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2.
Circ Res ; 123(5): 579-589, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-29921651

RESUMO

RATIONALE: Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory, and regenerative properties with a robust safety profile in large animal models of heart disease. OBJECTIVE: To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment-elevation myocardial infarction. METHODS AND RESULTS: CAREMI (Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With STEMI and Left Ventricular Dysfunction) was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial in patients with ST-segment-elevation myocardial infarction, left ventricular ejection fraction ≤45%, and infarct size ≥25% of left ventricular mass by cardiac magnetic resonance, who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at days 5 to 7. The primary end point was safety and included all-cause death and major adverse cardiac events at 30 days (all-cause death, reinfarction, hospitalization because of heart failure, sustained ventricular tachycardia, ventricular fibrillation, and stroke). Secondary safety end points included major adverse cardiac events at 6 and 12 months, adverse events, and immunologic surveillance. Secondary exploratory efficacy end points were changes in infarct size (percentage of left ventricular mass) and indices of ventricular remodeling by magnetic resonance at 12 months. Forty-nine patients were included (92% male, 55±11 years), 33 randomized to AlloCSC-01 and 16 to placebo. No deaths or major adverse cardiac events were reported at 12 months. One severe adverse events in each group was considered possibly related to study treatment (allergic dermatitis and rash). AlloCSC-01 elicited low levels of donor-specific antibodies in 2 patients. No immune-related adverse events were found, and no differences between groups were observed in magnetic resonance-based efficacy parameters at 12 months. The estimated treatment effect of AlloCSC-01 on the absolute change from baseline in infarct size was -2.3% (95% confidence interval, -6.5% to 1.9%). CONCLUSIONS: AlloCSC-01 can be safely administered in ST-segment-elevation myocardial infarction patients with left ventricular dysfunction early after revascularization. Low immunogenicity and absence of immune-mediated events will facilitate adequately powered studies to demonstrate their clinical efficacy in this setting. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02439398.


Assuntos
Mioblastos Cardíacos/transplante , Infarto do Miocárdio/terapia , Transplante de Células-Tronco/métodos , Disfunção Ventricular Esquerda/terapia , Idoso , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Mioblastos Cardíacos/citologia , Infarto do Miocárdio/complicações , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo , Disfunção Ventricular Esquerda/complicações
3.
Rev. esp. cardiol. (Ed. impr.) ; 71(5): 327-334, mayo 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-178529

RESUMO

Introducción y objetivos: Los armazones vasculares bioabsorbibles (AVB) tienen el potencial de restaurar la vasomotilidad, pero se desconocen las implicaciones clínicas. En este estudio se evalúan la angina y la isquemia a largo plazo tras el implante de AVB y stents farmacoactivos metálicos (SFAm). Métodos: Estudio multicéntrico, que incluyó a pacientes tras 24 ± 6 meses de evolución sin eventos a los que se realizó ecografía de estrés y se aplicó el Seattle Angina Questionnaire (SAQ). El objetivo primario fue el resultado positivo en la ecografía de estrés. Resultados: Se incluyó a 102 pacientes tratados con AVB y 106 con SFAm, sin diferencias basales significativas. Se produjo recurrencia de la angina en 18 pacientes (17,6%) con AVB frente a 25 (23,5%) con SFAm (p = 0,37), pero los resultados del SAQ fueron significativamente mejores en el grupo AVB (frecuencia de angina, 96.0 ± 8.0 frente a 89,2 ± 29,7; p = 0,02). La ecografía de estrés fue positiva en 11/92 (11,9%) con AVB frente a 9/96 (9,4%) con SFAm (p = 0,71) y se indujo angina en 2/102 (1,9%) frente a 7/106 (6,6%) (p = 0,18), pero el desempeño en el ejercicio fue mejor con AVB incluso en aquellos con tests positivos (duración del ejercicio, 9,0 ± 2,0 frente a 7,7 ± 1,8 min; p = 0,02). Un análisis por puntuación de propensión de tratamiento ofreció resultados similares. Conclusiones: El objetivo primario fue comparable en ambos grupos. La recurrencia de la angina fue similar entre los tratados con AVB y con SFAm. El mejor estado funcional, medido por SAQ y nivel de ejercicio, detectado en pacientes con AVB tendría que confirmarse en futuros estudios


Introduction and objectives: Bioresorbable vascular scaffolds (BVS) have the potential to restore vasomotion but the clinical implications are unknown. We sought to evaluate angina and ischemia in the long-term in patients treated with BVS and metallic drug-eluting stents (mDES). Methods: Multicenter study including patients with 24 ± 6 months of uneventful follow-up, in which stress echocardiography was performed and functional status was assessed by the Seattle Angina Questionnaire (SAQ). The primary endpoint was a positive result in stress echocardiography. Results: The study included 102 patients treated with BVS and 106 with mDES. There were no differences in the patients' baseline characteristics. Recurrent angina was found in 18 patients (17.6%) in the BVS group vs 25 (23.5%) in the mDES group (P = .37), but SAQ results were significantly better in the BVS group (angina frequency 96.0 ± 8.0 vs 89.2 ± 29.7; P = .02). Stress echocardiography was positive in 11/92 (11.9%) of BVS patients vs 9/96 (9.4%) of mDES patients in the (P = .71) and angina was induced in 2/102 (1.9%) vs 7/106 (6.6%) (P = .18), respectively, but exercise performance was better in the BVS group even in those with positive tests (exercise duration 9.0 ± 2.0 minutes vs 7.7 ± 1.8 minutes; P = .02). A propensity score matching analysis yielded similar results. Conclusions: The primary endpoint was similar in both groups. In addition, recurrent angina was similar in patients with BVS and mDES. The better functional status, assessed by means of SAQ and exercise performance, detected in patients receiving BVS should be confirmed in further studies


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Angina Pectoris/epidemiologia , Isquemia Miocárdica/epidemiologia , Stents Farmacológicos/estatística & dados numéricos , Stents Metálicos Autoexpansíveis/estatística & dados numéricos , Ecocardiografia sob Estresse/métodos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Exercício , Implantes Absorvíveis , Prótese Vascular
4.
EuroIntervention ; 13(17): 1995-2002, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29360062

RESUMO

AIMS: The aim of this study was to describe the incidence, mechanisms, management and outcomes of intracardiac shunts (ICS) following TAVI. METHODS AND RESULTS: This was a multicentre registry across 10 centres aimed at gathering all cases of ICS (1.1%) including infection-related (IRICS, 0.3%) or aseptic (AICS, 0.8%) shunts. Patients presented porcelain aorta (24% vs. 6.8%, p=0.024) and had been treated with predilation (88% vs. 68.5%, p=0.037) or post-dilation (59.1% vs. 19.3%, p<0.001) more often. Median time from intervention to diagnosis of ICS was 10 days (IQR: 2-108), being longer for IRICS (171 [63-249] vs. 3 [1-12] days, p=0.002). Interventricular septum (55.6%) and anterior mitral leaflet (57.2%) were the most common locations for AICS and IRICS, respectively. Most patients (76%) developed heart failure but 64% were medically managed. Seven patients (38.9%) underwent percutaneous closure of AICS. The in-hospital mortality rate was 44% (IRICS 100%, AICS 27.8%) compared to global TAVI recipients (8.1%, p<0.001). At one-year follow-up, 76% of the patients had died. ICS, logistic EuroSCORE, and moderate-severe residual aortic regurgitation were independent predictors of death. CONCLUSIONS: Post-TAVI ICS are an uncommon complication independently associated with high early mortality. Currently, most therapeutic alternatives yield poor results but percutaneous closure of AICS was feasible and is a promising alternative.


Assuntos
Complicações Intraoperatórias , Valva Mitral/lesões , Complicações Pós-Operatórias , Infecções Relacionadas à Prótese , Substituição da Valva Aórtica Transcateter/efeitos adversos , Septo Interventricular/lesões , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/cirurgia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Mortalidade Hospitalar , Humanos , Incidência , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/terapia , Masculino , Valva Mitral/diagnóstico por imagem , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Prognóstico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/terapia , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Espanha/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Substituição da Valva Aórtica Transcateter/métodos , Septo Interventricular/diagnóstico por imagem , Técnicas de Fechamento de Ferimentos/estatística & dados numéricos
5.
Rev Esp Cardiol (Engl Ed) ; 71(5): 327-334, 2018 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28461150

RESUMO

INTRODUCTION AND OBJECTIVES: Bioresorbable vascular scaffolds (BVS) have the potential to restore vasomotion but the clinical implications are unknown. We sought to evaluate angina and ischemia in the long-term in patients treated with BVS and metallic drug-eluting stents (mDES). METHODS: Multicenter study including patients with 24 ± 6 months of uneventful follow-up, in which stress echocardiography was performed and functional status was assessed by the Seattle Angina Questionnaire (SAQ). The primary endpoint was a positive result in stress echocardiography. RESULTS: The study included 102 patients treated with BVS and 106 with mDES. There were no differences in the patients' baseline characteristics. Recurrent angina was found in 18 patients (17.6%) in the BVS group vs 25 (23.5%) in the mDES group (P = .37), but SAQ results were significantly better in the BVS group (angina frequency 96.0 ± 8.0 vs 89.2 ± 29.7; P = .02). Stress echocardiography was positive in 11/92 (11.9%) of BVS patients vs 9/96 (9.4%) of mDES patients in the (P = .71) and angina was induced in 2/102 (1.9%) vs 7/106 (6.6%) (P = .18), respectively, but exercise performance was better in the BVS group even in those with positive tests (exercise duration 9.0 ± 2.0minutes vs 7.7 ± 1.8minutes; P = .02). A propensity score matching analysis yielded similar results. CONCLUSIONS: The primary endpoint was similar in both groups. In addition, recurrent angina was similar in patients with BVS and mDES. The better functional status, assessed by means of SAQ and exercise performance, detected in patients receiving BVS should be confirmed in further studies.


Assuntos
Angina Pectoris/terapia , Stents Farmacológicos , Ecocardiografia sob Estresse/métodos , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea/instrumentação , Tecidos Suporte , Implantes Absorvíveis , Idoso , Angina Pectoris/diagnóstico , Estudos de Coortes , Eletrocardiografia/métodos , Everolimo/farmacologia , Feminino , Seguimentos , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Intervenção Coronária Percutânea/métodos , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
6.
JACC Cardiovasc Interv ; 10(19): 1973-1981, 2017 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-28982562

RESUMO

OBJECTIVES: The aim of this study was to determine the prognosis and specific complications of patients with prosthetic mitral valves (PMVs) undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: TAVR is performed relatively often in patients with PMVs, but specific risks are not well described. METHODS: A multicenter analysis was conducted, including patients with severe symptomatic aortic stenosis who underwent TAVR at 10 centers. Patients' clinical characteristics and outcomes were evaluated according to the presence of a PMV. RESULTS: The mean age of the study population (n = 2,414) was 81 ± 8 years, and 48.8% were men. A total of 91 patients (3.77%) had PMVs. They were more commonly women, younger, and had higher surgical risk. PMVs were implanted a median of 14 years before TAVR, and most patients had mechanical prostheses (73.6%). Eighty-six patients (94.5%) were on long-term vitamin K inhibitor therapy, and bridging antithrombotic therapy was administered in 59 (64.8%). TAVR device embolization occurred in 6.7% (vs. 3.3% in the non-PMV group; p = 0.127), in all instances when distance between the PMV and the aortic annulus was <7 mm. Mortality rates did not show a difference, but the rate of bleeding was higher in patients with PMV (24.2% vs. 16.1%; p = 0.041), even in those treated via the transfemoral approach (22.2% vs. 13.9%; p = 0.048). Indeed, bleeding complications, prior atrial fibrillation, chronic obstructive pulmonary disease, surgical risk, and New York Heart Association functional class were independent predictors of mortality. CONCLUSIONS: TAVR presents similar mortality irrespective of the presence of a PMV. However, patients with PMVs had higher bleeding risk that was independently associated with higher mortality. Risk for valve embolization was relatively high, but it occurred only in patients with PMV-to-aortic annulus distances <7 mm.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Valva Mitral/cirurgia , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do Tratamento
7.
BMC Cardiovasc Disord ; 17(1): 212, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28764639

RESUMO

BACKGROUND: Thrombolysis is still used when primary angioplasty is delayed for a long time, but 25%-30% of patients require rescue angioplasty (RA). There are no established recommendations for antithrombotic management in RA. This registry analyzes regimens for antithrombotic management. METHODS: A retrospective, multicenter, observational registry of consecutive patients treated with RA at 8 hospitals. All variables were collected and follow-up took place at 6 months. RESULTS: The study included 417 patients. Antithrombotic therapy in RA was: no additional drugs 22.3%, unfractionated heparin (UFH) 36.6%, abciximab 15.5%, abciximab plus UFH 10.5%, bivalirudin 5.7%, enoxaparin 4.3%, and others 4.7%. Outcomes at 6 months were: mortality 9.1%, infarction 3.3%, definite or probable stent thrombosis 4.3%, revascularization 1.9%, and stroke 0.5%. Mortality was related to cardiogenic shock, age > 75 years, and anterior location. The stent thrombosis rate was highest with bivalirudin (12.5% at 6 months). The incidence of bleeding at admission was high (14.8%), but most cases were not severe (82% BARC ≤2). Variables independently associated with bleeding were: femoral access (OR 3.30; 95% CI 1.3-8.3: p = 0.004) and post-RA abciximab infusion (OR 2.26; 95% CI 1.02-5: p = 0.04). CONCLUSIONS: Antithrombotic treatment regimens in RA vary greatly, predominant strategies consisting of no additional drugs or UFH 70 U/kg. No regimen proved predictive of mortality, but bivalirudin was related to more stent thrombosis. There was a high incidence of bleeding, associated with post-RA abciximab infusion and femoral access.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Enoxaparina/administração & dosagem , Fibrinolíticos/administração & dosagem , Hirudinas/administração & dosagem , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Infarto do Miocárdio/terapia , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea , Terapia Trombolítica , Abciximab , Idoso , Anticorpos Monoclonais/efeitos adversos , Distribuição de Qui-Quadrado , Trombose Coronária/etiologia , Esquema de Medicação , Enoxaparina/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hirudinas/efeitos adversos , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Razão de Chances , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Espanha , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Falha de Tratamento
8.
Am J Cardiol ; 118(4): 578-84, 2016 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-27378142

RESUMO

Vascular complications in transcatheter aortic valve implantation using transfemoral approach are related to higher mortality. Complete percutaneous approach is currently the preferred technique for vascular access. However, some centers still perform surgical cutdown. Our purpose was to determine complications related to vascular access technique in the population of the Spanish TAVI National Registry. From January 2010 to July 2015, 3,046 patients were included in this Registry. Of them, 2,465 underwent transfemoral approach and were treated with either surgical cutdown and closure (cutdown group, n = 632) or percutaneous approach (puncture group, n = 1,833). Valve Academic Research Consortium-2 definitions were used to assess vascular and bleeding complications. Propensity matching resulted in 615 matched pairs. Overall, 30-day vascular complications were significantly higher in the puncture group (109 [18%] vs 42 [6.9%]; relative risk [RR] 2.60; 95% confidence interval [CI] 1.85 to 3.64, p <0.001) due mostly by minor vascular events (89 [15%] vs 25 [4.1%], RR 3.56, 95% CI 2.32 to 5.47, p <0.001). Bleeding rates were lower in the puncture group (18 [3%] vs 40 [6.6%], RR 0.45, 95% CI 0.26 to 0.78, p = 0.003) mainly driven by major bleeding (9 [1.5%] vs 21 [3.4%], RR 0.43, 95% CI 0.20 to 0.93, p = 0.03). At a mean follow-up of 323 days, complication rates remained significantly different between groups (minor vascular complications 90 [15%] vs 31 [5.1%], hazard ratio 2.99, 95% CI 1.99 to 4.50, p <0.001 and major bleeding 10 [1.6%] vs 21 [3.4%], hazard ratio 0.47, 95% CI 0.22 to 1.0, p = 0.04, puncture versus cutdown group, respectively). In conclusion, percutaneous approach yielded higher rates of minor vascular complications but lower rates of major bleeding compared with the surgical cutdown, both at 30-day and at mid-term follow-up in our population.


Assuntos
Estenose da Valva Aórtica/cirurgia , Dissecação/métodos , Artéria Femoral , Infarto do Miocárdio/epidemiologia , Hemorragia Pós-Operatória/epidemiologia , Punções/métodos , Sistema de Registros , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Fluoroscopia , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Modelos de Riscos Proporcionais , Espanha
9.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27267381

RESUMO

This article has been withdrawn, at the request of the Editor, due to the absence of the corresponding permissions for use of all the data/images. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

11.
J Am Coll Cardiol ; 67(3): 251-60, 2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26796388

RESUMO

BACKGROUND: Excessive myocardial collagen cross-linking (CCL) determines myocardial collagen's resistance to degradation by matrix metalloproteinase (MMP)-1 and interstitial accumulation of collagen fibers with impairment of cardiac function. OBJECTIVES: This study sought to investigate whether CCL and a newly identified biomarker of this alteration are associated with hospitalization for heart failure (HHF) or cardiovascular death in patients with HF and arterial hypertension in whom other comorbidities were excluded. METHODS: Endomyocardial biopsies and blood samples from 38 patients (invasive study), and blood samples from 203 patients (noninvasive study) were analyzed. Mean follow-ups were 7.74 ± 0.58 years and 4.72 ± 0.11 years, respectively. Myocardial CCL was calculated as the ratio between insoluble and soluble collagen. The ratio between the C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase-1 (CITP:MMP-1) was determined in blood samples. RESULTS: Invasive study: CCL was increased (p < 0.001) in patients compared with controls. Patients were categorized according to normal or high CCL values. Patients with high CCL exhibited higher risk for subsequent HHF (log-rank test p = 0.022), but not for cardiovascular death. CITP:MMP-1 was inversely associated with CCL (r = -0.460; p = 0.005) in all patients. Receiver operating characteristic curves rendered a CITP:MMP-1 cutoff ≤1.968 (80% sensitivity and 76% specificity) for predicting high CCL. Noninvasive study: Patients were categorized according to CITP:MMP-1 ratio values as normal ratio (>1.968) or low ratio (≤1.968). Patients with a low ratio exhibited higher risk for HHF (log-rank test p = 0.014), which remained significant after adjustment for relevant covariables (adjusted hazard ratio: 2.22; 95% CI: 1.37 to 3.59, p = 0.001). In addition, CITP:MMP-1-based categorization yielded significant integrated discrimination and net reclassification improvements (p = 0.003 and p = 0.009, respectively) for HHF over relevant risk factors. CITP:MMP-1 was not associated with the risk of cardiovascular death. CONCLUSIONS: Excessive myocardial CCL is associated with HHF in hypertensive patients with HF. In this population, the serum CITP:MMP-1 ratio identifies patients with increased CCL and high risk of HHF.


Assuntos
Colágeno Tipo I/metabolismo , Insuficiência Cardíaca , Metaloproteinase 1 da Matriz/sangue , Miocárdio/patologia , Idoso , Biomarcadores/sangue , Biópsia , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/complicações , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Espanha/epidemiologia , Estatística como Assunto , Volume Sistólico
14.
Eur J Heart Fail ; 17(4): 385-92, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25684565

RESUMO

AIMS: The aim of this study was to investigate whether galectin-3 (Gal-3) is associated with myocardial histological and molecular parameters related to fibrosis and with the circulating biomarkers of the extracellular generation of mature fibril-forming collagen types I (C-terminal propeptide of procollagen type I, PICP) and III (N-terminal propeptide of procollagen type III, PIIINP) in two independent studies of hypertensive patients with heart failure (HF). METHODS AND RESULTS: Endomyocardial biopsies and blood samples from 39 HF patients (invasive study), and blood samples from 220 HF patients (non-invasive study) were analysed. Necropsies (n = 7) and blood samples (n = 20) from healthy subjects were used as controls. In the invasive study myocardial mRNA and protein expression of Gal-3 and collagen types I and III, plasma Gal-3 and serum PICP and PIIINP were all significantly increased in patients compared with controls. Neither myocardial nor plasma Gal-3 were correlated with myocardial collagen and circulating biomarkers; whereas PICP was correlated with myocardial total (r = 0.819, P < 0.001) and collagen type I (r = 0.744, P < 0.001) deposition, PIIINP was not. In the non-invasive study both plasma Gal-3 and serum PICP were increased (P < 0.001) in patients compared with controls. No correlation was found between Gal-3 and PICP in HF patients. CONCLUSIONS: These findings show that although an excess of cardiac and systemic Gal-3 is present in patients with HF of hypertensive origin, this molecule is not associated with histological, molecular and biochemical parameters related to myocardial fibrosis in these patients.


Assuntos
Biomarcadores/sangue , Galectina 3/sangue , Insuficiência Cardíaca/sangue , Hipertensão/complicações , Miocárdio/patologia , Adulto , Idoso , Estudos de Coortes , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Ecocardiografia , Feminino , Fibrose , Galectina 3/genética , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , RNA Mensageiro/genética
15.
Catheter Cardiovasc Interv ; 83(1): E112-8, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24038838

RESUMO

OBJECTIVES: The study is made to describe the efficacy and safety of balloon postdilatation (BPD) for the treatment of residual aortic regurgitation (RAoR) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: A single-center observational study is made with 157 consecutive patients accepted to TAVI. The patients were divided into two groups (no BPD-period and BPD-period). Before BPD, RAoR ≥ 2 was seen in 25% of the patients in group 1 and in 29% of the patients in group 2 (P ≥ 0.593). BPD was carried out in 95% (n = 21) of the patients in group 2 with RAoR ≥ 2. Regurgitation improved one grade in 68% of the cases (n = 15), 2 grades in 14% (n = 3), and remained without change in 18% (n = 4). RAoR < 2 was achieved in 91% (n = 73) of the patients in group 2 versus 75% (n = 58) in group 1 (RR = 0.35, 95% CI 0.16-0.80, P = 0.013). We recorded no aortic ring ruptures, damage to the device or displacements. Slight central regurgitation not present before BPD was registered in one case. CONCLUSIONS: BPD offers a very good safety profile and reduces RAoR in a large percentage of cases. BPD should be considered for the treatment of moderate to severe RAoR following TAVI.


Assuntos
Insuficiência da Valva Aórtica/terapia , Estenose da Valva Aórtica/terapia , Valvuloplastia com Balão , Cateterismo Cardíaco/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/etiologia , Estenose da Valva Aórtica/diagnóstico , Valvuloplastia com Balão/efeitos adversos , Cateterismo Cardíaco/instrumentação , Feminino , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Desenho de Prótese , Índice de Gravidade de Doença , Espanha , Resultado do Tratamento
16.
Hypertension ; 63(3): 483-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24366078

RESUMO

Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied. Myocardial cardiotrophin-1 protein and mRNA and the fraction of myocardial volume occupied by collagen were increased in patients compared with controls (P<0.001). Cardiotrophin-1 overexpression in patients was localized in cardiomyocytes. Cardiotrophin-1 protein was correlated with collagen type I and III mRNAs (r=0.653, P<0.001; r=0.541, P<0.01) and proteins (r=0.588, P<0.001; r=0.556, P<0.005) in all subjects and with left ventricular end-diastolic wall stress (r=0.450; P<0.05) in patients. Plasma cardiotrophin-1 and N-terminal pro-brain natriuretic peptide and serum biomarkers of myocardial fibrosis (carboxy-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III) were increased (P<0.001) in patients compared with controls. Plasma cardiotrophin-1 was correlated with N-terminal pro-brain natriuretic peptide (r=0.386; P<0.005), carboxy-terminal propeptide of procollagen type I (r=0.550; P<0.001), and amino-terminal propeptide of procollagen type III (r=0.267; P<0.05) in all subjects. In vitro, cardiotrophin-1 stimulated the differentiation of human cardiac fibroblast to myofibroblasts (P<0.05) and the expression of procollagen type I (P<0.05) and III (P<0.01) mRNAs. These findings show that an excess of cardiotrophin-1 is associated with increased collagen in the myocardium of hypertensive patients with heart failure. It is proposed that exaggerated cardiomyocyte production of cardiotrophin-1 in response to increased left ventricular end-diastolic stress may contribute to fibrosis through stimulation of fibroblasts in heart failure of hypertensive origin.


Assuntos
Cardiomiopatias/metabolismo , Citocinas/genética , Regulação da Expressão Gênica , Insuficiência Cardíaca/metabolismo , Hipertensão/metabolismo , Miocárdio/metabolismo , RNA Mensageiro/genética , Cardiomiopatias/etiologia , Cardiomiopatias/genética , Citocinas/biossíntese , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Humanos , Hipertensão/complicações , Hipertensão/genética , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Reação em Cadeia da Polimerase em Tempo Real
17.
J Invasive Cardiol ; 25(8): 391-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23913603

RESUMO

AIMS: Although drug-eluting stents have dramatically reduced angiographic restenosis and clinical need for repeat revascularization procedures, some adverse effects, such as late stent thrombosis, have been described. We evaluated clinical performance of paclitaxel-eluting stents coated with a new bioactive polymer system (P-5) based on a copolymer of an acrylic derivative of triflusal in patients with coronary artery disease. METHODS AND RESULTS: This was a multicenter, observational, prospective study to assess the incidence of target lesion revascularization (TLR) at 6 months and clinical major adverse cardiac events (MACEs) at 1 and 6 months and 1 and 2 years post-stent implantation in 537 patients. After stent implantation, only 1 case of thrombus and acute occlusion was reported in 1 lesion (0.14%). The incidence of new TLR was 0.89% at 6 months, 1.08% at 1 year, and 1.49% at 2 years, with a cumulative incidence of 3.54%. MACEs included cardiac death (0.93%), myocardial infarction (0.37%), and cardiac surgery (0.19%). No cases of late or very late stent thrombosis were recorded. CONCLUSION: Under routine clinical practice, the implantation of paclitaxel-eluting stents coated with P-5 is associated with favorable clinical outcomes in both the short and long term (2 years) in patients with coronary artery disease.


Assuntos
Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Paclitaxel/uso terapêutico , Intervenção Coronária Percutânea/métodos , Polímeros , Salicilatos , Idoso , Reestenose Coronária/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Trombose/epidemiologia , Resultado do Tratamento
18.
Cardiovasc Res ; 99(1): 111-20, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23619422

RESUMO

AIMS: We investigated whether the pro-fibrotic matricellular protein osteopontin (OPN) is associated with the enzymes involved in the extracellular synthesis of fibril-forming collagen type I (i.e. procollagen C-proteinase, PCP) and its cross-linking to form insoluble fibrils (i.e. lysyl oxidase, LOX) in heart failure (HF) of hypertensive origin. METHODS AND RESULTS: OPN, PCP, and LOX were assessed by histochemical and molecular methods in the myocardium of 21 patients with hypertensive heart disease (HHD) and HF. Whereas the myocardial expression of OPN was very scarce in control hearts (n = 10), it was highly expressed in HF patients (P < 0.0001). OPN was directly correlated with LOX (r = 0.460, P = 0.041), insoluble collagen (r = 0.534, P = 0.015), pulmonary capillary wedge pressure (r = 0.558; P = 0.009), and left-ventricular (LV) chamber stiffness (r = 0.458, P = 0.037), and inversely correlated with LV ejection fraction (r = -0.513, P = 0.017) in all patients. OPN did not correlate with PCP and other parameters assessing collagen synthesis by fibroblasts or degradation by matrix metalloproteinases. In vitro studies showed that OPN significantly (P < 0.05) increases the expression and activity of LOX in human cardiac and dermal fibroblasts. CONCLUSION: An excess of OPN is associated with increased LOX and insoluble collagen, as well as with LV stiffness and systolic dysfunction in patients with HHD and HF. In addition, OPN up-regulates LOX in human fibroblasts. It is suggested that the OPN-LOX axis might facilitate the formation of insoluble collagen (i.e. stiff and resistant to degradation) and the subsequent alteration in LV mechanical properties and function in patients with HHD and HF.


Assuntos
Insuficiência Cardíaca/enzimologia , Miocárdio/enzimologia , Osteopontina/metabolismo , Proteína-Lisina 6-Oxidase/metabolismo , Idoso , Proteína Morfogenética Óssea 1/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Colágeno/metabolismo , Elasticidade , Feminino , Fibroblastos/enzimologia , Fibroblastos/patologia , Fibrose , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Pressão Propulsora Pulmonar , Volume Sistólico , Função Ventricular Esquerda
19.
Hypertension ; 60(3): 677-83, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22824984

RESUMO

We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. The expression of lysyl oxidase (LOX), which regulates CCL, was assessed by Western blot. Compared with patients with normal pulmonary capillary wedge pressure (≤12 mm Hg; n=16), patients with elevated pulmonary capillary wedge pressure (>12 mm Hg; n=22) exhibited increases of left ventricular chamber stiffness constant, fraction of myocardial volume occupied by total collagen tissue, fraction of myocardial volume occupied by collagen type I fibers, CCL, insoluble stiff collagen, and LOX. Pulmonary capillary wedge pressure was correlated with left ventricular chamber stiffness constant (r=0.639; P<0.001), insoluble stiff collagen (r=0.474; P<0.005), CCL (r=0.625; P<0.001), and LOX (r=0.410; P<0.05) in all of the patients but not with fraction of myocardial volume occupied by total collagen tissue or fraction of myocardial volume occupied by collagen type I fibers. In addition, CCL was correlated with insoluble stiff collagen (r=0.612; P<0.005), LOX (r=0.538; P<0.01), left ventricular chamber stiffness constant (r=0.535; P<0.005), peak filling rate (r=-0.343; P<0.05), ejection fraction (r=-0.430; P<0.01), and amino-terminal propeptide of brain natriuretic peptide (r=0.421; P<0.05) in all of the patients. These associations were independent of confounding factors. These findings indicate that, in hypertensive patients with stage C heart failure, it is only the quality of collagen (ie, degree of cross-linking) that associates with elevated filling pressures. It is suggested that LOX-mediated excessive CCL facilitates the increase in left ventricular stiffness with the resulting elevation of filling pressures in these patients.


Assuntos
Colágeno/química , Colágeno/metabolismo , Insuficiência Cardíaca/fisiopatologia , Hipertensão/fisiopatologia , Proteína-Lisina 6-Oxidase/fisiologia , Índice de Gravidade de Doença , Disfunção Ventricular Esquerda/fisiopatologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Colágeno Tipo I/química , Colágeno Tipo I/metabolismo , Comorbidade , Ecocardiografia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/metabolismo , Humanos , Hipertensão/epidemiologia , Hipertensão/metabolismo , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Pressão Propulsora Pulmonar/fisiologia , Volume Sistólico/fisiologia
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