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Background: Heart donation after circulatory death (DCD) involves mandatory exposure to warm ischemic injury (WII) due to donor cardiac arrest resulting from withdrawal of life-support (WLS). However, potential DCD donors may also experience a cardiac arrest and undergo cardiopulmonary resuscitation (CPR) and associated WII before WLS. We sought to investigate the effect of previous donor-CPR in DCD heart-transplantation (HT)., Methods: Between January-2020 and April-2023, we identified 11,415 adult HTs in UNOS of whom 9456 met study criteria and had information on donor-CPR. Follow-up was available till April-2024. Study cohort was divided into four groups based on DCD vs. donation after brain death (DBD) status and donor-CPR i.e., DCD/CPR+ (n = 387), DCD/noCPR (n = 305), DBD/CPR+ (n = 5158) and DBD/noCPR (n = 3606); and compared for HT characteristics and outcomes., Results: With DBD/noCPR HTs as reference cohort, there were no significant differences in mortality in other HT cohorts (DCD/CPR+, DCD/noCPR and DBD/CPR+) upto 1-year of follow up using Kaplan-Meier analysis; and both unadjusted and adjusted Cox hazards-ratio models. Results were similar in propensity-matched cohorts. Duration of donor-CPR (≤20 min vs >20 min) did not influence HT survival; and rates of in-hospital secondary outcomes were similar. The utilization rates of both adult DCD/CPR+ (3.39 % to 9.71 %) and DCD/noCPR donors (4.41 % to 10.34 %) increased significantly (p < 0.01) during study period., Conclusions: The utilization rates of both DCD/CPR+ and DCD/noCPR donors have increased at an equal pace. A significant proportion of DCD HTs were from donors with prior CPR, but this was not associated with worse short-term survival., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cardiogenic shock (CS) complicates Takotsubo syndrome (TTS), significantly affecting patient outcomes. Since avoiding catecholamines, particularly inotropic agents, is recommended in TTS, temporary mechanical circulatory support (MCS) shows promise as a bridge to recovery. However, there is no prospective data on its use in TTS., Methods: Patients from the prospective nationwide RETAKO registry were included and divided based on the use and type of MCS., Results: From a national TTS registry, 1591 consecutive patients were initially enrolled between 2003 and 2022. Of these, 322 patients (20.2 %) developed CS, and 31 (9.6 %) were treated with MCS [20 intra-aortic balloon pump (IABP) (64.5 %), 8 veno-arterial extracorporeal membrane oxygenation (25.8 %), and 3 Impella-CP (9.7 %)]. Compared to CS patients managed only with drugs, MCS recipients exhibited a more severe clinical profile, with worse ventricular function and more right ventricular involvement. Despite encountering more complications, such as major bleeding and atrial fibrillation, MCS did not significantly influence in-hospital mortality (19.4 % in the MCS group vs 13.1 % in the no MCS group, p = 0.33). After adjusting for other predictors of in-hospital mortality (invasive mechanical ventilation, inotropic-vasoactive score, age, and SCAI stage), MCS was not associated with higher mortality., Conclusion: Approximately 10 % of TTS patients complicated by CS were treated with MCS. Despite their more severe CS, patients treated with MCS had similar in-hospital mortality rates as those treated only with drugs, suggesting a potential benefit of MCS in selected cases., (Copyright © 2024. Published by Elsevier B.V.)

Aims: The optimal management of older patients with acute coronary syndrome (ACS) remains unclear. The most effective evaluation methods for frailty and malnutrition are yet to be delineated, despite being proposed as predictors of adverse outcomes. Consequently, this study aims to assess the significance of these factors in predicting in-hospital complications within this population., Methods and Results: In this single-center, intrahospital case-control study, 217 older patients (aged >70 years) with ACS were categorized into two groups based on the occurrence of net adverse clinical events (NACE) during hospitalization: the NACE (n = 59) and non-NACE (n = 158) groups. Demographic and clinical variables were collected, including assessments of frailty using the FRAIL Scale (FS), dependency using the Barthel Index, and nutritional status using both the Prognostic Nutritional Index (PNI) and Geriatric Nutritional Risk Index (GNRI). Regression models and receiver operating characteristics curves were constructed to predict NACE. Patients in the NACE group exhibited higher frailty (P < 0.001), increased dependency (P < 0.001), and poorer nutritional status (P <0.05) compared to those in the non-NACE group. The FS [OR (95% CI) = 2.03 (1.39-2.95), P < 0.001] and PNI [OR (95% CI) = 0.64 (0.41-0.99), P < 0.05] scores emerged as independent predictors of NACE in a multivariable model including age, sex, and traditional cardiovascular risk factors. This model demonstrated high discriminatory power [AUC (95% CI) = 0.834 (0.768-0.899), P < 0.001] for NACE., Conclusions: Frailty and nutritional status could significantly contribute to the stratification and identification of older adults with ACS who are at risk of developing in-hospital complications., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Recurrent acute myocardial infarction (RE-AMI) is a frequent complication after STEMI, and its association with stent thrombosis can be life-threatening. Intravenous atorvastatin (IV-atorva) administration during AMI has been shown to limit infarct size and adverse cardiac remodeling. We determined by cardiac magnetic resonance (CMR) whether the cardioprotection exerted by IV-atorva at the index AMI event translates into a better prognosis upon RE-AMI in dyslipidemic pigs., Methods and Results: Hypercholesterolemic pigs underwent a first AMI (90-minute coronary balloon occlusion). During ongoing ischemia, animals received IV-atorva or vehicle. Forty days later, animals underwent RE-AMI and were sacrificed on day43. All animals remained on p.o. atorvastatin and a high-cholesterol diet from the first AMI until sacrifice. Serial CMR analysis was performed on day3 post-AMI, prior- (day40) and post-RE-AMI (day43). No differences were detected in edema formation in both animal groups during AMI and RE-AMI. Gadolinium DE-CMR revealed smaller infarcts in IV-atorva-treated animals at index event at 3days and 40days post-AMI compared to vehicle-administered pigs (p<0.05). CMR analyses post-RE-AMI revealed smaller infarcts in the animals treated with IV-atorva at index event than in the vehicle-administered pigs. These IV-atorva at index event benefits were associated with higher LVEF and normal LV wall motion in the jeopardized myocardium at RE-AMI (p<0.05 vs. vehicle). The scar region of RE-AMI of animals treated with IV-atorva at index event showed reduced cardiac inflammatory infiltrate, apoptosis and senescence activation, and increased reparative fibrosis and neovessel formation vs. vehicle-administered pigs. Animals treated with IV-atorva at index event also showed lower CRP and higher IL-10 plasma levels in the setting of RE-AMI., Conclusions: The cardioprotection afforded by IV-atorva administration during an index-AMI event shows a legacy effect attenuating myocardial damage and preserving cardiac contractile function upon RE-AMI. The potential benefits of this intravenous approach should be tested in the clinical setting., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Safe deferral of revascularisation is a key aspect of physiology-guided percutaneous coronary intervention (PCI). While recent evidence gathered in the FAVOR III Europe trial showed that quantitative flow ratio (QFR) guidance did not meet non-inferiority to fractional flow reserve (FFR) guidance, it remains unknown if QFR might have a specific value in revascularisation deferral., Aims: We aimed to evaluate the safety of coronary revascularisation deferral based on QFR as compared with FFR., Methods: Patients randomised in the FAVOR III trial in whom PCI was deferred in at least one coronary artery, based on QFR or FFR>0.80, were included in the present substudy. The primary outcome was the 1-year rate of major adverse cardiac events (MACE), with results reported for two subsets of deferred patients: (1) any study lesion deferral and (2) complete study lesion deferral., Results: A total of 523 patients (55.2%) in the QFR group and 599 patients (65.3%) in the FFR group had at least one coronary revascularisation deferral. Of these, 433 patients (82.8%) and 511 (85.3%) patients, respectively, had complete study lesion deferral. In the "complete study lesion deferral" patient group, the occurrence of MACE was significantly higher in QFR-deferred patients as compared with FFR-deferred patients (24 [5.6%] vs 14 [2.8%], adjusted hazard ratio [HR] 2.07, 95% confidence interval [CI]: 1.07-4.03; p=0.03). In the subgroup of "any study lesion deferral", the MACE rate was 5.6% vs 3.6% (QFR vs FFR), adjusted HR 1.55, 95% CI: 0.88-2.73; p=0.13., Conclusions: QFR-based deferral of coronary artery revascularisation resulted in a higher incidence of 1-year MACE as compared with FFR-based deferral.

Background: Cytomegalovirus (CMV) infection is associated with worse outcomes after heart transplant (HT). CMV mismatch (donor positive, recipient negative serology, D+/R-) increases the risk of infection. Guidelines recommend 3 to 6 months of antiviral prophylaxis in these patients. An increase in primary CMV infections at our center prompted us to analyses this population in search of improvement., Methods: From 185 adult HT receptors in 10 years, we selected those with CMV D+/R-. Patients were followed until October 2023. We evaluated the patterns of transmission of CMV in accordance with current recommendations., Results: We assessed 35 HT recipients with CMV mismatch (median age of 48.8 ± 13.8 years, 71% men). Median follow-up was 5.5 years [1.9-7.4]. Median duration of CMV prophylaxis was 3.7 (±2.1) months post-HT. CMV infection occurred in 74% of patients (96% within the first 6 months after ending prophylaxis) and CMV disease in 26%. Half of them required hospital admission. One third had concomitant infections by other microorganisms. There were no significant differences in the duration of prophylaxis between patients with and without CMV infection. Survival on follow-up was 77%. 2 patients died during CMV infection due to other infection., Conclusions: CMV infection rate in D+/R- HT receptors remains high even after the prophylactic period recommended by current guidelines. A better knowledge of CMV-transmitted infection, coupled with the pursuit of a suitable equilibrium between the prevention of infection and rejection, have the potential to enhance the outcomes of this high-risk population through tailored protocols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: ADAS-3D software elaborates cardiac magnetic resonance (CMR) images to obtain a quantitative evaluation of dense scar and border zone (BZ), including BZ channels, which can be useful for ventricular tachycardia ablation and risk stratification. However, most prior reports with ADAS-3D used flexible thresholds (60% ± 5% and 40% ± 5% of maximum pixel signal intensity) to define dense scar and BZ. The impact of such variations of the threshold values on the measurements obtained with ADAS-3D is unknown., Objective: This study aimed to quantify the degree of change in ADAS-3D measurements when different thresholds for dense scar and BZ are employed., Methods: A single-center retrospective observational cohort study including 87 consecutive patients with previous myocardial infarction who underwent CMR was conducted. ADAS-3D software semiautomatically processed CMR sequences. We compared the scar measurements obtained with the 9 possible combinations of thresholds (55%/60%/65% and 35%/40%/45% of maximum pixel signal intensity)., Results: The overall comparison between thresholds showed highly significant differences (P < .001) in all scar parameters. Not a single patient maintained the same number of BZ channels with all the thresholds settings. A percentage difference of up to 200% in BZ channel numbers and channel mass was observed in all 36 comparisons. An absolute difference of up to 10 channels was also recorded. Of note, the highest median channel mass (obtained with the thresholds 35-65) was 59-fold higher compared with the lowest one (obtained with the 45-55 cutoffs)., Conclusion: Variations in threshold values result in statistically significant and high-magnitude changes in the quantification of scar parameters by ADAS-3D., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: The development of specific heart failure (HF) units has improved the management of patients with this disease due to improved organization and resource management. The Spanish Society of Cardiology (SEC) has defined 3 types of HF units (community, specialized, and advanced) based on their complexity and service portfolio. Our aim was to compare the characteristics, treatment, and outcomes of patients with HF according to the type of unit., Methods: We analyzed data from the SEC-Excelente-IC quality accreditation program registry, with 1716 patients consecutively included in two 1-month cutoffs (March and October) from 2019 to 2021 by 45 SEC-accredited HF units. We compared the characteristics, treatment and 1-year outcomes between the 3 types of units., Results: Of the 1716 patients, 13.2% were treated in community units, 65.9% in specialized units, and 20.9% in advanced units. The rates of mortality (27.5 vs 15.5/100 patients-year; P<.001), admissions for HF (39.7 vs 29.2/100 patients-year; P=.019), total decompensations (56.1 vs 40.5/100 patients-year; P=.003), and combined death/admission for HF (45.2 vs 31.4/100 patients-year; P=.005) were higher in community units than in specialized/advanced units. Follow-up in a community unit was an independent predictor of higher mortality and admissions at 1 year., Conclusions: Compared with follow-up by more specialized units, follow-up in a community unit was associated with a higher decompensation rate and increased 1-year mortality., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Systemic immune-mediated diseases (SIDs) are a well-known cause of dilated cardiomyopathy (DCM), a cardiac phenotype influenced by genetic predispositions and environmental factors., Objectives: This study sought to examine if an underlying genetic predisposition is present in patients with DCM and SID., Methods: Genotyped DCM-SID patients (n = 183) were enrolled at 3 European centers. Genetic variants were compared with healthy control subjects (n = 20,917), DCM patients without SID (n = 560), and individuals with a suspicion of an SID (n = 1,333). Clinical outcomes included all-cause mortality, heart failure hospitalization, and life-threatening arrhythmias., Results: The SID diagnosis preceded the DCM diagnosis by 4.8 months (Q1-Q3: -68.4 to +2.4 months). The prevalence of pathogenic/likely pathogenic (P/LP) variants in DCM patients with an SID from the Maastricht cohort was 17.1%, compared with 1.9% in healthy control subjects (P < 0.001). In the Madrid/Trieste cohort, the prevalence was 20.5% (P < 0.001). Truncating variants showed the strongest enrichment (10.7% [OR: 24.5] (Maastricht) and 16% [OR: 116.6 (Madrid/Trieste); both P < 0.001), with truncating TTN (titin) variant (TTNtv) being the most prevalent. Left ventricular ejection fraction at presentation was reduced in TTNtv-SID patients compared with DCM patients with SID without a P/LP (P = 0.016). The presence of a P/LP variant in DCM-SID had no impact on clinical outcomes over a median follow-up of 8.4 years (Q1-Q3: 4.9-12.1 years)., Conclusions: One in 6 DCM patients with an SID has an underlying P/LP variant in a DCM-associated gene. This highlights the role of genetic testing in those patients with immune-mediated DCM, and supports the concept that autoimmunity may play a role in unveiling a DCM phenotype in genotype-positive individuals., Competing Interests: Funding Support and Author Disclosures This work was supported by the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation (Dutch Cardiovascular Alliance Double Doses, 2020-B005). Dr Verdonschot was supported by a Dekker Clinical Scientist grant from the Dutch Heart Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Currently, there is little evidence on the prevalence and factors associated with sarcopenia risk or frailty risk in patients post heart transplantation (HTx). The objective of this study was to analyze the influence of sociodemographic, lifestyle, physical, and psychological factors on sarcopenia and frailty risk in patients post-HTx., Methods: 133 patients post-HTx (59.4% men, mean age 56.5 ± 12.7 years) participated in this cross-sectional study. The main outcomes were sarcopenia and frailty risk, and potential related predictors were comorbidities, time from transplantation, body mass index, sociodemographic factors, musculoskeletal pain, functional capacity, kinesiophobia, sleep problems, depression, physical activity, and diet quality. Multiple regression models were performed with all predictors, including polynomial regressions for predictors with a nonlinear relationship., Results: The predictor variables explained 73.93% of frailty's variance. Functional capacity (with a nonlinear relationship) and diet quality were significant predictors of frailty risk, while diabetes and physical activity were marginally significant. In addition, the predictors explained 73.52% of sarcopenia's variance. Diabetes, functional capacity (with a nonlinear relationship), and kinesiophobia were significant predictors of sarcopenia risk, while pain intensity and diet quality were marginally significant., Conclusion: Multivariate analysis conducted on patients post-HTx revealed that functional capacity was associated with both sarcopenia and frailty risk. Additionally, diet quality was a predictive factor of frailty, while diabetes and kinesiophobia were predictors of sarcopenia. These findings emphasize the importance of proper management to prevent frailty and sarcopenia, which share common associated factors., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Decision tree algorithms, obtained by machine learning, provide clusters of patients with similar clinical patterns by the identification of variables that best merge with a given dependent variable., Methods: We performed a multicenter registry, with 7 hospitals form Spain, of patients with, or high-risk of having, coronary heart disease (CHD). Elevated Lp(a) was defined as >50 mg/dl. Machine learning based decision trees were obtained by Chi-square automatic interaction detection., Results: We analyzed 2301 patients. Median Lp(a) was 26.7 (9.3-79.9) mg/dl and 887 (38.6 %) patients had Lp(a) >50 mg/dl. The machine learning algorithm identified 6 clusters based on LDLc, CHD, FH of premature CHD and age (Fig. 1). Clusters 1 (LDLc <100 mg/dl, no CHD and, no FH of CHD) and 3 (LDLc <100 mg/dl, CHD and, no FH and, age < 50 yo) had the lowest Lp(a) values (Fig. 2); patients classified in cluster 5 (LDLc >100 mg/dl, CHD and, FH of CHD) and 6 (LDLc >100 mg/dl) had the highest values. We collapsed clusters in 3 groups: group 1 with clusters 1 and 3; group 2 with clusters 2 and 4; group 3 with clusters 5 and 6. The 3 groups have significantly different (p < 0.001) and progressively higher Lp(a) values. The prevalence of Lp(a) >50 mg/dl was 15.4 % in group 1, 29.2 % in group 2 and 91.1 % in group 3; similarly, the prevalence of Lp(a) >180 mg/dl was 1.0 %, 3.0 % and 7.6 % respectively., Conclusions: A decision tree algorithm, performed by machine learning, identified patients with, or at high risk of having, CHD have higher probabilities of having elevated Lp(a)., Competing Interests: Declaration of competing interest Alberto Cordero reports a) honoraria for lectures from AstraZeneca, AMGEN, Bristol-Myers Squibb, Ferrer, Boehringer Ingelheim, MSD, Daiichy Sankio, Novartis, Novo Nordisk, Sanofi and Amarin; b) consulting fees from AstraZeneca, Ferrer, Sanofi, AMGEN, Novartis, Lilly, Novo Nordisk and Amarin., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The cytokine storm associated with SARS-CoV-2 infection is one of the most distinctive pathological signatures in COVID-19 patients. Macrophages respond to this pro-inflammatory challenge by reprogramming their functional and metabolic phenotypes. Interestingly, human macrophages fail to express the inducible form of the NO synthase (NOS2) in response to pro-inflammatory activation and, therefore, NO is not synthesized by these cells. The contribution of exogenously added NO, via a chemical NO-donor, on the immunometabolic changes associated with the cytokine storm is investigated. By using metabolic, transcriptomic, and functional assays the effect of NO in human macrophages is evaluated and found specific responses. Moreover, through integrative fluxomic analysis, pathways modified by NO that contribute to the expression of a particular phenotype in human macrophages are identified, which includes a decrease in mitochondrial respiration and TCA with a slight increase in the glycolytic flux. A significant ROS increase and preserved cell viability are observed in the presence of NO, which may ease the inflammatory response and host defense. Also, NO reverses the cytokine storm-induced itaconate accumulation. These changes offer additional clues to understanding the potential crosstalk between NO and the COVID-19 cytokine storm-dependent signaling pathways., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background and Objective: Patients with pulmonary hypertension (PH) may present with hypoxaemia at rest or during daily activities. There is no epidemiological data on the prescription of long-term oxygen therapy (LTOT) in patients with PH. The study sought to analyse the prevalence and incidence of LTOT prescription among patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Spain and to determine predictors for this prescription., Methods: A retrospective analysis was performed from the Spanish Registry of Pulmonary Arterial Hypertension (REHAP). Collected data included demographics and anthropometric measurements, functional class (FC), arterial blood gases, pulmonary function tests, haemodynamic measurements, six-minute walking distance (6MWD) and LTOT prescription. In addition, we assessed the prevalence and incidence of LTOT prescription by PH group and subtype and potential predictors for LTOT initiation in the first 5 years after diagnosis., Results: We analysed 4533 patients (69.9% PAH and 30.1% CTEPH), mostly female (64.5%), with a mean age of 53.0 ± 18.3 years. The prevalence of LTOT was 19.3% for all patients. The incidence of LTOT prescriptions decreased from 5.6% to 1.6% between 2010 and 2019, respectively. Predictors for LTOT prescription, excluding those that represent the indication for oxygen therapy were: FC (HR: 1.813), 6MWD (HR: 1.002), mean pulmonary arterial pressure (mPAP) (HR: 1.014), cardiac index (CI) (HR: 1.253), pulmonary vascular resistance (PVR) (HR: 1.023) and diffusing capacity of carbon monoxide (DL CO ) (HR: 1.294)., Conclusion: The prevalence of LTOT in PAH and CTEPH patients is close to 20%. FC, 6MWD, mPAP, CI, PVR and DL CO were predictors for LTOT prescription., (© 2024 Asian Pacific Society of Respirology.)

Aim: The aim was to study the effect of two low-calorie, high-protein (HP) diets, with most of the protein coming from animal or plant sources, on glycaemic and other cardiometabolic outcomes in subjects with overweight or obesity and glucose metabolism disorders., Materials and Methods: A total of 117 participants aged >18 years with body mass index over 27.5 kg/m 2 and prediabetes or type 2 diabetes mellitus (T2DM) were randomized to one of two HP low-calorie diets (35% of total calories from protein), in which 75% of the protein was from either plant-based sources (HPP) or animal sources (HPA). For both diets, 30% and 35% of the total calories were from fat and carbohydrates, respectively. The dietary intervention lasted 6 months., Results: Both diets improved body composition to a similar extent, including weight loss (-8.05 ± 5.12 kg for the HPA diet and -7.70 ± 5.47 kg for the HPP diet at 6 months) and fat mass, mainly visceral fat. Both diets had a similar beneficial effect on glucose metabolism, including fasting glucose, insulin, homeostasis model assessment of insulin resistance index and glycated haemoglobin. Other biochemical parameters, including lipid profiles, liver enzymes, adipokines and inflammatory biomarkers, similarly improved in both groups. Fasting incretins, mainly glucagon-like peptide 1, decreased significantly in both groups, and this effect correlated with weight loss., Conclusions: Low-calorie HP diets improved body composition, glucose metabolism and other cardiometabolic outcomes, regardless of protein source (either animal or plant sources), in outpatients with prediabetes or T2DM., Clinical Trial Registration: The clinical trial was registered in ClinicalTrials.gov (identifier: NCT05456347) https://clinicaltrials.gov/study/NCT05456347?term=NCT05456347&rank=1., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background and Aims: Recent reports have shown that subjects with high high-density lipoprotein cholesterol (HDLc) levels are paradoxically at increased risk for all-cause and cardiovascular mortality. The aim was to study the association of HDLc concentration with mortality in subjects with high cholesterol., Methods: We analyzed total mortality, cardiovascular mortality, and non-cardiovascular mortality in a cohort of 2992 subjects with primary hypercholesterolemia, who were followed for 10.2 years (range 1-25 years), with a total of 30,602 subject-years of follow-up., Results: During follow-up, 168 subjects died, with 52 (13.7 %), 105 (4.80 %), and 11 (2.60 %) in the low, normal, and high HDLc groups, respectively (p < 0.001). The risk of death was 2.89 times higher (95 % confidence interval (CI), 1.50-5.57, p < 0.001) in subjects in the low HDLc group compared to those in the high HDLc group and 1.48 times higher (95 % CI 0.80-2.76, p = 0.214) in the normal HDLc group compared to the high HDLc group. However, HDLc concentration and HDLc groups based on HDLc concentration were not independently associated with mortality in Cox regression analysis. Cardiovascular and non-cardiovascular mortalities showed similar results., Conclusions: All types of mortality were lower in subjects with primary hypercholesterolemia and with high HDLc in univariate analysis. Elevated HDLc was not associated with total, cardiovascular, and non-cardiovascular mortality when adjusted for major cardiovascular risk factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction and Objectives: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients., Methods: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies. Adverse cardiac events were defined as heart failure (HF), sustained ventricular tachycardia, ventricular assist device implantation, heart transplant, and/or maternal cardiac death during pregnancy, or labor and delivery, and up to the sixth postpartum month., Results: A total of 15 patients, all with DCM (31% of the total cohort and 50% of women with DCM) experienced adverse cardiac events. Obstetric and fetal or neonatal complications were observed in 14% of pregnancies (10 in DCM patients and 2 in genetic carriers). We analyzed the 30 women who had been evaluated before their first pregnancy (12 with overt DCM and 18 without the phenotype). Five of the 12 (42%) women with DCM had adverse cardiac events despite showing NYHA class I or II before pregnancy. Most of these women had a history of cardiac events before pregnancy (80%). Among the 18 women without phenotype, 3 (17%) developed DCM toward the end of pregnancy., Conclusions: Cardiac complications during pregnancy and postpartum were common in patients with genetic DCM and were primarily related to HF. Despite apparently good tolerance of pregnancy in unaffected genetic carriers, pregnancy may act as a trigger for DCM onset in a subset of these women., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: In patients with ischemic heart disease, coronary microvascular dysfunction is associated with cardiovascular risk factors and poor prognosis; however, data from healthy individuals are scarce., Objectives: The purpose of this study was to assess the impact of cardiovascular risk factors and subclinical atherosclerosis on coronary microvascular function in middle-aged asymptomatic individuals., Methods: Myocardial perfusion was measured at rest and under stress using cardiac magnetic resonance in 453 individuals and used to generate myocardial blood flow (MBF) maps and calculate myocardial perfusion reserve (MPR). Subclinical atherosclerosis was assessed using 3-dimensional vascular ultrasound of the carotid and femoral arteries and coronary artery calcium scoring at baseline and at 3-year follow-up., Results: Median participant age was 52.6 years (range: 48.9-55.8 years), and 84.5% were male. After adjusting for age and sex, rest MBF was directly associated with the number of the metabolic syndrome components present (elevated waist circumference, systolic and diastolic blood pressure, fasting glucose, and triglycerides and low high-density lipoprotein cholesterol), insulin resistance (homeostatic model assessment for insulin resistance), and presence of diabetes. MPR was reduced in the presence of several metabolic syndrome components, elevated homeostatic model assessment for insulin resistance, and diabetes. Stress MBF was inversely associated with coronary artery calcium presence and with global plaque burden. Higher stress MBF and MPR were associated with less atherosclerosis progression (increase in plaque volume) at 3 years., Conclusions: In asymptomatic middle-aged individuals free of known cardiovascular disease, the presence of cardiometabolic risk factors and systemic (poly-vascular) subclinical atherosclerosis are associated with impaired coronary microvascular function. Better coronary microvascular function reduces atherosclerosis progression at follow-up. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)., Competing Interests: Funding Support and Author Disclosures The PESA study is funded by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Santander Bank. Dr Ibanez is supported by the European Commission (grant numbers ERC-CoG 819775 and H2020-HEALTH 945118), La Caixa Foundation (HR22-00533, DIREQT2Heart), the Spanish Ministry of Science and Innovation (PID2019-110369RB-I00), and the Red Madrileña de Nanomedicina en Imagen Molecular-Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). Dr Devesa is an Alfonso Martin Escudero fellow and is scientifically supported by La Caixa Foundation. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MICIU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/AEI/10.13039/501100011033). Dr Sánchez-González is a Philips employee. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Investigations of very long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) according to clinical presentation are scarce. Here, we investigated the 10-year clinical outcomes of patients undergoing DES-PCI according to clinical presentation., Methods: Patient-level data from five randomized trials with 10-year follow-up after DES-PCI were pooled. Patients were dichotomized into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) groups as per clinical presentation. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST) and repeat revascularization involving the target lesion (TLR), target vessel (TVR) or non-target vessel (nTVR)., Results: Of the 9700 patients included in this analysis, 4557 presented with ACS and 5143 with CCS. Compared with CCS patients, ACS patients had a higher risk of all-cause death and nTVR in the first year, but comparable risk thereafter. In addition, ACS patients had a higher risk of MI [adjusted hazard ratio 1.21, 95% confidence interval (1.04-1.41)] and definite ST [adjusted hazard ratio 1.48, 95% confidence interval (1.14-1.92)], while the risk of TLR and TVR was not significantly different up to 10-year follow-up., Conclusions: Compared to CCS patients, ACS patients treated with PCI and DES implantation have an increased risk of all-cause death and repeat revascularization of remote vessels up to 1 year, with no significant differences thereafter and up to 10-year follow-up. ACS patients have a consistently higher risk of MI and definite ST. Whether these differences persist with current antithrombotic and secondary prevention therapies requires further investigation., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Inhibitory neuromuscular transmission in the gastrointestinal tract is mediated by intrinsic nitrergic and purinergic neurons. Purines activate G protein-coupled receptor P2Y 1 receptors, increasing intracellular Ca 2+ that activates small conductance calcium-activated potassium (SK Ca ) channels. Little is known about the effect of adrenergic receptor activation on intestinal smooth muscle. In vascular tissue, stimulation of α-adrenoceptors causes smooth muscle contraction, while their effect on intestinal tissue is poorly understood. This study aimed to pharmacologically characterize the effect of α-adrenoceptor activation in the rat colon, which shares similar inhibitory pathways to the human colon., Methods: Muscle bath experiments were performed with the rat proximal, mid, and distal colon oriented both circularly and longitudinally., Results: The α 1 -adrenoceptor agonist phenylephrine (PE) (10 -8 -10 -5  M) evoked concentration-dependent relaxations of the intestinal smooth muscle from all regions and orientations. However, in the mid-circular colon at low PE concentrations, a contraction sensitive to 10 -5  M phentolamine (non-selective α-adrenoceptor blocker), the neural blocker tetrodotoxin (TTX; 10 -6  M), and atropine (10 -6  M) was recorded. PE-induced relaxations were insensitive to TTX (10 -6  M) and the nonselective β-adrenoceptor blocker propranolol (10 -6  M). In contrast, PE-induced relaxations were blocked by phentolamine (10 -5  M), prazosin (10 -6  M) (α 1 -adrenoceptor blocker), and RS17053 (10 -6  M) (α 1A -blocker), but not by yohimbine (10 -6  M) (α 2 -adrenoceptor blocker). Apamin (10 -6  M), a SK Ca channel blocker, abolished PE-induced relaxations., Conclusions: Contractile responses in the circular muscle of the mid colon could be attributed to α-adrenoceptors located on enteric cholinergic neurons. Stimulation of α 1A -adrenoreceptors activates SK Ca channels to cause smooth muscle relaxation, which constitutes a signaling pathway that shares similarities with P2Y 1 receptors., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Introduction and Objectives: In the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation to prevent cardioembolism. Our objective was to test the efficacy of intraventricular blood stasis imaging for predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI., Methods: We designed a prospective clinical study, Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI), including patients with a first STEMI, an ejection fraction ≤ 45% and without atrial fibrillation to assess the performance of stasis metrics to predict cardioembolism. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and 6-month visits. From the stasis maps, we calculated the average residence time, R T , of blood inside the left ventricle and assessed its performance to predict the primary endpoint. The longitudinal strain of the 4 apical segments was quantified by speckle tracking., Results: A total of 66 patients were assigned to the primary endpoint. Of them, 17 patients had 1 or more events: 3 strokes, 5 silent brain infarctions, and 13 mural thromboses. No systemic embolisms were observed. R T (OR, 3.73; 95%CI, 1.75-7.9; P<.001) and apical strain (OR, 1.47; 95%CI, 1.13-1.92; P=.004) showed complementary prognostic value. The bivariate model showed a c-index=0.86 (95%CI, 0.73-0.95), a negative predictive value of 1.00 (95%CI, 0.94-1.00), and positive predictive value of 0.45 (95%CI, 0.37-0.77). The results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value., Conclusions: In patients with STEMI and left ventricular systolic dysfunction in sinus rhythm, the risk of cardioembolism may be assessed by echocardiography by combining stasis and strain imaging. Registered at ClinicalTrials.gov (NCT02917213)., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2024. Published by Elsevier B.V.)

Importance: The differences between the use of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) in the long term are unknown., Objective: To compare long-term outcomes of iFR- and FFR-based strategies to guide revascularization., Design, Setting, and Participants: The DEFINE-FLAIR multicenter study randomized patients with coronary artery disease to use either iFR or FFR as a pressure index to guide revascularization. Patients from 5 continents with coronary artery disease and angiographically intermediate severity stenoses who underwent hemodynamic interrogation with pressure wires were included. These data were analyzed from March, 13, 2014, through April, 27, 2021., Main Outcome Measures: Five-year major adverse cardiac events (MACE) (a composite of all-cause death, nonfatal myocardial infarction, and unplanned revascularization), as well as the individual components of the combined end point., Results: At 5 years of follow-up, no significant differences were found between the iFR (mean age [SD], 65.5 [10.8] years; 962 male [77.5%]) and FFR (mean age [SD], 65.2 [10.6] years; 929 male [74.3%]) groups in terms of MACE (21.1% vs 18.4%, respectively; hazard ratio [HR], 1.18; 95% CI, 0.99-1.42; P = .06). While all-cause death was higher among patients randomized to iFR, it was not driven by myocardial infarction (6.3% vs 6.2% in the FFR study arm; HR, 1.01; 95% CI, 0.74-1.38; P = .94) or unplanned revascularization (11.9% vs 12.2% in the FFR group; HR, 0.98; 95% CI, 0.78-1.23; P = .87). Furthermore, patients in whom revascularization was deferred on the basis of iFR or FFR had similar MACE in both study arms (17.9% in the iFR group vs 17.5% in the FFR group; HR, 1.03; 95% CI, 0.79-1.35; P = .80) with similar rates of the components of MACE, including all-cause death. On the contrary, in patients who underwent revascularization after physiologic interrogation, the incidence of MACE was higher in the iFR group (24.6%) compared with the FFR group (19.2%) (HR, 1.36; 95% CI, 1.07-1.72; P = .01)., Conclusions and Relevance: At 5-year follow up, an iFR based-strategy was not statistically different than an FFR strategy to guide revascularization in terms of MACE, nonfatal myocardial infarction, and unplanned revascularization., Trial Registration: ClinicalTrials.gov Identifier: NCT02053038.