RESUMO
BACKGROUND: Heart failure (HF) is a global problem responsible for significant morbidity and mortality. METHODS: This review describes the patient pathways and missed opportunities related to treatment for patients with HF. RESULTS: The contemporary management strategies in HF, including medical therapies, device therapy, transplant, and palliative care. Despite the strong evidence base for therapies that improve prognosis and symptoms, there remains a large number of patients that are not optimally managed. The treatment of patients with HF is highly influenced by those who are caring for them and varies widely across geographical regions. HF patients can be broadly classified into two key groups: those who have known HF, and those who are incidentally found to have reduced left ventricular systolic dysfunction or other cardiac abnormality when an echocardiogram is performed. While all patients are under the care of a general practitioner or family doctor, in other instances, non-cardiologist physicians, cardiologists, and specialist HF nurses-each will have varying levels of expertise in managing HF-are part of the broader team involved in the specialist management of patients with HF. CONCLUSIONS: There are many potential missed opportunities in HF treatment, which include general opportunities, medications, etiology-specific therapy, device therapy, therapies when initial treatments fail, and palliative care.
Assuntos
Antirreumáticos/efeitos adversos , Cardiomiopatia Restritiva/induzido quimicamente , Cardiomiopatia Restritiva/diagnóstico por imagem , Gastroplastia/efeitos adversos , Hidroxicloroquina/efeitos adversos , Ecocardiografia , Feminino , Coração/diagnóstico por imagem , Humanos , Hidroxicloroquina/administração & dosagem , Hipertrofia Ventricular Esquerda , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A series of insults on the donor heart result in pathophysiological changes that manifest as primary graft dysfunction (PGD) post-orthotopic heart transplantation. The objectives of this study were: (i) describe the pathophysiology of severe PGD using an established cardiovascular model; and (ii) the evolution of the pathophysiology during recovery from severe PGD. METHODS: Hemodynamic data from 20 consecutive patients with severe PGD (need for mechanical circulatory support, MCS) at baseline (T0), 6 h (T6) and "recovery" (explant of support), and 20 consecutive patients without severe PGD were used to model the pathophysiology using the cardiovascular model described by Burkhoff and Dickstein. RESULTS: There was a progressive (from T0 to T6) up- and leftward shift in the diastolic pressure-volume relationship, especially of the right ventricle (RV), resulting in reduced capacitance. RV end-systolic elastance (Ees) was significantly elevated in severe PGD but preload-recruitable stroke work (PRSW) was significantly lower compared to patients without severe PGD. "Recovery" (after liberation from MCS) was associated with improvement in RV Ees, chamber capacitance and PRSW, although they remained significantly lower than patients without severe PGD. CONCLUSION: Severe PGD of the dominant right heart failure phenotype is characterized by reduced chamber capacitance, increased "stiffness" and impaired contractility. Complete normalization was not required for successful weaning of MCS.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Disfunção Primária do Enxerto , Insuficiência Cardíaca/cirurgia , Transplante de Coração/efeitos adversos , Ventrículos do Coração , Humanos , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/etiologia , Doadores de TecidosRESUMO
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
PURPOSE OF REVIEW: Use of durable left ventricular assist devices (LVADs) has increased considerably in recent years because of the insufficient supply of donor hearts for cardiac transplantation and improvement in outcomes from refinements in technology. This review examines clinical utility of these devices and summarizes the most recent evidence supporting the use of LVAD therapy. RECENT FINDINGS: There continues to be significant advancements made in LVAD technology, which has resulted in improvements in the rates of adverse events and overall patient quality of life. Specifically, less invasive and improved surgical techniques have resulted in fewer incidence of pump thrombosis and stringent blood pressure management have been shown to significantly decrease stroke rates. SUMMARY: The continued advances in LVAD therapy have resulted in significant improvement in overall survival; however, complication rates remain relatively high. Future work will focus on improvements in adverse outcomes and ultimately the possibility that LVADs will be a viable alternative to transplantation in patients with end-stage heart failure.
Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Cardíaca/terapia , Transplante de Coração , Humanos , Qualidade de Vida , Doadores de TecidosRESUMO
UNLABELLED: There is a robust inverse graded association between glomerular filtration rate (GFR) and cardiovascular risk, but proof of causality is lacking. Emerging data suggest living kidney donation may be associated with increased cardiovascular mortality although the mechanisms are unclear. We hypothesized that the reduction in GFR in living kidney donors is associated with increased left ventricular mass, impaired left ventricular function, and increased aortic stiffness. This was a multicenter, parallel group, blinded end point study of living kidney donors and healthy controls (n=124), conducted from March 2011 to August 2014. The primary outcome was a change in left ventricular mass assessed by magnetic resonance imaging (baseline to 12 months). At 12 months, the decrease in isotopic GFR in donors was -30±12 mL/min/1.73m(2). In donors compared with controls, there were significant increases in left ventricular mass (+7±10 versus -3±8 g; P<0.001) and mass:volume ratio (+0.06±0.12 versus -0.01±0.09 g/mL; P<0.01), whereas aortic distensibility (-0.29±1.38 versus +0.28±0.79×10(-3) mm Hg(-1); P=0.03) and global circumferential strain decreased (-1.1±3.8 versus +0.4±2.4%; P=0.04). Donors had greater risks of developing detectable highly sensitive troponin T (odds ratio, 16.2 [95% confidence interval, 2.6-100.1]; P<0.01) and microalbuminuria (odds ratio, 3.8 [95% confidence interval, 1.1-12.8]; P=0.04). Serum uric acid, parathyroid hormone, fibroblast growth factor-23, and high-sensitivity C-reactive protein all increased significantly. There were no changes in ambulatory blood pressure. Change in GFR was independently associated with change in left ventricular mass (R(2)=0.28; P=0.01). These findings suggest that reduced GFR should be regarded as an independent causative cardiovascular risk factor. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01028703.
Assuntos
Doenças Cardiovasculares/etiologia , Sistema Cardiovascular/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Transplante de Rim , Doadores Vivos , Nefrectomia/efeitos adversos , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Seguimentos , Humanos , Incidência , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Método Simples-Cego , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Arteriosclerosis is an independent predictor of increased cardiovascular mortality in chronic kidney disease (CKD). Histologically it is characterized by hypertrophy and fibrosis of the arterial media wall leading to increased arterial stiffness and end-organ damage. Caveolin-1 acts as an intracellular signalling pathway chaperone in human fibrotic and vascular diseases. The purpose of this study was to assess the association between caveolin-1 (CAV1) single-nucleotide polymorphism (SNP) rs4730751 and arterial stiffness as measured by arterial pulse wave velocity (PWV) in an early-stage CKD cohort and in a cohort with more severe CKD. METHODS: Two prospectively maintained patient cohorts with non-dialysis CKD were studied: 144 patients in the Chronic Renal Impairment in Birmingham (CRIB) cohort and 147 patients in the Renal Impairment in Secondary Care (RIISC) cohort, with matched exclusion criteria and DNA sampling availability. At entry to each cohort database, each patient's initial arterial PWV was measured, as well as their anthropomorphic and biochemical data. CAV1 rs4730751 SNP genotyping was performed using Taqman technology. RESULTS: The CAV1 rs4730751 SNP CC genotype was associated with lower arterial PWV in both CRIB early stage CKD patients [8.1 versus 8.6 m/s; coefficient -0.780 (-1.412, -0.149); P = 0.016] and RIISC more advanced stage CKD patients [8.7 versus 9.4 m/s; coefficient -0.695 (-1.288, -0.102); P = 0.022]; these relationships held following adjustment for other important confounders. CONCLUSIONS: This replicated study suggests potential utility of the studied CAV1 SNP as a genetic biomarker in CKD and a role for CAV1 in the development of arteriosclerosis in this setting. Further studies are warranted to further explore the basic science driving these clinical observations.
Assuntos
Arteriosclerose/genética , Caveolina 1/genética , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/genética , Adulto , Idoso , Arteriosclerose/diagnóstico , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Rigidez Vascular/genéticaRESUMO
BACKGROUND: Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated. METHODS: 140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively. RESULTS: The median estimated glomerular filtration rate (eGFR) was 50 mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively). CONCLUSIONS: eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.
Assuntos
Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/genética , Função Ventricular Esquerda , Idoso , Proteína C-Reativa/metabolismo , Colesterol/sangue , Ecocardiografia Doppler em Cores , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/metabolismo , Radiografia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/fisiopatologiaRESUMO
OBJECTIVE: To determine the nature of the association between renal dysfunction and outcomes following transcatheter aortic valve implantation (TAVI) in all cases performed in the UK between 2007 and 2012. METHODS: The UK TAVI registry was established to report outcomes on all TAVI procedures performed within the UK. Data were collected prospectively on 3980 patients from 1 January 2007 until 31 December 2012. RESULTS: In total, 205 patients (5.5%) died during their admission. Moderate to advanced chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <45â mL/min/1.73â m(2)) was significantly associated with increased mortality, even after adjustment for risk factors (OR 1.45, 95% CI 1.03 to 2.05; p=0.04). For every 10â mL/min/1.73â m(2) decrease in eGFR, in-hospital mortality increased by 8.2% (95% CI 1.1% to 14.7%; p=0.03). In total 1119 patients (30.2%) died during the follow-up period (median 543â days). Moderate to advanced CKD (eGFR <45â mL/min/1.73â m(2)) was significantly associated with increased mortality, even after adjustment for risk factors (OR 1.36, 95% CI 1.17 to 1.58; p<0.001). For every 10â mL/min/1.73â m(2) decrease in eGFR, cumulative mortality increased by 4.4% (95% CI 1.2% to 7.5%; p=0.007). Preoperative kidney function and the need for preoperative dialysis treatment discriminated between patients who died and survived. However, predictive power was poor with none of the c-statistics being >0.6. CONCLUSIONS: Pre-procedural renal dysfunction is associated, in a graded fashion independently of dialysis status, with worse outcomes, including mortality in patients undergoing TAVI.
Assuntos
Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Complicações Pós-Operatórias/mortalidade , Insuficiência Renal Crônica/complicações , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Testes de Função Renal , Masculino , Estudos Prospectivos , Sistema de Registros , Taxa de Sobrevida , Reino UnidoRESUMO
PURPOSE: To compare cardiovascular magnetic resonance-feature tracking (CMR-FT) with spatial modulation of magnetization (SPAMM) tagged imaging for the calculation of short and long axis Lagrangian strain measures in systole and diastole. MATERIALS AND METHODS: Healthy controls (n = 35) and patients with dilated cardiomyopathy (n = 10) were identified prospectively and underwent steady-state free precession (SSFP) cine imaging and SPAMM imaging using a gradient-echo sequence. A timed offline analysis of images acquired at identical horizontal long and short axis slice positions was performed using CMR-FT and dynamic tissue-tagging (CIMTag2D). Agreement between strain and strain rate (SR) values calculated using these two different methods was assessed using the Bland-Altman technique. RESULTS: Across all participants, there was good agreement between CMR-FT and CIMTag for calculation of peak systolic global circumferential strain (-22.7 ± 6.2% vs. -22.5 ± 6.9%, bias 0.2 ± 4.0%) and SR (-1.35 ± 0.42 1/s vs. -1.22 ± 0.42 1/s, bias 0.13 ± 0.33 1/s) and early diastolic global circumferential SR (1.21 ± 0.44 1/s vs. 1.07 ± 0.30 1/s, bias -0.14 ± 0.34 1/s) at the subendocardium. There was satisfactory agreement for derivation of peak systolic global longitudinal strain (-18.1 ± 5.0% vs. -16.7 ± 4.8%, bias 1.3 ± 3.8%) and SR (-1.04 ± 0.29 1/s vs. -0.95 ± 0.32 1/s, bias 0.09 ± 0.26 1/s). The weakest agreement was for early diastolic global longitudinal SR (1.10 ± 0.40 1/s vs. 0.67 ± 0.32 1/s, bias -0.42 ± 0.40 1/s), although the correlation remained significant (r = 0.42, P < 0.01). CMR-FT generated these data over four times quicker than CIMTag. CONCLUSION: There is sufficient agreement between systolic and diastolic strain measures calculated using CMR-FT and myocardial tagging for CMR-FT to be considered as a potentially feasible and rapid alternative.
Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Técnicas de Imagem por Elasticidade/métodos , Ventrículos do Coração/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Disfunção Ventricular/fisiopatologia , Adulto , Cardiomiopatia Dilatada/complicações , Diástole , Módulo de Elasticidade , Humanos , Aumento da Imagem/métodos , Pessoa de Meia-Idade , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resistência ao Cisalhamento , Estresse Mecânico , Sístole , Disfunção Ventricular/etiologiaRESUMO
Chronic kidney disease (CKD) is an under-recognized, highly prevalent cardiovascular (CV) risk factor affecting 1 in 7 adults. Large epidemiological studies have clearly established a graded association between the severity of CKD and CV event rates. Although patients with end-stage renal disease who are undergoing dialysis are at greatest CV risk, the disease process is evident in the early stages of CKD with glomerular filtration rates as high as 75 ml/min/1.73 m(2). Indeed, these patients are at least 6 times more likely to die of CV disease than to reach end-stage CKD. Thus, the major impact of CKD on the population and the healthcare budget is not that of providing renal replacement therapy but the cost of death and disability from premature CV disease. Although end-stage CKD is characterized by a clustering of conventional atherosclerotic risk factors, it has little association with CV event rates. This is reflected in disproportionate levels of sudden cardiac death, heart failure, and stroke, rather than myocardial infarction. Thus it appears that nonatherosclerotic processes, including left ventricular hypertrophy and fibrosis, account for most of the excess CV risk. Over the past decade, the use of cardiac magnetic resonance in CKD has brought about an improved understanding of the adverse CV changes collectively known as uremic cardiomyopathy. The unique ability of cardiac magnetic resonance to provide a comprehensive noninvasive examination of cardiac structure and function, arterial function, myocardial tissue characterization (T1 mapping and inversion recovery imaging), and myocardial metabolic function (spectroscopy) is ideally suited to characterize the phenotype of CV disease in CKD and to provide insight into the mechanisms leading to uremic cardiomyopathy. Concerns relating to an association between gadolinium contrast agents and nephrogenic systemic fibrosis in dialysis recipients have led to the use of lower doses and lower-risk gadolinium agents that appear to minimize this risk.
Assuntos
Cardiomiopatias/etiologia , Imageamento por Ressonância Magnética , Insuficiência Renal Crônica/complicações , Cardiomiopatias/diagnóstico , Doenças Cardiovasculares/etiologia , Fibrose/etiologia , Gadolínio , Humanos , Razão de Chances , Fatores de RiscoRESUMO
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.
Assuntos
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
Serum phosphate independently predicts cardiovascular mortality in the general population and CKD, even when levels are in the normal range. Associations between serum phosphate, arterial stiffness, and left ventricular (LV) mass suggest a possible pathophysiological mechanism, potentially mediated by the phosphaturic hormone fibroblast growth factor-23 (FGF-23). To what extent the phosphate binder sevelamer modulates these effects is not well understood. In this single-center, randomized, double-blind, placebo-controlled trial, we enrolled 120 patients with stage 3 nondiabetic CKD. After a 4-week open-label run-in period, during which time all patients received sevelamer carbonate, we randomly assigned 109 patients to sevelamer (n=55) or placebo (n=54) for an additional 36 weeks. We assessed LV mass and systolic and diastolic function with cardiovascular magnetic resonance imaging and echocardiography, and we assessed arterial stiffness by carotid-femoral pulse wave velocity. The mean age was 55 years, and the mean eGFR was 50 ml/min per 1.73 m(2). After 40 weeks, we found no statistically significant differences between sevelamer and placebo with regard to LV mass, systolic and diastolic function, or pulse wave velocity. Only 56% of subjects took ≥ 80% of prescribed therapy; in this compliant subgroup, treatment with sevelamer associated with lower urinary phosphate excretion and serum FGF-23 but not serum phosphate, klotho, vitamin D, or cardiovascular-related outcomes of interest. In conclusion, this study does not provide evidence that sevelamer carbonate improves LV mass, LV function, or arterial stiffness in stage 3 nondiabetic CKD.
Assuntos
Quelantes/farmacologia , Poliaminas/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Hipertrofia Ventricular Esquerda/prevenção & controle , Masculino , Pessoa de Meia-Idade , Poliaminas/efeitos adversos , Poliaminas/uso terapêutico , Insuficiência Renal Crônica/fisiopatologia , Sevelamer , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
BACKGROUND: Patients with chronic kidney disease have an increased cardiovascular risk that is not fully explained by traditional risk factors but appears to be related to increased arterial stiffness. Cytomegalovirus (CMV) infection is associated with increased cardiovascular risk although the mechanisms for this are unknown. We examined whether CMV seropositivity was associated with increased arterial stiffness in patients with chronic kidney disease. METHODOLOGY AND PRINCIPAL FINDINGS: In 215 non-diabetic patients with chronic kidney disease, CMV seropositivity was determined using an anti-CMV IgG ELISA. Pulse wave velocity was measured and aortic distensibility assessed in the ascending, proximal descending and distal descending thoracic aorta. Patients seropositive for CMV had a higher pulse wave velocity and lower aortic distensibility at all 3 levels. These differences (except for ascending aortic distensibility) persisted in a subcohort matched for age, gender and renal function, and when the whole cohort was divided into quartiles of age. In multivariable analyses, CMV seropositivity was an independent determinant of pulse wave velocity and proximal and distal descending aortic distensibility. CONCLUSIONS: In patients with chronic kidney disease, CMV seropositivity is associated with increased arterial stiffness and decreased distensibility of the proximal descending and distal aorta. These findings suggest that further research is required to examine CMV as a possible cause of arterial disease and increased cardiovascular risk in patients with CKD and may be relevant more widely for CMV seropositive patients with normal renal function.
Assuntos
Citomegalovirus/patogenicidade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/virologia , Rigidez Vascular/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/virologia , Citomegalovirus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Chronic kidney disease (CKD) is associated with increased arterial stiffness, an independent predictor of adverse cardiovascular outcome. Effects of CKD on regional aortic stiffness are unknown. This study aimed to determine the effects of CKD and ageing on regional thoracic aortic distensibility using cardiac magnetic resonance (CMR) imaging. METHODS: This was a cross-sectional case control study comparing patients with stage II-IV non-diabetic CKD recruited from a university hospital with healthy controls. Aortic distensibility was measured in triplicate using CMR (1.5 T) at ascending, proximal descending and distal descending thoracic aortic levels and calculated using previously validated formulae. RESULTS: 189 patients and 40 controls were recruited. Distensibility was reduced at all three thoracic aortic levels in CKD patients compared to controls (2.8 vs. 4.1 × 10(-3) mmHg(-1); P < 0.0005 for ascending aorta). The cohort was divided into tertiles of age and glomerular filtration rate (GFR); distensibility decreased with increasing age (P < 0.0005) and decreasing GFR (P < 0.02). In univariate analyses age (r = -0.688, P < 0.0005), systolic blood pressure (r = -0.183, P = 0.006) and GFR (r = 0.172, P = 0.009) all correlated with ascending aortic distensibility. In a multivariate regression model age and GFR were independent predictors of aortic distensibility at all three levels with 50% of the variation in ascending aortic distensibility explained (P < 0.0005). CONCLUSIONS: Patients with early stage chronic kidney disease have reduced distensibility along the entire length of the thoracic aorta. This worsens with ageing and as kidney function declines, emphasizing the importance of early treatment whilst kidney function is still relatively preserved.
Assuntos
Envelhecimento/patologia , Aorta Torácica/patologia , Imagem Cinética por Ressonância Magnética , Insuficiência Renal Crônica/diagnóstico , Rigidez Vascular/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologiaRESUMO
End stage renal disease is associated with a very high risk of premature cardiovascular death and morbidity. Early stage chronic kidney disease (CKD) is also associated with an increased frequency of cardiovascular events and is a common but poorly recognised and undertreated risk factor. Cardiovascular disease in CKD can be attributed to two distinct but overlapping pathological processes, namely atherosclerosis and arteriosclerosis. While the risk of athero-thrombotic events such as myocardial infarction is elevated, arteriosclerosis is the predominant pathophysiological process involving fibrosis and thickening of the medial arterial layer. This results in increased arterial stiffness causing left ventricular hypertrophy and fibrosis and the exposure of vulnerable vascular beds such as the brain and kidney to high pressure fluctuations causing small vessel disease. These pathophysiological features are manifest by a high risk of lethal arrhythmia, congestive heart failure, myocardial infarction and stroke. Recent work has highlighted the importance of aldosterone and disordered bone mineral metabolism.
Assuntos
Arteriopatias Oclusivas , Insuficiência Renal Crônica/complicações , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/epidemiologia , Arteriopatias Oclusivas/etiologia , Diagnóstico por Imagem , Progressão da Doença , Saúde Global , Humanos , Incidência , Insuficiência Renal Crônica/fisiopatologia , Fatores de RiscoRESUMO
OBJECTIVES: We sought to (1) determine the bleeding rates after primary percutaneous coronary intervention (PPCI) in our institution, where the default strategy has been transradial (TR) access in combination with unfractionated heparin (UFH) plus eptifibatide, and (2) compare these with the outcomes of patients treated with bivalirudin in HORIZONS-AMI. BACKGROUND: HORIZONS-AMI demonstrated that in PPCI undertaken via the transfemoral route, routine use of bivalirudin was associated with lower bleeding rates and improved mortality compared to routine use of UFH plus glycoprotein IIb/IIIa inhibitor (GPI). METHODS: This was a single-center prospective registry of consecutive patients undergoing PPCI from January 2009 to August 2011 at the Queen Elizabeth Hospital Birmingham, UK. Thirty-day major bleeding was defined as per the HORIZONS-AMI criteria and also according to TIMI and GUSTO scales. RESULTS: Of the 432 consecutive patients, 350 fulfilled entry criteria for HORIZONS-AMI. In contrast with HORIZONS-AMI, these subjects were older (62.5 ± 13.7 yr vs. 59.8 ± 11.1 yr, P < 0.05) with a higher rate of cardiogenic shock (6.3% vs. 0.8%, P < 0.0001). Despite this higher risk population, the rate of major bleeding was favorable (3.7% [95% CI: 2.0-6.3%] vs. 4.9% [4.0-6.1%], P = 0.32). Similarly, TIMI major bleeding (2.0% [0.8-4.1%] vs. 3.1% [2.3-3.4%], P = 0.10) and GUSTO severe or life-threatening bleeding (0.6% [0.1-2.5%] vs. 0.4% [0.2-0.9%], P = 0.75) were comparable. CONCLUSIONS: Routine TR access for PPCI using UFH plus GPI is associated with a low 30-day rate of major bleeding equivalent to the bivalirudin arm of HORIZONS-AMI. Default transradial access for PPCI permits routine use of a GPI without the penalty of high bleeding rates.
Assuntos
Angioplastia Coronária com Balão/métodos , Anticoagulantes/efeitos adversos , Cateterismo Cardíaco , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Infarto do Miocárdio/terapia , Peptídeos/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Artéria Radial , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Antitrombinas/efeitos adversos , Cateterismo Cardíaco/efeitos adversos , Trombose Coronária/etiologia , Trombose Coronária/prevenção & controle , Inglaterra , Eptifibatida , Feminino , Hemorragia/diagnóstico , Hemorragia/prevenção & controle , Hirudinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Fragmentos de Peptídeos/efeitos adversos , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Sistema de Registros , Fatores de Risco , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Lymphangiogenesis is a highly regulated process involved in the pathogenesis of disease. Current in vivo models to assess lymphangiogenesis are largely unphysiologic. The zebrafish is a powerful model system for studying development, due to its rapid growth and transparency during early stages of life. Identification of a network of trunk lymphatic capillaries in zebrafish provides an opportunity to quantify lymphatic growth in vivo. METHODS AND RESULTS: Late-phase microangiography was used to detect trunk lymphatic capillaries in zebrafish 2- and 3-days post-fertilization. Using this approach, real-time changes in lymphatic capillary development were measured in response to modulators of lymphangiogenesis. Recombinant human vascular endothelial growth factor (VEGF)-C added directly to the zebrafish aqueous environment as well as human endothelial and mouse melanoma cell transplantation resulted in increased lymphatic capillary growth, while morpholino-based knockdown of vegfc and chemical inhibitors of lymphangiogenesis added to the aqueous environment resulted in decreased lymphatic capillary growth. CONCLUSION: Lymphatic capillaries in embryonic and larval zebrafish can be quantified using late-phase microangiography. Human activators and small molecule inhibitors of lymphangiogenesis, as well as transplanted human endothelial and mouse melanoma cells, alter lymphatic capillary development in zebrafish. The ability to rapidly quantify changes in lymphatic growth under physiologic conditions will allow for broad screening of lymphangiogenesis modulators, as well as help define cellular roles and elucidate pathways of lymphatic development.
Assuntos
Angiofluoresceinografia/métodos , Linfangiogênese/fisiologia , Vasos Linfáticos/anatomia & histologia , Peixe-Zebra/embriologia , Peixe-Zebra/fisiologia , Animais , Embrião não Mamífero , Células Endoteliais/transplante , Corantes Fluorescentes , Humanos , Linfangiogênese/efeitos dos fármacos , Vasos Linfáticos/efeitos dos fármacos , Vasos Linfáticos/fisiologia , Melanoma/patologia , Modelos Biológicos , Morfolinos/farmacologia , Células Tumorais Cultivadas/transplante , Fator C de Crescimento do Endotélio Vascular/farmacologiaRESUMO
BACKGROUND: Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study. METHODOLOGY AND PRINCIPAL FINDINGS: A total of 120 patients were recruited (54% male, mean age 55 ± 14 years, mean glomerular filtration rate 50 ± 13 ml/min/1.73 m(2)). Abdominal aortic calcification was assessed using lateral lumbar spine radiography and was present in 48%. Mean femoral Z-score measured using dual energy x-ray absorptiometry was 0.60 ± 1.06. Cardiovascular magnetic resonance imaging was used to determine left ventricular mass. One patient had left ventricular hypertrophy. Subjects with aortic calcification had higher left ventricular mass compared to those without (56 ± 16 vs. 48 ± 12 g/m(2), P = 0.002), as did patients with femoral Z-scores below zero (56 ± 15 vs. 49 ± 13 g/m(2), P = 0.01). In univariate analysis presence of aortic calcification correlated with left ventricular mass (r = 0.32, P = 0.001); mean femoral Z-score inversely correlated with left ventricular mass (r =â-0.28, P = 0.004). In a multivariate regression model that included presence of aortic calcification, mean femoral Z-score, gender and 24-hour systolic blood pressure, 46% of the variability in left ventricular mass was explained (P<0.001). CONCLUSIONS: In patients with stage 3 non-diabetic chronic kidney disease, lower mean femoral Z-score and presence of aortic calcification are independently associated with increased left ventricular mass. Further research exploring the pathophysiology that underlies these relationships is warranted.