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Background: Chronic kidney disease (CKD) and frailty are often present in older patients with heart failure (HF). Our aim was to evaluate the association of CKD and frailty in one-year mortality in a cohort of older (≥75 years) outpatients with HF METHODS: Our data come from the FRAGIC study ("impacto de la FRAGilidad y otros síndromes Geriátricos en el manejo clínico y pronóstico del paciente anciano ambulatorio con Insuficiencia Cardíaca"), a multicenter prospective registry conducted in 16 cardiology services in Spain which included ≥75 years outpatients with HF. Renal function was assessed according to CKD-EPI formula. A comprehensive geriatric assessment was performed and frailty was identified according to visual mobility scale (frail if VMS≥2). Survival rates were analyzed by Cox regression model., Results: We included 499 patients, mean age 81.4 ± 4.3 years, 38 % women. Mean estimated glomerular filtration rate (eGFR) was 52.1 ± 17.5 ml/min/1.72 m 2 . Patients were classified in normal renal function (eGFR≥60 ml/min/1.72m 2 , 182 patients, 36 %), moderately impaired (eGFR 30-59 ml/min/1.72m 2 , 261 patients, 52.7 %) and severely impaired (eGFR<30 ml/min/1.72m 2 , 56 patients, 11.3 %). Patients with severe CKD were older, more often female, and presented a worse clinical profile, with higher comorbidity burden and frailty. After a median follow up of 371 days, 58 patients (11.6 %) died. Mortality was higher in patients with worse renal function (8.8 %, 11 % and 21 % according to renal function subgroups, respectively, p = 0.036) and frailty in the univariate analysis. However, only frailty, according to VMS, but not severe renal dysfunction, was independently associated with one year mortality., Conclusions: Most HF patients≥75 years have renal dysfunction. CKD is a marker of worse prognosis in elderly patients with chronic HF, but it does not independently associate one-year mortality in the presence of frailty., Competing Interests: Declaration of competing interest The Authors declare that there is no conflict of interest, (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction and Objectives: In patients with established chronic coronary syndrome (CCS), the significance of persistent angina is controversial. We aimed to evaluate the prognostic role of persistent angina in symptomatic CCS patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiographic findings undergoing percutaneous revascularization., Methods: We analyzed 334 CCS patients with Canadian Cardiovascular Society angina class ≥2, perfusion deficits on stress CMR and severe lesions in angiography who underwent medical therapy optimization plus CMR-guided percutaneous revascularization. We investigated the association of persistent angina at 6 months postintervention with subsequent cardiac death, myocardial infarction, and hospital admission., Results: All patients had angina class ≥2 (mean: 2.8±0.7), abnormal stress CMR (mean ischemic burden: 5.8±2.7 segments), and severe angiographic lesions. The angina resolution rates were 81% at 6 months, and 81%, 81%, and 77% at 1, 2, and 5 years, respectively. During a median follow-up of 8.9 years, persistent angina was independently associated with higher rates of subsequent cardiac death (13% vs 4%; HR, 3.7; 95%CI, 1.5-9.2; P=.005), myocardial infarction (24% vs 6%; HR, 4.9; 95%CI, 2.4-9.9; P<.001), and hospital admission for heart failure (27% vs 13%; HR, 2.7; 95%CI, 1.5-5.2; P=.001)., Conclusions: In CCS patients with robust diagnostic evidence from symptoms, stress CMR, and angiography, persistent angina after percutaneous revascularization is a strong predictor of subsequent cardiac death, myocardial infarction, and hospital admission for heart failure., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Carbohydrate antigen 125 (CA125), a biomarker associated with fluid overload, has proven useful in managing diuretic therapy in heart failure. We aimed to evaluate the impact of diuretic optimization guided by CA125 before transcatheter aortic valve implantation (TAVI) on outcomes., Methods: This prospective interventional study enrolled patients scheduled for TAVI, in whom baseline CA125 was measured 2 weeks before TAVI. Patients with CA125 ≥ 20 U/mL underwent diuretic up-titration before TAVI. Three groups were included: group I) baseline CA125 <20 U/mL; IIa) CA125 ≥ 20 U/mL that decreased after treatment, and IIb) CA125 ≥ 20 U/mL that did not decrease. The primary outcome was changes in the Kansas City Cardiomyopathy Questionnaire at 3 and 12 months. The secondary endpoint was clinical events., Results: The study included 184 patients (115 group I, 46 IIa, and 23 IIb). Groups I and IIa exhibited early and sustained improvements in the Kansas City Cardiomyopathy Questionnaire (group I: 18.9 points [95%CI, 15.7-22.1; P <.001] at 90 days, and 18.1 [95%CI, 14.9-21.4, P <.001] at 1 year; group IIa: 21.1 points [95%CI, 15.4-26.7; P <.001] and 19.5 [95%CI, 13.9-25.1; P <.001] respectively). In contrast, in group IIb there was no significant improvement at 90 days (P=.12), with improvement being significant only at 1 year (17.8 points, 95%CI, 5.9-29.6; P=.003). Over a median follow-up of 20.7 months, there were 63 (27.83%) deaths or heart failure admissions. Multivariate analysis showed a lower risk of events in group I vs IIb (HR, 0.28; 95%CI, 0.14-0.58; P <.001), and IIa vs IIb (HR, 0.24; 95%CI, 0.11-0.55; P <.001)., Conclusions: Patients with persistently high CA125 despite diuretic therapy pre-TAVI showed slower functional recovery and poorer clinical outcomes after TAVI., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

We aimed to assess the correlation of cardiovascular magnetic resonance (CMR)-derived epicardial adipose tissue (EAT) with infarct size (IS) and residual systolic function in ST-segment elevation myocardial infarction (STEMI). We enrolled patients discharged for a first anterior reperfused STEMI submitted to undergo CMR. EAT, left ventricular (LV) ejection fraction (LVEF), and IS were quantified at the 1-week ( n = 221) and at 6-month CMR ( n = 167). At 1-week CMR, mean EAT was 31 ± 13 mL/m 2 . Patients with high EAT volume ( n = 72) showed larger 1-week IS. After adjustment, EAT extent was independently related to 1-week IS. In patients with large IS at 1 week (>30% of LV mass, n = 88), those with high EAT showed more preserved 6-month LVEF. This association persisted after adjustment and in a 1:1 propensity score-matched patient subset. Overall, EAT decreased at 6 months. In patients with large IS, a greater reduction of EAT was associated with more preserved 6-month LVEF. In STEMI, a higher presence of EAT was associated with a larger IS. Nevertheless, in patients with large infarctions, high EAT and greater subsequent EAT reduction were linked to more preserved LVEF in the chronic phase. This dual and paradoxical effect of EAT fuels the need for further research in this field.

Cardiovascular (CV) diseases remain a global health challenge, with ischemic heart disease (IHD) being the primary cause of both morbidity and mortality. Despite optimal pharmacological therapy, older patients with IHD exhibit an increased susceptibility to recurrent ischemic events, significantly impacting their prognosis. Inflammation is intricately linked with the aging process and plays a pivotal role in the evolution of atherosclerosis. Emerging anti-inflammatory therapies have shown promise in reducing ischemic events among high-risk populations. This review aims to explore the potential of targeted anti-inflammatory interventions in improving clinical outcomes and the quality of life for older patients with IHD.

There is an unmet need to create consensus documents on the management of cardiorenal patients since, due to the aging of the population and the rise of both pathologies, these patients are becoming more prevalent in daily clinical practice. Chronic kidney disease coexists in up to 40%-50% of patients with chronic heart failure cases. There have yet to be consensus documents on how to approach palliative care in cardiorenal patients. There are guidelines for patients with heart failure and chronic kidney disease separately, but they do not specifically address patients with concomitant heart failure and kidney disease. For this reason, our document includes experts from different specialties, who will not only address the justification of palliative care in cardiorenal patients but also how to identify this patient profile, the shared planning of their care, as well as knowledge of their trajectory and the palliative patient management both in the drugs that will help us control symptoms and in advanced measures. Dialysis and its different types will also be addressed, as palliative measures and when the decision to continue or not perform them could be considered. Finally, the psychosocial approach and adapted pharmacotherapy will be discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bonanad, Buades, Leiva, De la Espriella, Marcos, Núñez, García-Llana, Facila, Sánchez, Rodríguez-Osorio, Alonso-Babarro, Quiroga, Bompart Berroteran, Rodríguez, Maidana and Díez.)

Bempedoic acid is a selective inhibitor of the adenosine triphosphate citrate lyase that reduces low-density lipoprotein cholesterol (LDLc) levels by 17% to 28%. Although the Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (CLEAR-OUTCOMES) trials demonstrated the efficacy on cardiovascular outcomes there is a controversy related to the possible net clinical benefit. Thereafter, we performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome of the metanalysis was the incidence of major adverse cardiovascular events, defined by each study protocol. Secondary outcomes for the analyses were myocardial infarction, stroke, myocardial revascularization, cardiovascular death, and all-cause death. Results of 4 clinical trials evaluated contained a total of 17,324 patients; 9,236 received bempedoic acid for a median of 46.6 months. The mean baseline LDLc was 129.4 (22.8) mg/100 ml and treatment was associated with a mean LDLc reduction of 26.0 (12.6) mg/100 ml. Treatment with bempedoic acid significantly reduced the incidence of major adverse cardiovascular events (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.81 to 0.96), myocardial infarction (HR 0.76, 95% CI 0.66 to 0.89) and myocardial revascularization (HR 0.82, 95% CI 0.73 to 0.92); the crude incidence of stroke, cardiovascular or all-cause mortality were lower in patients in the bempedoic acid groups although no significant risk reduction was observed. No heterogeneity was observed in any of the end points. In conclusion, the metanalysis of the 4 clinical trials currently available with bempedoic acid provides reliable evidence of its clinical benefit with no signs of heterogeneity or harm., Competing Interests: Declaration of Competing Interest Dr. Cordero reports honoraria for lectures from AstraZeneca, AMGEN, Bristol-Myers Squibb, Ferrer, Boehringer Ingelheim, Merck Sharp & Dohme, Daiichy Sankio, Novartis, Novo Nordisk, Sanofi and Amarin; and consulting fees from AstraZeneca, Ferrer, Sanofi, AMGEN, Novartis, Lilly, Novo Nordisk and Amarin. Dr. Fernández reports honoraria for lectures from AstraZeneca, AMGEN, Ferrer, Merck Sharp & Dohme, Daiichi Sankio, Novartis, Novo Nordisk, Sanofi, and Amarin; and consulting fees from AstraZeneca, Sanofi, AMGEN, Novartis, Novo Nordisk, and Amarin. Dr. Castellano reports honoraria from Ferrer, Servier, Daiichi Sankyo, and Pfizer. Dr. Fácila reports honoraria for lectures from Eli Lilly Co, Daiichi Sankyo, Inc., Bayer, Pfizer, Novartis Boehringer Ingelheim, and consulting fees from AstraZeneca, Boehringer, Bayer. Dr. Rodriguez-Mañero reports research grants from Fundación Mutua Madrileña, Biosense Webster, Medtronic, and the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain). Dr. Bonanad has received fees from AstraZeneca; Amgen, Bayer; Boehringer; Bristol-Myers Squibb; Daiichi Sankyo; Ferrer; Novartis AG; Pfizer; Roche Pharma; Sanofi Pharma. Dr. González Juanatey reports honoraria for lectures from Eli Lilly Co, Daiichi Sankyo, Inc., Bayer, Pfizer, Abbott, Boehringer Ingelheim, Merck Sharp & Dohme, Ferrer, and Bristol-Myers Squibb; consulting fees from AstraZeneca, Ferrer, Bayer, Boehringer Ingelheim; and research grants from AstraZeneca, Boehringer Ingelheim and Daichi-Sankyo. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control., Methods: We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality., Results: Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03% vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p = 0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p = 0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality., Conclusions: Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction., (Copyright © 2023. Published by Elsevier Inc.)

Purpose of Review: The literature on the importance of sex in heart failure diagnosis is scarce. This review aims to summarize current knowledge on sex differences regarding the diagnosis of heart failure., Recent Findings: Comorbidities are frequent in patients with heart failure, and their prevalence differs between sexes; some differences in symptomatology and diagnostic imaging techniques were also found. Biomarkers also usually show differences between sexes but are not significant enough to establish sex-specific ranges. This article outlines current information related to sex differences in HF diagnosis. Research in this field remains to be done. Maintaining a high diagnostic suspicion, actively searching for the disease, and considering the sex is relevant for early diagnosis and better prognosis. In addition, more studies with equal representation are needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Non-ST segment elevation myocardial infarction (NSTEMI) is the most frequent type of acute coronary syndrome in the elderly. Antithrombotic therapy is the cornerstone of pharmacological therapy in the setting of an acute ischemic event, a clinical scenario in which thrombotic and bleeding risks ought to be considered, particularly in older patients. In this article, specific aspects of antithrombotic therapy in elderly patients with NSTEMI are reviewed, including pharmacokinetic and pharmacodynamic characteristics and different clinical situations. The role of frailty and other common geriatric conditions, that are associated with worse prognosis in elderly patients with cardiovascular disease, is also addressed., Competing Interests: JL Ferreiro reports: (a) speaker fees from Eli Lilly Co, Daiichi Sankyo, Inc., AstraZeneca, Roche Diagnostics, Pfizer, Abbott, Ferrer, Rovi, Boehringer Ingelheim, Bristol-Myers Squibb and Terumo; (b) consulting fees from AstraZeneca, Eli Lilly Co., Ferrer, Boston Scientific, Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Bristol-Myers Squibb and Biotronik; (c) research grant from AstraZeneca. The author declares no conflict of interest. Manuel Martínez-Sellés is serving as one of the Editorial Board members and Guest editors of this journal. We declare that Manuel Martínez-Sellés had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Pietro Scicchitano., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Background: Little is known about the occurrence and implications of persistent microvascular obstruction (MVO) after reperfused ST-segment elevation myocardial infarction (STEMI)., Objectives: The authors used cardiac magnetic resonance (CMR) to characterize the impact of persistent MVO on adverse left ventricular remodeling (ALVR)., Methods: A prospective registry of 471 STEMI patients underwent CMR 7 (IQR: 5-10) days and 198 (IQR: 167-231) days after infarction. MVO (≥1 segment) and ALVR (relative increase >15% at follow-up CMR) of left ventricular end-diastolic index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) were determined., Results: One-week MVO occurred in 209 patients (44%) and persisted in 30 (6%). The extent of MVO (P = 0.026) and intramyocardial hemorrhage (P = 0.001) at 1 week were independently associated with the magnitude of MVO at follow-up CMR. Compared with patients without MVO (n = 262, 56%) or with MVO only at 1 week (n = 179, 38%), those with persistent MVO at follow-up (n = 30, 6%) showed higher rates of ALVR-LVEDVI (22%, 27%, and 50%; P = 0.003) and ALVR-LVESVI (20%, 21%, and 53%; P < 0.001). After adjustment, persistent MVO at follow-up (≥1 segment) was independently associated with ΔLVEDVI (relative increase, %) (P < 0.001) and ΔLVESVI (P < 0.001). Compared with a 1:1 propensity score-matched population on CMR variables made up of 30 patients with MVO only at 1 week, patients with persistent MVO more frequently displayed ALVR-LVEDVI (12% vs 50%; P = 0.003) and ALVR-LVESVI (12% vs 53%; P = 0.001)., Conclusions: MVO persists in a small percentage of patients in chronic phase after STEMI and exerts deleterious effects in terms of LV remodeling. These findings fuel the need for further research on microvascular injury repair., Competing Interests: Funding Support and Author Disclosures This work was supported by Instituto de Salud Carlos III and Fondos Europeos de Desarrollo Regional FEDER (grant numbers PI20/00637, CIBERCV16/11/00486, CIBERCV16/11/00420, CIBERCV16/11/00479, and a postgraduate contract CM21/00175 to V.M.-G.), by Conselleria de Educación–Generalitat Valenciana (PROMETEO/2021/008) and by Sociedad Española de Cardiología (grant SEC/FEC-INV-CLI 21/024). Dr Gavara has received financial support from the Agencia Estatal de Investigación (grant FJC2020-043981-I/AEI/10.13039/501100011033). Dr Moratal has received financial support from the Conselleria d’Educació, Investigació, Cultura i Esport, Generalitat Valenciana (grants AEST/2019/037, AEST/2020/029). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Atrial fibrillation (AF) cannot be considered an isolated disease. Patients with AF should be managed using a comprehensive approach that is not limited to stroke prevention., Areas Covered: In this manuscript, the potential role of AF as a vascular disease that is managed as part of a holistic approach was reviewed., Expert Opinion: The residual risk of stroke in patients with AF reaches 1-2% annually, despite appropriate anticoagulation therapy. Additionally, patients with AF may develop cognitive impairment through stroke-independent pathways. Furthermore, patients with AF may have a higher risk of developing atherosclerotic vascular disease in various vascular beds and chronic kidney disease; conversely, patients with atherosclerotic disease may have an increased risk of developing AF. AF should be considered a truly systemic vascular disease, since it brings together several hemodynamic and systemic changes, including inflammation, oxidative stress, activation of the renin-angiotensin-aldosterone and sympathetic systems, as well as a prothrombotic state and endothelial dysfunction. In this regard, patients with AF should be treated based on a holistic approach that is not limited to oral anticoagulation but includes complete vascular protection.

Background: Current guidelines recommend extending the use of dual antiplatelet therapy (DAPT) beyond 1 year in patients with an acute coronary syndrome (ACS) and a high risk of ischaemia and low risk of bleeding. No data exist about the implementation of this strategy in older adults from routine clinical practice., Methods: We conducted a Spanish multicentre, retrospective, observational registry-based study that included patients with ACS but no thrombotic or bleeding events during the first year of DAPT after discharge and no indication for oral anticoagulants. High bleeding risk was defined according to the Academic Research Consortium definition. We assessed the proportion of cases of extended DAPT among patients 65 ≥ years that went beyond 1 year after hospitalisation for ACS and the variables associated with the strategy., Results: We found that 48.1% (928/1,928) of patients were aged ≥ 65 years. DAPT was continued beyond 1 year in 32.1% (298/928) of patients ≥ 65; which was a similar proportion as with their younger counterparts. There was no significant correlation between a high bleeding risk and DAPT duration. Contrastingly, there was a strong correlation between the extent of coronary disease and DAPT duration (p < 0.001). Other variables associated with extended DAPT were a higher left ventricle ejection fraction, a history of heart failure and a prior stent thrombosis., Conclusion: There was no correlation between age and extended use of DAPT beyond 1 year in older patients with ACS. DAPT was extended in about one-third of patients ≥ 65 years. The severity of the coronary disease, prior heart failure, left ventricle ejection fraction and prior stent thrombosis all correlated with extended DAPT., (© 2023. The Author(s).)

A non-neglectable percentage of patients with non-ST elevation myocardial infarction (NSTEMI) show non-obstructive coronary arteries (MINOCA). Specific data in older patients are scarce. We aimed to identify the clinical predictors of MINOCA in older patients admitted for NSTEMI and to explore the long-term prognosis of MINOCA. This was a single-center, observational, consecutive cohort study of older (≥70 years) patients admitted for NSTEMI between 2010 and 2014 who underwent coronary angiography. Univariate and multivariate Cox regression were performed to analyze the association of variables with MINOCA and all-cause mortality and with major adverse cardiac events (MACE), defined as a combined endpoint of all-cause mortality and nonfatal myocardial infarction and a combined endpoint of cardiovascular mortality, nonfatal myocardial infarction, and unplanned revascularization. The registry included 324 patients (mean age 78.8 ± 5.4 years), of which 71 (21.9%) were diagnosed with MINOCA. Predictors of MINOCA were female sex, left bundle branch block, pacemaker rhythm, chest pain at rest, peak troponin level, previous MI, Killip ≥2, and ST segment depression. Regarding prognosis, patients with obstructive coronary arteries (stenosis ≥50%) and the subgroup of MINOCA patients with plaques <50% had a similar prognosis; while MINOCA patients with angiographically smooth coronary arteries had a reduced risk of MACE. We conclude that the following: (1) in elderly patients admitted for NSTEMI, certain universally available clinical, electrocardiographic, and analytical variables are associated with the diagnosis of MINOCA; (2) elderly patients with MINOCA have a better prognosis than those with obstructive coronary arteries; however, only those with angiographically smooth coronary arteries have a reduced risk of all-cause mortality and MACE.

Residual ST-segment elevation after ST-segment elevation myocardial infarction (STEMI) has traditionally been considered a predictor of left ventricular (LV) dysfunction and ventricular aneurism. However, the implications in terms of long-term prognosis and cardiac magnetic resonance (CMR)-derived structural consequences are unclear. A total of 488 reperfused STEMI patients were prospectively included. The number of Q wave leads with residual ST-segment elevation > 1 mm (Q-STE) at pre-discharge ECG was assessed. LV ejection fraction (LVEF, %) and infarct size (IS, % of LV mass) were quantified in 319 patients at 6-month CMR. Major adverse cardiac events (MACE) were defined as all-cause death and/or re-admission for acute heart failure (HF), whichever occurred first. During a mean follow-up of 6.1 years, 92 MACE (18.9%), 39 deaths and 53 HF were recorded. After adjustment for baseline characteristics, Q-STE (per lead with > 1 mm) was independently associated with a higher risk of long-term MACE (HR 1.24 [1.07-1.44] per lead, p = 0.004), reduced (< 40%) LVEF (HR 1.36 [1.02-1.82] per lead, p = 0.04) and large (> 30% of LV mass) IS (HR 1.43 [1.11-1.85] per lead, p = 0.006) at 6-month CMR. Patients with Q-STE ≥ 2 leads (n = 172, 35.2%) displayed lower MACE-free survival, more depressed LVEF, and larger IS at 6-month CMR (p < 0.001 for all comparisons). Residual ST-segment elevation after STEMI represents a universally available tool that predicts worse long-term clinical and CMR-derived structural outcomes., (© 2022. The Author(s).)

Non-valvular atrial fibrillation (NVAF) is the most common arrhythmia in older patients. Although direct-acting oral anticoagulants (DOAC) are the antithrombotic treatment of choice, irrespective of age, certain factors may limit their use. The aim of the ACONVENIENCE study was to consult the opinion of a multidisciplinary panel of experts on the appropriateness of using OACs in elderly patients (>75 years) with NVAF associated with certain complex clinical conditions. A consensus project was performed on the basis of a systematic review of the literature, and application of a two-round Delphi survey. The agreement of 79 panellists on 30 Delphi-type statements was evaluated, and their opinion on the appropriateness of different oral anticoagulants in 16 complex clinical scenarios was assessed. A total of 27 consensus statements were agreed upon, including all statements addressing anticoagulation in older patients and in patients at high risk of bleeding complications, and most of those addressing frailty, dementia, risk of falling, and complex cardiac situations. It was almost unanimously agreed upon that advanced age should not influence the anticoagulation decision. Apixaban was the highest-rated therapeutic option in 14/16 situations, followed by edoxaban. There is a high degree of agreement on anticoagulation in older patients with NVAF. Age should not be the single limiting factor when prescribing OACs, and the decision should be made based on net clinical benefit and a comprehensive geriatric assessment. Apixaban, followed by edoxaban, was considered the most appropriate treatment in the various complex clinical situations examined.

Introduction and Objectives: Heart failure (HF) is prevalent in advanced ages. Our objective was to assess the impact of frailty on 1-year mortality in older patients with ambulatory HF., Methods: Our data come from the FRAGIC study (Spanish acronym for "Study of the impact of frailty and other geriatric syndromes on the clinical management and prognosis of elderly outpatients with heart failure"), a multicenter prospective registry conducted in 16 Spanish hospitals including outpatients ≥ 75 years with HF followed up by cardiology services in Spain., Results: We included 499 patients with a mean age of 81.4±4.3 years, of whom 193 (38%) were women. A total of 268 (54%) had left ventricular ejection fraction <40%, and 84.6% was in NYHA II functional class. The FRAIL scale identified 244 (49%) pre-frail and 111 (22%) frail patients. Frail patients were significantly older, were more frequently female (both, P <.001), and had higher comorbidity according to the Charlson index (P=.017) and a higher prevalence of geriatric syndromes (P <.001). During a median follow-up of 371 [361-387] days, 58 patients (11.6%) died. On multivariate analysis (Cox regression model), frailty detected with the FRAIL scale was marginally associated with mortality (HR=2.35; 95%CI, 0.96-5.71; P=.059), while frailty identified by the visual mobility scale was an independent predictor of mortality (HR=2.26; 95%CI, 1.16-4.38; P=.015); this association was maintained after adjustment for confounding variables (HR=2.13; 95%CI, 1.08-4.20; P=.02)., Conclusions: In elderly outpatients with HF, frailty is independently associated with mortality at 1 year of follow-up. It is essential to identify frailty as part of the comprehensive approach to elderly patients with HF., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Frailty is associated with increased mortality and hospitalizations in patients with heart failure (HF). However, there is little evidence regarding the burden of morbidity. In this study, we aimed to assess the association between frailty and recurrent all-cause HF hospitalizations in patients with stable chronic HF. This was an observational and prospective study that enrolled HF outpatients followed in a specialized HF unit of a single tertiary care center from 2017 to 2019. Frailty was assessed by Fried criteria. Robustness, prefrailty, and frailty were defined as 0, 1 to 2, and ≥3, respectively. The independent association between frailty status and recurrent hospitalizations was assessed through Famoye's bivariate Poisson regression model, and risk estimates were expressed as incidence rate ratios (IRR). A total of 277 patients were included. The mean age was 74 ± 10 years, 118 were women (42.6%), and 131 patients (47.3%) had left ventricular ejection fraction ≥50. According to Fried's score 61 patients (22%) were robust, 95 patients (34%) were prefrail, and 121 patients (44%) were frail. After a median follow-up of 2.21 (1.6 to 2.8) years, 52 patients (19%) died. We registered 348 all-cause hospitalizations in 144 patients (52%) and 178 HF hospitalizations in 108 patients (39%). Compared with robust patients, frailty was associated with a higher risk of all-cause and HF recurrent hospitalizations in multivariable analysis (IRR 2.01, 95% confidence interval 1.14 to 3.57, p = 0.017 and IRR 2.25, 95% confidence interval 1.16-4.36, p = 0.016, respectively). In conclusion, in patients with chronic HF, frailty identifies patients with an increased risk of total and recurrent all-cause and HF hospitalizations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: older patients with ST-segment elevation myocardial infarction (STEMI) represent a very high-risk population. Data on the prognostic value of cardiac magnetic resonance (CMR) in this scenario are scarce., Methods: the registry comprised 247 STEMI patients over 70 years of age treated with percutaneous intervention and included in a multicenter registry. Baseline characteristics, echocardiographic parameters and CMR-derived left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments) were prospectively collected. The additional prognostic power of CMR was assessed using adjusted C-statistic, net reclassification index (NRI) and integrated discrimination improvement index (IDI)., Results: during a 4.8-year mean follow-up, the number of first major adverse cardiac events (MACE) was 66 (26.7%): 27 all-cause deaths and 39 re-admissions for acute heart failure. Predictors of MACE were GRACE score (HR 1.03 [1.02-1.04], P < 0.001), CMR-LVEF (HR 0.97 [0.95-0.99] per percent increase, P = 0.006) and MVO (HR 1.24 [1.09-1.4] per segment, P = 0.001). Adding CMR data significantly improved MACE prediction compared to the model with baseline and echocardiographic characteristics (C-statistic 0.759 [0.694-0.824] vs. 0.685 [0.613-0.756], NRI = 0.6, IDI = 0.08, P < 0.001). The best cut-offs for independent variables were GRACE score > 155, LVEF < 40% and MVO ≥ 2 segments. A simple score (0, 1, 2, 3) based on the number of altered factors accurately predicted the MACE per 100 person-years: 0.78, 5.53, 11.51 and 78.79, respectively (P < 0.001)., Conclusions: CMR data contribute valuable prognostic information in older patients submitted to undergo CMR soon after STEMI. The Older-STEMI-CMR score should be externally validated., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Bendopnea is a clinical symptom of advanced heart failure with uncertain prognostic value. We aimed to evaluate whether bendopnea and the change in oxygen saturation when bending forward (bending oxygen saturation index [BOSI]) are associated with adverse outcomes in ambulatory chronic heart failure (CHF) patients., Methods and Results: We prospectively evaluated 440 subjects with symptomatic CHF. BOSI was defined as the difference between sitting and bending oxygen saturation (SpO 2 ). The endpoint was the total number of worsening heart failure (WHF) events (heart failure hospitalization or urgent heart failure visit requiring parenteral diuretic therapy). The mean age was 74 ± 10 years, 257 (58.6%) were male, and 226 (51.4%) had a left ventricular ejection fraction <50%. Bendopnea was present in 94 (21.4%) patients, and 120 (27.3%) patients had a BOSI ≥-3%. The agreement between BOSI ≥-3% and bendopnea was moderate (Gwet's AC 0.482, p < 0.001). At a median (p25%-p75%) follow-up of 2.17 years (0.88-3.16), we registered 441 WHF events in 148 patients. After multivariable adjustment, BOSI was independently associated with the risk for total WHF episodes (overall, p < 0.001). Compared to improvement/no change in SpO 2 when bending (BOSI 0%), those with BOSI ≥-3% showed an increased risk of WHF events (incidence rate ratio [IRR] 2.16, 95% confidence interval [CI] 1.67-2.79; p < 0.001). In contrast, bendopnea was not associated with the risk of total WHF episodes (IRR 1.04, 95% CI 0.83-1.31; p = 0.705)., Conclusions: In ambulatory and stable CHF patients, BOSI ≥-3% and not bendopnea was independently associated with an increased risk of total (first and recurrent) WHF episodes. Awareness of SpO 2 while assessing bendopnea may be a useful tool for predicting heart failure decompensations., (© 2022 European Society of Cardiology.)

Introduction: Frailty is common among patients with heart failure (HF). Our aim was to address the role of frailty in the management and prognosis of elderly men and women with HF., Methods and Results: Prospective multicenter registry that included 499 HF outpatients ≥75 years old. Mean age was 81.4 ± 4.3 years, and 193 (38%) were women. Compared with men, women were older (81.9 ± 4.3 vs. 81.0 ± 4.2 years, p = 0.03) and had higher left ventricular ejection fraction (46 vs. 40%, p < 0.001) and less ischemic heart disease (30 vs. 57%, p < 0.001). Women had a higher prevalence of frailty (22 vs. 10% with Clinical Frailty Scale, 34 vs. 15% with FRAIL, and 67% vs. 46% with the mobility visual scale, all p -values < 0.001) and other geriatric conditions (Barthel index ≤90: 14.9 vs. 6.2%, p = 0.003; malnutrition according to Mini Nutritional Assessment Short Formulary ≤11: 55% vs. 42%, p = 0.007; Pfeiffer cognitive test's errors: 1.6 ± 1.7 vs. 1.0 ± 1.6, p < 0.001; depression according to Yesavage test; p < 0.001) and lower comorbidity (Charlson index ≥4: 14.1% vs. 22.1%, p = 0.038). Women also showed worse self-reported quality of life (6.5 ± 2.1 vs. 6.9 ± 1.9, on a scale from 0 to 10, p = 0.012). In the univariate analysis, frailty was an independent predictor of mortality in men [Hazard ratio (HR) 3.18, 95% confidence interval (CI) 1.29-7.83, p = 0.012; HR 4.53, 95% CI 2.08-9.89, p < 0.001; and HR 2.61, 95% CI 1.23-5.43, p = 0.010, according to FRAIL, Clinical Frailty Scale, and visual mobility scale, respectively], but not in women. In the multivariable analysis, frailty identified by the visual mobility scale was an independent predictor of mortality (HR 1.95, 95% CI 1.04-3.67, p = 0.03) and mortality/readmission (HR 2.06, 95% CI 1.05-4.04, p = 0.03) in men., Conclusions: In elderly outpatients with HF frailty is more common in women than in men. However, frailty is only associated with mortality in men., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Díez-Villanueva, Jiménez-Méndez, Bonanad, Ortiz-Cortés, Barge-Caballero, Goirigolzarri, Esteban-Fernández, Pérez-Rivera, Cobo, Sanz-García, Formiga, Ariza-Solé, Martínez-Sellés and Alfonso.)

Background: Magnetic resonance imaging (MRI) is the most accurate imaging technique for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of LVEF assessment at any time after ST-segment elevation myocardial infarction (STEMI) for subsequent major adverse cardiac event (MACE) prediction is uncertain., Purpose: To explore the prognostic impact of MRI-derived LVEF at any time post-STEMI to predict subsequent MACE (cardiovascular death or re-admission for acute heart failure)., Study Type: Prospective., Population: One thousand thirteen STEMI patients were included in a multicenter registry., Field Strength/sequence: 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences., Assessment: Post-infarction MRI-derived LVEF (reduced [r]: <40%; mid-range [mr]: 40%-49%; preserved [p]: ≥50%) was sequentially quantified at 1 week and after >3 months of follow-up., Statistical Tests: Multi-state Markov model to determine the prognostic value of each LVEF state (r-, mr- or p-) at any time point assessed to predict subsequent MACE. A P-value <0.05 was considered to be statistically significant., Results: During a 6.2-year median follow-up, 105 MACE (10%) were registered. Transitions toward improved LVEF predominated and only r-LVEF (at any time assessed) was significantly related to a higher incidence of subsequent MACE. The observed transitions from r-LVEF, mr-LVEF, and p-LVEF states to MACE were: 15.3%, 6%, and 6.7%, respectively. Regarding the adjusted transition intensity ratios, patients in r-LVEF state were 4.52-fold more likely than those in mr-LVEF state and 5.01-fold more likely than those in p-LVEF state to move to MACE state. Nevertheless, no significant differences were found in transitions from mr-LVEF and p-LVEF states to MACE state (P-value = 0.6)., Data Conclusion: LVEF is an important MRI index for simple and dynamic post-STEMI risk stratification. Detection of r-LVEF by MRI at any time during follow-up identifies a subset of patients at high risk of subsequent events., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 2., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

The specific management of infective endocarditis (IE) in elderly patients is not specifically addressed in recent guidelines despite its increasing incidence and high mortality in this population. The term "elderly" corresponds to different ages in the literature, but it is defined by considerable comorbidity and heterogeneity. Cancer incidence, specifically colorectal cancer, is increased in older patients with IE and impacts its outcome. Diagnosis of IE in elderly patients is challenging due to the atypical presentation of the disease and the lower performance of imaging studies. Enterococcal etiology is more frequent than in younger patients. Antibiotic treatment should prioritize diminishing adverse effects and drug interactions while maintaining the best efficacy, as surgical treatment is less commonly performed in this population due to the high surgical risk. The global assessment of elderly patients with IE, with particular attention to frailty and geriatric profiles, should be performed by multidisciplinary teams to improve disease management in this population.

Age is associated with increased cardiovascular risk factors and cardiovascular disease, which constitutes the leading cause of morbidity and mortality in elderly population. In this text we thoroughly review current evidence regarding the impact on cardiovascular disease of the most important cardiovascular risk factors, especially prevalent and common in the elderly population. Diagnosis and treatment approaches are also addressed, also highlighting the importance of adequate primary and secondary prevention and management. Also, the relationship between cardiovascular disease and some comorbidities and geriatric conditions, such as frailty, particularly common in the elderly, is reviewed, together with some other issues, less often addressed but closely related to ageing, such as genetics, structural and electrical heart changes and oxidative stress. All such questions are of great importance in the comprehensive approach of risk factors and cardiovascular disease in the elderly., Competing Interests: The authors declare no conflict of interest. Manuel Martínez-Sellés is serving as one of the Editorial Board members/Guest editors of this journal. We declare that Manuel Martínez-Sellés had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Ichiro Wakabayashi, Klaus Groschner and Brian Tomlinson., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Clinical practice guidelines recommend extending dual antiplatelet therapy (DAPT) beyond 1 year after acute coronary syndrome (ACS) in patients with high ischemic risk and without high bleeding risk. The aim of this study was to identify variables associated with DAPT prolongation in a cohort of 1967 consecutive patients discharged after ACS without thrombotic or hemorrhagic events during the following year. The sample was stratified according to whether DAPT was extended beyond 1 year, and the factors associated with this strategy were analyzed. In 32.2% of the patients, DAPT was extended beyond 1 year. Overall, 770 patients (39.1%) were considered candidates for extended treatment based on PEGASUS criteria and absence of high bleeding risk, and DAPT was extended in 34.4% of them. The presence of a PEGASUS criterion was associated with extended DAPT in the univariate analysis, but not history of bleeding or a high bleeding risk. In the multivariate analysis, a history of percutaneous coronary intervention (odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.4-2.4), stent thrombosis (OR = 3.8, 95% CI 1.7-8.9), coronary artery disease complexity (OR = 1.3, 95% CI 1.1-1.5), reinfarction (OR = 4.1, 95% CI 1.6-10.4), and clopidogrel use (OR = 1.3, 95% CI 1.1-1.6) were significantly associated with extended use. DAPT was extended in 32.2% of patients who survived ACS without thrombotic or hemorrhagic events. This percentage was 34.4% when the candidates were analyzed according to clinical guidelines. Neither the PEGASUS criteria nor the bleeding risk was independently associated with this strategy.

Background: Cardiac magnetic resonance (CMR) performed early after ST-segment elevation myocardial infarction (STEMI) can improve major adverse cardiac event (MACE) risk prediction. We aimed to create a simple clinical-CMR risk score for early MACE risk stratification in STEMI patients., Methods: We performed a multicenter prospective registry of reperfused STEMI patients (n = 1118) in whom early (1-week) CMR-derived left ventricular ejection fraction (LVEF), infarct size and microvascular obstruction (MVO) were quantified. MACE was defined as a combined clinical endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (NF-MI) or re-admission for acute decompensated heart failure (HF)., Results: During a median follow-up of 5.52 [2.63-7.44] years, 216 first MACE (58 CV deaths, 71 NF-MI and 87 HF) were registered. Mean age was 59.3 ± 12.3 years and most patients (82.8%) were male. Based on the four variables independently associated with MACE, we computed an 8-point risk score: time to reperfusion >4.15 h (1 point), GRACE risk score > 155 (3 points), CMR-LVEF <40% (3 points), and MVO >1.5 segments (1 point). This score permitted MACE risk stratification: MACE per 100 person-years was 1.96 in the low-risk category (0-2 points), 5.44 in the intermediate-risk category (3-5 points), and 19.7 in the high-risk category (6-8 points): p < 0.001 in multivariable Cox survival analysis., Conclusions: A novel risk score including clinical (time to reperfusion >4.15 h and GRACE risk score > 155) and CMR (LVEF <40% and MVO >1.5 segments) variables allows for simple and straightforward MACE risk stratification early after STEMI. External validation should confirm the applicability of the risk score., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Sex influences outcome of patients with acute coronary syndrome (ACS). If there is a relationship between sex and physical performance is unknown., Methods: The analysis is based on older (≥70 years) ACS patients included in the FRASER, HULK, and LONGEVO SCA prospective studies. Physical performance was assessed by Short Physical Performance Battery (SPPB). The primary outcome was all-cause mortality., Results: The study included 1388 patients, and 441 (32%) were women. At presentation, women were older and more compromised than men. After a median follow-up of 998 [730-1168] days, all-cause death occurred in 334 (24.1%) patients. At univariate analysis, female sex was related to increased risk of death. After adjustments for confounding factors, female sex was no longer associated with mortality. Women showed poor physical performance compared with men (p < 0.001). SPPB values emerged as an independent predictor of death. Including clinical features and SPPB in the multivariable model, we observed a paradigm shift in the prognostic role of female sex that becomes a protective factor (HR 0.73, 95% CI 0.56-0.96). Sex and physical performance showed a significant interaction (p = 0.03). For lower SPPB values (poor physical performance), sex-related changes in mortality were not recorded, while in patients with higher SPPB values (preserved physical performance), female sex was associated with better survival., Conclusions: Two key findings emerged from the present real-life cohort of older ACS patients: (i) physical performance strongly influences long-term mortality; (ii) women with preserved physical performance have a better outcome compared to men., Trial Registration: www.clinicaltrials.gov NCT02386124 and NCT03021044., (© 2022. The Author(s).)

Purpose: Vasodilator stress cardiac magnetic resonance (VS-CMR) has become crucial in the workup of patients with known or suspected chronic coronary syndrome (CCS). Whether traditional exercise ECG testing (ExECG) contributes prognostic information beyond VS-CMR is unclear., Methods: We retrospectively included 288 patients with known or suspected CCS who had undergone ExECG and subsequent VS-CMR in our institution. Clinical, ExECG, and VS-CMR variables were recorded. We defined the serious adverse events (SAE) as a combined endpoint of acute coronary syndrome, admission for heart failure, or all-cause death., Results: During a mean follow-up of 4.2 ± 2.15 yr, we registered 27 SAE (15 admissions for acute coronary syndrome, eight admissions for heart failure, and four all-cause deaths). Once adjusted for clinical, ExECG, and VS-CMR parameters associated with SAE, the only independent predictors were HRmax in ExECG (HR = 0.98: 95% CI, 0.96-0.99; P = .01) and more extensive stress-induced perfusion defects (PDs, number of segments) in VS-CMR (HR = 1.19: 95% CI, 1.07-1.34; P < .01). Adding HRmax significantly improved the predictive power of the multivariable model for SAE, including PDs (continuous reclassification improvement index: 0.47: 95% CI, 0.10-0.81; P < .05). The annualized SAE rate was 1% (if PD < 2 segments and HRmax > 130 bpm), 2% (if PD < 2 segments and HRmax ≤ 130 bpm), 3.2% (if PD ≥ 2 segments and HRmax > 130 bpm), and 6.3% (if PD ≥ 2 segments and HRmax ≤ 130 bpm), P < .01, for the trend. In patients on β-blocker therapy, however, only PDs in VS-CMR, but not HRmax, predicted SAE., Conclusions: We conclude that ExECG contributes significantly to prognostic information beyond VS-CMR in patients with known or suspected CCS., Competing Interests: Conflicts of Interest: None., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)