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The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabetes and the prevention or for slowing down its complications, aiming to alleviate the personal and social burden of the disease.This review addresses current knowledge of the pathophysiological links between diabetes and cardiovascular complications, focusing on the role of epigenetic modifications, including DNA methylation and histone modifications. In addition, although the treatment of complications of diabetes with "epidrugs" is still far from being a reality and faces several challenges, we present the most promising molecules and approaches in this field.
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Doenças Cardiovasculares , Metilação de DNA , Epigênese Genética , Humanos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/terapia , Animais , Complicações do Diabetes/genética , Complicações do Diabetes/terapia , Diabetes Mellitus/genética , Histonas/metabolismoRESUMO
BACKGROUND: Postoperative atrial fibrillation (POAF) is the most frequent cardiac arrhythmia following cardiac operations. It has been associated with an increased risk of postoperative cerebrovascular complications, morbidity and mortality. The aim of this study is to evaluate if the type of venous cannulation to institute the cardiopulmonary bypass (CPB) during major cardiac surgery procedures can influence the rate of POAF and late FA onset. METHODS: We collected data from 2087 consecutive patients who have been operated at our Institution from January 2016 to December 2018. To obtain two homogenous groups we performed a propensity match analyzes: Group 1 for whom the blood drain of the CPB has been granted via peripheral cannulation (PC) through the right common femoral vein and Group 2 with patients who underwent central cannulation (CC) with insertion of a drainage cannula in the right atrium or in the superior and inferior vein cava. RESULTS: POAF has been observed as statistically similar between the two groups. At 1250-day follow-up, While the incidence of POAF was 2.9% and 8.7% in the PC and CC groups, respectively (p = .04). CONCLUSIONS: our data seems to show that the two groups do not differ in terms of POAF, while the CC group may have a significantly higher rate of atrial fibrillation in the follow-up period.
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BACKGROUND: Diabetes-induced trained immunity contributes to the development of atherosclerosis and its complications. This study aimed to investigate in humans whether epigenetic signals involved in immune cell activation and inflammation are initiated in hematopoietic stem/progenitor cells (HSPCs) and transferred to differentiated progeny. METHODS AND RESULTS: High glucose (HG)-exposure of cord blood (CB)-derived HSPCs induced a senescent-associated secretory phenotype (SASP) characterized by cell proliferation lowering, ROS production, telomere shortening, up-regulation of p21 and p27genes, upregulation of NFkB-p65 transcription factor and increased secretion of the inflammatory cytokines TNFα and IL6. Chromatin immunoprecipitation assay (ChIP) of p65 promoter revealed that H3K4me1 histone mark accumulation and methyltransferase SetD7 recruitment, along with the reduction of repressive H3K9me3 histone modification, were involved in NFkB-p65 upregulation of HG-HSPCs, as confirmed by increased RNA polymerase II engagement at gene level. The differentiation of HG-HSPCs into myeloid cells generated highly responsive monocytes, mainly composed of intermediate subsets (CD14hiCD16+), that like the cells from which they derive, were characterized by SASP features and similar epigenetic patterns at the p65 promoter. The clinical relevance of our findings was confirmed in sternal BM-derived HSPCs of T2DM patients. In line with our in vitro model, T2DM HSPCs were characterized by SASP profile and SETD7 upregulation. Additionally, they generated, after myeloid differentiation, senescent monocytes mainly composed of proinflammatory intermediates (CD14hiCD16+) characterized by H3K4me1 accumulation at NFkB-p65 promoter. CONCLUSIONS: Hyperglycemia induces marked chromatin modifications in HSPCs, which, once transmitted to the cell progeny, contributes to persistent and pathogenic changes in immune cell function and composition.
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Diabetes Mellitus Tipo 2 , Imunidade Treinada , Humanos , Fenótipo Secretor Associado à Senescência , Células-Tronco Hematopoéticas/metabolismo , Antígenos CD34/metabolismo , Epigênese Genética , Diabetes Mellitus Tipo 2/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismoRESUMO
OBJECTIVES: Right ventricular (RV) dysfunction is a significant cause of morbidity and mortality after cardiac surgery. Minimally invasive mitral valve surgery (MIMVS) increasingly is being performed. The authors aim was to evaluate postoperative RV function in patients who underwent MIMVS versus traditional mitral valve surgery. DESIGN: Six hundred seventy-five patients who underwent elective isolated mitral valve surgery at Centro Cardiologico Monzino from January 2016 to December 2019 were analyzed. After 1:1 propensity score matching, 60 patients were identified in the MIMVS (study group A) and 58 patients in the median sternotomy (control group B) and compared. SETTING: A university-affiliated scientific institute, monocentric. PARTICIPANTS: Patients. INTERVENTIONS: Mitral valve surgery. MEASUREMENTS AND MAIN RESULTS: No in-hospital deaths occurred. Aortic cross-clamp time (102 [87.5-119] v 83 [61-109] minutes, p = 0.0001), cardiopulmonary bypass duration (161.5 [142.5-181] v 105.5 [74-134] minutes, p < 0.0001) and intensive care unit stay (47 [44-72] v 45 [40-47] hours, p = 0.0015) were significantly longer in group A. The tricuspid annular plane systolic excursion was not different between group A and group B neither postoperatively (15 ± 3 v 14 ± 4 mm, p = 0.1) nor at three-month follow-up (18 ± 4 v 15 ± 3 mm, p = 0.3). No differences in peak postoperative lactates, inotropic score, central venous pressure, and pulmonary artery pulsatility index were observed. The length of hospital stay was significantly shorter in the minimally invasive group (ten [eight-13] v 12 [ten-17], p = 0.006). CONCLUSION: The authors study showed that the surgical strategy had no significant impact on postoperative RV function after mitral valve surgery.
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Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Esternotomia/efeitos adversos , Resultado do Tratamento , Função Ventricular DireitaRESUMO
During Ozaki procedure, relocating a valvular commissure could be technically demanding. This novel technique provides an easy tool to achieve valvular symmetry avoiding commissure shifting.
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Valva Aórtica , Catéteres , Valva Aórtica/cirurgia , HumanosRESUMO
The worldwide pandemic outbreak due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has created unprecedented challenges for public health services. Lombardy, region of the Northern Italy, has been the first area in the Western world whose organs and tissues procurement programs have had to face the virus pandemic emergency. We retrospectively collected and analyzed data about cardiovascular tissues (CT) in 2019 and in 2020. We aimed to describe the rapid evolution of SARS-CoV-2 regulation laws for tissue donor's selection and harvesting from February 2020 until January 2021. As expected the number of CT donors in 2020 was significantly lower than those of 2019 (66 vs. 99, p value 0.02). The total number of CT collected from donors have been 254 in 2019 and 206 in 2020 (p 0.28). Femoral arteries were the most required vascular tissues (55.5% in 2019 and 40% in 2020). Fifty-five and forty-eight pulmonary valves were implanted in 2019 and 2020, respectively. No differences were found for the types of CT requests between the 2 years. The median age of receivers of vascular tissues was 69.6 ± 14.6 years in the 2019 and 63.3 ± 14.9 years in 2020 (p < 0.01). The median age of receivers of pulmonary and aortic valves did not differ between the 2 years (9.32 ± 11.49 vs. 8.36 ± 10.66 and 48.67 ± 27.19 vs. 37.14 ± 31.97 respectively). Despite the dramatically reduction of donors, the number of CT collected has not decreased significantly and so far the CT distribution rate is comparable to those of 2019.
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COVID-19 , Pandemias , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Bancos de Tecidos , Estados UnidosRESUMO
Aortic valve disease is often treated with bioprosthetic valves. An alternative treatment is aortic valve neocuspidization which is a relatively new reparative procedure whereby the three aortic cusps are replaced with patient pericardium or bovine tissues. Recent research indicates that aortic blood flow is disturbed, and turbulence effects have yet to be evaluated in either bioprosthetic or aortic valve neocuspidization valve types in patient-specific settings. The aim of this study is to better understand turbulence production in the aorta and evaluate its effects on laminar and turbulent wall shear stress. Four patients with aortic valve disease were treated with either bioprosthetic valves (n=2) or aortic valve neocuspidization valvular repair (n=2). Aortic geometries were segmented from magnetic resonance images (MRI), and 4D flow MRI was used to derive physiological inlet and outlet boundary conditions. Pulsatile large-eddy simulations were performed to capture the full range of laminar, transitional and turbulence characteristics in the aorta. Turbulence was produced in all aortas with highest levels occurring during systolic deceleration. In the ascending aorta, turbulence production is attributed to a combination of valvular skew, valvular eccentricity, and ascending aortic dilation. In the proximal descending thoracic aorta, turbulence production is dependent on the type of arch-descending aorta connection (e.g., a narrowing or sharp bend) which induces flow separation. Laminar and turbulent wall shear stresses are of similar magnitude throughout late systolic deceleration and diastole, although turbulent wall shear stress magnitudes exceed laminar wall shear stresses between 27.3% and 61.1% of the cardiac cycle. This emphasises the significance of including turbulent wall shear stress to improve our comprehension of progressive arterial wall diseases. The findings of this study recommend that aortic valve treatments should prioritise minimising valvular eccentricity and skew in order to mitigate turbulence generation.
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Valvopatia Aórtica , Valva Aórtica , Humanos , Animais , Bovinos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Velocidade do Fluxo Sanguíneo/fisiologia , Hemodinâmica/fisiologia , Aorta , Estresse MecânicoRESUMO
BACKGROUND: Hybrid-convergent radiofrequency (RF) ablation targeting pulmonary veins (PVs) and left atrial posterior wall (LAPW) has shown better arrhythmic outcomes than an endocardial-only RF strategy, despite higher rates of complications. Comparisons with extensive pulsed field ablation (PFA) are currently lacking. OBJECTIVES: This study aimed to compare the efficacy and safety of the hybrid-convergent RF vs PFA of PVs and LAPW in long-standing persistent atrial fibrillation (LSPAF). METHODS: Ninety-three consecutive LSPAF patients, treated with 2-step hybrid-convergent RF ablation (hybrid group, n = 49) or with PFA of PVs and LAPW (PFA group, n = 44) were enrolled. Primary efficacy endpoint was defined as any atrial tachyarrhythmias (ATA) recurrence after the 3-month blanking period, over a follow-up time of 12 months. Periprocedural adverse events and late complications during follow-up were deemed primary safety outcomes. RESULTS: The hybrid and PFA groups had similar baseline characteristics; mean age was hybrid 63.8 ± 10.6 years vs PFA 66.0 ± 7.4 years; P = 0.105. PV and LAPW ablation were acutely successful in all patients. Step 1 hybrid-epicardial procedures were longer than PFA (166 [Q1-Q3: 140-205] minutes vs 107.5 [Q1-Q3: 82.5-12] minutes; P < 0.01). At 12-month follow-up, there was no difference in ATA recurrences between groups (hybrid 36.7% vs PFA 40.9%; P = 0.680; log-rank at survival analysis P = 0.539). After adjusting for confounders, a larger left atrial volume and recurrences during the blanking-period were predictors of ATA recurrences after ablation, regardless of procedural technique employed. PFA showed a better safety profile with a lower rate of major periprocedural complications compared with hybrid ablation (12% vs 0%; P = 0.028). CONCLUSIONS: Hybrid-convergent and PFA share comparable arrhythmic outcomes in LSPAF, but hybrid-convergent ablation carries higher periprocedural risks.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/cirurgia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Ablação por Cateter/métodos , Ablação por Cateter/efeitos adversos , Veias Pulmonares/cirurgia , Resultado do Tratamento , Recidiva , Átrios do Coração/cirurgia , Átrios do Coração/fisiopatologiaRESUMO
BACKGROUND AND AIMS: This study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging. METHODS: 730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created. RESULTS: In the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903-10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765-7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822-10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045-1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336-1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort. CONCLUSIONS: In patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.
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Tecido Adiposo , Doença da Artéria Coronariana , Aprendizado Profundo , Pericárdio , Valor Preditivo dos Testes , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Doença da Artéria Coronariana/diagnóstico por imagem , Idoso , Prognóstico , Medição de Risco , Função Ventricular Esquerda , Infarto do Miocárdio/diagnóstico por imagem , Fatores de Risco , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética/métodos , Reprodutibilidade dos Testes , Volume Sistólico , Estudos Retrospectivos , Tecido Adiposo EpicárdicoRESUMO
OBJECTIVES: Aortic valve neocuspidalization aims to replace the 3 aortic cusps with autologous pericardium pre-treated with glutaraldehyde, and it is a surgical alternative to the classical aortic valve replacement (AVR). Image-based patient-specific computational fluid dynamics allows the derivation of shear stress on the aortic wall [wall shear stress (WSS)]. Previous studies support a potential link between increased WSS and histological alterations of the aortic wall. The aim of this study is to compare the WSS of the ascending aorta in patients undergoing aortic valve neocuspidalization versus AVR with biological prostheses. METHODS: This is a prospective nonrandomized clinical trial. Each patient underwent a 4D-flow cardiac magnetic resonance scan after surgery, which informed patient-specific computational fluid dynamics models to evaluate WSS at the ascending aortic wall. The adjusted variables were calculated by summing the residuals obtained from a multivariate linear model (with ejection fraction and left ventricle outflow tract-aorta angle as covariates) to the mean of the variables. RESULTS: Ten patients treated with aortic valve neocuspidalization were enrolled and compared with 10 AVR patients. The aortic valve neocuspidalization group showed a significantly lower WSS in the outer curvature segments of the proximal and distal ascending aorta as compared to AVR patients (P = 0.0179 and 0.0412, respectively). WSS levels remained significantly lower along the outer curvature of the proximal aorta in the aortic valve neocuspidalization population, even after adjusting the WSS for the ejection fraction and the left ventricle outflow tract-aorta angle [2.44 Pa (2.17-3.01) vs 1.94 Pa (1.72-2.01), P = 0.02]. CONCLUSIONS: Aortic valve neocuspidalization hemodynamical features are potentially associated with a lower WSS in the ascending aorta as compared to commercially available bioprosthetic valves.
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Aorta , Valva Aórtica , Humanos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estudos Prospectivos , Aorta/diagnóstico por imagem , Aorta/cirurgia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Hemodinâmica , Estresse Mecânico , Velocidade do Fluxo SanguíneoRESUMO
INTRODUCTION: Lymphomas arising from cardiac myxomas represent a particularly rare pathology, with only few cases reported in the literature.Case presentation: We report a complete excision of a malignant lymphoma arising from a cardiac myxoma in a 44-year-old female patient. The myxoma presented like a floating mass within the left atrium with a maximum diameter of 3.5 cm. The clinical post-operative period was uneventful and the patient was dismissed on the 6th post-operative day. CONCLUSION: This case reinforces the concept of radical excision of cardiac neoplasms.
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Neoplasias Cardíacas , Linfoma , Mixoma , Adulto , Feminino , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Linfoma/cirurgia , Mixoma/diagnóstico por imagem , Mixoma/patologia , Mixoma/cirurgiaRESUMO
Objective: Endoscopic vessel harvest (EVH) is evolving as the standard of care for coronary artery bypass grafting. However, the increase in upfront equipment-related costs has resulted in reluctance of uptake globally. We investigated the costs involving a non-sealed technique for EVH versus open vessel harvesting techniques (OVH) for both the greater saphenous vein and radial artery with a 6-month follow-up. Methods: From September 2016 to December 2018, 226 patients underwent OVH while 251 patients underwent EVH using a reusable non-sealed system and a single-use radiofrequency sealing system. Cumulative costs for OVH versus EVH were calculated as a summation of total operative and in-hospital stay costs. Costs related to harvest site complication management were also analyzed for up to 6 months. Results: Total operative costs were greater in the EVH group (Can$2,283.70 [Can$1,377.60 to $4,183.50] vs Can$1,742.40 [Can$998.50 to $3,628.10], P < 0.001). Total length of stay was significantly shorter for the EVH group (5.9 [4 to 43] days vs 6.8 [4 to 55] days, P = 0.018). Cumulative costs were comparable at the end of the hospitalization period (EVH, Can$6,534.70 [Can$2,076.50 to $33,087.70] vs OVH, Can$6,112.50 [Can$3,322.30 to $45,503.50], P = 0.06). After discharge, harvest site-related complications occurred more frequently in the OVH group (27% vs 4.4%, P < 0.001), resulting in increased use of antibiotics (2.2% vs 0.8%, P = 0.02) as well as more frequent requirement for home nursing assistance in the OVH group (5.7% vs 0.8%, P = 0.002) at 6 months of follow-up. Conclusions: Cumulative costs did not show a statistical difference between OVH and EVH, with higher intraoperative costs for EVH being offset by higher harvest site management costs in the OVH group.
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Ponte de Artéria Coronária , Coleta de Tecidos e Órgãos , Custos e Análise de Custo , Endoscopia/métodos , Humanos , Veia Safena/transplanteRESUMO
OBJECTIVES: The European System for Cardiac Operation Risk Evaluation II (EuroSCORE II) is the most common tool used to evaluate the perioperative risk of mortality after cardiac surgery in Europe, and its use is currently recommended by the relevant guidelines. However, recently, its role has been questioned: Several papers have suggested that these algorithms may no longer be adequate for risk prediction due to an overestimation of adult cardiac surgical risk. Our goal was to validate the EuroSCORE II in the prediction of 30-day in-hospital mortality in patients undergoing open cardiac surgery in a high-volume hospital. METHODS: In this retrospective cohort study, we included all patients who underwent cardiac surgery from January 2016 to May 2022 within the departments of cardiac surgery of the Monzino Cardiology Centre in Milan, Italy. We evaluated the discrimination power of the EuroSCORE II by using the receiver operating characteristic curve and the corresponding area under the curve. We performed calibration plots to assess the concordance between the model's prediction and the observed outcomes. RESULTS: A total of 4,034 patients were included (mean age = 65.1 years; 68% males), of which 674 (16.7%) underwent isolated coronary artery bypass grafting. The EuroSCORE II showed a good discrimination power in predicting 30-day in-hospital mortality (area under the curve = 0.834). However, for interventions performed in an elective setting, very low values of the EuroSCORE II overestimated the observed mortality, whereas for interventions performed in an emergency setting, EuroSCORE II values above 10 extensively underestimated the observed mortality. CONCLUSIONS: Our study suggests that the EuroSCORE II seems not to be a reliable score in estimating the true risk of death, especially in high-risk patients.
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BACKGROUND: The aortic valve neocuspidalization (AVNeo) is an innovative surgical technique aiming at the reconstruction of the aortic valve using autologous pericardium. One of the main criticisms to AVNeo is the longer duration of the aortic clamping time (ACT) as compared to standard aortic valve replacement due to the sizing of the valve neocusps. METHODS: We retrospectively enrolled 30 consecutives patients underwent AVNeo. For each patient we developed a 3D aortic root model (ARM) based on CT-scan datasets. We retrospectively compared the leaflets measurements performed during surgery with those obtained on the corresponding ARMs. RESULTS: In 100% of cases no difference between the in vitro and in vivo measurements exceeded the acceptable error limit of 2 âmm. The correlation of each single in vitro versus in vivo measurements demonstrates a strong coincidence between the two different methods of sizing (r â> â0,9, p â< â.0001). By analyzing the data considering the annulus perimeter and not the single cusp size, the perfect coincidence was to be found in 89.9% with a slight acceptable discrepancy (2 âmm on total) in the remaining 10.1%. CONCLUSIONS: 3D-ARMs, printed from CT-scan, represent a reproducible process to obtain overlapping cusp sizes compared to those measured in-vivo, possibly reducing the ACT.
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Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by impaired left ventricular (LV) diastolic function, with normal LV ejection fraction. Aortic valve stenosis can cause an HFpEF-like syndrome by inducing sustained pressure overload (PO) and cardiac remodeling, as cardiomyocyte (CM) hypertrophy and fibrotic matrix deposition. Recently, in vivo studies linked PO maladaptive myocardial changes and DNA damage response (DDR) activation: DDR-persistent activation contributes to mouse CM hypertrophy and inflammation, promoting tissue remodeling, and HF. Despite the wide acknowledgment of the pivotal role of the stromal compartment in the fibrotic response to PO, the possible effects of DDR-persistent activation in cardiac stromal cell (C-MSC) are still unknown. Finally, this novel mechanism was not verified in human samples. This study aims to unravel the effects of PO-induced DDR on human C-MSC phenotypes. Human LV septum samples collected from severe aortic stenosis with HFpEF-like syndrome patients undergoing aortic valve surgery and healthy controls (HCs) were used both for histological tissue analyses and C-MSC isolation. PO-induced mechanical stimuli were simulated in vitro by cyclic unidirectional stretch. Interestingly, HFpEF tissue samples revealed DNA damage both in CM and C-MSC. DDR-activation markers γH2AX, pCHK1, and pCHK2 were expressed at higher levels in HFpEF total tissue than in HC. Primary C-MSC isolated from HFpEF and HC subjects and expanded in vitro confirmed the increased γH2AX and phosphorylated checkpoint protein expression, suggesting a persistent DDR response, in parallel with a higher expression of pro-fibrotic and pro-inflammatory factors respect to HC cells, hinting to a DDR-driven remodeling of HFpEF C-MSC. Pressure overload was simulated in vitro, and persistent activation of the CHK1 axis was induced in response to in vitro mechanical stretching, which also increased C-MSC secreted pro-inflammatory and pro-fibrotic molecules. Finally, fibrosis markers were reverted by the treatment with a CHK1/ATR pathway inhibitor, confirming a cause-effect relationship. In conclusion we demonstrated that, in severe aortic stenosis with HFpEF-like syndrome patients, PO induces DDR-persistent activation not only in CM but also in C-MSC. In C-MSC, DDR activation leads to inflammation and fibrosis, which can be prevented by specific DDR targeting.
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BACKGROUND: The Ozaki procedure is an innovative surgical technique aiming at the reconstruction of the aortic valve with autologous pericardium to overcome the limitations of commercially available prostheses. METHODS: We retrospectively analyzed 71 patients who underwent the Ozaki operation at our center between October 2014 and February 2020. RESULTS: No in-hospital death occurred. Freedom from major adverse valve-related events was 97%. The aortic gradients and transvalvular velocity were significantly lower at the 3-month echocardiographic control than at the predischarge echocardiography (10.93 ± 5.38, P < .01 vs 16.24 ± 7.67, P < .01, respectively). The median follow-up period was 20.7 months (range, 2 to 47). Four patients showed mild/moderate aortic insufficiency (5.6%), and none showed severe aortic valve insufficiency. No patients underwent reoperation. CONCLUSIONS: Midterm outcome follow-up of the Ozaki procedure showed optimal results in terms of mortality, transaortic valve gradients, freedom from major adverse valve-related events, and recurrence of aortic valve insufficiency.
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Valvopatia Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Pericárdio/transplante , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) is a well-established, low-impact surgical procedure for revascularization of the left descending coronary artery with the left internal mammary artery. This study aimed to evaluate safety, overall survival, and freedom from major adverse cardiocerebral-related events (MACCE) after 20 years of MIDCAB. METHODS: This study retrospectively collected a series of 141 patients who underwent MIDCAB between 1997 and 2017, to assess long-term outcome. A total of 133 patients who underwent revascularization of the left descending coronary artery with the left mammary artery through a full median sternotomy were analyzed. RESULTS: Actuarial survival rates on a Kaplan-Meier curve were 100%, 95%, 90%, 83%, and 70% at 1, 5, 10, 15, and 20 years, respectively. Freedom from MACCE, defined as myocardial infarction, stroke, and cardiac death, was 97%, 90%, 79%, 75%, and 61% at 1,5,10,15, and 20 years, respectively. At Cox multivariable analysis, age, cancer, and chronic renal insufficiency were found to be independent predictors affecting long-term survival, with a hazard ratio of 1.12 (P = .007), 17.63 (P < .001), and 5.16 (P = .03), respectively. The MIDCAB group showed a significantly shorter hospital length of stay and significantly lower rates of blood transfusions, cardiac-related events, and all-cause events compared with the full sternotomy group (P = .02 and P = .001, respectively). CONCLUSIONS: The very long-term clinical outcome of MIDCAB is satisfactory in terms of survival and freedom from MACCE. MIDCAB significantly reduces hospital length of stay and blood transfusions when compared with full sternotomy bypass surgery on the left descending coronary artery and appears to improve prognosis in terms of cardiac-related events and all-cause events effectively.
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Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/cirurgia , Previsões , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The Ozaki procedure is an innovative surgical technique aiming at the reconstruction of the aortic valve with autologous pericardium to overcome the limitations of commercially available prostheses. METHODS: We retrospectively analysed 71 patients who underwent Ozaki operation at our centre between October 2014 and February 2020. RESULTS: No in-hospital death occurred. Freedom from major adverse valve-related events (MAVRE) was 97%. The aortic gradients and transvalvular velocity are significantly lower at the 3-months echocardiographic control than at the pre-discharged echocardiography (10.93 ± 5.38, p= 0,0003 vs 16.24 ± 7.67 p= 0,0004 respectively). The median follow-up period was 20.7 months (range 2 to 47 months). Four patients showed mild/moderate aortic insufficiency (5.6%) and none showed severe aortic valve insufficiency. No patients underwent reoperation. CONCLUSIONS: Mid-term outcome follow-up of Ozaki procedure showed optimal results in term of mortality, transaortic valve gradients, freedom from MAVRE and recurrence of aortic valve insufficiency.
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INTRODUCTION: Type A aortic dissection (AAD) is a life-threatening disease with very high mortality. The gold standard treatment is surgical, as medical treatment has been proven to be ineffective. It is still unclear the role of preoperative neurological dysfunction in the prognosis of the patient. Therefore, the choice of performing surgery in patients with neurological symptoms is still left to the surgeon at the time of the diagnosis. The aim of this study is to make a narrative review of the current literature about the management of patients with neurological symptoms in AAD patients. EVIDENCE ACQUISITION: A bibliographical research was performed on PubMed, looking for papers containing the words: "((preoperative neurological symptoms in type a aortic dissection) OR brain injury type A aortic dissection) AND ("2010"[Date - Publication]: "3000"[Date - Publication])". A total of 35 papers were found. EVIDENCE SYNTHESIS: A total of 6 papers were chosen to be reviewed. All of them concluded that even patients with severe neurological symptoms (up to comatose state) had a good chance to recover neurological functions after surgery if treated in the first hours from the onset of symptoms. Interestingly, a hemorrhagic stroke was rarely found. CONCLUSIONS: Preoperative neurological dysfunction have been long considered a contraindication to surgery. Nevertheless, several authors show neurological and survival good results in patients with preoperative neurological dysfunction. They also stress the importance of surgical timing finding in 5 to 10 hours the surgical time limit to improve neurological dysfunction. A preoperative neurological dysfunction could be considered a strong advice towards surgical intervention. It is time to change and consider prompt surgery not only for survival but also for cerebral protection.