RESUMO
To understand the role of bone marrow mononuclear cells in the treatment of acute myocardial infarction, this overview offers a retrospective examination of strengths and limitations of 3 contemporaneous trials with attention to critical design features and provides an analysis of the combined data set and implications for future directions in cell therapy for acute myocardial infarction.
Assuntos
Transplante de Medula Óssea/métodos , Leucócitos Mononucleares/transplante , Infarto do Miocárdio/patologia , Infarto do Miocárdio/cirurgia , Transplante de Medula Óssea/tendências , Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Baseada em Transplante de Células e Tecidos/tendências , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/tendências , Bases de Dados Factuais/tendências , Humanos , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/fisiologia , Estudos Retrospectivos , Volume Sistólico/fisiologia , Resultado do TratamentoRESUMO
RATIONALE: Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal. OBJECTIVE: We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate. METHODS AND RESULTS: Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1(+)CD45(+) cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67(+)) Lin(-)c-Kit(+)CD135(-)CD115(+)CX3CR1(+)Ly6C(+)CD11b(-) subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1(+)CD45(+) adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE(-/-) and LDL-R(-/-) mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries. CONCLUSIONS: The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage progenitors in other tissues.
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Túnica Adventícia/citologia , Aterosclerose/patologia , Linhagem Celular/imunologia , Macrófagos/citologia , Células-Tronco/citologia , Transferência Adotiva , Túnica Adventícia/imunologia , Animais , Antígenos Ly/metabolismo , Aorta/citologia , Aorta/imunologia , Apolipoproteínas E/genética , Aterosclerose/imunologia , Feminino , Hiperlipidemias/imunologia , Hiperlipidemias/patologia , Imunofenotipagem , Antígenos Comuns de Leucócito/metabolismo , Macrófagos/metabolismo , Macrófagos/transplante , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de LDL/genética , Baço/citologia , Células-Tronco/imunologiaRESUMO
BACKGROUND: The impact of changing demographics on causes of long-term death after percutaneous coronary intervention (PCI) remains incompletely defined. METHODS AND RESULTS: We evaluated trends in cause-specific long-term mortality after index PCI performed at a single center from 1991 to 2008. Deaths were ascertained by scheduled prospective surveillance. Cause was determined via telephone interviews, medical records, autopsy reports, and death certificates. Competing-risks analysis of cause-specific mortality was performed using 3 time periods of PCI (1991-1996, 1997-2002, and 2003-2008). Final follow-up was December 31, 2012. A total of 19 077 patients survived index PCI hospitalization, of whom 6988 subsequently died (37%, 4.48 per 100 person-years). Cause was determined in 6857 (98.1%). Across 3 time periods, there was a 33% decline in cardiac deaths at 5 years after PCI (incidence: 9.8%, 7.4%, and 6.6%) but a 57% increase in noncardiac deaths (7.1%, 8.5%, and 11.2%). Only 36.8% of deaths in the recent era were cardiac. Similar trends were observed regardless of age, extent of coronary disease, or PCI indication. After adjustment for baseline variables, there was a 50% temporal decline in cardiac mortality but no change in noncardiac mortality. The decline in cardiac mortality was driven by fewer deaths from myocardial infarction/sudden death (P<0.001) but not heart failure (P=0.85). The increase in noncardiac mortality was primarily attributable to cancer and chronic diseases (P<0.001). CONCLUSIONS: This study found a marked temporal switch from predominantly cardiac to predominantly noncardiac causes of death after PCI over 2 decades. The decline in cardiac mortality was independent of changes in baseline clinical characteristics. These findings have implications for patient care and clinical trial design.
Assuntos
Angioplastia Coronária com Balão/mortalidade , Causas de Morte/tendências , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/terapia , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Distribuição por Idade , Idoso , Angina Estável/mortalidade , Angina Estável/terapia , Aneurisma Aórtico/mortalidade , Morte Súbita Cardíaca/epidemiologia , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Neoplasias/mortalidade , Acidente Vascular Cerebral/mortalidadeRESUMO
Well into the second decade since its conception, cell transplantation continues to undergo intensive evaluation for the treatment of myocardial infarction. At a mechanistic level, its objectives remain to replace lost cardiac cell mass with new functioning cardiomyocytes and vascular cells, thereby minimizing infarct size and scar formation, and improving clinical outcomes by preventing adverse left ventricular remodeling and recurrent ischemic events. Many different cell types, including pluripotent stem cells and various adult-derived progenitor cells, have been shown to have therapeutic potential in preclinical studies, while early phase human trial experience has provided divergent outcomes and fundamental lessons, emphasizing that there remain key issues to address and challenges to overcome before cell therapy can be applied to wider clinical practice. The purpose of this review is to provide a balanced update on recent seminal developments in this exciting field and look to the next important steps to ensure its forward progression.
Assuntos
Síndrome Coronariana Aguda/terapia , Transplante de Medula Óssea , Células Progenitoras Endoteliais/transplante , Células-Tronco Pluripotentes Induzidas/transplante , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/terapia , Regeneração , Humanos , Células-Tronco Pluripotentes/transplante , Resultado do TratamentoRESUMO
OBJECTIVE: To compare transcatheter aortic valve replacement (TAVR) outcomes during the period when public health emergency (PHE) flexibilities were in place with outcomes during a period before they were introduced. METHODS: Patients who received a native TAVR with either a SAPIEN 3 or SAPIEN 3 Ultra valve from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry between June 22, 2019, and August 30, 2022, were placed into one of two cohorts: (1) pre-PHE cohort, and (2) peri-PHE cohort. Outcomes included in-hospital events and events occurring 30 days post-TAVR. Patients were matched 1:1 on their propensity of receiving a TAVR during the pre- or peri-PHE periods. After matching, relative risk was calculated for each in-hospital outcome and HRs for outcomes 30 days post-TAVR. RESULTS: In this study, 173,434 patients met inclusion criteria; after 1:1 matching, there were 37,063 patients in each cohort. There was no difference between cohorts in in-hospital outcomes, including all-cause mortality, stroke, composite of mortality and stroke, pacemaker, or major vascular complications. Similarly, there was no statistically significant difference in 30-day outcomes between the cohorts. CONCLUSION: In this large-scale retrospective study of 74,126 patients undergoing TAVR procedures from 2019 to 2022, no significant differences existed in TAVR outcomes during the PHE period.
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BACKGROUND: Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO. OBJECTIVES: This study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data. METHODS: The international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores. RESULTS: Analysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT. CONCLUSIONS: LAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT.
Assuntos
Anticoagulantes , Apêndice Atrial , Fibrilação Atrial , Cateterismo Cardíaco , Contraindicações de Medicamentos , AVC Isquêmico , Sistema de Registros , Humanos , Apêndice Atrial/fisiopatologia , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/terapia , Feminino , Masculino , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Idoso , Fatores de Risco , Medição de Risco , Idoso de 80 Anos ou mais , Fatores de Tempo , Administração Oral , AVC Isquêmico/prevenção & controle , AVC Isquêmico/mortalidade , AVC Isquêmico/diagnóstico , AVC Isquêmico/etiologia , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/mortalidade , Falha de Tratamento , Hemorragia/induzido quimicamente , Recidiva , Pessoa de Meia-Idade , Estudos Retrospectivos , Europa (Continente)RESUMO
BACKGROUND: Hematopoiesis originates from the dorsal aorta during embryogenesis. Although adult blood vessels harbor progenitor populations for endothelial and smooth muscle cells, it is not known if they contain hematopoietic progenitor or stem cells. Here, we hypothesized that the arterial wall is a source of hematopoietic progenitor and stem cells in postnatal life. METHODS AND RESULTS: Single-cell aortic disaggregates were prepared from adult chow-fed C57BL/6 and apolipoprotein E-null (ApoE(-/-)) mice. In short- and long-term methylcellulose-based culture, aortic cells generated a broad spectrum of multipotent and lineage-specific hematopoietic colony-forming units, with a preponderance of macrophage colony-forming units. This clonogenicity was higher in lesion-free ApoE(-/-) mice and localized primarily to stem cell antigen-1-positive cells in the adventitia. Expression of stem cell antigen-1 in the aorta colocalized with canonical hematopoietic stem cell markers, as well as CD45 and mature leukocyte antigens. Adoptive transfer of labeled aortic cells from green fluorescent protein transgenic donors to irradiated C57BL/6 recipients confirmed the content of rare hematopoietic stem cells (1 per 4 000 000 cells) capable of self-renewal and durable, low-level reconstitution of leukocytes. Moreover, the predominance of long-term macrophage precursors was evident by late recovery of green fluorescent protein-positive colonies from recipient bone marrow and spleen that were exclusively macrophage colony-forming units. Although trafficking from bone marrow was shown to replenish some of the hematopoietic potential of the aorta after irradiation, the majority of macrophage precursors appeared to arise locally, suggesting long-term residence in the vessel wall. CONCLUSIONS: The postnatal murine aorta contains rare multipotent hematopoietic progenitor/stem cells and is selectively enriched with stem cell antigen-1-positive monocyte/macrophage precursors. These populations may represent novel, local vascular sources of inflammatory cells.
Assuntos
Aorta/citologia , Aorta/crescimento & desenvolvimento , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Monócitos/citologia , Transferência Adotiva , Animais , Antígenos Ly/metabolismo , Apolipoproteínas E/genética , Biomarcadores/metabolismo , Transplante de Medula Óssea , Linhagem da Célula/imunologia , Endotélio Vascular/citologia , Endotélio Vascular/crescimento & desenvolvimento , Proteínas de Fluorescência Verde/genética , Imunofenotipagem , Macrófagos/citologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/imunologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/crescimento & desenvolvimento , Quimeras de Transplante , Irradiação Corporal TotalRESUMO
OBJECTIVES: The purpose of this study was to evaluate the left main (LM) coronary artery anatomy using three-dimensional (3D) quantitative coronary angiography (QCA) software as compared to intravascular ultrasound (IVUS). BACKGROUND: Percutaneous intervention of the LM coronary artery is becoming more common in selected patients with LM coronary artery disease (CAD). Quantification of LM CAD by conventional angiography can be difficult. IVUS is considered the gold standard to evaluate LM anatomy and severity of CAD but entails additional steps, catheters, and expertise. Our objective was to compare a novel quantitative angiographic analysis system with IVUS for LM anatomy. METHODS: Fifty five patients underwent both coronary angiography and IVUS of the LM. LM measurements were analyzed with 3D QCA (IC-PRO, Paieon, Israel) software using IVUS as the reference standard. The measurements included proximal, middle, distal minimal luminal diameter (MLD) and area. Additionally, lesion MLD, minimal luminal area were recorded by both systems. Bland-Altman plots were used to investigate agreement between the two imaging systems. RESULTS: Of the 55 patients in our cohort, average age was 66 ± 11 years (25% female). By Bland-Altman analysis there was very good agreement between 3D QCA and IVUS for measures of MLD and minimal lumen area (MLA). However, there was poor concordance in the estimation of plaque burden between the two methods. CONCLUSIONS: Our data demonstrate that 3D QCA software has fair agreement when compared with IVUS for imaging of LM MLD and MLA. These results suggest that 3D QCA could potentially be helpful to guide intervention of the LM.
Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Imageamento Tridimensional , Interpretação de Imagem Radiográfica Assistida por Computador , Ultrassonografia de Intervenção , Idoso , Doença da Artéria Coronariana/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , SoftwareRESUMO
OBJECTIVE: To assess the anatomic characteristics of the left main coronary artery (LM), and the relation between anatomic and clinical factors and the LM bifurcation angle (BA) using a novel, three dimensional quantitative coronary angiography (3D QCA) software. BACKGROUND: Percutaneous intervention of the LM is a therapeutic option in selected patients with coronary artery disease (CAD). The anatomic features of the LM and its BA are determinants of procedural success and clinical outcome. However, those features and the factors that may affect the LM BA have not been fully described. METHODS: The LM anatomy was evaluated from angiograms of 203 patients (age = 66 ± 11 years, 31% female) with and without LM CAD using 3D QCA analysis (IC-PRO, Paieon, Israel). LM size as well as the proximal BA (between LM and LCX) and the distal BA (between left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX)) were measured in end-diastole. Angiographic and clinical findings were also recorded. RESULTS: 133/203 patients (65%) had no LM CAD. 3D QCA analysis demonstrated significant variability in the anatomy of the normal LM, including the LM branch vessels (LAD, LCX) diameter, and the LM BA. Among the 70 patients with LM CAD, 44 had distal LM disease. Importantly, patients with distal LM CAD had narrower proximal BA and a wider distal BA. Multivariate analysis (adjusted for clinical and anatomic variables) identified female sex (P = 0.02), trifurcation anatomy (P = 0.009), age > 75 years (P = 0.0009), and LM length > 12 mm (P = 0.001) as independent associates of the proximal BA. Independent associates of the distal BA were: trifurcation anatomy (P = 0.001), LM length > 12 mm (P < 0.0001), age > 75 years (P = 0.004), and a history of coronary bypass surgery (P = 0.04). CONCLUSIONS: The current study demonstrates significant variability in the anatomy of the LM. The LM BA differs between patients with and without distal LM CAD, and both anatomic and clinical factors may affect the LM BA. Our findings also emphasize the possible usefulness of 3D QCA in the assessment of the LM.
Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Anomalias dos Vasos Coronários/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Imageamento Tridimensional , Interpretação de Imagem Radiográfica Assistida por Computador , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Retrospectivos , Software , Adulto JovemRESUMO
BACKGROUND AND AIM OF THE STUDY: Patients with aortic stenosis (AS) and chronic obstructive pulmonary disease (COPD) have been considered at high risk for aortic valve replacement (AVR), which results in some patients being denied this life-saving operation. Hence, the study aim was to assess the operative, 30-day, and long-term mortality in individuals with COPD undergoing AVR for AS in the modern surgical era. METHODS: This retrospective cohort of patients had documented COPD (FEV1/FVC < 70%), and underwent isolated AVR for severe AS between 1993 and 2007 at the Mayo Clinic in Rochester, MN. RESULTS: Of the 68 patients who met the study criteria, 27 had mild/moderate COPD (FEV1 > 50%), 35 had severe COPD (FEV1 30-50%), and six had very severe COPD (FEV1 < 30%). The overall operative and 30-day mortality was 4.8%. More severe COPD was associated with a longer stay in the intensive care unit (42 h for mild/moderate versus 115 h for severe/very severe: p = 0.02), but did not influence the operative or 30-day mortalities. Female gender was associated with an increased length of hospital stay. Long-term mortality was significantly higher in patients with a history of cerebrovascular disease (HR 4.3, p < 0.001), NYHA class III or IV heart failure (class III HR 2.79, p = 0.05; class IV HR 3.97, p = 0.03), and increased age (HR 1.06, p = 0.003). The severity of COPD was an independent risk factor for long-term mortality. CONCLUSION: Patients with severe AS and COPD are at an acceptable risk for AVR (30-day mortality < 5%). The severity of COPD is not associated with an increased in-hospital or 30-day mortality, but does influence long-term mortality.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Doença Pulmonar Obstrutiva Crônica , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Risco Ajustado , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , TempoRESUMO
CONTEXT: While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed. OBJECTIVES: To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect. DESIGN, SETTING, AND PATIENTS: A randomized, 2 × 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute. INTERVENTIONS: Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI. MAIN OUTCOME MEASURES: The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size. RESULTS: The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P = .96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (−0.9% [95% CI, −6.6% to 4.9%], P = .76) or day 7 (1.1% [95% CI, −4.7% to 6.9%], P = .70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups. CONCLUSION: Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00684021.
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Transplante de Medula Óssea/métodos , Infarto do Miocárdio/terapia , Disfunção Ventricular Esquerda/terapia , Idoso , Método Duplo-Cego , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/complicaçõesRESUMO
BACKGROUND: Serum uric acid may serve as a marker for the activation of oxidative stress and may therefore be a marker for subsequent cardiovascular events. Our goal was to assess the association of serum uric acid levels and the outcomes of patients who have undergone percutaneous coronary intervention (PCI). METHODS: We performed a retrospective cohort study of patients who underwent PCI between 1/1/2000 and 12/31/2007. Data were retrieved from the Cardiac Lab Interventional Clinical Database as well as the medical records. Outcomes of mortality as well as major adverse cardiac events (MACE) that include death, myocardial infarction (MI), and target vessel revascularization were obtained. There were 10,632 unique patients who had a PCI at the Mayo Clinic in Rochester and allowed use of their records for research. During this time, 1,916 had a uric acid measure within 2 years prior to the day of PCI. RESULTS: Of the 1,916 patients in our cohort, 1,353 had normal uric acid levels and 563 had elevated uric acid. After multivariable analysis, there was a strong trend in association with follow-up mortality in patients with elevated uric acid (HR = 1.25, 95% CI 0.98-1.59, P = 0.07). The association with mortality or MI (HR = 1.15, 95% CI 0.93-1.43, P = 0.20) and the association with MACE (HR = 1.04, CI 0.86- 1.25, P = 0.71) were not significant. CONCLUSIONS: In a large single-center database with complete follow-up, elevated serum uric acid was associated with increased mortality in PCI patients. These data show a trend for uric acid in the pathophysiology of atherosclerotic coronary artery disease and highlight the need for further research.
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Angioplastia Coronária com Balão/efeitos adversos , Doença da Artéria Coronariana/terapia , Hiperuricemia/induzido quimicamente , Infarto do Miocárdio/terapia , Estresse Oxidativo , Ácido Úrico/sangue , Idoso , Estudos de Coortes , Intervalos de Confiança , Doença da Artéria Coronariana/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Hiperuricemia/mortalidade , Inflamação , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Infarto do Miocárdio/mortalidade , Estudos Retrospectivos , Fatores de Risco , Estatística como Assunto , Resultado do Tratamento , Ácido Úrico/metabolismoRESUMO
The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1+CD45+ progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1+CD45+ cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE-/- aortas. Although Sca-1+CD45+ cells from C57BL/6 aorta did not express CD31, they formed CD31+ colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1+CD45+ cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE-/- mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1+CD45+ cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.
Assuntos
Aterosclerose/patologia , Diferenciação Celular , Neovascularização Patológica/patologia , Células-Tronco/fisiologia , Vasa Vasorum/patologia , Túnica Adventícia/citologia , Túnica Adventícia/patologia , Animais , Antígenos Ly/metabolismo , Aorta/citologia , Aorta/patologia , Aterosclerose/etiologia , Dieta Aterogênica , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Feminino , Humanos , Antígenos Comuns de Leucócito/metabolismo , Macrófagos/fisiologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout para ApoE , Neovascularização Patológica/etiologia , Vasa Vasorum/citologiaRESUMO
OBJECTIVE: To assess early and late outcomes, including bleeding, in patients with thrombocytopenia undergoing percutaneous coronary intervention (PCI). PATIENTS AND METHODS: We performed a retrospective single-center study of patients with preprocedural thrombocytopenia (platelet count ≤100,000/µL; n=204) undergoing PCI between 2003 and 2015. Inhospital and late outcomes were compared with those of a matched control group without thrombocytopenia (n=1281). RESULTS: The most common causes of thrombocytopenia were liver disease, immune-mediated disease, and hematologic malignant neoplasms. Inhospital bleeding events after PCI were similar in patients with thrombocytopenia and matched controls (24 of 146 [16.4%] vs 179 of 1281 [14.0%]; P=.40) and were largely classified as minor using the Bleeding Academic Research Consortium (BARC) classification (89% BARC 1 or 2). There was no significant difference in inhospital death (4 of 146 [2.7%] vs 71 of 1281 [2.0%]; P=.56), but patients with thrombocytopenia had higher rates of platelet and red blood cell transfusion (18 of 146 [12.3%] vs 93 of 1281 [7.2%]; P=.05). During long-term follow-up, Kaplan-Meier estimated rates of bleeding events (BARC ≥2) were higher for thrombocytopenia (at 5 years, 7.9% vs 3.6%; P=.03). Patients with thrombocytopenia had a similar risk of long-term cardiac mortality, but significantly higher rates of noncardiac mortality (at 5 years, 28% vs 21%; P=.02). CONCLUSION: This study suggests that short-term outcomes after PCI in patients with thrombocytopenia were favorable. On long-term follow-up, thrombocytopenia was associated with a higher risk of long-term noncardiac mortality and bleeding.
Assuntos
Transfusão de Sangue/estatística & dados numéricos , Hemorragia/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Trombocitopenia/complicações , Distribuição por Idade , Idoso , Estudos de Casos e Controles , Causas de Morte , Comorbidade , Feminino , Seguimentos , Hemorragia/terapia , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Intervenção Coronária Percutânea/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Trombocitopenia/etiologiaRESUMO
BACKGROUND: Decellularized heart valves are emerging as a potential alternative to current bioprostheses for valve replacement. Whereas techniques of decellularization have been thoroughly examined, terminal sterilization techniques have not received the same scrutiny. METHODS: This study evaluated low-dose gamma irradiation as a sterilization method for decellularized heart valves. Incubation of valves and transmission electron microscopy evaluation after different doses of gamma irradiation were used to determine the optimal dose of gamma irradiation. Quantitative evaluation of mechanical properties was done by tensile mechanical testing of isolated cusps. Sterilized decellularized heart valves were tested in a sheep model (n = 3 [1 at 1,500 Gy and 2 at 3,000 Gy]) of pulmonary valve replacement. RESULTS: Valves sterilized with gamma radiation between 1,000 Gy and 3,000 Gy were found to be optimal with in vitro testing. However, in vivo testing showed deteriorating valve function within 2 months. On explant, the valve with 1,500 Gy gamma irradiation showed signs of endocarditis with neutrophils on hematoxylin and eosin staining, and positive gram stain resembling streptococcus infection. The 3,000 Gy valves had no evidence of infection, but the hematoxylin and eosin staining showed evidence of wound remodeling with macrophages and fibroblasts. Tensile strength testing showed decreased strength (0 Gy: 2.53 ± 0.98 MPa, 1,500 Gy: 2.03 ± 1.23 MPa, and 3,000 Gy: 1.26 ± 0.90 MPa) with increasing levels of irradiation. CONCLUSIONS: Low-dose gamma irradiation does not maintain the mechanical integrity of valves, and the balance between sterilization and damage may not be able to be achieved with gamma irradiation. Other methods of terminal sterilization must be pursued and evaluated.
Assuntos
Bioprótese , Raios gama , Próteses Valvulares Cardíacas , Valvas Cardíacas/lesões , Valvas Cardíacas/efeitos da radiação , Esterilização/métodos , Animais , Valvas Cardíacas/citologia , Técnicas In Vitro , Doses de Radiação , Ovinos , SuínosRESUMO
INTRODUCTION: Venous thromboembolism (VTE) is a recognized complication after joint replacement surgery, and prophylaxis is routinely used in patients without bleeding disorders. However, for patients with hemophilia, pharmacologic prophylaxis is highly variable and controversial because of the inherent bleeding risk. AIM: To review our institutional experience with outcomes of total knee or hip arthroplasty with regard to symptomatic VTE and use of VTE prophylaxis in patients with hemophilia and without inhibitors. METHODS: We reviewed records of 42 consecutive patients with hemophilia A or B who underwent 71 hip or knee replacements over a 39-year period. We also reviewed the literature to estimate the incidence of VTE after arthroplasty in the hemophilia population. RESULTS: All patients used compression stockings for up to 6weeks after surgery; additionally, 6 cases (10.5%; 57 with available data) used sequential intermittent compression devices and 2 (2.8%) postoperatively received low-molecular-weight heparin. One patient (1.4%) who received low-molecular-weight heparin had a symptomatic, lower-extremity, deep venous thrombosis 10days after hip replacement for traumatic fracture. None of the other 70 surgical cases had symptomatic VTE within 3months after the procedure. Analysis of pooled data from published series of hemophilia patients undergoing arthroplasty showed an estimated incidence of symptomatic VTE of 0.5%. CONCLUSION: Our study suggests that in patients with hemophilia, joint replacement surgery can be performed safely without routine pharmacologic VTE prophylaxis and without increasing risk of thromboembolic events. Pharmacologic VTE prophylaxis may be considered in select patients with known additional risk factors for VTE.
Assuntos
Artroplastia de Substituição , Hemofilia A/complicações , Hemofilia B/complicações , Quadril/cirurgia , Joelho/cirurgia , Tromboembolia Venosa/epidemiologia , Adolescente , Adulto , Idoso , Hemofilia A/cirurgia , Hemofilia B/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVES: This study tests the hypothesis that circulating mononuclear cells expressing osteocalcin (OCN) and bone alkaline phosphatase (BAP) are associated with distinct plaque tissue components in patients with early coronary atherosclerosis. BACKGROUND: Plaque characteristics implying vulnerability develop at the earliest stage of coronary atherosclerosis. Increasing evidence indicates that cells from the myeloid lineage might serve as important mediators of destabilization. Plaque burden and its components were assessed regarding their relationship to monocytes carrying both pro-inflammatory (CD14) and osteogenic surface markers OCN and BAP. METHODS: Twenty-three patients with angiographically non-obstructive coronary artery disease underwent coronary endothelial function assessment and virtual histology-intravascular ultrasound of the left coronary artery. Plaque composition was characterized in the total segment (TS) and in the target lesion (TL) containing the highest amount of plaque burden. Blood samples were collected simultaneously from the aorta and the coronary sinus. Circulating cell counts were then identified from each sample and a gradient across the coronary circulation was determined. RESULTS: Circulating CD14+/BAP+/OCN+ monocytes correlate with the extent of necrotic core and calcification (r=0.53, p=0.010; r=0.55, p=0.006, respectively). Importantly, coronary retention of CD14+/OCN+ cells also correlates with the amount of necrotic core and calcification (r=0.61, p=0.003; r=0.61, p=0.003) respectively. CONCLUSIONS: Our study links CD14+/BAP+/OCN+ monocytes to the pathologic remodeling of the coronary circulation and therefore associates these cells with plaque destabilization in patients with early coronary atherosclerosis.
Assuntos
Fosfatase Alcalina/sangue , Doença da Artéria Coronariana , Receptores de Lipopolissacarídeos/sangue , Monócitos/metabolismo , Osteocalcina/sangue , Placa Aterosclerótica , Adulto , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/fisiopatologia , Estatística como Assunto , Ultrassonografia de Intervenção/métodosRESUMO
BACKGROUND: Current risk models for predicting long-term mortality after percutaneous coronary intervention are restricted to all-cause mortality. We sought to develop novel risk models for the prediction of cardiac and noncardiac mortality after percutaneous coronary intervention. METHODS AND RESULTS: We retrospectively evaluated patients who underwent index percutaneous coronary intervention at Mayo Clinic from 2003 to 2008. Long-term deaths were ascertained through scheduled prospective surveillance. Cause of death was determined via telephone interviews, medical records, and autopsy reports. Fine and Gray extension of Cox proportional hazards models was used to model cause-specific cumulative incidence. Candidate variables and interactions were chosen a priori, without variable selection methods. Resulting models were mapped to an integer-based risk score. The study comprised 6636 patients followed up over a median of 62 months (25th, 75th percentiles: 45, 77 months). There were 1488 deaths, 518 (35%) cardiac, 938 (63%) noncardiac, and 32 (2%) unknown. The 5-year predicted cardiac mortality ranged from 0.6% to 97%, with a corrected c-statistic of 0.82. Risk factors for cardiac death included age, body mass index, ejection fraction, and history of congestive heart failure. The integer score for noncardiac death included age, medicine index, body mass index, current smoker, noncardiac Charlson index and cardiac Charlson index, and accommodated significant age-based interactions for smoking and the 2 Charlson indices. Predicted noncardiac mortality at 5 years ranged from 0.2% to 81%, with a corrected c-statistic of 0.77. CONCLUSIONS: We report novel risk models to predict cardiac and noncardiac long-term mortality after percutaneous coronary intervention.
Assuntos
Doenças Cardiovasculares/mortalidade , Modelos Estatísticos , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/mortalidade , Sistema de Registros , Idoso , Doenças Cardiovasculares/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Medição de RiscoRESUMO
OBJECTIVE: To perform a molecular autopsy of the RyR2-encoded cardiac ryanodine receptor/calcium release channel in medical examiner/coroner's cases of sudden unexplained death (SUD). METHODS: From September 1998 to March 2004, 49 cases of SUD were referred by medical examiners/coroners to the Sudden Death Genomics Laboratory at the Mayo Clinic in Rochester, Minn, for a cardiac channel molecular autopsy. Mutational analysis of 18 exons of RyR2 implicated previously in the pathogenesis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was performed on genomic DNA using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing. RESULTS: This cohort of 49 cases of SUD included 30 males, 13 with a family history of syncope, cardiac arrest, or sudden cardiac death (mean +/- SD age at death, 14.2 +/- 10.9 years). Six distinct RyR2 missense mutations (3 novel) were discovered in 7 cases (14%, 6 males, mean +/- SD age at death, 13.6 +/- 11.2 years) of SUD. The activities at the time of SUD were exertion (3), emotion (1), and unknown (3). The mutations, R420W, S2246L, N4097S, E4146K, T4158P, and R4497C, involved nonconservative amino acid substitutions in highly conserved residues across species and were not seen in 400 reference alleles. CONCLUSIONS: This study represents the first molecular autopsy of RyR2 in medical examiner-referred cases of SUD. A targeted analysis of only 18 of the 105 protein-encoding exons of the cardiac ryanodine receptor/calcium release channel revealed potential CPVT1-causing RyR2 mutations in 1 of every 7 cases of SUD. These findings suggest that postmortem genetic testing of RyR2 should be considered as a part of the comprehensive medicolegal autopsy investigation of a SUD case and that this potentially heritable and often elusive arrhythmia syndrome be scrutinized carefully in family members of those who experience SUD.