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.     

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.     

Índice de masa corporal y eficacia y seguridad del ticagrelor frente al prasugrel en pacientes con síndrome coronario agudo

Introduction and objectivesThe efficacy and safety of ticagrelor vs prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unstudied. We assessed the efficacy and safety of ticagrelor vs prasugrel in patients with ACS according to BMI.MethodsPatients (n = 3987) were grouped into 3 categories: normal weight (BMI < 25 kg/m²; n = 1084), overweight (BMI ≥ 25 to < 30 kg/m²; n = 1890), and obesity (BMI ≥ 30 kg/m²; n = 1013). The primary efficacy endpoint was the 1 year incidence of all-cause death, myocardial infarction, or stroke. The secondary safety endpoint was the 1 year incidence of Bleeding Academic Research Consortium type 3 to 5 bleeding.ResultsThe primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the normal weight group (11.7% vs 7.5%; HR, 1.62; 95%CI, 1.09-2.42; P = .018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the overweight group (8.3% vs 6.2%; HR, 1.36; 95%CI, 0.97-1.91; P = .076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the obesity group (8.6% vs 7.3%; HR, 1.18; 95%CI, 0.76-1.84; P = .451). The 1-year incidence of bleeding events did not differ between ticagrelor and prasugrel in patients with normal weight (6.5% vs 6.6%; P = .990), overweight (5.6% vs 5.0%; P = .566) or obesity (4.4% vs 2.8%; P = .219). There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (P_int = .578) or secondary endpoint (P_int = .596).ConclusionsIn patients with ACS, BMI did not significantly impact the treatment effect of ticagrelor vs prasugrel in terms of efficacy or safety.Clinical Trial Registration: NCT01944800.     

Impact of left atrial and diastolic ventricular dysfunction on mortality in patients with aortic stenosis

BackgroundDiastolic dysfunction (DD) is common in severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF ≥ 50%).AimTo determine the impact of American Society of Echocardiography/European Association of Cardiovascular Imaging-recommended DD grading and left atrial strain on mortality in a cohort of patients with severe AS and preserved LVEF.MethodsWe studied patients with severe AS (aortic valve area indexed < 0.6 cm²/m² and/or aortic valve area < 1 cm²), LVEF ≥ 50% and no or mild AS-related symptoms. The endpoint was all-cause mortality.ResultsA total of 387 patients (median age 76 years; 53% women) were studied. During a median follow-up of 57 (interquartile range 37; 83) months, 158 patients died. After adjustment for prognostic factors, patients with grade II or III DD had an increased mortality risk versus patients with grade I DD (adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.11–2.38; P = 0.013; aHR 4.73, 95% CI 2.49–8.99; P < 0.001; respectively). Adding peak atrial longitudinal strain (PALS) ≤ 14% to a multivariable model including DD grade improved predictive performance, with better global model fit, reclassification and discrimination. Patients with grade III DD or grade II DD + PALS ≤ 14% displayed an increased mortality risk versus patients with grade I DD + PALS > 14% (aHR 4.17, 95% CI 2.46–7.06; P < 0.0001). Those with grade I DD + PALS ≤ 14% or grade II DD + PALS > 14% were at intermediate risk (aHR 1.63, 95% CI 1.07–2.49; P = 0.024).ConclusionsOur results demonstrate the strong relationship between DD and mortality in patients with severe AS and preserved LVEF. Patients with grade III or grade II DD and impaired PALS are at very high risk. These data demonstrate the importance of a comprehensive assessment of diastolic function in patients with severe AS.     

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.     

Resultados en España de la encuesta de la Sociedad Europea de Cardiología sobre terapia de resincronización cardiaca (CRT-Survey II)

Introduction and objectivesWe describe the results for Spain of the Second European Cardiac Resynchronization Therapy Survey (CRT-Survey II) and compare them with those of the other participating countries.MethodsWe included patients undergoing CRT device implantation between October 2015 and December 2016 in 36 participating Spanish centers. We registered the patients’ baseline characteristics, implant procedure data, and short-term follow-up information until hospital discharge.ResultsImplant success was achieved in 95.9%. The median [interquartile range] annual implantation rate by center was significantly lower in Spain than in the other participating countries: 30 implants/y [21-50] vs 55 implants/y [33-100]; P = .00003. In Spanish centers, there was a lower proportion of patients ≥ 75 years (27.9% vs 32.4%; P = .0071), a higher proportion in NYHA class II (46.9% vs 36.9%, P < .00001), and a higher percentage with electrocardiographic criteria of left bundle branch block (82.9% vs 74.6%; P < .00001). The mean length of hospital stay was significantly lower in Spanish centers (5.8 ± 8.5 days vs 6.4 ± 11.6; P < .00001). Spanish patients were more likely to receive a quadripolar LV lead (74% vs 56%, P < .00001) and to be followed up by remote monitoring (55.8% vs 27.7%; P < .00001).ConclusionsThe CRT-Survey II shows that, compared with other participating countries, fewer patients in Spain aged ≥ 75 years received a CRT device, while more patients were in New York Heart Association functional class II and had left bundle branch block. In addition, the length of hospital stay was shorter, and there was greater use of quadripolar LV leads and remote CRT monitoring.Full English text available from:www.revespcardiol.org/en     

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.     

Dilatación de la aurícula izquierda en deportistas de alta competición y electrofisiología auricular

Introduction and objectivesThere are scarce data on left atrial (LA) enlargement and electrophysiological features in athletes.MethodsMulticenter observational study in competitive athletes and controls. LA enlargement was defined as LA volume indexed to body surface area ≥ 34 mL/m². We analyzed its relationship with atrial electrocardiography parameters.ResultsWe included 356 participants, 308 athletes (mean age: 36.4 ± 11.6 years) and 48 controls (mean age: 49.3 ± 16.1 years). Compared with controls, athletes had a higher mean LA volume index (29.8 ± 8.6 vs 25.6 ± 8.0 mL/m², P = .006) and a higher prevalence of LA enlargement (113 [36.7%] vs 5 [10.4%], P < .001), but there were no relevant differences in P-wave duration (106.3 ± 12.5 ms vs 108.2 ± 7.7 ms; P = .31), the prevalence of interatrial block (40 [13.0%] vs 4 [8.3%]; P = .36), or morphology-voltage-P-wave duration score (1.8 ± 0.84 vs 1.5 ± 0.8; P = .71). Competitive training was independently associated with LA enlargement (OR, 14.7; 95%CI, 4.7-44.0; P < .001) but not with P-wave duration (OR, 1.02; 95%CI, 0.99-1.04), IAB (OR, 1.4; 95%CI, 0.7-3.1), or with morphology-voltage-P-wave duration score (OR, 1.4; 95%CI, 0.9-2.2).ConclusionsLA enlargement is common in adult competitive athletes but is not accompanied by a significant modification in electrocardiographic parameters.     

Comparación de seguridad y efectividad entre los accesos radiales derecho e izquierdo en la intervención coronaria percutánea

Introduction and objectivesThere is a paucity of data comparing the left radial approach (LRA) and right radial approach (RRA) for percutaneous coronary intervention (PCI) in all-comers populations and performed by operators with different experience levels. Thus, we sought to compare the safety and clinical outcomes of the RRA and LRA during PCI in “real-world” patients with either stable angina or acute coronary syndrome (ACS).MethodsTo overcome the possible impact of the nonrandomized design, a propensity score was calculated to compare the 2 radial approaches. The study group comprised 18 716 matched pairs with stable angina and 46 241 with ACS treated with PCI and stent implantation between 2014 and 2017 in 151 tertiary invasive cardiology centers in Poland (the ORPKI Polish National Registry).ResultsThe rates of death and periprocedural complications were similar for the RRA and LRA in stable angina patients. A higher radiation dose was observed with PCI via the LRA in both clinical presentations (stable angina: 1067.0 ± 947.1 mGy vs 1007.4 ± 983.5 mGy, P = .001; ACS: 1212.7 ± 1005.5 mGy vs 1053.5 ± 1029.7 mGy, P = .001). More contrast was used in LRA procedures but only in ACS patients (174.2 ± 75.4 mL vs 167.2 ± 72.1 mL, P = .001). Furthermore, periprocedural complications such as coronary artery dissection (0.16% vs 0.09%, P = .008), no-reflow phenomenon (0.65% vs 0.49%, P = .005), and puncture site bleeding (0.09% vs 0.05%, P = .04) were more frequently observed with the LRA in ACS patients. There was no difference in mortality between the 2 groups (P = .90).ConclusionsOur finding of poorer outcomes with the LRA may be related to lower operator experience with this approach. While both the LRA and RRA are safe in the setting of stable angina, the LRA was associated with a higher rate of periprocedural complications during PCI in ACS patients.Full English text available from:www.revespcardiol.org/en     

Transcatheter aortic valve implantation using the SAPIEN 3 valve to treat aortic regurgitation: The French multicentre S3AR study

BackgroundTranscatheter aortic valve implantation now has a major role in the treatment of patients with severe aortic stenosis. However, evidence is scarce on its feasibility and safety to treat patients with pure aortic regurgitation.AimsWe sought to evaluate the results of transcatheter aortic valve implantation using the balloon-expandable SAPIEN 3 transcatheter heart valve (Edwards Lifesciences, Irvine, CA, USA) in patients with pure aortic regurgitation on native non-calcified valves.MethodsWe conducted a retrospective and prospective French multicentre observational study. We included all patients with symptomatic severe pure aortic regurgitation on native non-calcified valves, contraindicated to or at high risk for surgical valve replacement, who underwent transcatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve.ResultsA total of 37 patients (male sex, 73%) with a median age of 81 years (interquartile range 69–85 years) were screened using transthoracic echocardiography and computed tomography and were included at eight French centres. At baseline, 83.8% of patients (n = 31) had dyspnoea New York Heart Association class ≥ III. The device success rate was 94.6% (n = 35). At 30 days, the all-cause mortality rate was 8.1% (n = 3) and valve migration occurred in 10.8% of cases (n = 4). Dyspnoea New York Heart Association class ≤ II was seen in 86.5% of patients (n = 32), and all survivors had aortic regurgitation grade ≤ 1. At 1-year follow-up, all-cause mortality was 16.2% (n = 6), 89.7% (n = 26/29) of survivors were in New York Heart Association class ≤ II and all had aortic regurgitation grade ≤ 2.ConclusionTranscatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve seems promising to treat selected high-risk patients with pure aortic regurgitation on non-calcified native valves, contraindicated to surgical aortic valve replacement.     

Effect of maternal lifestyle intervention on metabolic health and adiposity of offspring: Findings from the Finnish Gestational Diabetes Prevention Study (RADIEL)

AimTo assess in women at high risk of gestational diabetes mellitus (GDM) the effect of a lifestyle intervention on the metabolic health of their offspring around 5 years after delivery.MethodsFor the original Finnish gestational diabetes prevention study (RADIEL), 720 women with a prepregnancy body mass index (BMI) ≥ 30 kg/m² and/or previous GDM were enrolled before or during early pregnancy and allocated to either an interventional (n = 126) or conventional (n = 133) care group. The present 5-year follow-up substudy assessed the metabolic health outcomes of their offspring. Age- and gender-standardized residuals of metabolic health components (waist circumference, mean arterial pressure, high-density lipoprotein and triglyceride levels, and fasting insulin/glucose ratio) were also combined to determine the accumulation of metabolic effects. Body composition was assessed by electrical bioimpedance.ResultsOffspring of women in the intervention group had a less optimal metabolic profile after the 5-year follow-up compared with offspring in the usual care group (P = 0.014). This difference in metabolic health was primarily related to lipid metabolism, and was more prominent among boys (P = 0.001) than girls (P = 0.74). Neither GDM, gestational weight gain, prepregnancy BMI, offspring age nor timing of randomization (before or during pregnancy) could explain the detected difference, which was also more pronounced among the offspring of GDM pregnancies (P = 0.010). Offspring body composition was similar in both groups (P > 0.05).ConclusionThe lifestyle intervention aimed at GDM prevention was associated with unfavourable metabolic outcomes among offspring at around 5 years of age.     

No inferioridad de la titulación de enfermera de insuficiencia cardiaca en comparación con la de cardiólogo de insuficiencia cardiaca. Ensayo aleatorizado multicéntrico ETIFIC

Introduction and objectivesBeta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin-II-receptor-blockers (ARB), and mineralocorticoid-receptor antagonists decrease mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. The effect is dose-dependent. Careful titration is recommended. However, suboptimal doses are common in clinical practice. This study aimed to compare the safety and efficacy of dose titration of the aforementioned drugs by HF nurses vs HF cardiologists.MethodsETIFIC was a multicenter (n = 20) noninferiority randomized controlled open label trial. A total of 320 hospitalized patients with new-onset HF, reduced ejection fraction and New York Heart Association II-III, without beta-blocker contraindications were randomized 1:1 in blocks of 4 patients each stratified by hospital: 164 to HF nurse titration vs 156 to HF cardiologist titration (144 vs 145 analyzed). The primary endpoint was the beta-blocker mean relative dose (% of target dose) achieved at 4 months. Secondary endpoints included ACE inhibitors, ARB, and mineralocorticoid-receptor antagonists mean relative doses, associated variables, adverse events, and clinical outcomes at 6 months.ResultsThe mean ± standard deviation relative doses achieved by HF nurses vs HF cardiologists were as follows: beta-blockers 71.09% ± 31.49% vs 56.29% ± 31.32%, with a difference of 14.8% (95%CI, 7.5-22.1), P < .001; ACE inhibitors 72.61% ± 29.80% vs 56.13% ± 30.37%, P < .001; ARB 44.48% ± 33.47% vs 43.51% ± 33.69%, P = .93; and mineralocorticoid-receptor antagonists 71% ± 32.12% vs 70.47% ± 29.78%, P = .86; mean ± standard deviation visits were 6.41 ± 2.82 vs 2.81 ± 1.58, P < .001, while the number (%) of adverse events were 34 (23.6) vs 30 (20.7), P = .55; and at 6 months HF hospitalizations were 1 (0.69) vs 9 (5.51), P = .01.ConclusionsETIFIC is the first multicenter randomized trial to demonstrate the noninferiority of HF specialist-nurse titration vs HF cardiologist titration. Moreover, HF nurses achieved higher beta-blocker/ACE inhibitors doses, with more outpatient visits and fewer HF hospitalizations.Trial registry number: NCT02546856.     

Five-year mortality in patients with diabetic foot ulcer during 2009–2010 was lower than expected

AimMortality rates are decreasing in patients with diabetes. However, as this observation also concerns patients with diabetic foot ulcer (DFU), additional data are needed. For this reason, our study evaluated the 5-year mortality rate in patients with DFU during 2009–2010 and identified risk factors associated with mortality.MethodsConsecutive patients who attended a clinic for new DFU during 2009–2010 were followed until healing and at 1 year. Data on mortality were collected at year 5. Multivariate Cox proportional-hazards model was used to identify mortality risk factors.ResultsA total of 347 patients were included: mean age was 65 ± 12 years, diabetes duration was 16 [10; 27] years; 13% were on dialysis; and 7% had an organ transplant. At 5 years, 49 patients (14%) were considered lost to follow-up. Total mortality rate at 5 years was 35%, and 16% in patients with neuropathy. On multivariate analyses, mortality was positively associated with: age [hazard ratio (HR): 1.05 (1.03–1.07), P < 0.0001]; duration of diabetes [HR: 1.02 (1.001–1.03], P = 0.03]; PEDIS perfusion grade 2 vs. 1 [HR: 2.35 (1.28–4.29), P = 0.006)]; PEDIS perfusion grade 3 vs. 1 [HR: 3.14 (1.58–6.24), P = 0.001); and ulcer duration at year 1 [HR 2.09 (1.35–3.22), P = 0.0009].ConclusionMortality rates were not as high as expected despite the large number of comorbidities, suggesting that progress has been made in the health management of these patients. In particular, patients with neuropathic foot ulcer had a survival rate of 84% at 5 years.     

Cierre de orejuela izquierda en pacientes mayores de 85 años: seguridad y eficacia del registro EWOLUTION

Introduction and objectivesElderly patients with atrial fibrillation are at greater risk of both cardioembolic events and major bleeding than younger patients. Left atrial appendage occlusion (LAAO) could be an attractive alternative for these patients, but there are limited data on outcomes with LAAO in patients ≥ 85 years old. The aim of the present study was to assess the safety and efficacy of LAAO in patients ≥ 85 years old.MethodsA total of 1025 patients included in the EWOLUTION registry who underwent LAAO were analyzed and 84 patients ≥ 85 years old were identified and compared with the younger cohort.ResultsPatients ≥ 85 years old had higher estimated stroke and hemorrhagic risks than younger patients (CHA₂DS₂-VASc: 5.2 ± 1.2 vs 4.4 ± 1.6, P < .0001; HAS-BLED: 2.7 ± 1.1 vs 2.3 ± 1.2; P = .003; ≥ 85 years vs < 85 years). Procedural success was high and similar in both groups (98.8% vs 98.5%; P = .99). There were no differences in 7-day device- or procedure-related adverse event rates (2.6% in ≥ 85 years vs 3.1% in < 85 years; P = .80). Despite the higher baseline stroke risk, there was no difference at follow-up between the groups in the annualized stroke rate (0.8/100 patient-years in ≥ 85 years vs 1.3/100 patient-years in < 85 years; P = .649).ConclusionsLAAO in patients ≥ 85 years is safe and effective even though these patients are at high risk for embolic and hemorrhagic events. LAAO may be a reasonable alternative to oral anticoagulation in these patients.     

Clustering of patients with inconclusive non-invasive stress testing referred for vasodilator stress cardiovascular magnetic resonance

BackgroundInconclusive non-invasive stress testing is associated with impaired outcome. This population is very heterogeneous, and its characteristics are not well depicted by conventional methods.AimsTo identify patient subgroups by phenotypic unsupervised clustering, integrating clinical and cardiovascular magnetic resonance data to unveil pathophysiological differences between subgroups of patients with inconclusive stress tests.MethodsBetween 2008 and 2020, consecutive patients with a first inconclusive non-invasive stress test referred for stress cardiovascular magnetic resonance were followed for the occurrence of major adverse cardiovascular events (defined as cardiovascular death or myocardial infarction). A cluster analysis was performed on clinical and cardiovascular magnetic resonance variables.ResultsOf 1402 patients (67% male; mean age 70 ± 11 years) who completed the follow-up (median 6.5 years, interquartile range 5.6–7.5 years), 197 experienced major adverse cardiovascular events (14.1%). Three distinct phenogroups were identified based upon unsupervised hierarchical clustering of principal components: phenogroup 1 = history of percutaneous coronary intervention with viable myocardial infarction and preserved left ventricular ejection fraction; phenogroup 2 = atrial fibrillation with preserved left ventricular ejection fraction; and phenogroup 3 = coronary artery bypass graft with non-viable myocardial scar and reduced left ventricular ejection fraction. Using survival analysis, the occurrence of major adverse cardiovascular events (P = 0.007), cardiovascular mortality (P = 0.002) and all-cause mortality (P < 0.001) differed among the three phenogroups. Phenogroup 3 presented the worse prognosis. In each phenogroup, ischaemia was associated with major adverse cardiovascular events (phenogroup 1: hazard ratio 2.79, 95% confidence interval 1.61–4.84; phenogroup 2: hazard ratio 2.59, 95% confidence interval 1.69–3.97; phenogroup 3: hazard ratio 3.16, 95% confidence interval 1.82–5.49; all P < 0.001).ConclusionsCluster analysis of clinical and cardiovascular magnetic resonance variables identified three phenogroups of patients with inconclusive stress testing, with distinct prognostic profiles.     

Función endotelial y microvascular distal a stents farmacoactivos sin polímero y captadores de células endoteliales. Estudio aleatorizado FUNCOMBO

Introduction and objectivesThe vasomotor function of new-generation drug-eluting stents designed to enhance stent healing and reendothelialization is unknown. This study aimed to compare the endothelial function of the infarct-related artery (IRA) treated with bioactive circulating endothelial progenitor cell-capturing sirolimus-eluting stents (COMBO) vs polymer-free biolimus-eluting stents (BioFreedom) in ST-segment elevation myocardial infarction patients at 6 months. Secondary objectives were to compare the microcirculatory function of the IRA and stent healing at 6 months.MethodsSixty patients were randomized to bioactive sirolimus-eluting stent vs polymer-free biolimus-eluting stents implantation. At 6 months, patients underwent coronary angiography with vasomotor, microcirculatory and optical coherence tomography examinations. Endothelial dysfunction of the distal coronary segment was defined as ≥ 4% vasoconstriction to intracoronary acetylcholine infusion.ResultsEndothelial dysfunction was similarly observed between groups (64.0% vs 62.5%, respectively; P = .913). Mean lumen diameter decreased by 16.0 ± 20.2% vs 16.1 ± 21.6% during acetylcholine infusion (P = .983). Microcirculatory function was similar in the 2 groups: coronary flow reserve was 3.23 ± 1.77 vs 3.23 ± 1.62 (P = .992) and the index of microcirculatory resistance was 24.8 ± 16.8 vs 21.3 ± 12.0 (P = .440). Optical coherence tomography findings were similar: uncovered struts (2.3% vs 3.2%; P = .466), malapposed struts (0.1% vs 0.3%; P = .519) and major evaginations (7.1% vs 5.6%; P = .708) were observed in few cases.ConclusionsEndothelial dysfunction of the IRA was frequent and was similarly observed with new-generation drug-eluting stents designed to enhance stent reendothelialization at 6 months. Endothelial dysfunction was observed despite almost preserved microcirculatory function and complete stent coverage. Larger and clinically powered studies are needed to assess the role of residual endothelial dysfunction in ST-segment elevation myocardial infarction patients.Registered in ClinicalTrials.gov: NCT04202172Full English text available from:www.revespcardiol.org/en     

Relationship between renal capacity to reabsorb glucose and renal status in patients with diabetes

AimsInterindividual variability in capacity to reabsorb glucose at the proximal renal tubule could contribute to risk of diabetic kidney disease. Our present study investigated, in patients with diabetes, the association between fractional reabsorption of glucose (FR_GLU) and degree of renal disease as assessed by urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR).MethodsFR_GLU [1-(glucose clearance/creatinine clearance)] was assessed in 637 diabetes patients attending our tertiary referral centre, looking for correlations between FR_GLU and UAE (normo-, micro-, macro-albuminuria) and Kidney Disease: Improving Global Outcomes (KDIGO) eGFR categories: >90 (G1); 90–60 (G2); 59–30 (G3); and < 30–16 (G4) mL/min/1.73 m². Patients were stratified by admission fasting plasma glucose (FPG) into three groups: low (<6 mmol/L); intermediate (6–11 mmol/L); and high (>11 mmol/L).ResultsMedian (interquartile range, IQR) FR_GLU levels were blood glucose-dependent: 99.90% (0.05) for low (n = 106); 99.90% (0.41) for intermediate (n = 288); and 96.36% (12.57) for high (n = 243) blood glucose categories (P < 0.0001). Also, FR_GLU increased with renal disease severity in patients in the high FPG group: normoalbuminuria, 93.50% (17.74) (n = 135); microalbuminuria, 96.56% (5.94) (n = 77); macroalbuminuria, 99.12% (5.44) (n = 31; P < 0.001); eGFR G1, 94.13% (16.24) (n = 111); G2, 96.35% (11.94) (n = 72); G3 98.88% (7.59) (n = 46); and G4, 99.11% (2.20) (n = 14; P < 0.01). On multiple regression analyses, FR_GLU remained significantly and independently associated with UAE and eGFR in patients in the high blood glucose group.ConclusionHigh glucose reabsorption capacity in renal proximal tubules is associated with high UAE and low eGFR in patients with diabetes and blood glucose levels > 11 mmol/L.     

Brecha de sexo en la miocardiopatía hipertrófica

Introduction and objectivesKey sex differences have been explored in multiple cardiac conditions. However, sex impact in hypertrophic cardiomyopathy outcome is unclear. We aimed to characterize sex impact in overall and cardiovascular (CV) mortality in a nationwide hypertrophic cardiomyopathy registry.MethodsWe analyzed 1042 adult patients, 429 (41%) women, from a national registry of hypertrophic cardiomyopathy, with mean age at diagnosis 53 ± 16 years and a mean follow-up of 65 ± 75 months. At baseline, women were older (56 ± 16 vs 51 ± 15 years; P < .001), more symptomatic (56.4%, vs 51.7%; P < .001) and had more heart failure (42.0% vs 24.2%. P < .001), diastolic dysfunction (75.2% vs 64.1% P = .001), moderate/severe mitral regurgitation (33.4% vs 21.7%; P = .003), and higher B-type natriuretic peptide levels (920 [366-2412] mg/dL vs 487 [170-1087] mg/dL; P < .001). Women underwent fewer stress tests and cardiac magnetic resonance.ResultsKaplan-Meier survival curves showed higher overall (8.4% vs 5.0%; P = .026) and CV mortality (5.5% vs 2.2%; P = .004) in women. Cox proportional hazard regression showed that female sex was an independent predictor of overall (HR, 2.05; 95%CI, 1.11–3.78; P = .021) and CV mortality (HR, 3.16; 95%CI, 1.25–7.99; P = .015). Women had more heart failure-related death (2.6% vs 0.8%, P = .024). Despite similar sudden cardiac death (SCD) risk, women received fewer implantable cardioverter-defibrillators (10.9% vs 15.6%; P = .032) and, in patients without cardioverter-defibrillators, SCD occurred more commonly in women (1.8% vs 0.4%; P = .031).ConclusionsIn this nationwide registry, female sex was an independent predictor of overall and CV-related death, with more heart failure-related death. Despite similar SCD risk, women were undertreated with implantable cardioverter-defibrillators. These data highlight the need for an improved clinical approach in women with HCM.