RESUMEN
Red blood cell (RBC) transfusion therapy is often performed in patients with acute heart failure (AHF) and anemia; however, its impact on subsequent cardiovascular events is unclear. We examined whether RBC transfusion influences major adverse cardiovascular events (MACE) after discharge in patients with AHF and anemia.We classified patients with AHF and anemia (nadir hemoglobin level < 10 g/dL) according to whether they received RBC transfusion during hospitalization. The endpoint was MACE (composite of all-cause death, non-fatal acute coronary syndrome/stroke, or heart failure readmission) 180 days after discharge. For survival analysis, we used propensity score matching analysis with the log-rank test. As sensitivity analysis, we performed inverse probability weighting analysis and multivariable Cox regression analysis.Among 448 patients with AHF and anemia (median age, 81 years; male, 55%), 155 received RBC transfusion and 293 did not. The transfused patients had worse clinical features than the non-transfused patients, with lower levels of nadir hemoglobin and serum albumin and a lower estimated glomerular filtration rate. In the propensity-matched cohort of 87 pairs, there was no significant difference in the MACE-free survival rate between the 2 groups (transfused, 73.8% vs. non-transfused, 65.3%; P = 0.317). This result was consistent in the inverse probability weighting analysis (transfused, 76.0% vs. non-transfused, 68.7%; P = 0.512), and RBC transfusion was not significantly associated with post-discharge MACE in the multivariable Cox regression analysis (adjusted hazard ratio: 1.468, 95% confidence interval: 0.976-2.207; P = 0.065).In conclusion, this study suggests that RBC transfusions for anemia may not improve clinical outcomes in patients with AHF.
Asunto(s)
Síndrome Coronario Agudo , Anemia , Insuficiencia Cardíaca , Humanos , Masculino , Anciano de 80 o más Años , Transfusión de Eritrocitos/efectos adversos , Cuidados Posteriores , Alta del Paciente , Anemia/complicaciones , Anemia/terapia , Hemoglobinas/análisis , Síndrome Coronario Agudo/etiología , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/terapiaRESUMEN
Standard non-invasive methods for diagnosing and selecting the best treatment for osteomyelitis in patients with multiple chronic conditions remain to be established. We aimed to evaluate the ability of quantitative 67 Ga-citrate single-photon emission computed tomography (67 Ga-SPECT/CT) to determine the indication for either non-surgical treatment or osteotomy in patients with lower-limb osteomyelitis (LLOM) associated with diabetes mellitus and lower-extremity ischemia, based on monitoring of inflammatory activity in bone tissue. This single-centre prospective study conducted from January 2012 to July 2017 included 90 consecutive patients with suspected LLOM. Regions of interest were drawn on SPECT images during quantification of Ga accumulation. Subsequently, the inflammation-to-background ratio (IBR) was calculated by dividing the maximal accumulated lesion number by the mean number for the distal femur bone marrow of the unaffected side. Osteotomy was performed in 28 of 90 patients (31%). The osteotomy rate was higher for patients with IBR >8.4 (71.4%) than for those with IBR ≤8.4 (5.5%) (p < 0.001, sensitivity: 0.89, specificity: 0.84). In the multivariate Cox regression analysis, IBR >8.4 was an independent risk factor for osteotomy (hazard ratio [HR]: 19.0, 95% confident interval [CI]: 5.6-63.9, p < 0.001). Transcutaneous oxygen tension (TcPO2 ) was identified as an independent risk factor for lower-limb amputation (HR: 0.96, 95% CI: 0.92-0.99, p = 0.01). The current results indicate that quantitative 67 Ga-SPECT/CT is useful for distinguishing patients with LLOM likely to require osteotomy.
Asunto(s)
Osteomielitis , Radiofármacos , Humanos , Estudios Prospectivos , Radiofármacos/farmacología , Radiofármacos/uso terapéutico , Cicatrización de Heridas , Tomografía Computarizada de Emisión de Fotón Único/efectos adversos , Osteomielitis/diagnóstico por imagen , Osteomielitis/cirugía , Inflamación , Radioisótopos de Galio/uso terapéutico , Osteotomía/efectos adversos , Tomografía Computarizada por Rayos X/efectos adversosRESUMEN
A 77-year-old female presented with loss of consciousness, blood pressure of 90/60 mmHg, and heart rate of 47 bpm. At admission, highly sensitive Trop-T and lactate were elevated, and an electrocardiogram revealed an infero-posterior ST elevation myocardial infarction. Echocardiography revealed a depressed left ventricular ejection fraction with abnormal wall motion in the infero-posterior region and hyperkinetic apical movement along with severe mitral regurgitation (MR). Coronary angiography showed a hypoplastic right coronary artery, 100% thrombotic occlusion of the dominant left circumflex (LCx) artery, and 75% stenosis in the left anterior descending (LAD) artery. Substantial hemodynamic improvement with the reduction of acute ischemic MR was achieved by the initiation of an Impella 2.5, which is a transvalvular axial flow pump, and successful percutaneous coronary intervention (PCI) was conducted with stents to the LCx. The patient was weaned off the Impella 2.5 in 5 days, received staged PCI to LAD, and was later discharged after completion of the staged PCI to LAD.
Asunto(s)
Insuficiencia de la Válvula Mitral , Infarto del Miocardio , Intervención Coronaria Percutánea , Femenino , Humanos , Anciano , Choque Cardiogénico/terapia , Choque Cardiogénico/complicaciones , Infarto del Miocardio/complicaciones , Intervención Coronaria Percutánea/efectos adversos , Insuficiencia de la Válvula Mitral/complicaciones , Insuficiencia de la Válvula Mitral/diagnóstico , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
Although the primary percutaneous coronary intervention (PCI) is an established treatment for acute ST-elevation myocardial infarction (STEMI), relevant guidelines do not recommend it for recent-STEMI cases with a totally occluded infarcted related artery (IRA). However, PCI is allowed in Japan for recent-STEMI cases, but little is known regarding its outcomes. We aimed to examine the details and outcomes of PCI procedures in recent-STEMI cases with a totally occluded IRA and compared the findings with those in acute-STEMI cases.Among the 903 consecutive patients admitted with acute coronary syndrome, 250 were treated with PCI for type I STEMI with a totally occluded IRA. According to the time between symptom onset and diagnosis, patients were divided into the recent-STEMI (n = 32) and acute-STEMI (n = 218) groups. The background, procedure details, and short-term outcomes were analyzed. No significant differences between the groups were noted regarding patient demographics, acute myocardial infarction severity, or IRA distribution. Although the stent number and type were similar, significant differences were observed among PCI procedures, including the number of guidewires used, rate of microcatheter or double-lumen catheter use, and application rate of thrombus aspiration. The thrombolysis rate in the myocardial infarction flow 3-grade post-PCI did not differ significantly between the groups. Both groups had a low frequency of procedure-related complications. The in-hospital mortality rates were 0% and 4.6% in the recent-STEMI and acute-STEMI groups, respectively (P > 0.05).Although recent-STEMI cases required complicated PCI techniques, their safety, success rate, and in-hospital mortality were comparable to those of acute-STEMI cases.
Asunto(s)
Infarto de la Pared Anterior del Miocardio , Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio/diagnóstico , Japón , Resultado del TratamientoRESUMEN
Patients with acute myocardial infarction (AMI) triaged as life-threatening are transferred to our emergency medical care center (EMCC). However, data on these patients remain limited. We aimed to compare the characteristics and AMI prognosis of patients transferred to our EMCC with those transferred to our cardiovascular intensive care unit (CICU) using whole and propensity-matched cohorts.We analyzed the data of 256 consecutive AMI patients transferred from the scene to our hospital by ambulance between 2014 and 2017. The EMCC and CICU groups comprised 77 and 179 patients, respectively. There were no significant between-group age or sex differences. Patients in the EMCC group had more disease severity score and had the left main trunk identified as the culprit more frequently (12% versus 0.6%, P < 0.001) than those in the CICU group; however, the number of patients with multiple culprit vessels did not differ. The EMCC group had a longer door-to-reperfusion time (75 [60, 109] minutes versus 60 [40, 86] minutes, P< 0.001) and a higher in-hospital mortality (19% versus 4.5%, P < 0.001), especially from non-cardiac causes (10% versus 0.6%, P < 0.001), than the CICU group. However, peak myocardial creatine phosphokinase did not significantly differ between the groups. The EMCC group had a significantly higher 1-year post-discharge mortality than the CICU group (log-rank, P = 0.032); this trend was maintained after propensity score matching, although the difference was not statistically significant (log-rank, P = 0.094).AMI patients transferred to the EMCC exhibited more severe disease and worse overall in-hospital and non-cardiac mortality than those transferred to the CICU.
Asunto(s)
Cuidados Posteriores , Infarto del Miocardio , Humanos , Masculino , Femenino , Alta del Paciente , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Pronóstico , Hospitales , Mortalidad Hospitalaria , Estudios RetrospectivosRESUMEN
BACKGROUND: The development of heart failure is associated with fluid balance, including that of extracellular water (ECW) and intracellular water (ICW). This study determined whether sodium-glucose cotransporter 2 inhibitors affect fluid balance and improve heart failure in patients after acute myocardial infarction. METHODS AND RESULTS: EMBODY was a prospective, randomized, double-blinded, placebo-controlled trial of Japanese patients with acute myocardial infarction and type 2 diabetes. Overall, 55 patients who underwent bioelectrical impedance analysis were randomized to receive once daily 10 mg empagliflozin or placebo 2 weeks after acute myocardial infarction onset. We investigated the time course of body fluid balance measured using the bioelectrical impedance analysis device, InBody. The primary end points were changes in body fluid balance from weeks 0 to 24. Changes between baseline and week 24 in the empagliflozin and placebo groups were -0.21 L (Pâ¯=â¯.127) and +0.40 L (Pâ¯=â¯.001) in ECW (Pâ¯=â¯.001) and -0.23 L (Pâ¯=â¯.264) and +0.74 L (P < .001) in ICW (P < .001), respectively. In a stratified analysis, the rise in ECW and ICW was significantly attenuated in the empagliflozin group in contrast to the placebo group in participants with a body mass index of 25 or higher but not in those with a body mass index of less than 25. CONCLUSIONS: Early sodium-glucose cotransporter 2 inhibitor administration may attenuate changes in ECW and ICW.
Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Infarto del Miocardio , Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos , Insuficiencia Cardíaca/complicaciones , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Estudios Prospectivos , Equilibrio HidroelectrolíticoRESUMEN
Essential thrombocythemia (ET) and polycythemia vera (PV), are common Philadelphia-negative myeloproliferative neoplasms (MPN). Patients with MPN have a high rate of cardiovascular complications and often have acquired JAK2V617F and CALR genetic mutations. In this study, we aimed to analyze vascular endothelial function in patients with MPN.We evaluated 27 outpatients, including 10 patients diagnosed with MPN, flow-mediated dilatation (FMD), and nitroglycerin-mediated dilation (NMD), between September 2014 and August 2016. We measured serum adiponectin, which protects vascular endothelial function, and serum asymmetric dimethyl arginine (ADMA), which inhibits the production of adiponectin. The presence or absence of JAK2V617F and CALR mutations was evaluated in patients with MPN.Venous thrombosis was observed more frequently in patients with MPN than in those without. Seven MPN patients were diagnosed with PV, and 3 MPN patients were diagnosed with ET. JAK2V617F and CALR mutations were found in 5 and 3 MPN patients, respectively. FMD was significantly lower in JAK2V617F-positive MPN patients than in JAK2V617F-negative MPN patients, although NMD, adiponectin, and ADMA were similar in both groups. Adiponectin levels were higher and ADMA levels were lower in CALR-positive MPN patients than in CALR-negative MPN patients. There was no difference in FMD and NMD prevalence between the 2 groups. Furthermore, we had 3 representative MPN patients who were complicated with coronary spasm, possibly caused by MPN-related endothelial dysfunction.We found that patients with MPN presented with endothelial dysfunction, which was related to the presence of genetic mutations and was sometimes associated with cardiovascular disease.
Asunto(s)
Trastornos Mieloproliferativos , Policitemia Vera , Trombocitemia Esencial , Enfermedades Vasculares , Adiponectina , Calreticulina/genética , Humanos , Janus Quinasa 2/genética , Mutación , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Policitemia Vera/genética , Trombocitemia Esencial/genéticaRESUMEN
BACKGROUND: Alcohol septal ablation (ASA) is a treatment option in patients with drug-refractory symptomatic hypertrophic obstructive cardiomyopathy (HOCM). In many patients, right bundle branch block (RBBB) develops during ASA because septal branches supply the right bundle branch. However, the clinical significance of procedural RBBB is uncertain.MethodsâandâResults:We retrospectively reviewed 184 consecutive patients with HOCM who underwent ASA. We excluded 40 patients with pre-existing RBBB (n=10), prior pacemaker implantation (n=15), mid-ventricular obstruction type (n=10), and those lost to follow-up (n=5), leaving 144 patients for analysis. Patients were divided into 2 groups according to the development (n=95) or not (n=49) of procedural RBBB. ASA conferred significant decreases in the left ventricular pressure gradient (LVPG) in both the RBBB and no-RBBB group (from 74±48 to 27±27 mmHg [P<0.001] and from 75±45 to 31±33 mmHg [P<0.001], respectively). None of the RBBB patients developed further conduction system disturbances. The percentage reduction in LVPG at 1 year after the procedure was significantly greater in the RBBB than no-RBBB group (66±24% vs. 49±45%; P=0.035). Procedural RBBB was not associated with pacemaker implantation after ASA, but was associated with reduction in repeat ASA (odds ratio 0.34; 95% confidence interval 0.13-0.92; P=0.045). CONCLUSIONS: Although RBBB frequently occurs during the ASA procedure, it does not adversely affect clinical outcomes.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Cardiomiopatía Hipertrófica , Bloqueo de Rama , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Tabiques Cardíacos/cirugía , Humanos , Estudios RetrospectivosRESUMEN
Gastrointestinal (GI) bleeding worsens the outcomes of critically ill patients in the intensive care unit (ICU). Owing to a lack of corresponding data, we aimed to investigate whether GI bleeding during cardiovascular-ICU (C-ICU) admission in acute cardiovascular (CV) disease patients is a risk factor for subsequent CV events. Totally, 492 consecutive C-ICU patients (40.9% acute coronary syndrome, 22.8% heart failure) were grouped into GI bleeding (n = 27; 12 upper GI and 15 lower GI) and non-GI bleeding (n = 465) groups. Thirty-nine patients died or developed CV events during hospitalization, and 453 were followed up from the date of C-ICU discharge to evaluate subsequent major adverse CV events. The GI bleeding group had a higher Acute Physiology and Chronic Health Evaluation II score (20.2 ± 8.2 vs. 15.1 ± 6.8, p < 0.001), higher frequency of mechanical ventilator use (29.6% vs. 13.1%, p = 0.039), and longer C-ICU admission duration (8 [5-16] days vs. 5 [3-8] days, p < 0.001) than the non-GI bleeding group. The in-hospital mortality rate did not differ between the groups. Of those who were followed-up, CV events after C-ICU discharge were identified in 34.6% and 14.3% of patients in the GI and non-GI bleeding groups, respectively, during a median follow-up period of 228 days (log rank, p < 0.001). GI bleeding was an independent risk factor for subsequent CV events (adjusted hazard ratio: 2.23, 95% confidence interval: 1.06-4.71; p = 0.035). GI bleeding during C-ICU admission was independently associated with subsequent CV events in such settings.
Asunto(s)
Enfermedades Cardiovasculares , Hemorragia Gastrointestinal , Enfermedad Aguda , Enfermedades Cardiovasculares/epidemiología , Cuidados Críticos , Enfermedad Crítica , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/etiología , Humanos , Unidades de Cuidados IntensivosRESUMEN
BACKGROUND: Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium-glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity. METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and type 2 diabetes mellitus (T2DM) in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency-to-high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT. RESULTS: Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were + 11.6 and + 9.1 ms in the empagliflozin (P = 0.02) and placebo groups (P = 0.06), respectively. Change in LF/HF ratio was - 0.57 and - 0.17 in the empagliflozin (P = 0.01) and placebo groups (P = 0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P = 0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed. CONCLUSIONS: This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM might be effective in improving cardiac nerve activity without any adverse events. TRIAL REGISTRATION: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442 .
Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Frecuencia Cardíaca , Infarto del Miocardio/tratamiento farmacológico , Sistema Nervioso Parasimpático/fisiopatología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Sistema Nervioso Simpático/fisiopatología , 3-Yodobencilguanidina , Anciano , Presión Sanguínea , Peso Corporal , Muerte Súbita Cardíaca , Diabetes Mellitus Tipo 2/complicaciones , Método Doble Ciego , Electrocardiografía Ambulatoria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Cintigrafía , Radiofármacos , Ácido Úrico/sangreRESUMEN
OBJECTIVE: Bioresorbable vascular grafts are biologically active grafts that are entirely reconstituted by host-derived cells through an inflammation-mediated degradation process. Calcification is a detrimental condition that can severely affect graft performance. Therefore, prevention of calcification is of great importance to the success of bioresorbable arterial vascular grafts. The objective of this study was to test whether fast-degrading (FD) bioresorbable arterial grafts with high cellular infiltration will inhibit calcification of grafts. METHODS: We created two versions of bioresorbable arterial vascular grafts, slow-degrading (SD) grafts and FD grafts. Both grafts had the same inner layer composed of a 50:50 poly(l-lactic-co-ε-caprolactone) copolymer scaffold. However, the outer layer of SD grafts was composed of poly(l-lactic acid) nanofiber, whereas the outer layer of FD grafts was composed of a combination of poly(l-lactic acid) and polyglycolic acid nanofiber. Both grafts were implanted in 8- to 10-week-old female mice (n = 15 in the SD group, n = 10 in the FD group) as infrarenal aortic interposition conduits. Animals were observed for 8 weeks. RESULTS: von Kossa staining showed calcification in 7 of 12 grafts in the SD group but zero in the FD group (P < .01, χ2 test). The cell number in the outer layer of FD grafts was significantly higher than in the SD grafts (SD, 0.87 ± 0.65 × 103/mm2; FD, 2.65 ± 1.91 × 103/mm2; P = .02). CONCLUSIONS: The FD bioresorbable arterial vascular graft with high cellular infiltration into the scaffold inhibited calcification of grafts.
Asunto(s)
Implantes Absorbibles , Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Calcificación Vascular/prevención & control , Animales , Aorta Abdominal/patología , Implantación de Prótesis Vascular/efectos adversos , Células Endoteliales/patología , Femenino , Regulación de la Expresión Génica , Ácido Láctico/química , Ratones Endogámicos C57BL , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Nanofibras , Osteogénesis/genética , Poliésteres/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Diseño de Prótesis , Factores de Tiempo , Calcificación Vascular/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/patologíaRESUMEN
Stenosis is a critical problem in the long-term efficacy of tissue-engineered vascular grafts (TEVGs). We previously showed that host monocyte infiltration and activation within the graft drives stenosis and that TGF-ß receptor 1 (TGF-ßR1) inhibition can prevent it, but the latter effect was attributed primarily to inhibition of mesenchymal cell expansion. In this study, we assessed the effects of TGF-ßR1 inhibition on the host monocytes. Biodegradable TEVGs were implanted as inferior vena cava interposition conduits in 2 groups of C57BL/6 mice (n = 25/group): unseeded grafts and unseeded grafts with TGF-ßR1 inhibitor systemic treatment for the first 2 wk. The TGF-ßR1 inhibitor treatment effectively improved TEVG patency at 6 mo compared to the untreated control group (91.7 vs. 48%, P < 0.001), which is associated with a reduction in classic activation of mononuclear phagocytes. Consistent with these findings, the addition of rTGF-ß to LPS/IFN-γ-stimulated monocytes enhanced secretion of inflammatory cytokines TNF-α, IL-12, and IL-6; this effect was blocked by TGF-ßR1 inhibition (P < 0.0001). These findings suggest that the TGF-ß signaling pathway contributes to TEVG stenosis by inducing classic activation of host monocytes. Furthermore, blocking monocyte activation by TGF-ßR1 inhibition provides a viable strategy for preventing TEVG stenosis while maintaining neotissue formation.-Lee, Y.-U., de Dios Ruiz-Rosado, J., Mahler, N., Best, C. A., Tara, S., Yi, T., Shoji, T., Sugiura, T., Lee, A. Y., Robledo-Avila, F., Hibino, N., Pober, J. S., Shinoka, T., Partida-Sanchez, S., Breuer, C. K. TGF-ß receptor 1 inhibition prevents stenosis of tissue-engineered vascular grafts by reducing host mononuclear phagocyte activation.
Asunto(s)
Leucocitos Mononucleares/fisiología , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Animales , Prótesis Vascular , Constricción Patológica , Citocinas/genética , Citocinas/metabolismo , Ratones , Ratones Endogámicos C57BL , Receptores de Factores de Crecimiento Transformadores beta/genética , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
OBJECTIVE: Despite successful translation of bioresorbable vascular grafts for the repair of congenital heart disease, stenosis remains the primary cause of graft failure. In this study, we investigated the efficacy of long-term treatment with the antiplatelet drugs, aspirin and cilostazol, in preventing stenosis and evaluated the effect of these drugs on the acute phase of inflammation and tissue remodeling. APPROACH AND RESULTS: C57BL/6 mice were fed a drug-mixed diet of aspirin, cilostazol, or normal chow during the course of follow-up. Bioresorbable vascular grafts, composed of poly(glycolic acid) mesh sealed with poly(l-lactide-co-ε-caprolactone), were implanted as inferior vena cava interposition conduits and followed up for 2 weeks (n=10 per group) or 24 weeks (n=15 per group). Both aspirin and cilostazol suppressed platelet activation and attachment onto the grafts. On explant at 24 weeks, well-organized neotissue had developed, and cilostazol treatment resulted in 100% graft patency followed by the aspirin (67%) and no-treatment (60%) groups (P<0.05). Wall thickness and smooth muscle cell proliferation in the neotissue of the cilostazol group were decreased when compared with that of the no-treatment group at 24 weeks. In addition, cilostazol was shown to have an anti-inflammatory effect on neotissue at 2 weeks by regulating the recruitment and activation of monocytes. CONCLUSIONS: Cilostazol prevents stenosis of bioresorbable vascular graft in a mouse inferior vena cava implantation model up to 24 weeks and is accompanied by reduction of smooth muscle cell proliferation and acute inflammation.
Asunto(s)
Implantes Absorbibles , Prótesis Vascular , Oclusión de Injerto Vascular/prevención & control , Insuficiencia Cardíaca/cirugía , Tetrazoles/farmacología , Remodelación Vascular/efectos de los fármacos , Vena Cava Inferior/cirugía , Animales , Aspirina/farmacología , Proliferación Celular , Cilostazol , Modelos Animales de Enfermedad , Procedimiento de Fontan/métodos , Oclusión de Injerto Vascular/patología , Insuficiencia Cardíaca/patología , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Inhibidores de Agregación Plaquetaria/farmacología , Falla de Prótesis , Resultado del TratamientoRESUMEN
OBJECTIVE: Autologous grafts are used to repair atherosclerotic cardiovascular diseases; however, many patients lack suitable donor graft tissue. Recently, tissue engineering techniques have emerged to make biologically active blood vessels. We applied this technique to produce arterial grafts using established biodegradable materials without cell seeding. The grafts were evaluated in vivo for vessel remodeling during 12 months. METHODS: Poly(L-lactide-co-ε-caprolactone) scaffolds reinforced by poly(lactic acid) (PLA) fiber were prepared as arterial grafts. Twenty-eight cell-free grafts were implanted as infrarenal aortic interposition grafts in 8-week-old female SCID/Bg mice. Serial ultrasound and micro computed tomography angiography were used to monitor grafts after implantation. Five grafts were harvested for histologic assessments and reverse transcription-quantitative polymerase chain reaction analysis at time points ranging from 4 months to 1 year after implantation. RESULTS: Micro computed tomography indicated that most implanted mice displayed aneurysmal changes (three of five mice at 4 months, four of five mice at 8 months, and two of five mice at 12 months). Histologic assessments demonstrated extensive tissue remodeling leading to the development of well-circumscribed neovessels with an endothelial inner lining, a neointima containing smooth muscle cells and elastin, and a collagen-rich extracellular matrix. There were a few observed calcified deposits, located around residual PLA fibers at 12 months after implantation. Macrophage infiltration into the scaffold, as evaluated by F4/80 immunohistochemical staining, remained after 12 months and was focused mostly around residual PLA fibers. Reverse transcription-quantitative polymerase chain reaction analysis revealed that gene expression of Itgam, a marker for macrophages, and of matrix metalloproteinase 9 was higher than in native aorta during the course of 12 months, indicating prolonged inflammation (Itgam at 8 months: 11.75 ± 0.99 vs native aorta, P < .01; matrix metalloproteinase 9 at 4 months: 4.35 ± 3.05 vs native aorta, P < .05). CONCLUSIONS: In this study, we demonstrated well-organized neotissue of cell-free biodegradable arterial grafts. Although most grafts experienced aneurysmal change, such findings provide insight into the process of tissue-engineered vascular graft remodeling and should allow informed rational design of the next generation of arterial grafts.
Asunto(s)
Aorta/cirugía , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Ingeniería de Tejidos/métodos , Remodelación Vascular , Animales , Aorta/diagnóstico por imagen , Aorta/metabolismo , Aorta/patología , Aorta/fisiopatología , Aortografía/métodos , Femenino , Regulación de la Expresión Génica , Ácido Láctico/química , Ratones SCID , Poliésteres/química , Polímeros/química , Diseño de Prótesis , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Ultrasonografía Doppler , Grado de Desobstrucción Vascular , Microtomografía por Rayos XRESUMEN
OBJECTIVE: SSc causes intractable ischaemic ulcers. To avoid major amputation, we examined the safety and efficacy of therapeutic vascular angiogenesis for digital ulcers due to SSc. METHODS: A single-centre, open-label pilot study was conducted in patients with an ischaemic digital ulcer [n = 40, mean age 65 years (s.d. 8), Rutherford class III-5 or III-6) due to lcSSc (n = 11) or arteriosclerosis obliterans (ASO; n = 29). Bone marrow mononuclear cells (0.4-5.1 × 10(10) cells in total) were administered into the ischaemic limbs. We evaluated short-term safety and efficacy by means of a pain scale, (99m)Tc-tetrofosmin scintigraphy and transcutaneous oxygen tension (TcPO2) before and 4 weeks after treatment. Also, the 2-year outcome was compared. RESULTS: There was a case of amputation in each group within 4 weeks after therapy. The pain scale significantly decreased in both groups [lcSSc 93 mm (s.d. 9) to 11 (s.d. 16), P < 0.01; ASO 77 mm (s.d. 22) to 16 (s.d. 13), P < 0.01] and TcPO2 significantly improved [lcSSc 9.0 mmHg (s.d. 9) to 35 (s.d. 14), P < 0.01; ASO 18 mmHg (s.d. 10) to 29 (s.d. 21), P < 0.05). At the 2-year follow-up, the limb amputation rate was 9.1% in lcSSc and 20.7% in ASO (P = 0.36), while the recurrence rate was 18.2% in lcSSc and 17.2% in ASO (P = 0.95). All-cause mortality was 27.3% in lcSSc and 17.2% in ASO (P = 0.65). CONCLUSION: In patients with lcSSc, bone marrow mononuclear cell implantation provides clinical benefit and is safe, without major adverse reactions, and may become an effective strategy. TRIAL REGISTRATION: UMIN-CTR, http://www.umin.ac.jp/ctr/index-j.htm, no. UMIN000004112.
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Trasplante de Médula Ósea , Neovascularización Fisiológica/fisiología , Esclerodermia Sistémica/complicaciones , Úlcera/etiología , Úlcera/cirugía , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/cirugía , Anciano , Arteriosclerosis Obliterante/complicaciones , Arteriosclerosis Obliterante/cirugía , Determinación de Punto Final , Femenino , Dedos/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Seguridad del Paciente , Enfermedad Arterial Periférica/etiología , Enfermedad Arterial Periférica/cirugía , Proyectos Piloto , Resultado del TratamientoRESUMEN
The development of vascular bioengineering has led to a variety of novel treatment strategies for patients with cardiovascular disease. Notably, combining biodegradable scaffolds with autologous cell seeding to create tissue-engineered vascular grafts (TEVG) allows for in situ formation of organized neovascular tissue and we have demonstrated the clinical viability of this technique in patients with congenital heart defects. The role of the scaffold is to provide a temporary 3-dimensional structure for cells, but applying TEVG strategy to the arterial system requires scaffolds that can also endure arterial pressure. Both biodegradable synthetic polymers and extracellular matrix-based natural materials can be used to generate arterial scaffolds that satisfy these requirements. Furthermore, the role of specific cell types in tissue remodeling is crucial and as a result many different cell sources, from matured somatic cells to stem cells, are now used in a variety of arterial TEVG techniques. However, despite great progress in the field over the past decade, clinical effectiveness of small-diameter arterial TEVG (<6mm) has remained elusive. To achieve successful translation of this complex multidisciplinary technology to the clinic, active participation of biologists, engineers, and clinicians is required.
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Implantes Absorbibles , Prótesis Vascular , Cardiopatías Congénitas/terapia , Ingeniería de Tejidos/métodos , Andamios del Tejido , Animales , Cardiopatías Congénitas/fisiopatología , Humanos , Ingeniería de Tejidos/tendenciasAsunto(s)
Presión Arterial/fisiología , Contrapulsador Intraaórtico/efectos adversos , Cardiomiopatía de Takotsubo/fisiopatología , Obstrucción del Flujo Ventricular Externo/fisiopatología , Contrapulsación , Electrocardiografía , Hemodinámica , Humanos , Cardiomiopatía de Takotsubo/complicaciones , Obstrucción del Flujo Ventricular Externo/complicacionesRESUMEN
BACKGROUND: Lower extremity artery disease is strongly associated with morbidity and is typically addressed through revascularization interventions. We assessed the clinical outcomes of patients with chronic limb-threatening ischemia (CLTI) without revascularization who did and did not undergo repetitive hyperbaric oxygen therapy (HBOT). METHODS: Between April 2002 and March 2017, the records of 58 patients with CLTI (Rutherford classification 4 in 19% and 5 in 81%) were evaluated retrospectively. HBOT was performed at 2.8 atm of oxygen (HBOT group). The control group included those who could not continue HBOT and historical controls. Patients in poor general health or with an indication for revascularization therapy were excluded. We examined major adverse events (MAEs) and limb salvage rates. Independent predictors and risk stratification were analyzed using a multivariate regression analysis. RESULTS: The mean age was 71±13 years. Of all patients, 67% had diabetes and 43% were undergoing hemodialysis. The mean follow-up period was 4.3±0.8 years. The overall survival rate was 84.5% and 81.0% at 1 and 3 years, respectively. The Cox regression analysis indicated that high body mass index (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.76-0.97; p=0.01), well-nourished (OR: 1.21; 95% CI: 1.01-1.45), and HBOT (OR: 0.05; 95% CI: 0.01-0.26; p<0.001) independently predicted absence of MAEs. For major limb amputation, the ankle-brachial index (OR: 0.2; 95% CI: 0.05-0.86; p=0.03) and HBOT (OR: 0.04; 95% CI: 0.004-0.32; p=0.003) were independent predictors. CONCLUSIONS: Repetitive, stand-alone HBOT was associated with MAE-free survival and limb salvage in patients with CLTI.
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Procedimientos Endovasculares , Oxigenoterapia Hiperbárica , Enfermedad Arterial Periférica , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Isquemia Crónica que Amenaza las Extremidades , Enfermedad Arterial Periférica/terapia , Oxigenoterapia Hiperbárica/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Isquemia/terapia , Factores de Riesgo , Enfermedad CrónicaRESUMEN
BACKGROUND: Guideline-directed medical therapy (GDMT) is important in heart failure management; however, polypharmacy itself may impact heart failure. Although measures against polypharmacy are needed, current discussion on unilateral drug tapering (including the drugs that should be tapered) is insufficient. In this study, we investigated the relationship between the number of prescribed GDMT drugs and prognosis in patients with heart failure. METHODS: In this single-centre retrospective study, 3,146 eligible patients with heart failure were included and divided into four groups based on the median number of prescribed GDMT drugs and the median number of drugs not included in the GDMT (ni-GDMT) at the time of hospital discharge. The definition of GDMT was based on various Japanese guidelines. The primary outcome was all-cause mortality within 3 years of hospital discharge. RESULTS: A total of 252 deaths were observed during the 3-year follow-up period. Kaplan-Meier analysis revealed that groups with GDMT drug count ≥ 5 and ni-GDMT drug count < 4 had the lowest mortality, and those with GDMT drug count < 5 and ni-GDMT drug count ≥ 4 had the highest mortality (log-rank, P < 0.001). Cox regression analysis revealed a significant association between ni-GDMT drug count and all-cause mortality, even after adjustment for number of GDMT medications, age, male, left ventricular ejection function < 40%, hemoglobin, albumin levels, and estimated glomerular filtration rate [HR = 1.06 (95% CI: 1.01-1.11), P = 0.020]. Conversely, the GDMT drug count was not associated with increased mortality rates. CONCLUSIONS: The ni-GDMT drug count was significantly associated with 3-year mortality in patients with heart failure. Conversely, the GDMT drug count did not worsen the prognosis. Polypharmacy measures should consider ni-GDMT drug quantity to improve the prognosis and outcomes in patients with heart failure.
RESUMEN
AIMS: Plasma volume status (PVS), a measure of plasma volume, has been evaluated as a prognostic marker for chronic heart failure. Although the prognostic value of PVS has been reported, its significance in patients with acute decompensated heart failure (ADHF) admitted to the cardiovascular intensive care unit (CICU) remains unclear. In this study, we examined the relationship between PVS and long-term mortality in patients with ADHF admitted to the CICU. METHODS: Between January 2018 and December 2020, 363 consecutive patients with ADHF were admitted to the Nippon Medical School Hospital CICU. Of the 363 patients, 206 (mean age, 74.9 ± 12.9 years; men, 64.6%) were enrolled in this study. Patients who received red blood cell transfusions, underwent dialysis, were discharged from the CICU or died in the hospital were excluded from the study. We measured the PVS of the patients at admission, transfer to the general ward (GW) and discharge using the Kaplan-Hakim formula. The patients were assigned to four groups according to the quartiles of their PVS measured at each of the three abovementioned timepoints. We examined the association between PVS and all-cause mortality during the observation period (1134 days). The primary endpoint of this study was all-cause mortality. RESULTS: The Kaplan-Meier analysis showed that the high PVS group had a significantly higher mortality rate at admission, transfer to the GW and discharge than the other groups (log-rank test: P = 0.016, P = 0.005 and P < 0.001, respectively). Univariate Cox regression analysis showed that age, body mass index, history of heart failure, use of beta-blockers, albumin level, blood urea nitrogen level, N-terminal pro-brain natriuretic peptide level and left ventricular ejection fraction were significantly different among the PVS groups and thus were not significant prognostic factors for ADHF. Furthermore, the multivariate analysis revealed that PVS at discharge [hazard ratio (HR) = 1.06 (1.00-1.12), P = 0.048] was an independent poor prognostic factor for ADHF. CONCLUSIONS: This study highlights the effect of PVS measured at different timepoints on the prognoses of ADHF patients. Regular assessment of PVS, particularly at discharge, is crucial for optimising patient management and achieving favourable outcomes in cases of ADHF.