The CNIC polypill (Acetylsalicylic acid + Atorvastatin + Rampril) in secondary prevention of cardiovascular disease in patients with type 2 diabetes: A comparative analysis with alternative therapeutic approaches.

BACKGROUND: Patients with type 2 DM (T2DM) and established cardiovascular disease (CVD) are at high risk of recurrent CV events. We analysed the use of the CNIC-polypill (acetylsalicylic acid, ramipril, and atorvastatin) compared with other therapeutic strategies in patients with T2DM and CVD from the retrospective NEPTUNO study. METHODS: Patients were stratified into four therapeutic approaches: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. Outcomes included the 2-year cumulative incidence and risk of recurrent major adverse CV events (MACE) and CV death, risk factors control, medication persistence, and utilisation of healthcare resources and costs. RESULTS: After two years, T2DM patients treated with Monocomponents, Equipotent drugs, or Other therapies had increased recurrent MACE risk compared to CNIC-polypill (11 %, 23 %, and 44 %, respectively; P < 0.05) and shorter median time to CV events (305-377 vs. 396 days; P < 0.05). The CNIC-polypill group achieved a significant 11.2 % increase in patients reaching LDL-c targets <70 mg/dL, outperforming other strategies. It also exhibited superior triglyceride control and a higher proportion achieving the <130/80 mmHg blood pressure goal. The CNIC-polypill cohort displayed significantly higher 24-month persistence (71.5 % vs. 54.7 %-58.3 %, p < 0.05) and lower mean adjusted costs per patient (€5083 vs. €6000-€6523; p < 0.05). In a comparative analysis, T2DM patients had lower baseline LDL-c and total cholesterol levels than non-T2DM counterparts yet experienced a higher incidence of recurrent MACE over two years. CONCLUSION: The CNIC-polypill (ASA, atorvastatin and ramipril) emerged as a promising treatment for patients with CVD, particularly those with T2DM, offering improved clinical outcomes and economic efficiency.

Ramipril After Transcatheter Aortic Valve Implantation in Patients Without Reduced Ejection Fraction: The RASTAVI Randomized Clinical Trial.

BACKGROUND: Patients with aortic stenosis may continue to have an increased risk of heart failure, arrhythmias, and death after successful transcatheter aortic valve implantation. Renin-angiotensin system inhibitors may be beneficial in this setting. We aimed to explore whether ramipril improves the outcomes of patients with aortic stenosis after transcatheter aortic valve implantation. METHODS AND RESULTS: PROBE (Prospective Randomized Open, Blinded Endpoint) was a multicenter trial comparing ramipril with standard care (control) following successful transcatheter aortic valve implantation in patients with left ventricular ejection fraction >40%. The primary end point was the composite of cardiac mortality, heart failure readmission, and stroke at 1-year follow-up. Secondary end points included left ventricular remodeling and fibrosis. A total of 186 patients with median age 83 years (range 79-86), 58.1% women, and EuroSCORE-II 3.75% (range 3.08-4.97) were randomized to receive either ramipril (n=94) or standard treatment (n=92). There were no significant baseline, procedural, or in-hospital differences. The primary end point occurred in 10.6% in the ramipril group versus 12% in the control group (P=0.776), with no differences in cardiac mortality (ramipril 1.1% versus control group 2.2%, P=0.619) but lower rate of heart failure readmissions in the ramipril group (3.2% versus 10.9%, P=0.040). Cardiac magnetic resonance analysis demonstrated better remodeling in the ramipril compared with the control group, with greater reduction in end-systolic and end-diastolic left ventricular volumes, but nonsignificant differences were found in the percentage of myocardial fibrosis. CONCLUSIONS: Ramipril administration after transcatheter aortic valve implantation in patients with preserved left ventricular function did not meet the primary end point but was associated with a reduction in heart failure re-admissions at 1-year follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03201185.

Colchicine in acutely decompensated heart failure: the COLICA trial.

BACKGROUND AND AIMS: Acute heart failure (AHF) promotes inflammatory activation, which is associated with worse outcomes. Colchicine has proven effective in other cardiovascular conditions characterized by inflammatory activation, but has never been evaluated in the setting of AHF. METHODS: This multicenter, randomized, double-blind and placebo-controlled trial included patients with AHF, requiring ≥40 mg of intravenous furosemide, regardless of their left ventricular ejection fraction (LVEF) and inpatient or outpatient setting. Patients were randomized within the first 24 hours of presentation to receive either colchicine or placebo, with loading dose of 2 mg followed by 0.5 mg every 12 hours for 8 weeks. RESULTS: A total of 278 patients (median age 75 years, LVEF 40%, baseline N-terminal pro-B-type natriuretic peptide [NT-proBNP] 4390 pg/mL) were randomized to colchicine (n=141) or placebo (n=137). The primary endpoint, the time-averaged reduction in NT-proBNP levels at 8 weeks, did not differ between the colchicine group (-62.2%, 95% confidence interval [CI] -68.9% to -54.2%) and the placebo group (-62.1%, 95% CI -68.6% to -54.3%) (ratio of change 1.0). The reduction in inflammatory markers was significantly greater with colchicine: ratio of change 0.60 (p<0.001) for C-reactive protein and 0.72 (p=0.019) for interleukin-6. No differences were found in new worsening heart failure episodes (14.9% with colchicine vs. 16.8% with placebo, p=0.698); however, the need for intravenous furosemide during follow-up was lower with colchicine (p=0.043). Diarrhea was slightly more common with colchicine, but it did not result in differences in medication withdrawal (8.5% vs. 8.8%). CONCLUSIONS: Colchicine was safe and effective in reducing inflammation in patients with AHF, however colchicine and placebo exhibited comparable effects on reducing NT-proBNP and preventing new worsening heart failure events.

Anthracycline-induced cardiovascular toxicity: validation of the Heart Failure Association and International Cardio-Oncology Society risk score.

BACKGROUND AND AIMS: Baseline cardiovascular toxicity risk stratification is critical in cardio-oncology. The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) score aims to assess this risk but lacks real-life validation. This study validates the HFA-ICOS score for anthracycline-induced cardiovascular toxicity. METHODS: Anthracycline-treated patients in the CARDIOTOX registry (NCT02039622) were stratified by the HFA-ICOS score. The primary endpoint was symptomatic or moderate to severe asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), with all-cause mortality and cardiovascular mortality as secondary endpoints. RESULTS: The analysis included 1066 patients (mean age 54 ± 14 years; 81.9% women; 24.5% ≥65 years). According to the HFA-ICOS criteria, 571 patients (53.6%) were classified as low risk, 333 (31.2%) as moderate risk, 152 (14.3%) as high risk, and 10 (0.9%) as very high risk. Median follow-up was 54.8 months (interquartile range 24.6-81.8). A total of 197 patients (18.4%) died, and 718 (67.3%) developed CTRCD (symptomatic: n = 45; moderate to severe asymptomatic: n = 24; and mild asymptomatic: n = 649). Incidence rates of symptomatic or moderate to severe symptomatic CTRCD and all-cause mortality significantly increased with HFA-ICOS score [hazard ratio 28.74, 95% confidence interval (CI) 9.33-88.5; P < .001, and hazard ratio 7.43, 95% CI 3.21-17.2; P < .001) for very high-risk patients. The predictive model demonstrated good calibration (Brier score 0.04, 95% CI 0.03-0.05) and discrimination (area under the curve 0.78, 95% CI 0.70-0.82; Uno's C-statistic 0.78, 95% CI 0.71-0.84) for predicting symptomatic or severe/moderate asymptomatic CTRCD at 12 months. CONCLUSIONS: The HFA-ICOS score effectively categorizes patients by cardiovascular toxicity risk and demonstrates strong predictive ability for high-risk anthracycline-related cardiovascular toxicity and all-cause mortality.

FABP4 Enhances Lipidic and Fibrotic Cardiac Structural and Ca2+ Dynamic Changes.

BACKGROUND: Adipocyte FABP4 (fatty acid-binding protein 4) is augmented in the epicardial stroma of patients with long-standing persistent atrial fibrillation. Because this molecule is released mainly by adipocytes, our objective was to study its role in atrial cardiomyopathy, focusing our attention on fibrosis, metabolism, and electrophysiological changes. These results might clarify the role of adiposity as a mediator of atrial cardiomyopathy. METHODS: We used several preclinical cellular models, epicardial and subcutaneous stroma primary cell cultures from patients undergoing open heart surgery, human atrial fibroblasts, atrial cardiomyocytes derived from human induced pluripotent stem cells and isolated from adult mice, and Nav1.5 transfected Chinese hamster ovary cells. Fibrosis, glucose, mitochondrial and adipogenesis activity, gene expression, and proteomics were determined by wound healing, enzymatic, colorimetric, fluorescence assays, real-time quantitative polymerase chain reaction, and TripleTOF proteomics. Molecular changes were analyzed by Raman confocal microspectroscopy, calcium dynamics by confocal microscopy, and ion currents by patch clamp. Epicardial, subcutaneous, and atrial fibroblasts and cardiomyocytes were incubated with FABP4 at 100 ng/mL. RESULTS: Our results showed that FABP4 induced fibrosis, glucose metabolism, and lipid accumulation on epicardial and subcutaneous stroma cells and atrial fibroblasts. Besides, it modified lipid content and calcium dynamics in atrial cardiomyocytes without effects on INa. CONCLUSIONS: FABP4 exerts fibrotic and metabolic changes on epicardial stroma and modifies lipid content and calcium dynamic on atrial cardiomyocytes. These results suggest its possible role as an atrial cardiomyopathy mediator.

Biocompatibility Testing of UV-Curable Polydimethylsiloxane for Human Umbilical Vein Endothelial Cell Culture on-a-Chip.

Polydimethylsiloxane (PDMS) is extensively used to fabricate biocompatible microfluidic systems due to its favorable properties for cell culture. Recently, ultraviolet-curable PDMS (UV-PDMS) has shown potential for enhancing manufacturing processes and final optical quality while retaining the benefits of traditional thermally cured PDMS. This study investigates the biocompatibility of UV-PDMS under static and flow conditions using human umbilical vein endothelial cells (HUVECs). UV-PDMS samples were treated with oxygen plasma and boiling deionized water to assess potential improvements in cell behavior compared with untreated samples. We evaluated HUVECs adhesion, growth, morphology, and viability in static cultures and microchannels fabricated with UV-PDMS to test their resistance to flow conditions. Our results confirmed the biocompatibility of UV-PDMS for HUVECs culture. Moreover, plasma-oxygen-treated UV-PDMS substrates exhibited superior cell growth and adhesion compared to untreated UV-PDMS. This enhancement enabled HUVECs to maintain their morphology and viability under flow conditions in UV-PDMS microchannels. Additionally, UV-PDMS demonstrated improved optical quality and more efficient handling and processing, characterized by shorter curing times and simplified procedures utilizing UV light compared to traditional PDMS.

Influence of the pressure wire on the fractional flow reserve calculation: CFD analysis of an ideal vessel and clinical patients with stenosis.

BACKGROUND AND OBJECTIVE: Fractional Flow Reserve (FFR) is generally considered the gold standard in hemodynamics to assess the impact of a stenosis on the blood flow. The standard procedure to measure involves the displacement of a pressure guide along the circulatory system until it is placed next to the lesion to be analyzed. The main objective of the present study is to analyze the influence of the pressure guide on the invasive FFR measurements and its implications in clinical practice. METHODS: We studied the influence of pressure wires on the measurement of Fractional Flow Reserve (FFR) through a combination of Computational Fluid Dynamics (CFD) simulations using 45 clinical patient data with 58 lesions and ideal geometries. The analysis is conducted considering patients that were subjected to a computer tomography and also have direct measurements using a pressure guide. Influence of the stenosis severity, degree of occlusion and blood viscosity has also been studied. RESULTS: The influence of pressure wires specifically affects severe stenosis with a lumen diameter reduction of 50 % or greater. This type of stenosis leads to reduced hyperemic flow and increased coronary pressure drop. Thus, we identified that the placement of wires during FFR measurements results in partial obstruction of the coronary artery lumen, leading to increased pressure drop and subsequent reduction in blood flow. The severity of low FFR values associated with severe stenosis may be prone to overestimation when compared to stenosis without severe narrowing. These results have practical implications, particularly in the interpretation of lesions falling within the "gray zone" (0,75-0,80). CONCLUSIONS: The pressure wire's presence significantly alters the flow on severe lesions, which has an impact on the FFR calculation. In contrast, the impact of the pressure wire appears to be reduced when the FFR is larger than 0.8. The findings provide critical information for physicians, emphasizing the need for cautious interpretation of FFR values, particularly in severe stenosis. It also offers insights into improving the correlation between FFRct models and invasive measurements by incorporating the influence of pressure wires.

Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists and cancer mortality. A real-world registry.

INTRODUCTION AND OBJECTIVES: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, but their association with cancer remains unclear. The aim of this study was to compare the effect of combined treatment (SGLT2i and GLP1ra) and monotherapy (SGLT2i or GLP1ra) on hospitalization and/or death from cancer in a general population and a subgroup of patients with cardiovascular disease (CVD). METHODS: We conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome. RESULTS: We included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P<.001; and HR, 0.1928; 95%CI, 0.071-0.5219; P=.001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P<.049; and HR, 0.1329; 95%CI, 0.024-0.6768; P=.014, respectively). CONCLUSIONS: Initiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis.

Carbohydrate antigen 125 on epicardial fat and its association with local inflammation and fibrosis-related markers.

BACKGROUND: Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis. METHODS: Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively. RESULTS: The median age was 71 (63-74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels. CONCLUSION: Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis).

Characterization of patients with extensive left atrial myopathy referred for atrial fibrillation ablation: incidence, predictors, and outcomes.

BACKGROUND: Although atrial fibrosis has a relevant impact on ablation success rate, experimental studies have reported that extensive fibrosis may be accompanied by a reduced burden secondary to a prominent depression of atrial excitability. OBJECTIVES: We aimed to identify clinical and echocardiographic factors associated with extensive left atrial myopathy (ELAM), to analyze the predictive ability of established scores (AF score, APPLE, and DR-FLASH) and assess outcomes in terms of AF recurrence, left atrial flutter, and post-procedural heart failure admissions. METHODS: A total of 950 consecutive patients undergoing the first AF ablation were included. A 3D electroanatomical mapping system (CARTO3, Biosense Webster) was created using a multipolar mapping catheter (PentaRay, Biosense Webster). ELAM was defined as ≥ 50% low voltage area. A subanalysis with four groups was also created (< 10%; 10-20%; 10-20%; and > 30%). Logistic regressions, Cox proportional hazards models, and log-rank test were used to test the predictors independently associated with the presence of ELAM and AF recurrence. The model was prospectively validated in a cohort of 150 patients obtaining an excellent ability for prediction AUC 0.90 (CI 95% 0.84-0.96). RESULTS: Overall, 78 (8.42%) presented ELAM. Age, female sex, persistent AF, first-degree AV block, and E/e' were significant predictors. The model incorporating these factors outperformed the existing scores (AUC = 0.87). During a mean follow-up of 20 months (IQR 9 to 36), patients with ELAM presented a higher rate of AF recurrence (42.02% vs 26.01%, p = 0.030), left atrial flutter (26.03% vs 8.02%, p < 0.001), and post-procedural heart failure admissions (12.01% vs 0.61%, p < 0.001) than non-ELAM patients. CONCLUSIONS: This study reveals the incidence and clinical factors associated with ELAM in AF, highlighting age, female, persistent AF, first-degree AV block, and E/e'. Importantly, the presence of ELAM is associated with poorer outcomes in terms of recurrence and HF admission.

[Effectiveness of the CNIC polypill in secondary cardiovascular prevention in the subgroup of patients of the NEPTUNO study using atorvastatin doses of 20 mg]. / Efectividad de la polipíldora CNIC en prevención cardiovascular secundaria en el subgrupo de pacientes del estudio NEPTUNO con dosis de atorvastatina de 20 mg.

Objective: To analyse the incidence and risk of recurrent major adverse cardiovascular events (MACE), level of risk factor control, treatment persistence and cost of the CNIC polypill version containing acetylsalicylic acid (ASA) 100 mg, atorvastatin 20 mg (A20), and ramipril 2.5, 5.0 or 10 mg in secondary cardiovascular prevention patients. Method: Subanalysis of the observational, retrospective, multicentre, NEPTUNO study in patients treated for two years with the CNIC polypill A20, the same monocomponents as single drugs, equipotent drugs, and other therapies. Results: 922 patients were included in each group. The risk of recurrent MACE was lower among CNIC A20 polypill users than all others (21%, 23% and 26% increased risk among the monocomponents, equipotent or other therapy cohorts, respectively; p < 0.05). The magnitude of the mean change in low-density lipoprotein cholesterol and blood pressure, as well as the increase in the proportion of patients achieving target goals, was also greater among patients treated with the CNIC A20 polypill than in any of the other cohorts (all p < 0.001). Treatment persistence was significantly higher in patients treated with the CNIC A20 polypill (p < 0.001) and was a less costly strategy than any other therapeutic option. Conclusions: In patients in secondary cardiovascular prevention, the CNIC A20 polypill (ASA 100 mg, atorvastatin 20 mg, and ramipril 2.5, 5.0 or 10 mg) constitutes a valid therapeutic option with similar benefits and outcomes to the version of the polypill with atorvastatin 40 mg.

Objetivo: Analizar la incidencia y el riesgo de eventos adversos cardiovasculares mayores (MACE) recurrentes, el nivel de control de factores de riesgo, la persistencia al tratamiento y el coste de la versión de la polipíldora CNIC que contiene 100 mg de ácido acetilsalicílico (AAS), 20 mg de atorvastatina (A20) y 2.5/5.0 ó 10 mg de ramipril en pacientes en prevención cardiovascular secundaria. Método: Subanálisis del estudio observacional, retrospectivo y multicéntrico NEPTUNO en pacientes tratados durante 2 años con la polipíldora CNIC A20, los mismos monocomponentes por separado, medicamentos equipotentes uotras terapias. Resultados: Se incluyeron 922 pacientes en cada grupo. El riesgo de sufrir un MACE recurrente en el grupode polipíldora CNIC A20 fue menor que en todas las demás cohortes (21%, 23% y 26% de aumento del riesgo en las cohortesde monocomponentes, equipotentes u otras terapias, respectivamente; p < 0.05). La magnitud del cambio en el colesterol unidoa lipoproteínas de baja densidad y la presión arterial, así como el incremento en la proporción de pacientes que alcanzaron losobjetivos establecidos, fueron mayores en los pacientes tratados con la polipíldora CNIC A20 que en cualquiera de las otrascohortes (p < 0.001). La persistencia al tratamiento fue mayor en los pacientes tratados con la polipíldora CNIC A20 (p < 0.001)y esta estrategia resultó ser menos costosa que cualquier otra opción terapéutica. Conclusiones: En pacientes en prevencióncardiovascular secundaria, la polipíldora CNIC A20 (AAS 100 mg; atorvastatina 20 mg; ramipril 2.5/5.0 ó 10 mg) constituye unaopción terapéutica válida con beneficios y resultados similares a la versión de la polipíldora con 40 mg de atorvastatina.

Population-based disease-group analysis of Spanish excess mortality in the early COVID-19 pandemic period.

BACKGROUND AND AIM: Increased mortality during the COVID-19 pandemic is not explained exclusively by COVID-19 infection and its complications. We analysed non-COVID-19 causes of mortality in a population analysis based on data from the Spanish National Institute of Statistics. METHODS: Using monthly mortality data in Spain (January 2010-December 2020), we analysed deaths associated with cancer, blood, endocrine, mental, nervous, cardiovascular, respiratory and digestive diseases and explored the COVID-19 impact using a difference-in-difference strategy. We calculated monthly interannual variations in mortality and computed percentage change in terms of the log of deaths in month h of year t minus the log of deaths in month h in the previous year t-1. RESULTS: In 2020 in Spain, mortality increased 17.9% compared with 2019. COVID-19 was the leading cause of death (n=60 358), followed by ischaemic heart disease (n=29 654). Throughout 2020, monthly interannual variations in cardiovascular mortality showed an average upward trend of 1.7%, while digestive, cancer and blood diseases showed a downward trend. CONCLUSIONS: During the COVID-19 pandemic in Spain in 2020, excess mortality was primarily related to cardiovascular mortality while mortality associated with digestive, cancer and blood diseases was reduced.

Colchicine in acute heart failure: Rationale and design of a randomized double-blind placebo-controlled trial (COLICA).

AIMS: Heart failure (HF) elicits a pro-inflammatory state, which is associated with impaired clinical outcomes, but no anti-inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin-1 axis are overactivated during episodes of acute HF. Colchicine, an anti-inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients. METHODS: COLICA is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new-onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m2). The primary efficacy endpoint is the time-averaged proportional change in NT-proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events. CONCLUSION: COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF.

Latin-American guidelines of recommendations at discharge from an acute coronary syndrome.

The diagnostic criteria, treatments at the time of admission, and drugs used in patients with acute coronary syndrome are well defined in countless guidelines. However, there is uncertainty about the measures to recommend during patient discharge planning. This document brings together the most recent evidence and the standardized and optimal treatment for patients at the time of discharge from hospitalization for an acute coronary syndrome, for comprehensive and safe care in the patient's transition between care from the acute event to the outpatient care, with the aim of optimizing the recovery of viable myocardium, guaranteeing the most appropriate secondary prevention, reducing the risk of a new coronary event and mortality, as well as the adequate reintegration of patients into daily life.

Los criterios diagnósticos, los tratamientos en el momento de la admisión y los fármacos utilizados en pacientes con síndrome coronario agudo están bien definidos en innumerables guías. Sin embargo, existe incertidumbre acerca de las medidas para recomendar durante la planificación del egreso de los pacientes. Este documento reúne las evidencias más recientes y el tratamiento estandarizado y óptimo para los pacientes al momento del egreso de una hospitalización por un síndrome coronario agudo, para un cuidado integral y seguro en la transición del paciente entre la atención del evento agudo y el cuidado ambulatorio, con el objetivo de optimizar la recuperación de miocardio viable, garantizar la prevención secundaria más adecuada, reducir el riesgo de un nuevo evento coronario y la mortalidad, así como la adecuada reinserción de los pacientes en la vida cotidiana.

[Classification tree obtained by artificial intelligence for the prediction of heart failure after acute coronary syndromes]. / Árboles de clasificación obtenidos mediante inteligencia artificial para la predicción de insuficiencia cardiaca tras el síndrome coronario agudo.

BACKGROUND: Coronary heart disease is the leading cause of heart failure (HF), and tools are needed to identify patients with a higher probability of developing HF after an acute coronary syndrome (ACS). Artificial intelligence (AI) has proven to be useful in identifying variables related to the development of cardiovascular complications. METHODS: We included all consecutive patients discharged after ACS in two Spanish centers between 2006 and 2017. Clinical data were collected and patients were followed up for a median of 53months. Decision tree models were created by the model-based recursive partitioning algorithm. RESULTS: The cohort consisted of 7,097 patients with a median follow-up of 53months (interquartile range: 18-77). The readmission rate for HF was 13.6% (964 patients). Eight relevant variables were identified to predict HF hospitalization time: HF at index hospitalization, diabetes, atrial fibrillation, glomerular filtration rate, age, Charlson index, hemoglobin, and left ventricular ejection fraction. The decision tree model provided 15 clinical risk patterns with significantly different HF readmission rates. CONCLUSIONS: The decision tree model, obtained by AI, identified 8 leading variables capable of predicting HF and generated 15 differentiated clinical patterns with respect to the probability of being hospitalized for HF. An electronic application was created and made available for free.

Combined Sodium-Glucose-Transporters Inhibitors and Glucagon-Like-Peptide Receptor Agonist Compared With Monotherapy Improves Long-Term Survival: A Real-World Registry.

BACKGROUND: The benefits of new glucose-lowering agents on cardiovascular disease have been demonstrated in randomized clinical trials. However, more evidence is required to assess the additive value of a combined therapy based on sodium-glucose transporter inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1ra) in a real-world population. METHODS: A nonconcurrent prospective study was conducted using integrated electronic medical records from primary care and hospitals obtained through "big data" technologies in a healthy area in Galicia. The study involved patients who were given SGLT2i, GLP1ra, or both treatments between January 2018 and June 2022 and were categorized as either mono- or combined therapy (SGLT2i, GLP1ra, or both). The cumulative risk for different events: hospitalization or mortality, or both, for 1) coronary artery disease, 2) heart failure, 3) cerebrovascular accident, and all-cause mortality were represented by Kaplan-Meier curves and multivariate Cox regression analysis to obtain the hazard ratio (HR) and (95% confidence interval [CI]). Validation was performed in a subpopulation with propensity score matching. RESULTS: The patients (15,549) who were included were median (standard deviation) 68 (12) years old, with 41% of them being female and 46% experiencing obesity. The median (interquartile range) of follow-up was 19 (8-33) months. The Kaplan-Meier analysis determined that the cumulative risk for coronary artery disease and cerebrovascular accident events was similar among the 3 different therapy groups. However, the combined therapy vs SGLT2i reduced the risk of heart failure events (HR 0.69; 95% CI, 0.56-0.87) or all-cause mortality (HR 0.68; 95% CI, 0.54-0.86). Multivariate Cox regression analysis, after matching with a propensity score, confirmed the benefits of combined therapy regarding SGLT2i or GLP1ra monotherapy. CONCLUSION: Compared with SGLT2i or GLP1ra alone, combined therapy SGLT2i + GLP1ra reduces heart failure risk and all-cause mortality in a real-world population.

The CNIC-polypill (acetylsalicylic acid, atorvastatin, and ramipril), an effective and cost-saving secondary prevention strategy compared with other therapeutic options in patients with ischaemic heart disease.

Aims: The retrospective NEPTUNO study evaluated the effectiveness of the Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (including acetylsalicylic acid, ramipril, and atorvastatin) vs. other therapeutic approaches in secondary prevention for cardiovascular (CV) disease. In this substudy, the focus was on the subgroup of patients with ischaemic heart disease (IHD). Methods and results: Patients on four strategies: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. The primary endpoint was the incidence of recurrent major adverse CV events (MACEs) after 2 years. After matching, 1080 patients were included in each cohort. The CNIC-polypill cohort had a significantly lower incidence of recurrent MACE compared with monocomponents, equipotent drugs, and other therapies cohorts (16.1 vs. 24, 24.4, and 24.3%, respectively; P < 0.001). The hazard ratios (HRs) for recurrent MACE were higher in monocomponents (HR = 1.12; P = 0.042), equipotent drugs (HR = 1.14; P = 0.031), and other therapies cohorts (HR = 1.17; P = 0.016) compared with the CNIC-polypill, with a number needed to treat of 12 patients to prevent a MACE. The CNIC-polypill demonstrated a greater reduction in LDL cholesterol (LDL-c; -56.1 vs. -43.6, -33.3, and -33.2% in the monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) and systolic blood pressure (-13.7 vs. -11.5, -10.6, and -9.1% in the CNIC-polypill, monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) compared with other cohorts. The CNIC-polypill intervention was less costly and more effective than any other therapeutic option, with €2317-€2407 cost savings per event prevented. Conclusion: In IHD, the CNIC-polypill exemplifies a guideline-recommended secondary prevention treatment linked to better outcomes and cost saving compared with other therapeutic options.

Enhancing patient outcomes: Integrating electronic cardiology consultation in primary care for cancer patients.

BACKGROUND: The prevalence of cancer patients with concomitant cardiovascular (CV) disease is on the rise due to improved cancer prognoses. The aim of this study is to evaluate the long-term outcomes of cancer patients referred to a cardiology department (CD) via primary care using e-consultation. METHODS: We analysed data from cancer patients with prior referrals to a CD between 2010 and 2021 (n = 6889) and compared two care models: traditional in-person consultations and e-consultations. In e-consultation model, cardiologists reviewed electronic health records (e-consultation) to determine whether the demand could be addressed remotely or necessitated an in-person consultation. We used an interrupted time series regression model to assess outcomes during the two periods: (1) time to cardiology consultation, (2) rates of all-cause and CV related hospital admissions and (3) rates of all-cause and CV-related mortality within the first year after the initial consultation or e-consultation at the CD. RESULTS: Introduction of e-consultation for cancer patients referred to cardiology care led to a 51.8% reduction (95%CI: 51.7%-51.9%) in waiting times. Furthermore, we observed decreased 1-year incidence rates, with incidence rate ratios (iRRs) [IC95%] of .75 [.73-.77] for CV-related hospitalizations, .43 [.42-.44] for all-cause hospitalizations, and .87 [.86-.88] for all-cause mortality. CONCLUSIONS: Compared to traditional in-person consultations, an outpatient care program incorporating e-consultation for cancer patients significantly reduced waiting times for cardiology care and demonstrated safety, associated with lower rates of hospital admissions.