Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year. Objective: To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up. Design, Setting, and Participants: The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle. Interventions: Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy. Main outcomes and measures: The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions. Results: Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, -188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (-28 [95% CI, -63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points. Conclusions and Relevance: In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior. Trial registration: ClinicalTrials.gov Identifier: NCT03208153.

Association between subclinical atherosclerosis burden and unrecognized myocardial infarction detected by cardiac magnetic resonance in middle-aged adults.

AIMS: Evidence on the association between subclinical atherosclerosis (SA) and cardiovascular (CV) events in low-risk populations is scant. To study the association between SA burden and an ischemic scar (IS), identified by cardiac magnetic resonance (CMR), as a surrogate of CV endpoint, in a low-risk population. METHODS: A cohort of 712 asymptomatic middle-aged individuals from the Progression of Early SA (PESA-CNIC-Santander) study (median age 51 years, 84% male, median SCORE2 3.37) were evaluated on enrollment and at 3-year follow-up with 2D/3D vascular ultrasound (VUS) and coronary artery calcification scoring (CACS). A cardiac magnetic study (CMR) was subsequently performed, and IS defined as the presence of subendocardial or transmural late gadolinium enhancement (LGE). RESULTS: On CMR, 132 (19.1%) participants had positive LGE, and IS was identified in 20 (2.9%) participants. Individuals with IS had significantly higher SCORE2 at baseline and higher CACS and peripheral SA burden (number of plaques by 2DVUS and plaque volume by 3DVUS) at both SA evaluations. High CACS and peripheral SA (number of plaques) burden were independently associated with the presence of IS, after adjusting for SCORE2 (OR for 3rd tertile, 8.31; 95% CI 2.85-24.2; p<0.001; and 2.77; 95% CI, 1.02-7.51; p=0.045, respectively) and provided significant incremental diagnostic value over SCORE2. CONCLUSIONS: In a low-risk middle-aged population, SA burden (CAC and peripheral plaques) was independently associated with a higher prevalence of IS identified by CMR. These findings reinforce the value of SA evaluation to early implement preventive measures.

Sex differences in population versus in-hospital use of aortic valve replacement procedures in Spain.

BACKGROUND AND AIMS: It is not well known if sex differences in the use and results of aortic valve replacement (AVR) are changing. The aim of the study is to assess the time trends in the differences by sex in the utilisation of AVR procedures in hospitals and in the community. METHODS: Retrospective observational analysis using data from the Spanish National Hospitalizations Administrative Database. All hospitalisations between 2016 and 2021 with a main diagnosis of aortic stenosis (ICD-10 codes: I35.0 and I35.2) were included. Time trends in hospitalisation, AVRs and hospital outcomes were analysed. Crude utilisation and population-standardised rates were calculated. RESULTS: During the study period, 64 384 hospitalisations in 55 983 patients (55.5% men) with 36 915 (65,9%) AVR were recorded. Of these, 15 563 (42.2%) were transcatheter and 21 432 (58.0%) surgical. At hospital level, transcatheter procedures were more frequently performed in women (32.3% vs 24.2%, p < 0.001) and surgical in men (42.9% vs. 32.5%, p < 0.001) but at the population level, surgical and transcatheter aortic valve replacements were used more frequently in men (12.6 surgical and 8.0 transcatheter per 100 000 population) vs women (6.4 and 5.8, respectively; p < 0.001 for both comparisons). Transcatheter procedures shifted from 17.3% in 2016 to 38.0% in 2021, overtaking surgical procedures in 2018 for women and 2021 for men. CONCLUSIONS: TAVR has displaced SAVR as the most frequent AVR procedure in Spain by 2020. This occurred earlier in women, who despite the greater weight of their age group in the older population, receive fewer AVRs, both SAVR and TAVR.

Diabetes mellitus and presentation, care and outcomes of patients with NSTEMI: the Association for Acute Cardiovascular Care-European Association of Percutaneous Cardiovascular Interventions EURObservational Research Programme NSTEMI Registry of the European Society of Cardiology.

AIM: Diabetes mellitus (diabetes) is common amongst patients with NSTEMI. We describe presentation, care and outcomes of patients admitted with NSTEMI by diabetes status. METHODS: Prospective cohort study including 2928 patients (1104 with prior diabetes, 1824 without) admitted to hospital with NSTEMI from 287 centres in 59 countries. Quality of care was evaluated based on 12 guideline-recommended care interventions. Outcomes included in-hospital acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack (TIA), BARC Type ≥ 3 bleeding and death, as well as 30-day mortality. RESULTS: Patients with diabetes had higher comorbidity burden and more frequently presented with Killip Class II-IV heart failure (10.2% vs 3.7%, P < 0.001), haemodynamic instability (7.1% vs 3.7%, P < 0.001) and ongoing chest pain (43.1% vs 37.0%, P < 0.001), than those without diabetes. Overall, care quality received was similar by diabetes status (60.0% vs 60.5% received ≥ 80% of eligible care interventions, P = 0.786), but patients with diabetes experienced higher rates of in-hospital acute heart failure (15.3% vs 6.8% P < 0.001), cardiogenic shock (4.5% vs 2.5%, P = 0.002), stroke/TIA (2.0% vs 0.8%, P = 0.006) and death (2.5% vs 1.4%, P = 0.022), and higher 30-day mortality (3.3% vs 2.0%, P = 0.025). Of NSTEMI with diabetes, only 1.9% and 9.0% received prescription for GLP-1 RAs and SGLT2 inhibitors, respectively, on discharge, and only 45.9% were referred for cardiac rehabilitation. CONCLUSION: NSTEMI patients with diabetes, compared to those without, present more clinically unwell and have worse outcomes despite receiving equal quality of care. Prescription of cardiovascular-protective glycaemic agents is an actionable target to reduce risk of further events.

Sex-specific presentation, care, and clinical events in individuals admitted with NSTEMI: the ACVC-EAPCI EORP NSTEMI registry of the European Society of Cardiology.

AIMS: Women have historically been disadvantaged in terms of care and outcomes for non-ST-segment elevation myocardial infarction (NSTEMI). We describe patterns of presentation, care, and outcomes for NSTEMI by sex in a contemporary and geographically diverse cohort. METHODS AND RESULTS: Prospective cohort study including 2947 patients (907 women, 2040 men) with Type I NSTEMI from 287 centres in 59 countries, stratified by sex. Quality of care was evaluated based on 12 guideline-recommended care interventions. The all-or-none scoring composite performance measure was used to define receipt of optimal care. Outcomes included acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding, or death in-hospital, as well as 30-day mortality. Women admitted with NSTEMI were older, more comorbid, and more frequently categorized as at higher ischaemic (GRACE >140, 54.0% vs. 41.7%, P < 0.001) and bleeding (CRUSADE >40, 51.7% vs. 17.6%, P < 0.001) risk than men. Women less frequently received invasive coronary angiography (ICA; 83.0% vs. 89.5%, P < 0.001), smoking cessation advice (46.4% vs. 69.5%, P < 0.001), and P2Y12 inhibitor prescription at discharge (81.9% vs. 90.0%, P < 0.001). Non-receipt of ICA was more often due to frailty for women than men (16.7% vs. 7.8%, P = 0.010). At ICA, more women than men had non-obstructive coronary artery disease or angiographically normal arteries (15.8% vs. 6.3%, P < 0.001). Rates of in-hospital adverse outcomes and 30-day mortality were low and did not differ by sex. CONCLUSION: In contemporary practice, women presenting with NSTEMI, compared with men, less frequently receive antiplatelet prescription, smoking cessation advice, or are considered eligible for ICA.

Secondary Prevention Therapies in Real-World Patients with Myocardial Infarction: Eligibility Based on Randomized Trials Supporting European and American Guidelines.

OBJECTIVE: We aimed to evaluate the applicability of the eligibility criteria of randomized controlled trials (RCTs) cited in guideline recommendations in a real-world cohort of patients receiving secondary prevention after acute myocardial infarction from the EPICOR registries. METHODS: Recommendations provided by American and European guidelines for acute myocardial infarction were classified into general (applying to all patients) and specific (applying to patients with left ventricular dysfunction or heart failure). Randomized controlled trials cited in these recommendations were selected, and their entry criteria were applied to our international cohort of 18,117 patients. RESULTS: There were 91.5% patients eligible for beta blockers (84.6% for general, and 5.9% for specific recommendations), 97.7% eligible for renin-angiotensin system inhibitor (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers [ACEI/ARB]) recommendations (69.9% for general, 27.9% for specific) and 4.1% eligible for mineralocorticoid receptor antagonists (only specific recommendations). The percentages of patients with eligibility criteria who were discharged with a prescription of the recommended therapies were 80%-85% for beta blockers, 70%-75% for ACEI/ARB, and 29% for mineralocorticoid receptor antagonists. There were large regional variations in the percentage of eligible patients and in those receiving the medications (eg, 95% in Northern Europe and 57% in Southeast Asia for beta blockers). CONCLUSION: Most real-world acute myocardial infarction patients are eligible for secondary prevention therapy in both general and specific guideline recommendations, and the percentage of those on beta blockers and ACEI/ARB at hospital discharge is high. There are large regional variations in the proportion of patients receiving recommended therapies. Local targeted interventions are needed for quality improvement.

Robustness of [18F]FDG PET/CT radiomic analysis in the setting of drug-induced cardiotoxicity.

BACKGROUND AND OBJECTIVES: Standardization of radiomic data acquisition protocols is still at a very early stage, revealing a strong need to work towards the definition of uniform image processing methodologies The aim of this study is to identify sources of variability in radiomic data derived from image discretization and resampling methodologies prior to image feature extraction. Furthermore, to identify robust potential image-based biomarkers for the early detection of cardiotoxicity. METHODS: Image post-acquisition processing, interpolation, and volume of interest (VOI) segmentation were performed. Four experiments were conducted to assess the reliability in terms of the intraclass correlation coefficient (ICC) of the radiomic features and the effects of the variation of voxel size and gray level discretization. Statistical analysis was performed separating the patients according to cardiotoxicity diagnosis. Differences of texture features were studied with Mann-Whitney U test. P-values <0.05 after multiple testing correction were considered statistically significant. Additionally, a non-supervised k-Means clustering algorithm was evaluated. RESULTS: The effect of the variation in the voxel size demonstrated a non-dependency relationship with the values of the radiomic features, regardless of the chosen discretization method. The median ICC values were 0.306 and 0.872 for absolute agreement and consistency, respectively, when varying the discretization bin number. The median ICC values were 0.678 and 0.878 for absolute agreement and consistency, respectively, when varying the discretization bin size. A total of 16 first order, 6 Gray Level Co-occurrence Matrix (GLCM), 4 Gray Level Dependence Matrix (GLDM) and 4 Gray Level Run Length Matrix (GLRLM) features demonstrated statistically significant differences between the diagnosis groups for interim scans (P<0.05) for the fixed bin size (FBS) discretization methodology. However, no statistically significant differences between diagnostic groups were found for the fixed bin number (FBN) discretization methodology. Two clusters based on the radiomic features were identified. CONCLUSIONS: Gray level discretization has a major impact on the repeatability of the radiomic features. The selection of the optimal processing methodology has led to the identification of texture-based patterns for the differentiation of early cardiac damage profiles.

Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years.

BACKGROUND: Atherosclerosis is a systemic disease that frequently begins early in life. However, knowledge about the temporal disease dynamics (ie, progression or regression) of human subclinical atherosclerosis and their determinants is scarce. OBJECTIVES: This study sought to investigate early subclinical atherosclerosis disease dynamics within a cohort of middle-aged, asymptomatic individuals by using multiterritorial 3-dimensional vascular ultrasound (3DVUS) imaging. METHODS: A total of 3,471 participants from the PESA (Progression of Early Subclinical Atherosclerosis) cohort study (baseline age 40-55 years; 36% female) underwent 3 serial 3DVUS imaging assessments of peripheral arteries at 3-year intervals. Subclinical atherosclerosis was quantified as global plaque volume (mm3) (bilateral carotid and femoral plaque burden). Multivariable logistic regression models for progression and regression were developed using stepwise forward variable selection. RESULTS: Baseline to 6-year subclinical atherosclerosis progression occurred in 32.7% of the cohort (17.5% presenting with incident disease and 15.2% progressing from prevalent disease at enrollment). Regression was observed in 8.0% of those patients with baseline disease. The effects of higher low-density lipoprotein cholesterol (LDL-C) and elevated systolic blood pressure (SBP) on 6-year subclinical atherosclerosis progression risk were more pronounced among participants in the youngest age stratum (Pinteraction = 0.04 and 0.02, respectively). CONCLUSIONS: Over 6 years, subclinical atherosclerosis progressed in one-third of middle-age asymptomatic subjects. Atherosclerosis regression is possible in early stages of the disease. The impact of LDL-C and SBP on subclinical atherosclerosis progression was more pronounced in younger participants, a finding suggesting that the prevention of atherosclerosis and its progression could be enhanced by tighter risk factor control at younger ages, with a likely long-term impact on reducing the risk of clinical events. (Progression of Early Subclinical Atherosclerosis [PESA; also PESA-CNIC-Santander]; NCT01410318).

Impact of the MEESSI-AHF tool to guide disposition decision-making in patients with acute heart failure in the emergency department: a before-and-after study.

OBJECTIVES: To determine the impact of risk stratification using the MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with acute heart failure) scale to guide disposition decision-making on the outcomes of ED patients with acute heart failure (AHF), and assess the adherence of emergency physicians to risk stratification recommendations. METHODS: This was a prospective quasi-experimental study (before/after design) conducted in eight Spanish EDs which consecutively enrolled adult patients with AHF. In the pre-implementation stage, the admit/discharge decision was performed entirely based on emergency physician judgement. During the post-implementation phase, emergency physicians were advised to 'discharge' patients classified by the MEESSI-AHF scale as low risk and 'admit' patients classified as increased risk. Nonetheless, the final decision was left to treating emergency physicians. The primary outcome was 30-day all-cause mortality. Secondary outcomes were days alive and out of hospital, in-hospital mortality and 30-day post-discharge combined adverse event (ED revisit, hospitalisation or death). RESULTS: The pre-implementation and post-implementation cohorts included 1589 and 1575 patients, respectively (median age 85 years, 56% females) with similar characteristics, and 30-day all-cause mortality was 9.4% and 9.7%, respectively (post-implementation HR=1.03, 95% CI=0.82 to 1.29). There were no differences in secondary outcomes or in the percentage of patients entirely managed in the ED without hospitalisation (direct discharge from the ED, 23.5% vs 24.4%, OR=1.05, 95% CI=0.89 to 1.24). Adjusted models did not change these results. Emergency physicians followed the MEESSI-AHF-based recommendation on patient disposition in 70.9% of cases (recommendation over-ruling: 29.1%). Physicians were more likely to over-rule the recommendation when 'discharge' was recommended (56.4%; main reason: need for hospitalisation for a second diagnosis) than when 'admit' was recommended (12.8%; main reason: no appreciation of severity of AHF decompensation by emergency physician), with an OR for over-ruling the 'discharge' compared with the 'admit' recommendation of 8.78 (95% CI=6.84 to 11.3). CONCLUSIONS: Implementing the MEESSI-AHF risk stratification tool in the ED to guide disposition decision-making did not improve patient outcomes.

Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis.

OBJECTIVE: Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown. RESEARCH DESIGN AND METHODS: 821 asymptomatic individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study (50.6 [46.9-53.6] years, 83.7% male) underwent two whole-body 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance (18F-FDG PET-MR) 4.8 ± 0.6 years apart. Presence of myocardial 18F-FDG uptake was evaluated qualitatively and quantitatively. No myocardial uptake was grade 0, while positive uptake was classified in grades 1-3 according to target-to-background ratio tertiles. RESULTS: One hundred fifty-six participants (19.0%) showed no myocardial 18F-FDG uptake, and this was significantly associated with higher prevalence of MetS (29.0% vs. 13.9%, P < 0.001), hypertension (29.0% vs. 18.0%, P = 0.002), and diabetes (11.0% vs. 3.2%, P < 0.001), and with higher insulin resistance index (HOMA-IR, 1.64% vs. 1.23%, P < 0.001). Absence of myocardial uptake was associated with higher prevalence of early atherosclerosis (i.e., arterial 18F-FDG uptake, P = 0.004). On follow-up, the associations between myocardial 18F-FDG uptake and risk factors were replicated, and MetS was more frequent in the group without myocardial uptake. The increase in HOMA-IR was associated with a progressive decrease in myocardial uptake (P < 0.001). In 82% of subjects, the categorization according to presence/absence of myocardial 18F-FDG uptake did not change between baseline and follow-up. MetS regression on follow-up was associated with a significant (P < 0.001) increase in myocardial uptake. CONCLUSIONS: Apparently healthy individuals without cardiac 18F-FDG uptake have higher HOMA-IR and higher prevalence of MetS traits, cardiovascular risk factors, and early atherosclerosis. An improvement in cardiometabolic profile is associated with the recovery of myocardial 18F-FDG uptake at follow-up.

Sex-Specific Associations of Obstructive Sleep Apnea Risk With Patient Characteristics and Functional Outcomes After Acute Myocardial Infarction: Evidence From the VIRGO Study.

Background Though associations between obstructive sleep apnea (OSA) and cardiovascular outcomes are well described, limited data exist regarding the impact of OSA on sex-specific outcomes after acute myocardial infarction (AMI). Methods and Results The VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolled 3572 adults aged 18 to 55 years with AMI from the United States and Spain during 2008 to 2012. We included patients for whom the Berlin Questionnaire for OSA was scored at the time of AMI admission (3141; 2105 women, 1036 men). We examined the sex-specific association between baseline OSA risk with functional outcomes including health status and depressive symptoms at 1 and 12 months after AMI. Among both groups, 49% of patients were at high risk for OSA (1040 women; 509 men), but only 4.7% (148) of patients had a diagnosed history of OSA. Though patients with a high OSA risk reported worse physical and mental health status and depression than low-risk patients in both sexes, the difference in these functional outcomes was wider in women than men. Moreover, women with a high OSA risk had worse health status, depression, and quality of life than high-risk men, both at baseline and at 1 and 12 months after AMI. Conclusions Young women with a high OSA risk have poorer health status and more depressive symptoms than men at the time of AMI, which may place them at higher risk of poorer health outcomes over the year following the AMI. Further, the majority of patients at high risk of OSA are undiagnosed at the time of presentation of AMI.

Sex differences in patterns of referral and resource utilization in the cardiology clinic: an outpatient analysis.

Aims: Women may have different management patterns than men in specialised care. Our aim was to assess potential sex differences in referral, management and outcomes of patients attending outpatient cardiac consultations. Methods and results: Retrospective observational analysis of patients ≥18 years referred for the first time from primary care to a tertiary hospital cardiology clinic in 2017-2018, comparing reasons for referral, decisions and post-visit outcomes by sex.A total of 5,974 patients, 2,452 (41.0%) men aged 59.2 ± 18.6 years and 3,522 (59.0%) women aged 64.5 ± 17.9 years (P < 0.001) were referred for a first cardiology consultation. The age-related referral rates were higher in women. The most common reasons for consultation were palpitations in women (n = 676; 19.2%) and ECG abnormalities in men (n = 570; 23.2%). Delays to cardiology visits and additional tests were similar. During 24 months of follow-up, women had fewer cardiology hospitalisations (204; 5.8% vs. 229; 9.3%; P = 0.003) and lower mortality (65; 1.8% vs. 66; 2.7%; P = 0.028), but those aged <65 years had more emergency department visits (756; 48.5% vs. 560; 39.9%, P < 0.001) than men. Conclusion: There are substantial sex differences in primary care cardiology referral patterns, including causes, rates, decisions and outcomes, which are only partially explained by age differences. Further research is needed to understand the reasons for these differences.

Evolución de la asistencia cardiovascular en el Sistema Nacional de Salud de España. Datos del proyecto RECALCAR 2011-2020 / Trends in cardiovascular care in the National Health System in Spain. Data from the RECALCAR project 2011-2020

Introducción y objetivos: El proyecto RECALCAR (Recursos y Calidad en Cardiología), iniciativa de la Sociedad Española de Cardiología, pretende estandarizar la información para generar evidencia sobre los resultados en salud cardiovascular. Su objetivo es analizar la evolución de los recursos y la actividad de las unidades y los servicios de cardiología y conocer los resultados en la asistencia cardiovascular durante la última década en España. Métodos: Este estudio se basa en las dos fuentes anuales de datos del proyecto RECALCAR: una encuesta sobre recursos y actividad de las unidades y servicios de cardiología (2011-2020) y el conjunto mínimo básico de datos del Sistema Nacional de Salud (2011-2019), referido a insuficiencia cardiaca (IC), infarto agudo de miocardio con (IAMCEST) y sin (IAMSEST) elevación del segmento ST. Resultados: La encuesta incluye el 70% de las unidades y servicios de cardiología de España. Se ha observado una disminución en el número de camas de hospitalización y la estancia media y un incremento notable en el número de estudios de imagen cardiaca y procedimientos terapéuticos percutáneos. Los ingresos por IC ajustados por edad y sexo han disminuido, aunque su mortalidad y el porcentaje de reingresos han ido en aumento. La evolución de la mortalidad y los reingresos ha sido muy favorable en el IAMCEST; en el IAMSEST, aunque positiva, ha sido menos relevante. Conclusiones: La información aportada por el proyecto RECALCAR demuestra una evolución favorable en la última década en recursos, actividad y resultados en determinados procesos cardiovasculares y constituye una fuente esencial para mejoras futuras y facilitar la toma de decisiones en política sanitaria. (AU)

Introduction and objectives: The RECALCAR project (Resources and Quality in Cardiology), an initiative of the Spanish Society of Cardiology, aims to standardize information to generate evidence on cardiovascular health outcomes. The objective of this study was to analyze trends in the resources and activity of cardiology units and/or services and to identify the results of cardiovascular care during the last decade in Spain. Methods: The study was based on the 2 annual data sources of the RECALCAR project: a survey on resources and activity of cardiology units and/or services (2011-2020) and the minimum data set of the National Health System (2011-2019), referring to heart failure (HF), STEMI, and non-STEMI. Results: The survey included 70% of cardiology units and/or services in Spain. The number of hospital beds and length of stay decreased, while there was a notable increase in the number of cardiac imaging studies and percutaneous therapeutic procedures performed. Age- and sex-adjusted admissions for HF tended to decrease, despite an increase in mortality and the percentage of readmissions. In contrast, the trend in mortality and readmissions was highly favorable in STEMI; in non-STEMI, although positive, the trend was less marked. Conclusions: The information provided by the RECALCAR project shows a favorable trend in the last decade in resources, activity and results of certain cardiovascular processes and constitutes an essential source for future improvements and decision-making in health policy. (AU)

Pronóstico a largo plazo de la extensión de la TAPD en una cohorte consecutiva de pacientes con IAMCEST / Long-term outcomes of extended DAPT in a real-life cohort of consecutive STEMI patients

Introducción y objetivos: La duración adecuada de la doble terapia antiagregante (DAPT) después de un infarto de miocardio con elevación del segmento ST (IAMCEST) está todavía en discusión. Métodos: Analizamos el efecto de la DAPT extendida a 5 años sobre la mortalidad global, mortalidad cardiovascular y reingreso o mortalidad cardiovascular, en una cohorte multicéntrica de pacientes con IAMCEST supervivientes al año. Resultados: Se incluyeron 3.107 pacientes hospitalizados por IAMCEST de los que el 93% recibió DAPT al alta. A los 5 años se mantenía en 275 pacientes con un perfil alto de gravedad. La mortalidad cardiovascular de los pacientes con antiagregación simple (SAPT) frente a DAPT a 5 años fue de 1,4 y 3,6% (p <0,01), respectivamente. La mortalidad no-cardiovascular fue del 3,3 frente a 5,8% (p=0,049) a 5 años, respectivamente. La incidencia del evento combinado a un año fue del 14,6% en SAPT frente a 11,8% en DAPT (p=0,496), y del 11,4 frente a 46,5% (p <0,001) a 5 años, respectivamente. El mantenimiento de la DAPT hasta los 5 años se asoció de forma independiente a mayor mortalidad: por cualquier causa (HR=2,16; IC95%, 1,40-3,33), cardiovascular (HR=2,83; IC95%, 1,37-5,84) y rehospitalización cardiovascular y mortalidad (HR=5,20; IC95%, 3,96-6,82). Un análisis emparejado por puntuación de propensión, y uno con ponderación de probabilidad inversa, confirman estos resultados. Conclusiones: Nuestros resultados sugieren la hipótesis de que, en supervivientes a un año de IAMCEST, alargar la DAPT hasta 5 años en pacientes de alto riesgo no mejora su pronóstico a largo plazo. (AU)

Introduction and objectives: Dual antiplatelet therapy (DAPT) duration after ST-segment elevation myocardial infarction (STEMI) remains a matter of debate. Methods: We analyzed the effect of DAPT on 5-year all-cause mortality, cardiovascular mortality, and cardiovascular readmission or mortality in a cohort of 1-year survivor STEMI patients. Results: A total of 3107 patients with the diagnosis of STEMI were included: 93% of them were discharged on DAPT, a therapy that persisted in 275 high-risk patients at 5 years. Cardiovascular mortality in patients on single antiplatelet therapy vs DAPT at 5 years was 1.4% vs 3.6% (P <.01), respectively, whereas noncardiovascular mortality was 3.3% vs 5.8% (P=.049) at 5 years. Cardiovascular readmission or mortality in patients with single antiplatelet therapy vs DAPT was 11.4% vs 46.5% (P <.001). Extended DAPT was independently associated with worse 5-year all-cause mortality (HR, 2.16; 95%CI, 1.40-3.33), cardiovascular mortality (HR, 2.83; 95%CI, 1.37-5.84), and cardiovascular readmission or mortality (HR, 5.20; 95%CI, 3.96-6.82). These findings were confirmed in propensity score matching and inverse probability weighting analyses. Conclusions: Our results suggest the hypothesis that, in 1-year STEMI survivors, extending DAPT up to 5 years in high-risk patients does not improve their long-term prognosis. (AU)

Impact of standard modifiable cardiovascular risk factors on 2-year all-cause mortality: Insights from an international cohort of 23,489 patients with acute coronary syndrome.

BACKGROUND: Controversial findings have been reported in the literature regarding the impact of the absence of standard modifiable cardiovascular risk factors (SMuRFs) on long-term mortality risk in patients with acute coronary syndrome (ACS). While the prognostic additive value of SMuRFs has been well described, the prognostic role of prior cardiovascular disease (CVD) by sex is less well-known in patients with and without SMuRFs. METHODS: EPICOR and EPICOR Asia are prospective, observational registries conducted between 2010 and 2014, which enrolled ACS patients in 28 countries across Europe, Latin America, and Asia. Association between SMuRFs (diabetes, dyslipidaemia, hypertension, and smoking) and 2-year postdischarge mortality was evaluated using adjusted Cox models stratified by geographical region. RESULTS: Among 23,489 patients, the mean age was 60.9 ± 11.9 years, 24.3% were women, 4,582 (20.1%) presented without SMuRFs, and 16,055 (69.5%) without prior CVD. Patients with SMuRFs had a higher crude 2-year postdischarge mortality (HR 1.86; 95% CI, 1.56-2.22; P < .001), compared to those without SMuRFs. After adjustment for potential confounding, the association between SMuRFs and 2-year mortality risk was substantially attenuated (HR 1.17, 95% CI 0.98-1.41; P = .087), regardless of the type of ACS. The risk conferred by prior CVD was added to the underlying risk of SMuRFs to provide risk-specific phenotypes (eg, women with SMuRFs and with prior CVD were at higher risk of dying than women without SMuRFs and without CVD; HR 1.67, 95% CI 1.34-2.06). CONCLUSIONS: In this large-scale international ACS cohort the absence of SMuRFs was not associated with a lower adjusted 2-year postdischarge mortality risk. Patients with both SMuRFs and prior CVD had a higher mortality irrespective of their sex.

Differences in clinical outcomes, health care resource utilization and costs in heart failure patients according to left ventricular ejection fraction.

INTRODUCTION AND OBJECTIVES: The impact of left ventricular ejection fraction (LVEF) on health care resource utilization (HCRU) and cost in heart failure (HF) patients is not well known. We aimed to compare outcomes, HCRUs and costs according to LVEF groups. METHODS: Retrospective, observational study of all patients with an emergency department (ED) visit or admission to a tertiary hospital in Spain 2018 with a primary HF diagnosis. We excluded patients with newly diagnosed heart failure. One-year clinical outcomes, costs and HCRUs were compared according to LVEF (reduced [HFrEF], mildly reduced [HFmrEF], and preserved [HFpEF]). RESULTS: Among 1287 patients with a primary diagnosis of HF in the ED, 365 (28.4%) were discharged to home (ED group), and 919 (71.4%) were hospitalized (hospital group [HG]). In total, 190 patients (14.7%) had HFrEF, 146 (11.4%) HFmrEF, and 951 (73.9%) HFpEF. The mean age was 80.1±10.7 years; 57.1% were female. The median [interquartile range] of costs per patient/y was €1889 [259-6269] in the ED group and €5008 [2747-9589] in the HG (P <.001). Hospitalization rates were higher in patients with HFrEF in the ED group. The median costs of HFrEF per patient/y were higher in patients in both groups: €4763 [2076-17 155] vs €3900 [590-8013] for HFmrEF vs €3812 [259-5486] for HFpEF in the ED group, and €6321 [3335-796] vs €6170 [3189-10484] vs €4636 [2609-8977], respectively, in the hospital group (all P <.001). This difference was driven by the more frequent admission to intensive care units, and greater use of diagnostic and therapeutic tests among HFrEF patients. CONCLUSIONS: In HF, LVEF significantly impacts costs and HCRU. Costs were higher in patients with HFrEF, especially those requiring hospitalization, than in those with HFpEF.

Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study.

AIMS: Epigenetic age is emerging as a personalized and accurate predictor of biological age. The aim of this article is to assess the association of subclinical atherosclerosis with accelerated epigenetic age and to investigate the underlying mechanisms mediating this association. METHODS AND RESULTS: Whole blood methylomics, transcriptomics, and plasma proteomics were obtained for 391 participants of the Progression of Early Subclinical Atherosclerosis study. Epigenetic age was calculated from methylomics data for each participant. Its divergence from chronological age is termed epigenetic age acceleration. Subclinical atherosclerosis burden was estimated by multi-territory 2D/3D vascular ultrasound and by coronary artery calcification. In healthy individuals, the presence, extension, and progression of subclinical atherosclerosis were associated with a significant acceleration of the Grim epigenetic age, a predictor of health and lifespan, regardless of traditional cardiovascular risk factors. Individuals with an accelerated Grim epigenetic age were characterized by an increased systemic inflammation and associated with a score of low-grade, chronic inflammation. Mediation analysis using transcriptomics and proteomics data revealed key pro-inflammatory pathways (IL6, Inflammasome, and IL10) and genes (IL1B, OSM, TLR5, and CD14) mediating the association between subclinical atherosclerosis and epigenetic age acceleration. CONCLUSION: The presence, extension, and progression of subclinical atherosclerosis in middle-aged asymptomatic individuals are associated with an acceleration in the Grim epigenetic age. Mediation analysis using transcriptomics and proteomics data suggests a key role of systemic inflammation in this association, reinforcing the relevance of interventions on inflammation to prevent cardiovascular disease.

Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial.

BACKGROUND: Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting. OBJECTIVES: The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation. METHODS: The effects of ivabradine on atrioventricular node and ventricular cells were studied by in vitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite ß-blocker or calcium channel blocker treatment. RESULTS: Ivabradine 1 µM inhibited "funny" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 µM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10). CONCLUSION: Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.