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The role of immune system components in the development of myocardial remodeling in chronic kidney disease (CKD) and kidney transplantation remains an open question. Our aim was to investigate the associations between immune cell subpopulations in the circulation of CKD patients and kidney transplant recipients (KTRs) with subclinical indices of myocardial performance. We enrolled 44 CKD patients and 38 KTRs without established cardiovascular disease. A selected panel of immune cells was measured by flow cytometry. Classical and novel strain-related indices of ventricular function were measured by speckle-tracking echocardiography at baseline and following dipyridamole infusion. In CKD patients, the left ventricular (LV) relative wall thickness correlated with the CD14++CD16- monocytes (ß = 0.447, p = 0.004), while the CD14++CD16+ monocytes were independent correlates of the global radial strain (ß = 0.351, p = 0.04). In KTRs, dipyridamole induced changes in global longitudinal strain correlated with CD14++CD16+ monocytes (ß = 0.423, p = 0.009) and CD4+ T-cells (ß = 0.403, p = 0.01). LV twist and untwist were independently correlated with the CD8+ T-cells (ß = 0.405, p = 0.02 and ß = -0.367, p = 0.03, respectively) in CKD patients, whereas the CD14++CD16+ monocytes were independent correlates of LV twist and untwist in KTRs (ß = 0.405, p = 0.02 and ß = -0.367, p = 0.03, respectively). Immune cell subsets independently correlate with left ventricular strain and torsion-related indices in CKD patients and KTRs without established CVD.
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Trasplante de Riñón , Monocitos , Insuficiencia Renal Crónica , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Insuficiencia Renal Crónica/inmunología , Persona de Mediana Edad , Monocitos/metabolismo , Monocitos/inmunología , Ecocardiografía , Adulto , Receptores de Lipopolisacáridos/metabolismo , Enfermedades Cardiovasculares/etiología , Anciano , Receptores de Trasplantes , Sistema Inmunológico , Receptores de IgG/metabolismoRESUMEN
INTRODUCTION: Uremic patients exhibit remarkably increased rates of mortality and cardiovascular (CV) events, but risk prediction in this setting remains difficult. Systemic mitochondrial dysfunction is pervasive in end-stage kidney disease and may contribute to CV complications. We tested the clinical significance of circulating MOTS-c, a small mitochondrial-derived peptide, as a biomarker for improving mortality and CV risk prediction in hemodialysis (HD) patients. METHODS: We conducted a prospective, observational, multicenter study on 94 prevalent HD patients. The study endpoint was a composite of all-cause mortality and non-fatal CV events. The diagnostic and prognostic capacities of predictive models based on cohort-related risk factors were tested before and after the inclusion of MOTS-c. RESULTS: MOTS-c levels were higher in HD patients than in controls (p < 0.001) and even more elevated (p = 0.01) in the 53 individuals experiencing the combined endpoint during follow-up (median duration: 26.5 months). MOTS-c was independently associated with the endpoint at either multivariate logistic (OR 1.020; 95% CI: 1.011-1.109; p = 0.03) or Cox regression analyses (HR 1.004; 95% CI: 1.000-1.025; p = 0.05) and the addition of this biomarker to prognostic models including the other cohort-related risk predictors (age, left ventricular mass, evidence of diastolic dysfunction, diabetes, pulse pressure) significantly improved the calibration, risk variability explanation, discrimination (receiver operating characteristic area under the curve from 0.727 to 0.743; C-index from 0.658 to 0.700), and particularly, the overall reclassification capacity (NRI 15.87%; p = 0.01). CONCLUSIONS: In HD patients, the mitochondrial-derived peptide MOTS-c may impart significant information to refine CV risk prediction, beyond cohort-related risk factors. Future investigations are needed to generalize these findings in larger and more heterogeneous cohorts.
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Biomarcadores , Enfermedades Cardiovasculares , Fallo Renal Crónico , Diálisis Renal , Humanos , Diálisis Renal/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/sangre , Estudios Prospectivos , Biomarcadores/sangre , Fallo Renal Crónico/terapia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/complicaciones , Factores de Riesgo , Proteínas Mitocondriales/sangre , Pronóstico , Estudios de CohortesRESUMEN
BACKGROUND: Mortality and cardiovascular (CV) risk prediction in individuals with end-stage kidney disease (ESKD) on chronic hemodialysis (HD) remains challenging due to the multitude of implicated factors. In a multicenter ESKD-HD cohort, we tested the prognostic yield of the assessment of circulating Humanin, a small mitochondrial-derived peptide involved in CV protection, on CV events and mortality. METHODS: We conducted a prospective, observational, pilot study on 94 prevalent HD patients. The prognostic capacity of circulating Humanin levels was tested on a primary composite (all-cause mortality + non-fatal CV events) and a secondary exploratory endpoint (all-cause mortality alone). RESULTS: Baseline Humanin level was comparable in patients reaching the primary or secondary endpoint as compared to others (p = 0.69 and 0.76, respectively). Unadjusted followed by multivariable Cox regression analyses adjusted for age, left ventricular mass index (LVMi), E/e', pulse pressure and diabetes mellitus indicated a non-linear relationship between Humanin levels and the composite outcome with the highest Hazard Ratio (HR) associated with very low (< 450.7 pg/mL; HR ranging from 4.25 to 2.49) and very high (> 759.5 pg/mL; HR ranging from 5.84 to 4.50) Humanin values. Restricted cubic splines fitting univariate and multivariate Cox regression analyses visually confirmed a curvilinear trend with an increasing risk observed for lower and higher Humanin values around the median, respectively. A similar, u-shaped association was also evidenced with the secondary endpoint. CONCLUSIONS: Altered Humanin levels may impart prognostic information in ESKD-HD patients at risk of death or CV events. Future investigations are needed to confirm whether Humanin measurement could improve CV and mortality risk prediction beyond traditional risk models.
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Background/Objectives: Patient care in Cardiac Intensive Care Units (CICU) has evolved but data on patient characteristics and outcomes are sparse. This retrospective observational study aimed to define clinical characteristics and risk factors of CICU patients, their in-hospital and 30-day mortality, and compare it with established risk scores. Methods: Consecutive patients (n = 294, mean age 70 years, 74% males) hospitalized within 15 months were studied; APACHE II, EHMRG, GWTG-HF, and GRACE II were calculated on admission. Results: Most patients were admitted for ACS (48.3%) and acute decompensated heart failure (ADHF) (31.3%). Median duration of hospitalization was 2 days (IQR = 1, 4). In-hospital infection occurred in 20%, 18% needed mechanical ventilation, 10% renal replacement therapy and 4% percutaneous ventricular assist devices (33%, 29%, 20% and 4%, respectively, for ADHF). In-hospital and 30-day mortality was 18% and 11% for all patients (29% and 23%, respectively, for ADHF). Established scores (especially APACHE II) had a good diagnostic accuracy (area under the curve-AUC). In univariate and multivariate analyses in-hospital intubation and infection, history of coronary artery disease, hypotension, uremia and hypoxemia on admission were the most important risk factors. Based on these, a proposed new score showed a diagnostic accuracy of 0.954 (AUC) for in-hospital mortality, outperforming previous scores. Conclusions: Patients are admitted mainly with ACS or ADHF, the latter with worse prognosis. Several patients need advanced support; intubation and infections adversely affect prognosis. Established scores predict mortality satisfactorily, but larger studies are needed to develop CICU-directed scores to identify risk factors, improve prediction, guide treatment and staff training.
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AIMS: The impact of newly detected diabetes mellitus (NDDM) on metabolic parameters and extent of myocardial necrosis in patients with acute coronary syndrome (ACS) is not fully explored. We examined the impact of NDDM on cardiometabolic characteristics and myocardial necrosis in ACS patients. METHODS: CALLINICUS-Hellas Registry is an ongoing prospective multicenter observational study evaluating the adherence to lipid-lowering therapy (LLT) among ACS patients in Greece. Three groups were created: a) patients with NDDM (abnormal fasting glucose, HbA1c ≥ 6.5 % and no previous history of DM), b) patients without known DM and HbA1c < 6.5 % (non-DM) and c) patients with prior DM. RESULTS: The prevalence of NDDM among 1084 patients was 6.9 %. NDDM patients had lower HDL-C [38 (32-45) vs 42 (36-50) mg/dL] and higher triglycerides levels [144 (104-231) vs 115 (87-152) mg/dL] compared to non-DM patients (p < 0.05). NDDM patients featured both higher body mass index [29.5 (26.4-34.3) vs 27.1 (24.9-29.9) kg/m2] and waist circumference [107 (100-114) vs 98 (91-106) cm] compared to non-DM patients (p < 0.05). In addition, NDDM patients had more extensive myocardial necrosis than patients with prior DM. CONCLUSIONS: ACS patients with NDDM have an adverse cardiometabolic profile similar to patients with prior DM and have more extensive myocardial insult.
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Síndrome Coronario Agudo , Humanos , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Diabetes Mellitus/epidemiología , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Glucemia/metabolismo , Glucemia/análisis , Grecia/epidemiología , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/sangre , Sistema de Registros , PrevalenciaRESUMEN
The fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive and invasive imaging modalities. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy. METHODS: Search of the bibliographic database for articles published from 2011 to 2023 using the following search terms: invasive FFR and non-invasive FFR. Pooled analysis of the sensitivity and specificity, with the corresponding confidence intervals from 32% to 94%. In addition, the summary processing times were determined. RESULTS: In total, 24 studies published between 2011 and 2023 were included, with a total of 13,591 patients and 3345 vessels. The diagnostic accuracy of the invasive and non-invasive techniques at the per-patient level was 89% (95% CI, 85-92%) and 76% (95% CI, 61-80%), respectively, while on the per-vessel basis, it was 92% (95% CI, 82-88%) and 81% (95% CI, 75-87%), respectively. CONCLUSION: These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice.
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BACKGROUND: A significant proportion of pulmonary embolisms (PEs) occurs in patients during hospitalisation for another reason. However, limited data regarding differences between out-of-hospital PE (OHPE) and in-hospital PE (IHPE) is available. We aimed to compare these groups regarding their clinical characteristics, biochemical markers, and echocardiographic indices. METHODS: This was a prospective, single-arm, single-centre study. Adult consecutive patients with non-COVID-related PE from September 2019 to March 2022 were included and followed up for 12 months. RESULTS: The study included 180 (84 women) patients, with 89 (49.4%) suffering from IHPE. IHPE patients were older, they more often had cancer, were diagnosed earlier after the onset of symptoms, they had less frequent pain and higher values of high sensitivity troponin I and brain natriuretic peptide levels compared to OHPE patients. Echocardiographic right ventricular (RV) dysfunction was detected in similar proportions in the 2 groups. IHPE had increased in-hospital mortality (14.6% vs. 3.3%, p = 0.008) and similar post-discharge to 12-month mortality with OHPE patients. CONCLUSIONS: In this prospective cohort study, IHPE differed from OHPE patients regarding age, comorbidities, symptoms, and levels of biomarkers associated with RV dysfunction. IHPE patients had higher in-hospital mortality compared to OHPE patients and a similar risk of death after discharge.
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Background: Pericardial effusion is common in pregnancy, with causes similar to the general population. Usually, it is found in the third trimester and disappears spontaneously after labour; however, there is a risk of progression to tamponade. Management is based on expert opinion, since few studies have been published. Case summary: A woman with enlargement of a known, chronic, presumably idiopathic pericardial effusion, in the 17th gestation week, presented with mild dyspnoea, without specific echocardiographic signs of cardiac tamponade. She received double antithrombotic treatment with aspirin 100â mg, started before conception, and a prophylactic dose of tinzaparin 4500â IU, started at the beginning of the pregnancy due to obstetrical antiphospholipid syndrome. A multidisciplinary team consisting of the treating obstetrician-gynaecologist, haematologist, cardiothoracic surgeon, and cardiologist discussed the management, taking into account the large size of the effusion and the significant increase during pregnancy, the possibility of further increase during the third trimester, the antiplatelet and antithrombotic treatment, which increased the haemorrhagic risk, and the difficulty and risk to intervene later in pregnancy. A surgical pericardial window was proposed to the patient and family and was performed uneventfully. Discussion: This case demonstrates the importance of a multidisciplinary team approach and shared decision-making in the management of these complex cardio-obstetric patients in order to achieve optimal therapeutic results.
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Obesity and unfavorable metabolic profiles increase the risk for cardiovascular complications in adults. Although it is important to distinguish different metabolic health states at an early stage, there are limited data on the related value of biomarkers in childhood. We aimed to identify biomarkers for the detection of different metabolic health states in children with and without obesity. The serum levels of metabolic regulators (fibroblast growth factor 21 [FGF21], leptin, adiponectin and insulin-like growth factor binding protein 1) and vascular indices (flow-mediated dilation [FMD] and carotid intima-media thickness) were assessed in 78 children. Differences between the metabolically healthy and unhealthy state within children with normal weight (MHN vs. MUN), and within children with overweight/obesity (MHO vs. MUO) were investigated; the discriminatory power of the biomarkers was studied. Both MUN and MUO groups expressed altered lipid and glucose homeostasis compared to their healthy counterparts. The metabolic unhealthy state in children with normal weight was linked to higher FGF21 levels which had good discriminatory ability (area under the curve [AUC]: 0.71, 95% CI: 0.54-0.88; p = 0.044). In overweight/obese children, leptin was increased in the metabolically unhealthy subgroup (AUC: 0.81, 95% CI: 0.68-0.95; p = 0.01). There was a decrease in FMD indicating worse endothelial function in overweight/obese children versus those with normal weight. Distinct states of metabolic health exist in both children with normal weight and overweight/obese children. FGF21 and leptin may help to identify the metabolic unhealthy state in children with normal weight and in overweight/obese children, respectively, early in life.
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BACKGROUND: Despite patients undergoing chronic hemodialysis (HD) being notoriously prone to adverse cardiovascular (CV) events, risk prediction in this population remains challenging. miRNA 122-5p, a short, non-coding RNA predominantly involved in lipid and carbohydrate metabolism, has recently been related to the onset and progression of CV disease. METHODS: We run a pilot, multicenter, longitudinal, observational study to evaluate the clinical significance and prognostic usefulness of circulating miRNA 122-5p in a multicentric cohort of 74 individuals on maintenance HD. RESULTS: Patients displayed lower circulating miRNA 122-5p as compared to healthy controls (p = 0.004). At correlation analyses, ALT (ß = 0.333; p = 0.02), E/e' (ß = 0.265; p = 0.02) and CRP (ß = -0.219; p = 0.041) were independent predictors of miRNA 122-5p levels. During a median follow-up of 22 months (range of 1-24), 30 subjects (40.5%) experienced a composite endpoint of all-cause mortality and fatal/non-fatal CV events. Baseline circulating miRNA 122-5p was higher in these subjects (p = 0.01) and it predicted a significantly higher risk of endpoint occurrence (Kaplan-Meier crude HR 3.192; 95% CI 1.529-6.663; p = 0.002; Cox regression adjusted HR 1.115; 95% CI 1.009-1.232; p = 0.03). CONCLUSIONS: Altered miRNA 122-5p levels in HD patients may reflect hepatic and CV damage and may impart important prognostic information for improving CV risk prediction in this particular setting.
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Enfermedades Cardiovasculares , MicroARN Circulante , MicroARNs , Humanos , Estudios Prospectivos , Diálisis Renal/efectos adversos , Enfermedades Cardiovasculares/etiología , MicroARNs/genéticaRESUMEN
BACKGROUND: Serum natriuretic peptides (NPs) have an established role in heart failure (HF) diagnosis. Saliva NT-proBNP that may be easily acquired has been studied little. METHODS: Ninety-nine subjects were enrolled; thirty-six obese or hypertensive with dyspnoea but no echocardiographic HF findings or raised NPs served as controls, thirteen chronic HF (CHF) patients and fifty patients with acute decompensated HF (ADHF) requiring hospital admission. Electrocardiogram, echocardiogram, 6 min walking distance (6MWD), blood and saliva samples, were acquired in all participants. RESULTS: Serum NT-proBNP ranged from 60-9000 pg/mL and saliva NT-proBNP from 0.64-93.32 pg/mL. Serum NT-proBNP was significantly higher in ADHF compared to CHF (p = 0.007) and in CHF compared to controls (p < 0.05). There was no significant difference in saliva values between ADHF and CHF, or between CHF and controls. Saliva and serum levels were positively associated only in ADHF patients (R = 0.352, p = 0.012). Serum NT-proBNP was positively associated with NYHA class (R = 0.506, p < 0.001) and inversely with 6MWD (R = -0.401, p = 0.004) in ADHF. Saliva NT-proBNP only correlated with age in ADHF patients. CONCLUSIONS: In the current study, saliva NT-proBNP correlated with serum values in ADHF patients, but could not discriminate between HF and other causes of dyspnoea. Further research is needed to explore the value of saliva NT-proBNP.
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INTRODUCTION: The self-expanding, resheathable, repositionable transcatheter aortic heart valve Portico is being used successfully for transcatheter aortic valve implantation procedures (TAVI) in patients with severe aortic stenosis. The aim of this study was to evaluate outcomes at 2 years after TAVI with the Portico valve. METHODS: Multicenter registry of clinical, echocardiographic and survival data from consecutive patients treated with the Portico TAVI system (Abbott, Chicago, IL, USA) in three cath labs in Northern Greece and Epirus during 2017-2020. The primary end point was all-cause mortality at 24 months. Secondary end points included procedural outcomes (efficacy and safety) and echocardiographic measurements. RESULTS: A total of 90 patients (81 ± 6 years, 50% females, mean age 81 ± 6 years) were included in the registry. The indication for implantation was severe, symptomatic aortic stenosis (NYHA III, IV) in eighty-two (91.1%) and degeneration of a prosthetic aortic valve in eight (8.9%) patients. All patients were categorized as high surgical risk (mean Logistic Euroscore 25.9 ± 10, Euroscore II 7.7 ± 4.4 and STS score 10.8 ± 8.9). The procedure was performed transfemorally in all patients, under general anesthesia in 95.6%, under TOE guidance in 21.1%, with native valve predilatation in 46.7%, and the "resheath" option was used in 31.1% of the cases. The implantation was successful in 97.8% and there was a need for a second valve in 2.2% of the cases. Complications included permanent pacemaker implantation (16.7%), access cite complications (15.6%), arrythmias (23.3%), paravalvular leak (moderate 7.8%, severe 1.1%), acute kidney injury (7.8%), no strokes and one death during the procedure. Aortic valve peak velocity, peak and mean pressure gradients, were significantly reduced after the procedure. All-cause mortality at 1, 12 and 24 months was 4.4%, 6.7% and 7.8%, respectively. CONCLUSIONS: TAVI with the Portico system comprises an effective and safe solution for the management of severe, symptomatic aortic stenosis in high-risk surgical patients.
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Background: Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, putting them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite the fact that an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodeling and worse CV outcomes, scarce evidence exists on their role in this setting. Methods: We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectively followed (median 22 months). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events. Results: Circulating levels of all miRNAs were lower in HD patients as compared with healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint (P < .001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox regression analyses [hazard ratio (HR) ranging from 0.943 to 0.995; P = .05 to .02] while Kaplan-Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal receiver operating characteristic-derived cut-off value (P ranging from .001 to <.0001; crude HRs 7.95 to 8.61). Conclusions: Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short mid-term. Future studies on larger HD populations are needed to generalize these findings.
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BACKGROUND: Myocardial perfusion imaging via single-photon emission computed tomography (SPECT MPI) is a well-established method of diagnosing coronary artery disease (CAD). The purpose of this study was to assess the role of SPECT MPI in predicting major cardiovascular events. METHODS: The study population was composed of 614 consecutive patients (mean age: 67 years, 55% male) referred for SPECT MPI due to symptoms of stable CAD. The SPECT MPI was performed using a single-day protocol. We conducted a follow-up on all patients at 12 months via a telephone interview. RESULTS: The majority of our patients (78%) presented findings suggestive of reversible ischemia, fixed defects or both. Extensive perfusion defects were found in 18% of the population, while LV dilation was found in 7%. During the 12-month follow-up, 16 deaths, 8 non-fatal MIs and 20 non-fatal strokes were recorded. There was no significant association of SPECT findings with the combined endpoint of all-cause death, non-fatal MI and non-fatal stroke. The presence of extensive perfusion defects was an independent predictor of mortality at 12 months (HR: 2.90, 95% CI: 1.05, 8.06, p = 0.041). CONCLUSIONS: In a high-risk patient population with suspected stable CAD, only large reversible perfusion defects in SPECT MPI were independently associated with mortality at 1 year. Further trials are needed to validate our findings and refine the role of SPECT MPI findings in the diagnosis and prognosis of cardiovascular patients.
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AIM: To investigate abnormalities in myocardial strain and classic echocardiographic indices and coronary flow reserve (CFR), in younger versus older CKD patients. METHODS: Sixty consecutive CKD patients (<60 years old n = 30, ≥60 years old n = 30) and 30 healthy controls (age- and gender-matched with younger CKD patients) were recruited. An echocardiographic assessment including myocardial strain indices (i.e. global longitudinal strain -GLS -, TWIST, UNTWIST rate) was performed at baseline and following dipyridamole administration in all participants. RESULTS: Younger CKD patients had higher E/e', left ventricular mass index and relative wall thickness and lower E' (p < .005 for all) compared to healthy controls. Older CKD patients had lower E/A and E' (p < .05 for both) compared to younger CKD patients; these differences did not remain significant after adjustment for age. CFR was higher in healthy controls compared to younger and older CKD patients (p < .05 for both) without a significant difference between CKD groups. There were no significant differences in GLS, TWIST or UNTWIST values among the three groups of patients. Dipyridamole-induced changes did not differ significantly among the three groups. CONCLUSIONS: Compared to healthy controls, impaired coronary microcirculation and left ventricular diastolic function, but not myocardial strain abnormalities, are found in young CKD patients and deteriorate with aging.
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Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Humanos , Persona de Mediana Edad , Microcirculación , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular Izquierda , Insuficiencia Renal Crónica/complicaciones , EcocardiografíaRESUMEN
Maladaptive activation of the immune system plays a key role in the pathogenesis of chronic kidney disease (CKD). Our aim was to investigate differences in circulating immune cells between type 2 cardiorenal syndrome (CRS-2) patients and CKD patients without cardiovascular disease (CVD). CRS-2 patients were prospectively followed up, with the primary endpoint being all-cause and cardiovascular mortality. METHOD: A total of 39 stable males with CRS-2 and 24 male CKD patients matched for eGFR (CKD-EPI) were enrolled. A selected panel of immune cell subsets was measured by flow cytometry. RESULTS: Compared to CKD patients, CRS-2 patients displayed higher levels of proinflammatory CD14++CD16+ monocytes (p = 0.04) and T regulatory cells (Tregs) (p = 0.03), lower lymphocytes (p = 0.04), and lower natural killer cells (p = 0.001). Decreased lymphocytes, T-lymphocytes, CD4+ T-cells, CD8+ T-cells, Tregs, and increased CD14++CD16+ monocytes were associated with mortality at a median follow-up of 30 months (p < 0.05 for all). In a multivariate model including all six immune cell subsets, only CD4+ T-lymphocytes remained independent predictors of mortality (OR 0.66; 95% CI 0.50-0.87; p = 0.004). CONCLUSION: Patients with CRS-2 exhibit alterations in immune cell profile compared to CKD patients of similar kidney function but without CVD. In the CRS-2 cohort, CD4+ T-lymphocytes independently predicted fatal cardiovascular events.
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Diagnosis of coronary artery disease is mainly based on invasive imaging modalities such as X-ray angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Computed tomography coronary angiography (CTCA) is also used as a non-invasive imaging alternative. In this work, we present a novel and unique tool for 3D coronary artery reconstruction and plaque characterization using the abovementioned imaging modalities or their combination. In particular, image processing and deep learning algorithms were employed and validated for the lumen and adventitia borders and plaque characterization at the IVUS and OCT frames. Strut detection is also achieved from the OCT images. Quantitative analysis of the X-ray angiography enables the 3D reconstruction of the lumen geometry and arterial centerline extraction. The fusion of the generated centerline with the results of the OCT or IVUS analysis enables hybrid coronary artery 3D reconstruction, including the plaques and the stent geometry. CTCA image processing using a 3D level set approach allows the reconstruction of the coronary arterial tree, the calcified and non-calcified plaques as well as the detection of the stent location. The modules of the tool were evaluated for efficiency with over 90% agreement of the 3D models with the manual annotations, while a usability assessment using external evaluators demonstrated high usability resulting in a mean System Usability Scale (SUS) score equal to 0.89, classifying the tool as "excellent".
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BACKGROUND: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We aim to compare the effect of empagliflozin, liraglutide and their sequential combination on arterial stiffness indices in patients with type 2 diabetes (T2D). METHODS: This was a randomized single blind study evaluating the effect of empagliflozin vs liraglutide in adult patients with T2D. Patients were randomized to liraglutide titrated gradually to 1.8 mg or empagliflozin 25 mg in 1:1 ratio. Three months later empagliflozin was added to the liraglutide group, and liraglutide was added to the empagliflozin group. Patients were assessed with non-invasive tests for arterial stiffness (i.e., carotid-femoral PWV and AIx of aortic pressure) at baseline, 3-month and 9-month visits (final visit was extended for 3 months from the initial design due to Covid 19 pandemic). The primary outcome was the between-group difference of PWV change (ΔPWV) and ΔAIx at 3 months. Secondary outcomes included the between-group difference of ΔPWV and ΔAIx at 9 months, as well as the ΔPWV and ΔAIx between baseline and 9-month visit when total study population was assessed. RESULTS: A total of 62 patients with T2D (30 started liraglutide; 32 empagliflozin, mean age 63 years, 25 % with established cardiovascular disease) participated in the study. We failed to show any significant between-group differences of ΔPWV and ΔΑΙx at 3 and 9 months, as well as between-group difference of ΔPWV and ΔAIx for the total study population between baseline and 9-month visit. In contrast, systemic vascular resistance and lipoprotein(a) levels improved, showing better results with liraglutide than empagliflozin. Favorable effects were also observed on body weight, body mass index, body and visceral fat, blood pressure, HbA1c, and uric acid levels. CONCLUSION: No evidence of a favorable change in arterial stiffness indices was seen with empagliflozin or liraglutide or their combination in this study. Well-designed powerful studies are needed to address any potential effects on arterial stiffness in selected populations.