 19)% p=0.41). Patients with ventricular arrhythmias (n=8) had lower septal longitudinal strain and increased extent total and interstitial fibrosis in myectomy specimens, but no differences were demonstrated in LGE. Reduced longitudinal septal strain and increased extent of interstitial fibrosis predicted ventricular arrhythmias independently of age and gender. CONCLUSIONS: In myectomised HCM patients, reduced longitudinal septal strain correlated better with interstitial and total fibrosis in myectomy specimens, and was a more powerful tool to predict arrhythmias than LGE.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Ecocardiografia Doppler , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Idoso , Arritmias Cardíacas/etiologia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/cirurgia , Meios de Contraste , Estudos Transversais , Feminino , Fibrose , Gadolínio DTPA , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Valor Preditivo dos Testes , Fatores de Risco
19.
Heart ; 99(19): 1415-20, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23846611

RESUMO

OBJECTIVE: To examine the effect of balloon pulmonary angioplasty (BPA) on chronic thromboembolic pulmonary hypertension (CTEPH) in patients with inoperable disease or persistent pulmonary hypertension after pulmonary endarterectomy. DESIGN: Observational cohort study. SETTING: Referred patients with inoperable or persistent CTEPH. PATIENTS: Twenty consecutive CTEPH patients (10 females), aged 60±10 years. INTERVENTIONS BPA MAIN OUTCOME MEASURES: Right heart catheterisation, functional capacity (cardiopulmonary exercise testing (CPET) and NYHA class) and blood sampled biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T examined at the time of diagnosis and repeated in all patients 3 months after the last BPA. RESULTS: Seventy-three catheterisations were performed with 18.6±6.1 BPAs per patient on segmental and subsegmental arteries. Two deaths occurred following the first BPA, with an overall 10% periprocedural death rate. Reperfusion oedema complicated seven procedures. Comparisons before and after BPA showed significant haemodynamic improvements, including decreased mean pulmonary artery pressure (mPAP) (45±11 mm Hg vs 33±10 mm Hg; p<0.001) and increased cardiac output (4.9±1.6 L/min vs 5.4±1.9 L/min; p=0.011). Reduced right ventricular strain was indicated by significantly lower plasma levels of NT-proBNP and troponin T. Significant improvement in functional capacity was evident as assessed by NYHA class (3.0±0.5 vs 2.0±0.5; p<0.001) and CPET (13.6±5.6 mL/kg/min vs 17.0±6.5 mL/kg/min; p<0.001). Seventeen patients (85%) were alive after 51±30 months of follow-up. CONCLUSIONS: BPA may offer an alternative form of treatment in selected CTEPH patients. While prognostic markers such as haemodynamics, functional capacity and biomarkers improve, significant periprocedural complications must be recognised. Randomised trials are warranted.


Assuntos
Angioplastia com Balão , Hipertensão Pulmonar/terapia , Embolia Pulmonar/terapia , Idoso , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/mortalidade , Pressão Arterial , Biomarcadores/sangue , Cateterismo Cardíaco , Débito Cardíaco , Doença Crônica , Endarterectomia , Teste de Esforço , Tolerância ao Exercício , Feminino , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Noruega , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/cirurgia , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Troponina T/sangue , Função Ventricular Direita
20.
Clin Transplant ; 27(4): 613-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23803161

RESUMO

Organs available for solid organ transplantation are mainly procured from brain dead donors. The inflammation associated with brain death may reduce organ quality and increase organ immunogenicity, thus leading to inferior recipient outcome. We hypothesized that the extensive surgical procedure performed during multiorgan procurement enhances the levels of systemic inflammatory biomarkers. We measured the levels of 27 cytokines and the terminal complement complex (TCC) in plasma samples from brain dead organ donors (n = 34) drawn before and at three specific time points during procurement surgery. Baseline levels of G-CSF, interferon-γ, IL-1ra, IL-4, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, macrophage inflammatory protein (MIP)-1ß, platelet derived growth factor (PDGF), regulated upon activation T cell expressed and secreted, and tumor necrosis factor-α were significantly elevated in brain dead donors compared with normal individuals (n = 14), but they were not associated with time on ventilator or any other registered clinical variable. Notably, the secretion of G-CSF, IL1-ra, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1ß, PDGF, and TCC, the latter reflecting ongoing complement activation, increased significantly during surgery. None of the biomarker increases were correlated with operation duration. Multiorgan procurement surgery significantly adds to the inflammatory response revealed by both pro- and anti-inflammatory biomarkers associated with brain death. Future studies should determine whether this is associated with inferior recipient outcome.


Assuntos
Biomarcadores/sangue , Morte Encefálica/patologia , Transplante de Órgãos , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Doadores de Tecidos , Coleta de Tecidos e Órgãos/efeitos adversos , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Adulto Jovem
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