Unsupervised clustering of patients with severe aortic stenosis: A myocardial continuum

BackgroundTraditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS).AimsTo investigate a new classification system for severe AS using phenomapping.MethodsConsecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤ 1 cm² were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable.ResultsIn total, 613 patients were initially recruited, with a mean ± standard deviation AVA of 0.72 ± 0.17 cm². Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n = 1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46–3.26; P < 0.001).ConclusionsArtificial intelligence re-emphasizes the significance of cardiac remodelling in the prognosis of patients with severe AS and highlights AS not only as an isolated valvular condition, but also a global disease.     

Prevalence of liver fibrosis in an unselected general population with high prevalence of obesity and diabetes mellitus. Time for screening?

IntroductionCirrhosis and liver cancer are currently common causes of death worldwide. The global epidemic of obesity has increased the incidence of nonalcoholic fatty liver disease (NAFLD) and cirrhosis in recent years. Advanced fibrosis increases the morbimortality rate in NAFLD. The Mexican population has one of the highest prevalence of obesity and diabetes mellitus (DM) worldwide.AimTo determine the prevalence of advanced liver fibrosis in Mexican general population.MethodsAdult individuals, without a history of liver disease nor heavy alcohol consumption were randomly sampled from 20,919 participants of a health and nutrition survey applied to the general population. Clinical and laboratory evaluations were performed to calculate the NAFLD fibrosis score (NFS) (an extensively validated non-invasive method). Two cut-off points were used. Advanced fibrosis was defined as a result >0.676.ResultsIn total 695 individuals were included. The mean age was 47.8 ± 16.4. The majority were between 20 and 50 years (59%), 70.2% were female, 35.5% showed obesity and 15.8% DM. The 93% had normal serum ALT. Based on the NFS results, 56 individuals (8.1%) had a high probability of fibrosis. Most patients from this subgroup showed normal serum ALT (92.9%), 89.3% were >45 yr. old, 52% were obese and 27% suffered from DM.ConclusionsBased on these results, 8.1% of Mexican general population without a history of liver disease is at high risk of having advanced liver fibrosis and complications and death derived from cardiovascular disease and cirrhosis. Most of them showed normal ALT serum levels.     

Higher liver stiffness scores are associated with early kidney dysfunction in patients with histologically proven non-cirrhotic NAFLD

AimThe association between Liver fibrosis (LF), as assessed by either histology or Liver stiffness measurement (LSM), and the presence of Early kidney dysfunction (EKD) was investigated in this study, as was also the diagnostic performance of LSM for identifying the presence of EKD in patients with Non-alcoholic fatty liver disease (NAFLD).Materials and methodsA total of 214 adults with non-cirrhotic biopsy-proven NAFLD were recruited from two independent medical centres. Their histological stage of LF was quantified using Brunt's criteria. Vibration-controlled Transient elastography (TE), using M-probe (FibroScan®) ultrasound, was performed in 154 patients and defined as significant when LSM was ≥ 8.0 kPa. EKD was defined as the presence of microalbuminuria with an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m². Logistic regression modelling was used to estimate the likelihood of having EKD with NAFLD (LSM–EKD model).ResultsThe prevalence of EKD was higher in patients with vs without LF on histology (22.14% vs 4.82%, respectively; P < 0.001) and, similarly, EKD prevalence was higher in patients with LSM ≥ 8.0 kPa vs LSM < 8.0 kPa (23.81% vs 6.59%, respectively; P < 0.05). The area under the ROC curve of the LSM–EKD model for identifying EKD was 0.80 (95% CI: 0.72–0.89). LF detected by either method was associated with EKD independently of established renal risk factors and potential confounders.ConclusionLF was independently associated with EKD in patients with biopsy-proven NAFLD. Thus, TE-measured LSM, a widely used technique for quantifying LF, can accurately identify those patients with NAFLD who are at risk of having EKD.     

Appraising diagnostic performance of ELF test by pathological staging and digital quantification of liver fibrosis

Introduction and objectivesA crucial issue when appraising the performance of non-invasive markers is the limitations of the reference standard they are compared to. Digital image analysis (DIA) was suggested as a reproducible approach expressing fibrosis numerically as a proportionate area (PA) (%). We aimed to evaluate ELF test with direct reference to PA (%), thereby explore the improvement in accuracy to discriminate significant fibrosis which may actually have been underestimated by categorical pathological staging.Materials and methodsPA (%) data were obtained by DIA of trichrome-stained liver biopsies of 52 chronic hepatitis patients. Paired serum samples of patients and additional 36 controls were performed to measure ELF test. Diagnostic performance characteristics of ELF test was derived in predicting significant fibrosis in the patient cohort, and also, in distinguishing healthy controls from patients with significant fibrosis.ResultsWe found an AUROC value of 0.73 for ELF to predict significant fibrosis as assessed by DIA and a lower AUROC value of 0.66 when assessed by conventional pathology. Importantly, ELF test provided considerably high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis defined by Ishak F≥2 and TPA ≥ 5% (AUROCs 0.93 and 0.94, respectively) with optimal ELF cut-off point of 8.4 for both.ConclusionsDigital quantification could represent a better reference standard than conventional pathology allowing a better discriminatory capability for ELF test. ELF test provided high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis suggesting a role as a screening strategy in the community setting.     

Association between epicardial adipose tissue and left ventricular function in type 2 diabetes mellitus: Assessment using two-dimensional speckle tracking echocardiography

Background and aimsEpicardial adipose tissue (EAT) is the visceral fat between the myocardium and the visceral pericardium. Dysfunctional EAT can cause cardiovascular diseases. The aim of this study was to investigate the association between EAT and left ventricular function in type 2 diabetes mellitus (T2DM) patients by two-dimensional speckle tracking echocardiography (2D-STE).MethodsWe prospectively enrolled 116 T2DM patients who were divided into two groups according to their left ventricular global longitudinal strain (GLS): 53 with GLS <18% and 63 with GLS ≥18%. The thickness of EAT was measured as the echo-free space between the free wall of the right ventricle and the visceral layer of pericardium at end-systole. LV systolic function was evaluated by GLS measured by 2D-STE. LV diastolic function was defined as the ratio of the early diastolic transmitral flow velocity (E) to average mitral annular velocity ($\overline{e}$).ResultsCompared with patients with GLS ≥18% group, the age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), glycosylated hemoglobinA1c (HbA1c), E/$\overline{e}$, and thickness of EAT were higher in patients with GLS <18% group (all P < 0.05). Multivariate linear regression analysis revealed that the thickness of EAT was independently associated with left ventricular GLS and E/$\overline{e}$.ConclusionsThickened EAT is associated with impaired left ventricular function in T2DM patients. To investigate the association between EAT and left ventricular function can help us gain a deeper understanding of the pathogenesis of impaired cardiac function in T2DM patients.     

Associations of serum magnesium levels and calcium–magnesium ratios with mortality in patients with coronary artery disease

AimsLow magnesium (Mg) and high calcium (Ca) levels are linked to increased cardiovascular disease (CVD) risk in the general population. This prospective study assessed whether there are any independent associations of serum Mg levels and Ca–Mg ratios with mortality in patients with coronary artery disease (CAD).MethodsThis prospective cohort study included 3380 CAD patients. Cox regression models were used to estimate associations of serum Mg and Ca–Mg ratio with risk of mortality.ResultsA total of 562 deaths (331 due to CVD) were recorded during a 7.59-year (median) follow-up. Spline plots displayed U-shaped associations between serum Mg levels and Ca–Mg ratios and risk of mortality. When compared with a moderate group, adjusted hazard ratios (95% confidence intervals) for low Mg levels and high Ca–Mg ratios were 1.59 (1.30–1.95) and 1.31 (1.06–1.61) for all-cause mortality, and 1.71 (1.32–2.22) and 1.44 (1.09–1.89) for CVD mortality, respectively. There was also a tendency to increase risk of mortality in patients with high serum Mg levels and low Ca–Mg ratios. Associations of low serum Mg and high Ca–Mg ratio with risk of mortality did not change when stratified by gender, body mass index, CAD type, estimated glomerular filtration rate, use of diuretics, or history of diabetes or hypertension.ConclusionThis study demonstrated that a moderate Ca–Mg ratio (range: 3.91–4.70) had the lowest mortality risk, and that low serum Mg and high Ca–Mg ratio were independent risk factors of mortality in CAD patients. Nevertheless, the optimal dose–response of Mg and Ca for mitigating CAD risk still requires further investigation.     

Intracoronary imaging in addition to coronary angiography for patients with out-of-hospital cardiac arrest: More information for better care?

About 70% of out-of-hospital cardiac arrests are related to an ischaemic heart disease in Western countries. Percutaneous coronary intervention has been shown to improve the prognosis of survivors when an unstable coronary lesion is identified as the potential cause of the cardiac arrest. Acute complete coronary occlusion is often demonstrated among patients with ST-segment elevation on electrocardiogram after the return of spontaneous circulation. In patients without ST-segment elevation, routine coronary angiography has been shown to be not superior to conservative management. However, an electrocardiogram-based decision to perform immediate coronary angiography could be insufficient to identify unstable coronary lesions, which are frequently associated with intermediate coronary stenosis. Intracoronary imaging can be helpful to detect plaque rupture or erosion and intracoronary thrombus, but could also lead to better stent implantation, and help to reduce the risk of stent thrombosis. In patients with coronary lesions without the instability characteristic, conservative management should be the default strategy, and a search for another cause of the cardiac arrest should be systematic. In the present review, we sought to describe the potential benefit of intracoronary imaging in patients with out-of-hospital cardiac arrest.     

Metabolic and psychological effects of short-term increased consumption of less-processed foods in daily diets: A Pilot Study

AimThis study evaluated whether the consumption of locally produced food without additives might have a positive effect on known risk factors for non-communicable diseases (NCDs) such as hypertension, and levels of fasting glucose and visceral adipose tissue (VAT). Attention was focused on various types of cheese, sausages, fresh pasta, pastries, biscuits and chocolate without additives to make them palatable and durable for transport.MethodsHealthy volunteers were randomized to purchase the foods under study from either local producers not using additives (group 1) or supermarkets (group 2). At baseline and after 6 months, both groups underwent evaluation for weight, blood pressure, VAT, serum sodium, potassium, fasting glucose, insulin, C-peptide and creatinine levels, and also the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI-II) by examiners blinded to group allocation. At baseline, the state part of the STAI and Wechsler Adult Intelligence Scale IV were also performed, and body mass index, HOMA index and estimated glomerular filtration rate calculated.ResultsData for 159 subjects (89 in group 1, 70 in group 2) were analyzed. Baseline evaluations did not differ between groups. At 6 months, HOMA scores and fasting glucose levels were lower in group 1 than in group 2 (P < 0.01). Also, in group 1, VAT (P = 0.006), systolic blood pressure (P = 0.001) and BDI-II score (P = 0.0005) were decreased, whereas serum fasting glucose (P = 0.04) and C-peptide (P = 0.03) levels, and diastolic blood pressure (P = 0.02), were increased in group 2.ConclusionConsumption of the locally produced food under study improved some of the major risk factors for NCDs after 6 months.