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/complicaçõesRESUMO
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 TratamentoRESUMO
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 TratamentoRESUMO
OBJECTIVES: The crossover balloon occlusion technique (CBOT) facilitates primary access hemostasis in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR). The CBOT is usually performed through the contralateral femoral artery. The aim of this study was to evaluate, in patients undergoing TAVR, the safety and feasibility of transradial CBOT using the new Oceanus balloon dilatation catheter (iVascular). METHODS: This multicenter study included 104 patients (mean age, 81 ± 7 years; 43% women) undergoing transfemoral TAVR. A modified CBOT through the radial artery was performed in all patients with the Oceanus balloon catheter. Data regarding transradial CBOT, balloon performance, vascular complications, and 30-day clinical events were recorded. RESULTS: Up to 21% of patients had a height >170 cm and 17% presented with severe aortic/iliofemoral tortuosity. The transradial CBOT (left radial 74%, right radial 26%) was performed using either the 140 cm Oceanus (37.5%) or the 200 cm Oceanus (62.5%) balloon catheter. The balloon reached the femoral artery in all patients, and balloon inflation achieved an appropriate vessel closure in 98%. There were no complications related to the balloon catheter, and only 1 patient (1.0%) suffered a minor vascular complication related to the secondary radial access. The 30-day rates of primary access major vascular complications and death were 3.8% and 1.9%, respectively. CONCLUSION: In patients undergoing transfemoral TAVR, transradial CBOT with the Oceanus balloon dilatation catheter was feasible and safe. A balloon length up to 200 cm allowed the use of this technique (from right or left radial access) in all patients regardless of patient height or the presence of a challenging vascular anatomy.
Assuntos
Estenose da Valva Aórtica , Oclusão com Balão , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Feminino , Artéria Femoral/cirurgia , Hemostasia , Humanos , Masculino , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
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 , Avaliação de Processos e Resultados em Cuidados de Saúde , 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 numéricosRESUMO
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 , Alicerces Teciduais , 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 TratamentoRESUMO
OBJECTIVE: To investigate whether the glycoprotein (gp130)-mediated survival pathway, which protects cardiomyocytes from apoptosis, is depressed in left ventricular hypertrophy hypertensive patients with chronic heart failure. METHODS: Transvenous endomyocardial biopsies were obtained in 52 hypertensive patients with left ventricular hypertrophy: 28 without heart failure and 24 with heart failure. gp130 and gp130-dependent antiapoptotic pathways p42/44 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) as well as gp130 agonist cardiotrophin-1 were analyzed by reverse transcriptase-polymerase chain reaction and western blot. Apoptosis was assessed by DNA end-labeling (TUNEL), caspase-3 immunostaining and caspase substrate poly(ADP-ribose) polymerase cleavage. RESULTS: gp130 protein expression (P < 0.05) and p42/44 MAPK and PI3K/Akt activation (P < 0.01) were decreased in heart-failure hypertensive patients compared with nonheart-failure hypertensive individuals. No changes in gp130 mRNA expression were found between the two groups. Cardiotrophin-1 was increased (P < 0.05) at both the mRNA and protein levels in heart-failure hypertensive individuals compared with nonheart-failure hypertensive individuals. Cardiomyocyte apoptosis was increased (P < 0.01) in heart-failure hypertensive individuals compared with nonheart-failure hypertensive individuals. Inverse correlations (P < 0.01) occurred between cardiomyocyte apoptosis and p42/44 MAPK and PI3K/Akt activation in all hypertensive patients. Cardiotrophin-1 correlated inversely (r = -0.554, P < 0.05) with gp130 in all hypertensive individuals. In cultured HL-1 cardiomyocytes, cardiotrophin-1 decreased (P < 0.05) the gp130:phosphorylated gp130 (at Ser782) ratio and increased (P < 0.05) gp130ubiquitination. CONCLUSIONS: An association exists between depression of the gp130 cytoprotective pathway and stimulation of cardiomyocyte apoptosis in hypertensive patients that develop heart failure. Whether the excess of cardiotrophin-1 induces ligand-induced receptor down-regulation in these patients requires further study.
Assuntos
Receptor gp130 de Citocina/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Hipertensão/metabolismo , Hipertensão/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Estudos de Casos e Controles , Receptor gp130 de Citocina/genética , Citocinas/genética , Citocinas/metabolismo , Regulação para Baixo , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/genética , Humanos , Hipertensão/complicações , Hipertensão/genética , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-Idade , Transdução de SinaisRESUMO
OBJECTIVE: To investigate whether cardiac expression of the nuclear peroxisome proliferator-activated receptor alpha (PPARalpha) is altered in patients with hypertensive heart disease (HHD). METHODS: We studied endomyocardial septal biopsies from 24 patients with essential hypertension divided into three groups: 6 without left ventricular hypertrophy (LVH) (HT group), 10 with LVH (LVH group), and 8 with LVH and heart failure (HF) (HF group). The expression of two PPARalpha isoforms (the native active and the truncated inhibitory) was analyzed by Western blot and reverse transcription polymerase chain reaction (RT-PCR), and two PPARalpha target genes were evaluated by RT-PCR. Histomorphological features were evaluated in a second myocardial sample from LVH and HF groups. RESULTS: Whereas the expression of native PPARalpha protein was lower (p<0.05) in LVH and HF groups than in the HT group, truncated PPARalpha protein was overexpressed (p<0.001) in the HF group as compared with LVH and HT groups. The mRNA expression of native and truncated PPARalpha was similar in the three groups of hypertensives. In addition, a progressive decrease (p for trend<0.05) in the two PPARalpha target genes mRNA expression was observed among HT, LVH and HF groups. The amount of truncated PPARalpha protein correlates directly with cardiomyocytes apoptosis and inversely with cardiomyocytes density in patients with HHD. In addition, the expression of truncated PPARalpha protein was directly correlated with left ventricular volumes, and inversely with ejection fraction in all hypertensives. CONCLUSIONS: These findings suggest that post-transcriptional regulation of PPARalpha isoforms is altered in patients with HHD, namely in those developing HF. An excess of the truncated inhibitory isoform may be involved in hypertensive left ventricular failure and remodeling.
Assuntos
Endocárdio/enzimologia , Hipertensão/enzimologia , Hipertrofia Ventricular Esquerda/enzimologia , PPAR alfa/genética , Isoformas de Proteínas/genética , RNA Mensageiro/análise , 3-Hidroxiacil-CoA Desidrogenases/genética , Idoso , Apoptose , Western Blotting , Carnitina O-Palmitoiltransferase/genética , Ecocardiografia , Endocárdio/patologia , Feminino , Fibrose , Expressão Gênica , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/patologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-Idade , PPAR alfa/análise , PPAR alfa/metabolismo , Isoformas de Proteínas/análise , Isoformas de Proteínas/metabolismo , Receptor X Retinoide gama/análise , Receptor X Retinoide gama/genética , Receptor X Retinoide gama/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não ParamétricasRESUMO
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 TratamentoRESUMO
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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 SistólicoRESUMO
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 , EspanhaRESUMO
BACKGROUND: This study was designed to investigate whether myocardial collagen content is related to myocardial stiffness in patients with essential hypertension. METHODS AND RESULTS: The study was performed in 34 patients with hypertensive heart disease. Nineteen of these patients were also evaluated after 12 months of treatment with losartan. Transvenous endomyocardial biopsies of the interventricular septum were performed to quantify collagen volume fraction (CVF). Left ventricular (LV) chamber stiffness (K(LV)) was determined from the deceleration time of the early mitral filling wave as measured by Doppler echocardiography. Histological analysis at baseline revealed the presence of 2 subgroups of patients: 8 with severe fibrosis and 26 with nonsevere fibrosis. Values of CVF and K(LV) were significantly higher in the 2 subgroups of hypertensives than in normotensives. In addition, compared with patients with nonsevere fibrosis, patients with severe fibrosis exhibited significantly increased values of CVF and K(LV). After treatment, CVF and K(LV) decreased significantly in patients with severe fibrosis (n=7). None of these parameters changed significantly after treatment in patients with nonsevere fibrosis (n=12). CVF was directly correlated with K(LV) (r=0.415, P<0.02) in all hypertensives. CONCLUSIONS: These findings show a strong association between myocardial collagen content and LV chamber stiffness in patients with essential hypertension. Our results also suggest that the ability of losartan to induce regression of severe myocardial fibrosis is associated with diminution of myocardial stiffness in hypertensive patients.
Assuntos
Anti-Hipertensivos/uso terapêutico , Fibrose Endomiocárdica/tratamento farmacológico , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Pressão Sanguínea/efeitos dos fármacos , Análise por Conglomerados , Colágeno/análise , Colágeno/metabolismo , Ecocardiografia Doppler , Fibrose Endomiocárdica/complicações , Fibrose Endomiocárdica/fisiopatologia , Feminino , Testes de Função Cardíaca , Humanos , Hipertensão/classificação , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Valores de Referência , Indução de Remissão , Resultado do Tratamento , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: We investigated whether increased collagen type I synthesis and deposition contribute to enhancement of myocardial fibrosis and deterioration of cardiac function in patients with hypertensive heart disease (HHD). METHODS AND RESULTS: We studied 65 hypertensives with left ventricular hypertrophy subdivided into 2 groups: 34 patients without heart failure (HF) and 31 patients with HF. Transvenous endomyocardial biopsies of the interventricular septum were performed to quantify the amount of fibrotic tissue and the extent of collagen type I deposition. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, was measured by radioimmunoassay in serum samples from the coronary sinus and the antecubital vein. Compared with normotensives, the amount of collagen tissue, the extent of collagen type I deposition, and coronary and peripheral PIP were increased (P<0.01) in the 2 groups of hypertensives. These parameters were also increased (P<0.01) in HF hypertensives compared with non-HF hypertensives. Coronary PIP was higher (P<0.01) than peripheral PIP in hypertensives but not in normotensives. The amount of collagen tissue was inversely correlated with the ejection fraction and directly correlated with both coronary and peripheral PIP in all hypertensives. CONCLUSIONS: These findings suggest that an excess of cardiac collagen type I synthesis and deposition may be involved in the enhancement of myocardial fibrosis that accompanies the development of HF in HHD. In addition, our data show that the heart secretes PIP via the coronary sinus into the peripheral circulation in patients with HHD. Thus, PIP determined in peripheral blood can be a useful marker of myocardial fibrosis in these patients.
Assuntos
Colágeno Tipo I/biossíntese , Fibrose Endomiocárdica/metabolismo , Insuficiência Cardíaca/metabolismo , Hipertensão/complicações , Biomarcadores , Biópsia , Fibrose Endomiocárdica/diagnóstico por imagem , Fibrose Endomiocárdica/etiologia , Fibrose Endomiocárdica/patologia , Feminino , Fibrose , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Humanos , Hipertensão/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/sangue , Pró-Colágeno/metabolismo , UltrassonografiaRESUMO
OBJECTIVES: This individually randomized, open-label, parallel-group pilot study was designed to test the hypothesis that the ability of loop diuretics to interfere with cardiac fibrosis in chronic heart failure (CHF) may be different between compounds. BACKGROUND: The apparent mortality and cardiac benefits seen in studies comparing torasemide with furosemide in CHF suggest that torasemide may have beneficial effects beyond diuresis (e.g., on the process of cardiac fibrosis). METHODS: Patients with New York Heart Association functional class II to IV CHF received diuretic therapy with either 10 to 20 mg/day oral torasemide (n = 19) or 20 to 40 mg/day oral furosemide (n = 17), in addition to their existing standard CHF therapy for eight months. At baseline and after eight months, right septal endomyocardial biopsies were obtained to quantify collagen volume fraction (CVF) with an automated image analysis system. Serum carboxy-terminal peptide of procollagen type I (PIP) and serum carboxy-terminal telopeptide of collagen type I (CITP), indexes of collagen type I synthesis and degradation, respectively, were measured by specific radioimmunoassays. RESULTS: In torasemide-treated patients, CVF decreased from 7.96 +/- 0.54% to 4.48 +/- 0.26% (p < 0.01), and PIP decreased from 143 +/- 7 to 111 +/- 3 microg/l (p < 0.01). Neither CVF nor PIP changed significantly in furosemide-treated patients. In all patients, CVF was directly correlated with PIP (r = 0.88, p < 0.001) before and after treatment. No changes in CITP were observed with treatment in either group. CONCLUSIONS: These findings suggest that loop diuretics possess different abilities to reverse myocardial fibrosis and reduce collagen type I synthesis in patients with CHF.
Assuntos
Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Sulfonamidas/uso terapêutico , Colágeno Tipo I/efeitos dos fármacos , Diuréticos/administração & dosagem , Ecocardiografia , Fibrose Endomiocárdica/patologia , Feminino , Furosemida/administração & dosagem , Furosemida/uso terapêutico , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sulfonamidas/administração & dosagem , Torasemida , Resultado do TratamentoRESUMO
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/genéticaRESUMO
INTRODUCTION: Myocardial bridging with systolic compression (milking) of the left anterior descending coronary artery may be associated with myocardial ischemia. Little information is available about the long-term prognosis of patients with this coronary anomaly. MATERIAL AND METHODS: A review was made of coronary angiographies of patients diagnosed as ischemic heart disease made between 1994 and 1999 in two centers. The long-term follow-up of patients with myocardial bridging and systolic compression of the left anterior descending coronary artery was analyzed. Data were collected by reviewing medical records and completed by telephone interview. RESULTS: Prevalence: 0.72%. Milking was observed in 60 patients, but 25 of them were excluded due to associated hypertrophic cardiomyopathy, severe valvular disease, or coronary artery disease. The clinical follow-up was available for all patients (median: 43 months, range: 12-80 months). Mean age 55.7 years (SD = 11.9). Men 74%. CLINICAL PRESENTATION: angina 26 patients, atypical chest pain with positive non-invasive test 8, acute myocardial infarction 1. During follow-up, 1 patient died of sudden cardiac death. Seven patients continued to present stable angina CCS class I-II, coronary angiography was repeated in 5 patients, and one required percutaneous revascularization for symptoms. In 63% of cases, antianginal drugs were still needed at the end of follow-up period (beta-blockers or calcium antagonists). CONCLUSIONS: Patients with myocardial bridging and systolic compression of the left anterior descending artery have a good long-term prognosis, although more than half of them continue regular treatment with antianginal drugs. In a small percentage of cases percutaneous intervention must be performed and ischemic heart disease may appear in more aggressive forms (acute myocardial infarction or sudden death).
Assuntos
Anomalias dos Vasos Coronários/complicações , Cardiopatias Congênitas/complicações , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sístole , Fatores de TempoRESUMO
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 RealAssuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Cardiopatia Reumática/cirurgia , Substituição da Valva Aórtica Transcateter/instrumentação , Idoso , Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Falha de Prótese , Reoperação , Resultado do TratamentoRESUMO
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.