Cuantificación de la fibrosis auricular derecha mediante resonancia magnética cardiaca: verificación del método para la estandarización de umbrales

Introduction and objectivesLate gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) allows noninvasive detection of left atrial fibrosis in patients with atrial fibrillation (AF). However, whether the same methodology can be used in the right atrium (RA) remains unknown. Our aim was to define a standardized threshold to characterize RA fibrosis in LGE-CMR.MethodsA 3 Tesla LGE-CMR was performed in 53 individuals; the RA was segmented, and the image intensity ratio (IIR) calculated for the RA wall using 1 557 767 IIR pixels (40 994 ± 10 693 per patient). The upper limit of normality of the IIR (mean IIR + 2 standard deviations) was estimated in healthy volunteers (n = 9), and patients who had undergone previous typical atrial flutter ablation (n = 9) were used to establish the dense scar threshold. Paroxysmal and persistent AF patients (n = 10 each) were used for validation. IIR values were correlated with a high-density bipolar voltage map in 15 patients undergoing AF ablation.ResultsThe upper normality limit (total fibrosis threshold) in healthy volunteers was set at an IIR  =  1.21. In the postablation group, 60% of the maximum IIR pixel (dense fibrosis threshold) was calculated as IIR  =  1.29. Endocardial bipolar voltage showed a weak but significant correlation with IIR. The overall accuracy between the electroanatomical map and LGE-CMR to characterize fibrosis was 56%.ConclusionsAn IIR  >  1.21 was determined to be the threshold for the detection of right atrial fibrosis, while an IIR  >  1.29 differentiates interstitial fibrosis from dense scar. Despite differences between the left and right atria, fibrosis could be assessed with LGE-CMR using similar thresholds in both chambers.     

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.     

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.     

Asociación del consumo máximo de oxígeno con la actividad física y el sedentarismo en el síndrome metabólico. Utilidad de los cuestionarios

Introduction and objectivesTo analyze whether variations in physical activity (PA) and sedentary behaviors are accompanied by differences in maximal oxygen consumption (VO_2max).MethodsWe conducted a prospective cross-sectional study of 243 participants (82 women), aged 65.0 ± 4.9 years old, with metabolic syndrome and overweight/obesity who performed a maximal exercise test with expired gas analysis. PA was evaluated using subjective methods, the REGICOR and RAPA 1 self-reported questionnaires, and objective methods, the chair test and accelerometry. Sedentariness was analyzed with the Nurses’ Health Study questionnaire and accelerometry.ResultsVO_2max was higher in participants who reported they adhered to the recommendations of the PA guidelines in the REGICOR questionnaire (21.3 ± 4.6 vs 18.0 ± 4.4 mL/kg/min; P < .001) and was 18% higher in those who reported more PA in the RAPA 1 questionnaire than the less active group (P < .001). The chair test (> 15 vs ≤ 15 repetitions) also showed significant differences in VO_2max (21.2 ± 4.8 vs 18.7 ± 4.5 ml/Kg/min; P < .001). Correlations between PA variables and VO_2max were significant but low (r: 0.2 to 0.4). Sedentary activities showed less relationship with VO_2max.ConclusionsParticipants with metabolic syndrome and overweight/obesity who reported adhering to PA recommendations achieved higher VO_2max. The self-reported questionnaires and the chair test identified significant variations in VO_2max. Sedentary activities do not appear to modify VO_2max.Full English text available from:www.revespcardiol.org/en     

Minimal agreement between basophil activation test and immunoassay in diagnosis of penicillin allergy

IntroductionBasophil activation test (BAT) and immunoassays are the most widely used in vitro tests to diagnose IgE-mediated allergic reactions to penicillin. However, studies to determine if one test is interdependent from another are limited.ObjectiveThe present study aimed to measure the agreement between BAT and immunoassay in diagnosis of penicillin allergy.MethodBAT was performed using penicillin G (Pen G), penicillin V (Pen V), penicilloyl-polylysine (PPL), minor determinant mix (MDM), amoxicillin (Amx) and ampicillin (Amp) in 25 patients. Immunoassay of total IgE (tIgE) and specific IgE (sIgE) antibodies to Pen G, Pen V, Amx and Amp were quantified. Skin prick test (SPT) using PPL-MDM, Amx, Amp and Clavulanic acid were also performed.ResultsMinimal agreement was observed between BAT and immunoassay (k = 0.25). Of two BAT-positive patients, one patient is positive to Amx (59.27%, SI = 59) and Amp (82.32%, SI = 82) but sIgE-negative to all drug tested. This patient is also SPT-positive to both drugs. Another patient is BAT-positive to Pen G (10.18%, SI = 40), Pen V (25.07%, SI = 100) and Amp (19.52%, SI = 79). In sIgE immunoassay, four patients were sIgE-positive to at least one of the drugs tested. The sIgE level of three patients was between low and moderate and they were BAT-negative. One BAT-positive patient had a high level of sIgE antibodies (3.50–17.5 kU/L) along with relatively high specific to total IgE ratio ≥0.002 (0.004–0.007).ConclusionsThe agreement between BAT and immunoassay is minimal. Performing both tests provides little increase in the sensitivity of allergy diagnosis work-up for immediate reactions to penicillin.     

Clinical significance of myocardial contraction fraction in significant primary mitral regurgitation

BackgroundThe optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) − the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume − is a volumetric measure of LV myocardial shortening independent of size or geometry.AimTo assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice.MethodsClinical, Doppler-echocardiographic and outcome data prospectively collected in 174 patients (mean age 62 years, 27% women) with significant primary MR and no or mild symptoms were analysed. The impact of MCF< or ≥30% on cardiac events (cardiovascular death, acute heart failure or MV surgery) was studied.ResultsDuring an estimated median follow-up of 49 (22–77) months, cardiac events occurred in 115 (66%) patients. The 4-year estimates of survival free from cardiac events were 21 ± 5% for patients with MCF <30% and 40 ± 6% for those with ≥30% (P < 0.001). MCF <30% was associated with a considerable increased risk of cardiac events after adjustment for established clinical risk factors, MR severity and current recommended class I triggers for MV surgery (adjusted hazard ratio: 2.33, 95% confidence interval: 1.51−3.58; P < 0.001). Moreover, MCF < 30% improved the predictive performance of models, with better global fit, reclassification and discrimination.ConclusionsMCF < 30% is strongly associated with occurrence of cardiac events in patients with significant primary MR due to prolapse. Further studies are needed to assess the direct impact of MCF on patient management and outcomes.     

Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy,antiplatelet therapy and inflammation

BackgroundCoronavirus disease 2019 (COVID-19) is associated with an inflammatory cytokine burst and a prothrombotic coagulopathy. Platelets may contribute to microthrombosis, and constitute a therapeutic target in COVID-19 therapy.AimTo assess if platelet activation influences mortality in COVID-19.MethodsWe explored two cohorts of patients with COVID-19. Cohort A included 208 ambulatory and hospitalized patients with varying clinical severities and non-COVID patients as controls, in whom plasma concentrations of the soluble platelet activation biomarkers CD40 ligand (sCD40L) and P-selectin (sP-sel) were quantified within the first 48 hours following hospitalization. Cohort B was a multicentre cohort of 2878 patients initially admitted to a medical ward. In both cohorts, the primary outcome was in-hospital mortality.ResultsIn cohort A, median circulating concentrations of sCD40L and sP-sel were only increased in the 89 critical patients compared with non-COVID controls: sP-sel 40,059 (interquartile range 26,876–54,678) pg/mL; sCD40L 1914 (interquartile range 1410–2367) pg/mL (P < 0.001 for both). A strong association existed between sP-sel concentration and in-hospital mortality (Kaplan-Meier log-rank P = 0.004). However, in a Cox model considering biomarkers of immunothrombosis, sP-sel was no longer associated with mortality, in contrast to coagulopathy evaluated with D-dimer concentration (hazard ratio 4.86, 95% confidence interval 1.64–12.50). Moreover, in cohort B, a Cox model adjusted for co-morbidities suggested that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality (hazard ratio 1.05, 95% CI 0.80–1.37; P = 0.73).ConclusionsAlthough we observed an association between excessive biomarkers of platelet activation and in-hospital mortality, our findings rather suggest that coagulopathy is more central in driving disease progression, which may explain why prehospitalization antiplatelet drugs were not a protective factor against mortality in our multicentre cohort.     

Valor pronóstico de la fibrosis hepática valorada por el índice FIB4 en pacientes ingresados por síndrome coronario agudo

Introduction and objectivesLiver fibrosis is present in nonalcoholic liver disease (NAFLD) and both precede liver failure. Subclinical forms of liver fibrosis might increase the risk of cardiovascular events. The objective of this study was to describe the prognostic value of the FIB-4 index on in-hospital mortality and postdischarge outcomes in patients with acute coronary syndrome (ACS).MethodsRetrospective study including all consecutive patients admitted for ACS between 2009 and 2019. According to the FIB-4 index, patients were categorized as < 1.30, 1.30-2.67 or > 2.67. Heart failure (HF) and major bleeding (MB) were assessed taking all-cause mortality as a competing event and subhazard ratios (sHR) are presented. Recurrent events were evaluated by the incidence rate ratio (IRR).ResultsWe included 3106 patients and 6.66% had a FIB-4 index ≥ 1.3. A multivariate analysis verified a higher risk of in-hospital mortality associated with the FIB-4 index (OR, 1.24; P = .016). Patients with a FIB-4 index > 2.67 had a 2-fold higher in-hospital mortality risk (OR, 2.35; P = .038). After discharge (median follow-up 1112 days), the FIB-4 index had no prognostic value for mortality. In contrast, patients with FIB-4 index ≥ 1.3 had a higher risk of first (sHR, 1.61; P = .04) or recurrent (IRR, 1.70; P = .001) HF readmission. Similarly, FIB-4 index ≥ 1.30 was associated with a higher MB risk (sHR, 1.62; P = .030).ConclusionsThe assessment of liver fibrosis by the FIB-4 index identifies ACS patients not only at higher risk of in-hospital mortality but also at higher risk of HF and MB after discharge.Full English text available from:www.revespcardiol.org/en     

The relationship of family history and risk of type 2 diabetes differs by ancestry

AimType 2 diabetes (T2DM) in a first-degree relative is a risk factor for incident diabetes. Americans of African ancestry (AA) have higher rates of T2DM than Americans of European ancestry (EA). Thus, we aimed to determine whether the presence, number and kinship of affected relatives are associated with race-specific T2DM incidence in a prospective study of participants from the Genetic Study of Atherosclerosis Risk (GeneSTAR), who underwent baseline screening including a detailed family history.MethodsNondiabetic healthy siblings (n = 1405) of patients with early-onset coronary artery disease (18–59 years) were enrolled (861 EA and 544 AA) and followed for incident T2DM (mean 14 ± 6 years).ResultsBaseline age was 46.2 ± 7.3 years and 56% were female. T2DM occurred in 12.3% of EA and 19.1% of AA. Among EA, 32.6% had ≥ 1 affected first-degree relatives versus 53.1% in AA, P < 0.0001. In fully adjusted Cox proportional hazard analyses, any family history was related to incident T2DM in EA (HR = 2.53, 95% CI: 1.58–4.06) but not in AA (HR = 1.01, 0.67–1.53). The number of affected relatives conferred incremental risk of T2DM in EA with HR = 1.82 (1.08–3.06), 4.83 (2.15–10.85) and 8.46 (3.09–23.91) for 1, 2, and ≥ 3 affected, respectively. In AA only ≥ 3 affected increased risk (HR = 2.45, 1.44–4.19). Specific kinship patterns were associated with incident T2DM in EA but not in AA.ConclusionsThe presence of any first-degree relative with T2DM does not discriminate risk in AA given the high race-specific prevalence of diabetes. Accounting for the number of affected relatives may more appropriately estimate risk for incident diabetes in both races.     

Comparative non-persistence in the first year of treatment with oral anticoagulants in patients with atrial fibrillation: A French comprehensive nationwide study

BackgroundDirect oral anticoagulants (DOACs) were developed as an alternative to vitamin K antagonists (VKAs) and are commonly used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Unlike VKAs, DOACs do not require Internal Normalized Ratio (INR) monitoring, but regular intake is as important for effective anticoagulation.ObjectivesThis study examined treatment persistence among patients receiving oral anticoagulants (OACs) for NVAF.MethodsWithin the French healthcare claims database (SNDS), we assessed and compared the rates of non-persistence (≥ 30-day treatment gap) among patients with NVAF initiating an OAC between January 2014 and December 2016. The time-to-event of non-persistence was computed and plotted using a cumulative incidence function accounting for the competing risk of mortality. After adjusting on confounding factors, the risk for non-persistence was compared between apixaban and each other OACs using a Cox proportional hazard model, or Fine and Gray models.ResultsIn a cohort of 321,501 OAC-naive patients with NVAF, the cumulative incidence of non-persistence at 12 months considering competing risk was 44.3%, 31.0%, 41.3% and 46.8% for VKAs, apixaban, rivaroxaban and dabigatran, respectively. Median therapy duration before non-persistence ranged between 70 and 121 days. Non-persistence was lower with apixaban compared with VKAs (HR = 0.63, 95%CI = [0.62–0.64]), rivaroxaban (HR = 0.71, 95%CI = [0.70–0.73]), and dabigatran (HR = 0.60, 95%CI = [0.59–0.62]).ConclusionsIn this nationwide observational study, non-persistence rates of oral anticoagulant treatment were high in patients treated for NVAF. Apixaban-treated patients seem to experience lowest discontinuation rates 12 months after treatment initiation compared to patients treated with any other OAC.     

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials

Background and aimsA dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF.MethodsSystematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60–90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator.ResultsThe initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I² = 74%, Chi² = 11.57, p = 0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio = 0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio = 0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF.ConclusionIn a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.     

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.     

Management and long-term outcomes of patients with chronic inflammatory diseases experiencing ST-segment elevation myocardial infarction: The SCALIM registry

BackgroundPatients with chronic inflammatory diseases (CIDs) are at increased risk of cardiovascular events. However, the prognostic impact of CID after an acute coronary event has been poorly studied.AimsTo examine the effect of history of CID on long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI).MethodsWe analysed data from SCALIM, a regional registry that prospectively enrolled patients with STEMI between June 2011 and May 2019. The presence of CID (including inflammatory bowel diseases, rheumatic conditions, inflammatory skin diseases, multiple sclerosis, vasculitis and autoimmune diseases) was identified. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction, ischaemic stroke, peripheral vascular events and rehospitalization for cardiovascular conditions.ResultsData from 1941 patients with STEMI (mean age 64.8 ± 14.1 years, 75.1% men) were analyzed. The prevalence of any CID was 4.6% (n = 89). After a mean follow-up of 3.4 ± 2.6 years, the overall death rate was 16.2%, with similar 5-year survival between patients with and without CID (74.2% vs. 81.9%, respectively; P = 0.121), with no significant mortality excess (hazard ratio: 1.15, 95% confidence interval: 0.73 ? 1.82; P = 0.55). However, among CID patients, 35 (39.3%) were on corticosteroid therapy and showed decreased 5-year survival (52.8% vs. 89.5% without corticosteroids; P = 0.001). We found no increased rate of secondary endpoints, except for peripheral vascular events (5-year survival free of peripheral events: 93.3% vs. 98.6% in those without CID; P = 0.005).ConclusionsApproximately 1 in 20 patients with STEMI has CID. We found no effect of CID on long-term survival. However, patients on corticosteroid therapy appeared to have higher rates of death during follow-up. Whether this finding is related to the use of corticosteroids or to the more progressive nature of their condition warrants further investigation.     

El cociente de flujo cuantitativo en pacientes con estenosis aórtica grave y lesiones coronarias intermedias

Introduction and objectivesQuantitative flow ratio (QFR) is a novel noninvasive method for evaluating coronary physiology. However, data on the QFR in patients with aortic stenosis (AS) and coronary artery disease are scarce. Thus, we compared the diagnostic performance of the QFR with that of the resting distal to aortic coronary pressure (Pd/Pa) ratio, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR), as well as angiographic indices.MethodsA total of 221 AS patients with 416 vessels undergoing FFR/iFR measurements were enrolled in the study.ResultsThe mean percent diameter stenosis (%DS) was 58.6% ± 13.4% and the mean Pd/Pa ratio, FFR, iFR, and QFR were 0.95 ± 0.03, 0.85 ± 0.07, 0.90 ± 0.04, and 0.84 ± 0.07, respectively. A FFR ≤ 0.80 was noted in 26.0% of interrogated vessels, as well as an iFR ≤ 0.89 in 33.2% and QFR ≤ 0.80 in 31.7%. The QFR had better agreement with FFR (intraclass correlation coefficient [ICC], 0.96; 95% confidence interval [95%CI], 0.95-0.96) than with the iFR (ICC, 0.79; 95%CI, 0.75-0.82) and Pd/Pa ratio (ICC, 0.52; 95%CI, 0.44-0.58). In addition, the QFR showed better diagnostic accuracy (98.6% vs 94.2%; P < .001) and discriminant function (area under the curve = 0.996 vs 0.988; P < .001) when the iFR was used as the reference instead of FFR.ConclusionsIn patients with AS, the QFR has good agreement with both FFR and iFR. However, the agreement appears to be even better when the iFR is used as the reference, presumably due to the complex nature of the coronary physiology in the assessment of coronary artery disease in patients with severe AS.     

PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD

AimWe aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism.Materials and methodsWe enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a ‘strict-normal’ TSH group (TSH level 0.4 to 2.5 mIU/L; n = 283) and a ‘high-normal’ TSH group (TSH level 2.5 to 5.3 mIU/L with normal thyroid hormones; n = 44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes.ResultsCompared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298–8.284; P = 0.012).ConclusionIn euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.     

Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis

Introduction and objectivesNon-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. It is often related to metabolic syndrome, presenting an increased risk of advanced liver disease and cardiovascular-related death. In some etiologies of chronic liver disease, thrombocytopenia has been associated not only with advanced stages of fibrosis but also with autoimmune disease. In NAFLD, however, its prevalence and related factors are still unknown. The aim of this study is to evaluate the prevalence of thrombocytopenia in NAFLD patients without cirrhosis and to investigate its related risk factors.Patients and methodsThis was a retrospective study carried out in two tertiary hospitals in the South and Southeast regions of Brazil. Patients diagnosed with NAFLD by liver biopsy were included. Those with other causes of liver disease and/or cirrhosis were excluded. For analysis, patients were divided into two groups, with and without thrombocytopenia. Data was analyzed using a significance level of 5%.Results441 non-cirrhotic patients with NAFLD (evaluated by liver biopsy) were included in the study. The prevalence of thrombocytopenia was 3.2% (14/441 patients). In the comparative analysis between groups, thrombocytopenia was associated with male sex (p = 0.007) and level of hemoglobin (p = 0.023).ConclusionThrombocytopenia is an infrequent event in NAFLD patients without cirrhosis and is related with male sex and higher hemoglobin levels.     

Transcatheter edge-to-edge repair following surgical valve repair with ring implantation: Results from the multicentre “Clip-in-Ring” registry

BackgroundManagement of mitral regurgitation recurrence after failed surgical valve repair with ring implantation is controversial.AimTo describe the French experience regarding midterm safety and efficacy of transcatheter edge-to-edge mitral valve repair (TEER) in patients with failed surgical valve repair with ring implantation.MethodsThe “Clip-in-Ring” registry is a multicentre registry conducted in 11 centres in France, approved by local institutional review boards, of consecutive TEER following surgical valve repair with ring implantation. Outcomes were Mitral Valve Academic Research Consortium (MVARC) technical success, modified 30-day device and procedural success (where 10 mmHg is considered as a cut-off for significant mitral stenosis) and MVARC complications.ResultsTwenty-three patients were studied: mean age, 69 ± 10 years; male sex, 74%; EuroSCORE II, 16 ± 17; left ventricular ejection fraction, 53 ± 12%; mitral regurgitation grade 3+/4+, 17%/78%; New York Heart Association class III/IV, 47%/22%; median surgery to TEER delay, 23 (6–94) months. Technical success was 100%. At discharge, residual mitral regurgitation grade was ≤ 2+ in 87% and median transmitral gradient was 4 (3–5) mmHg. Thirty-day modified MVARC device and procedural success was 82%: four patients (17%) had residual mitral regurgitation grade > 2+, including two patients who needed complementary surgery. No patient had a 30-day transmitral gradient > 7 mmHg. No patient died or had a stroke or any life-threatening complications. One patient presented a vascular access complication requiring transfusion. No other MVARC-2 adverse event was reported.ConclusionsTEER in patients with failed mitral ring is feasible and safe. Further studies should delineate its exact role in the therapeutic armamentarium for this medical issue.     

Perfil lipoproteico por espectroscopia nuclear magnética en pacientes con insuficiencia cardiaca crónica comparado con controles emparejados

Introduction and objectivesAdvanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population.MethodsThis cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using ¹H magnetic resonance spectroscopy.ResultsThe 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P < .001) and HDL (25.7 vs 27.9 μmol/L; P < .001) particle concentrations, with this last difference being mediated by a significantly lower concentration of the small subfraction of HDL (15.2 vs 18.6 μmol/L; P < .001). Mean very low-density lipoprotein, LDL, and HDL particle size was significantly higher in patients with HF vs controls. All HDL-related differences from controls persisted after adjustment for New York Heart Association functional class or body mass index. We found strong negative correlations of known cardiac biomarkers (N-terminal pro-brain natriuretic peptide and interleukin-1 receptor-like 1) with total and small LDL and HDL fractions and HDL particle size.ConclusionsPatients with chronic HF significantly differ in their lipoprotein profile compared with unaffected controls. Further research is needed to better understand the pathogenic relevance of this difference.     

Lipid-lowering efficacy and safety of alirocumab in a real-life setting in France: Insights from the ODYSSEY APPRISE study

BackgroundRecently, a multicentre, prospective, single-arm, phase 3b, open-label trial was conducted to determine the safety and efficacy of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting. This study enrolled patients at high cardiovascular risk, with heterozygous familial hypercholesterolaemia (HeFH) or non-familial hypercholesterolaemia (non-FH). Results showed that alirocumab was well tolerated and resulted in a clinically signi?cant reduction in low-density lipoprotein cholesterol (LDL-C).AimThis ancillary analysis aimed to describe the characteristics of the French patients enrolled in the study, the main results observed in this population according to their familial hypercholesterolaemia status, and adherence to treatment.MethodsFrench data were analysed separately from the original dataset of the study.ResultsAmong 215 French patients in the ODYSSEY APPRISE trial, 63.7% had non-FH, with a mean LDL-C concentration of 5.0 ± 1.8 mmol/L at baseline. The mean duration of alirocumab exposure was 72.4 ± 42.5 weeks, with only 48.4% of patients receiving statins concomitantly. At week 12, a mean reduction in LDL-C of 56.5 ± 17.8% was observed: 51.2 ± 22.8% in HeFH; 59.5 ± 13.2% in non-FH. This improvement in LDL-C started from week 4 and remained stable and sustained until week 120 in both populations. The overall incidence of severe treatment-emergent adverse events (TEAEs) was 33.5%. The most frequent TEAEs were myalgia (15.8%) and asthenia (15.3%). No tolerance or efficacy differences were observed between patients with or without established coronary artery disease or other cardiovascular disease, whatever the age of these events or considering the concomitant use of other lipid-lowering therapies.ConclusionsIn the French setting, alirocumab was well tolerated, safe and highly effective at reducing LDL-C. These findings support the use of alirocumab to manage hypercholesterolaemia in patients at high cardiovascular risk.     

Resultados de la ablación con catéter con mínimo o nulo empleo de fluoroscopia en pacientes pediátricos con taquiarritmias supraventriculares

Introduction and objectivesIonizing radiation exposure in catheter ablation procedures carries health risks, especially in pediatric patients. Our aim was to compare the safety and efficacy of catheter ablation guided by a nonfluoroscopic intracardiac navigation system (NFINS) with those of an exclusively fluoroscopy-guided approach in pediatric patients.MethodsWe analyzed catheter ablation results in pediatric patients with high-risk accessory pathways or supraventricular tachycardia referred to our center during a 6-year period. We compared fluoroscopy-guided procedures (group A) with NFINS guided procedures (group B).ResultsWe analyzed 120 catheter ablation procedures in 110 pediatric patients (11 ± 3.2 years, 70% male); there were 62 procedures in group A and 58 in group B. We found no significant differences between the 2 groups in procedure success (95% group A vs 93.5% group B; P = .53), complications (1.7% vs 1.6%; P = .23), or recurrences (7.3% vs 6.9%; P = .61). However, fluoroscopy time (median 1.1 minutes vs 12 minutes; P < .0005) and ablation time (median 96.5 seconds vs 133.5 seconds; P = .03) were lower in group B. The presence of structural heart disease was independently associated with recurrence (P = .03).ConclusionsThe use of NFINS to guide catheter ablation procedures in pediatric patients reduces radiation exposure time. Its widespread use in pediatric ablations could decrease the risk of ionizing radiation.