Mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: a systematic review and network meta-analysis of 32 randomized trials.

INTRODUCTION: Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy and safety of MRAs in HFrEF. MATERIALS AND METHODS: MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until April 8, 2024 for RCTs examining the efficacy and/or safety of MRAs in HFrEF. Double-independent study selection, extraction and quality assessment were performed. Random-effects frequentist NMA models were used. Evidence certainty was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Totally, 32 RCTs (15685 patients) were analyzed. Eplerenone ranked above spironolactone in all-cause mortality (hazard ratio {HR}=0.78, 95% confidence interval {CI} [0.66,0.91], GRADE:"Moderate"), cardiovascular death (HR=0.74, 95%CI [0.53, 1.04], GRADE:"Low") and in all safety outcomes. Spironolactone was superior to eplerenone in the composite of cardiovascular death or hospitalization (HR=0.67, 95%CI [0.50,0.89], GRADE:"Moderate"), HF hospitalization (HR=0.61, 95%CI [0.43,0.86], GRADE:"Moderate"), all-cause hospitalization (HR=0.51, 95%CI [0.26,0.98], GRADE:"Moderate") and cardiovascular hospitalization (HR=0.56, 95%CI [0.37,0.84], GRADE:"Moderate"). Canrenone ranked first in all-cause mortality, the composite outcome and HF hospitalization. Finerenone ranked first in hyperkalemia (risk ratio [RR]=1.56, 95%CI [0.89,2.74], GRADE:"Moderate"), renal injury (RR=0.56, 95%CI [0.24,1.29]), any adverse event (RR=0.84, 95%CI [0.75,0.94], GRADE:"Moderate"), treatment discontinuation (RR=0.89, 95%CI [0.64,1.23]) and hypotension (RR=1.06, 95%CI [0.12,9.41]). CONCLUSIONS: MRAs are effective in HFrEF with certain safety disparities. Spironolactone and eplerenone exhibited similar efficacy, however, eplerenone demonstrated superior safety. Finerenone was the safest MRA, while canrenone exhibited considerable efficacy, nonetheless, evidence for these MRAs were scarce.

Intravenous Landiolol for Rate Control in Supraventricular Tachyarrhythmias in Patients with Left Ventricular Dysfunction: A Systematic Review and Meta-Analysis.

Background: This systematic review explores the effects of landiolol administration in individuals presenting with supraventricular tachyarrhythmia (SVT) and concurrent left ventricular dysfunction, without being septic or in a peri-operative period. Methods: We systematically searched PubMed, Cochrane, Web of Science, and Scopus databases, retrieving a total of 15 eligible studies according to prespecified eligibility criteria. Results: Patients treated with landiolol experienced a substantial reduction in heart rate (HR) (mean HR reduction: 42 bpm, 95% confidence intervals (CIs): 37-47, I2 = 82%) and were more likely to achieve the target HR compared to those receiving alternative antiarrhythmic therapy (pooled odds ratio (OR): 5.37, 95% CIs: 2.87-10.05, I2 = 0%). Adverse events, primarily hypotension, occurred in 14.7% of patients receiving landiolol, but no significant difference was observed between the landiolol and alternative antiarrhythmic receiving groups (pooled OR: 1.02, 95% CI: 0.57-1.83, I2 = 0%). No significant difference was observed between the two groups concerning sinus rhythm restoration (pooled OR: 0.97, 95% CI: 0.25-3.78, I2 = 0%) and drug discontinuation due to adverse events (pooled OR: 5.09, 95% CI: 0.6-43.38, I2 = 0%). Conclusion: While further research is warranted, this systematic review highlights the potential benefits of landiolol administration in the management of SVTs in the context of left ventricular dysfunction.

The Role of Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in Heart Failure.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF and is associated with poor outcomes, only limited alternative pharmaceutical options are available in clinical practice. The objective of this narrative review is to provide a comprehensive analysis of the current evidence on the effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on diuretic resistance in HF patients. The primary emphasis is placed on clinical data that assess the impact of SGLT-2 inhibitors on fluid balance, symptom improvement, and clinical outcomes and secondarily on safety profile and potential adverse effects associated with SGLT-2 inhibitor use in acute decompensated HF. The current evidence on the efficacy of SGLT-2 on diuretic resistance remains controversial. Findings from observational and randomized studies are quite heterogenous; however, they converge on the notion that although SGLT-2 inhibitors show promise for mitigating diuretic resistance in HF, their diuretic effect may not be potent enough to be widely used to relieve objective signs of congestion in patients with HF. Importantly, the introduction of SGLT-2 inhibitors in HF treatment appears to be generally well tolerated, with manageable adverse effects. Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT-2 inhibitors on diuretic resistance in HF.

Residual leaks following percutaneous left atrial appendage occlusion and outcomes: a meta-analysis.

BACKGROUND AND AIMS: Residual leaks are not infrequent after left atrial appendage occlusion. However, there is still uncertainty regarding their prognostic implications. The aim of this study is to evaluate the impact of residual leaks after left atrial appendage occlusion. METHODS: A literature search was conducted until 19 February 2023. Residual leaks comprised peri-device leaks (PDLs) on transoesophageal echocardiography (TEE) or computed tomography (CT), as well as left atrial appendage patency on CT. Random-effects meta-analyses were performed to assess the clinical impact of residual leaks. RESULTS: Overall 48 eligible studies (44 non-randomized/observational and 4 randomized studies) including 61 666 patients with atrial fibrillation who underwent left atrial appendage occlusion were analysed. Peri-device leak by TEE was present in 26.1% of patients. Computed tomography-based left atrial appendage patency and PDL were present in 54.9% and 57.3% of patients, respectively. Transoesophageal echocardiography-based PDL (i.e. any reported PDL regardless of its size) was significantly associated with a higher risk of thromboembolism [pooled odds ratio (pOR) 2.04, 95% confidence interval (CI): 1.52-2.74], all-cause mortality (pOR 1.16, 95% CI: 1.08-1.24), and major bleeding (pOR 1.12, 95% CI: 1.03-1.22), compared with no reported PDL. A positive graded association between PDL size and risk of thromboembolism was noted across TEE cut-offs. For any PDL of >0, >1, >3, and >5 mm, the pORs for thromboembolism were 1.82 (95% CI: 1.35-2.47), 2.13 (95% CI: 1.04-4.35), 4.14 (95% CI: 2.07-8.27), and 4.44 (95% CI: 2.09-9.43), respectively, compared with either no PDL or PDL smaller than each cut-off. Neither left atrial appendage patency, nor PDL by CT was associated with thromboembolism (pOR 1.45 and 1.04, 95% CI: 0.84-2.50 and 0.52-2.07, respectively). CONCLUSIONS: Peri-device leak detected by TEE was associated with adverse events, primarily thromboembolism. Residual leaks detected by CT were more frequent but lacked prognostic significance.

Prognostic implications of thyroid disease in patients with atrial fibrillation.

Atrial fibrillation (AF) is often accompanied by thyroid disease (THD). This study aimed to explore the relationship between THD and the occurrence of significant clinical outcomes in patients with AF. This post hoc analysis utilized data from the MISOAC-AF trial (NCT02941978), which enrolled hospitalized patients with AF. Patients were categorized based on their THD history into hyperthyroidism, hypothyroidism, or euthyroidism. Cox regression models were employed to calculate unadjusted and adjusted hazard ratios (aHRs). The primary outcomes of interest included all-cause mortality, cardiovascular death, and hospitalizations during the follow-up period. The study included 496 AF patients (mean age 73.09 ± 11.10 years) with available THD data, who were followed-up for a median duration of 31 months. Among them, 16 patients (3.2%) had hyperthyroidism, 141 (28.4%) had hypothyroidism, and 339 (68.4%) had no thyroid disease. Patients with hypothyroidism exhibited higher rates of hospitalization during follow-up (aHR: 1.57, 95% CI 1.12 to 2.20, p = 0.025) compared to the euthyroid group. Elevated levels of thyroid-stimulating hormone (TSH) were correlated with an increased risk of cardiovascular mortality (aHR: 1.03, 95% CI 1.01 to 1.05, p = 0.007) and hospitalizations (aHR: 1.06, 95% CI 1.01 to 1.12, p = 0.03). Conversely, lower levels of triiodothyronine (T3) were associated with higher risks of all-cause mortality (aHR: 0.51, 95% CI 0.31 to 0.82, p = 0.006) and cardiovascular mortality (aHR: 0.42, 95% CI 0.23 to 0.77, p = 0.005). Among patients with AF, hypothyroidism was associated with increased hospitalizations. Furthermore, elevated TSH levels and decreased T3 levels were linked to higher cardiovascular and all-cause mortality risks, respectively.

Diagnostic Puzzles and Cause-Targeted Treatment Strategies in Myocardial Infarction with Non-Obstructive Coronary Arteries: An Updated Review.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a distinct subtype of myocardial infarction (MI), occurring in about 8-10% of spontaneous MI cases referred for coronary angiography. Unlike MI with obstructive coronary artery disease, MINOCA's pathogenesis is more intricate and heterogeneous, involving mechanisms such as coronary thromboembolism, coronary vasospasm, microvascular dysfunction, dissection, or plaque rupture. Diagnosing MINOCA presents challenges and includes invasive and non-invasive strategies aiming to differentiate it from alternative diagnoses and confirm the criteria of elevated cardiac biomarkers, non-obstructive coronary arteries, and the absence of alternate explanations for the acute presentation. Tailored management strategies for MINOCA hinge on identifying the underlying cause of the infarction, necessitating systematic diagnostic approaches. Furthermore, determining the optimal post-MINOCA medication regimen remains uncertain. This review aims to comprehensively address the current state of knowledge, encompassing diagnostic and therapeutic approaches, in the context of MINOCA while also highlighting the evolving landscape and future directions for advancing our understanding and management of this intricate myocardial infarction subtype.

Association of Length of Stay With the Clinical Trajectory of Hospitalized Patients With Atrial Fibrillation: Staying Less Is More?

Data predicting the length of stay (LOS) in patients with concurrent atrial fibrillation (AF) are scarce. This study aimed to investigate the potential predictors for prolonged LOS and its prognostic value. In this observational post hoc analysis of the MISOAC-AF (Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with non-valvular Atrial Fibrillation) randomized trial logistic regression analyses were conducted to identify the parameters associated with prolonged LOS (defined as >7 days according to diagnostic accuracy analyses). Kaplan-Meier and Cox regression analyses were performed to generate survival curves and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the primary end point of all-cause mortality and for the secondary end points during a median 3.7-year follow-up. Of the 1,057 patients studied, 462 (43.7%) were hospitalized for ≥7 days. Heart failure with reduced ejection fracture (aHR 1.75, 95% CI 1.17 to 2.63), permanent AF (aHR 1.72, 95% CI 1.29 to 2.31), history of coronary artery disease (aHR 2.32, 95% CI 1.59 to 3.39), and advanced or end-stage chronic kidney disease (aHR 1.54, 95% CI 1.15 to 2.06) were independently associated with prolonged hospitalization. Prolonged LOS was independently linked with increased all-cause mortality rates (aHR 1.68, 95% CI 1.25 to 2.26), cardiovascular mortality (aHR 1.92, 95% CI 1.36 to 2.72), major bleeding (aHR 3.07, 95% CI 1.07 to 8.78), and the composite outcome of cardiovascular death or rehospitalization (aHR 1.31, 95% CI 1.04 to 1.66). Each extra day of LOS was an independent predictor of all-cause mortality (aHR 1.03, 95% CI 1.02 to 1.04). Hospitalized patients with concurrent AF carry a substantial morbidity burden being prone to extended LOS. A jointed approach seems reasonable to reduce the LOS in patients with AF.

Risk of arterial thromboembolism, bleeding and mortality in atrial fibrillation patients with comorbid cancer: A systematic review and meta-analysis.

AIMS: Atrial fibrillation (AF) and cancer often co-exist. Each has been associated with an increased risk of morbidity and mortality. The aim of this meta-analysis was to synthesize available data regarding the incidence of arterial thromboembolism (TE), bleeding, and all-cause mortality in patients with AF with or without cancer. METHODS: Literature search was conducted in PubMed, Ovid MEDLINE, WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases to identify studies that included patients with AF and accounted for cancer status with the incidence of TE (ischemic stroke, transient ischemic attack, or arterial thrombosis), major or clinically relevant non-major bleeding, and all-cause mortality. A random-effects meta-analysis was used. RESULTS: Overall, 17 studies were included (3,149,547 patients). The risk of TE was similar in patients with AF with comorbid cancer compared with that in AF alone (pooled odds ratio [pOR] 0.97, 95% Confidence Interval [CI] 0.85-1.11, I2 = 87%). Major or clinically relevant non-major bleeding (pOR 1.65, 95% CI 1.35-2.02, I2 = 98%) and all-cause death (pOR 2.17, 95% CI 1.83-2.56, I2 = 98%) were significantly higher in patients with AF with cancer than in patients with AF only. The history of TE and hypertension and mean age were significant moderators of TE risk. CONCLUSION: In patients with AF, the presence of cancer is associated with a similar risk of TE as well as an increased risk of bleeding and all-cause death compared with the absence of cancer.

Changes in CHA2DS2-VASc score and risk of ischemic stroke among patients with atrial fibrillation.

AIMS: The CHA2DS2-VASc score is fundamental to stroke risk assessment in atrial fibrillation. However, stroke-related risk factors can be modified later in life. This study aimed to assess the association of changes in CHA2DS2-VASc score over time (Delta CHA2DS2-VASc score) with the risk of ischemic stroke. MATERIALS AND METHODS: This is an observational analysis of 1127 atrial fibrillation patients previously enrolled in the MISOAC-AF trial. After a median 2.6-year follow-up period, baseline and follow-up CHA2DS2-VASc scores were used to extract the Delta CHA2DS2-VASc score. The stroke predicting accuracies of the baseline, follow-up, and Delta CHA2DS2-VASc scores were assessed through regression analyses. RESULTS: The mean baseline, follow-up, and Delta CHA2DS2-VASc scores were 4.2, 4.8, and 0.6 respectively. Ischemic stroke occurred in 54 (4.4%) patients, of which 83.3% had a Delta CHA2DS2-VASc score ≥1, contrary to 40.1% of the stroke-free group. The stroke risk per 1-point increase of the CHA2DS2-VASc score was not significantly associated with the baseline score (aHR=1.14; 95%CI: 0.93-1.41; p=0.201), whereas a significant association was observed with the follow-up (aHR=2.58; 95% CI: 2.07-3.21; p<0.001) and Delta (aHR=4.56; 95%CI: 3.50-5.94; p<0.001) scores. C-index assessment indicated that follow-up and Delta CHA2DS2-VASc scores were more potent predictors of ischemic stroke compared to baseline. CONCLUSION: In atrial fibrillation patients, changes in CHA2DS2-VASc score over time were associated with the incidence of stroke. The improved predictability of follow-up and Delta CHA2DS2-VASc scores indicates that stroke risk is not a static parameter. TRIAL REGISTRATION: This is an observational, post-hoc analysis of the MISOAC-AF randomized controlled trial, registered on ClinicalTrials.gov (identifier: NCT02941978; registered: October 21, 2016).

Oral anticoagulation challenges and therapeutic dilemmas in the very elderly: to treat and how to treat octogenarians and nonagenarians?

The proportion of very elderly patients, namely octogenarians and nonagenarians, is expected to rise substantially over the next decades. This population is more prone to age­dependent diseases associated with higher thromboembolic and bleeding risks. The very elderly are under­represented in oral anticoagulation (OAC) clinical trials. However, real­world evidence is accumulating, in parallel with an increase in OAC coverage in this patient group. OAC treatment seems to be more beneficial in the oldest age spectrum. Direct oral anticoagulants (DOACs) have the dominant market share in most clinical scenarios necessitating OAC treatment, proving at least as safe and effective as conventional vitamin K antagonists. Dose adjustments due to age or renal function often need to be made in DOAC­treated very elderly patients. When prescribing OAC in this population, an individualized, yet holistic, approach accounting for comorbidities, comedications, altered physiological function, pharmacovigilance, frailty, compliance, and risk of falls is useful. However, given the limited randomized­level evidence on OAC treatment in the very elderly, there are still pending questions. This review will discuss recent evidence, important practical aspects, and future directions for anticoagulation treatment in atrial fibrillation, venous thromboembolism, and peripheral artery disease in octogenarians and nonagenarians.

First-in-man transradial percutaneous closure of ventricular septal defect with an Amplatzer Duct Occluder IΙ in an adult patient: a case report.

Background: Transcatheter closure of perimembranous ventricular septal defect (VSD) is a promising alternative to surgical closure but has been associated with conduction disorders. Vascular access via multiple large vessels is associated with procedure-related complications, undermining the benefit of percutaneous approaches. In this case, we present the first-in-man transcatheter closure of a perimembranous VSD with an Amplatzer Duct Occluder IΙ in an adult patient via a single transradial artery access. Case summary: A 62-year-old female was admitted to the hospital due to gradually worsening fatigue and shortness of breath on exertion. Transoesophageal echocardiogram (TOE) revealed a VSD size of 4-6 mm and a left ventricular ampulla size of 12 mm. A percutaneous VSD closure with the Amplatzer Duct Occluder II was decided. The angiography and TOE showed successful device placement and excellent procedural results. The patient was discharged home the next day after the procedure. The patient did not report any post-procedural complications during the 8-month follow-up. Echocardiographic assessment showed a gradual decrease in left ventricular dimensions. Discussion: Transcatheter closure of perimembranous VSD is a promising alternative to surgical closure, but it is not free of complications. Traditional VSD occluders rely on multivessel access and complex formation of arteriovenous loops. In this case, we report the feasibility of perimembranous VSD closure with an Amplatzer Duct Occluder IΙ via a single radial artery access in an adult patient. This approach is a much simpler technique with several potential advantages and should be considered in selected adult patients and in similar clinical scenarios.

Cardioselective versus Non-Cardioselective Beta-Blockers and Outcomes in Patients with Atrial Fibrillation and Chronic Obstructive Pulmonary Disease.

Background: Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) have been independently associated with increased mortality; however, there is no evidence regarding beta-blocker cardioselectivity and long-term outcomes in patients with AF and concurrent COPD. Methods: This post hoc analysis of the MISOAC-AF randomized trial (NCT02941978) included patients hospitalized with comorbid AF. At discharge, all patients were classified according to the presence of COPD; patients with COPD on beta-blockers were classified according to beta-blocker cardioselectivity. Adjusted hazard ratios (aHRs) were calculated by using multivariable Cox regression models. The primary outcome was all-cause mortality, and the secondary outcomes were cardiovascular mortality and hospitalizations. Results: Of 1103 patients with AF, 145 (13%) had comorbid COPD. Comorbid COPD was associated with an increased risk of all-cause (aHR, 1.33; 95% confidence interval (CI), 1.02 to 1.73) and cardiovascular mortality (aHR 1.47; 95% CI, 1.10 to 1.99), but not with increased risk of hospitalizations (aHR 1.10; 95% CI, 0.82 to 1.48). The use of cardioselective versus non-cardioselective beta-blockers was associated with similar all-cause mortality (aHR 1.10; 95% CI, 0.63 to 1.94), cardiovascular mortality (aHR 1.33; 95% CI, 0.71 to 2.51), and hospitalizations (aHR 1.65; 95% CI 0.80 to 3.38). Conclusions: In recently hospitalized patients with AF, the presence of COPD was independently associated with increased risk of all-cause and cardiovascular mortality. No difference between cardioselective and non-cardioselective beta-blockers, regarding clinical outcomes, was identified.

A Systematic Review and Meta-Analysis of Basal and Post-Stress Circulating Cortisol Concentration in an Important Marine Aquaculture Fish Species, European Sea Bass, Dicentrarchus labrax.

BACKGROUND: European sea bass is a species characterized by high and dispersed cortisol levels. The aim of the present study was to analyze all published data on basal and post-acute stress cortisol levels in this species. METHODS: For this systematic review and meta-analysis the Web of Science and Scopus databases were searched for papers reporting plasma or serum cortisol levels in E. sea bass, without language or date restrictions. Data were extracted directly for the reported results and were analyzed separately for basal and post-acute stress levels, as well their standardized mean differences (SMD) using random-effects meta-analyses. RESULTS: Of 407 unique records identified, 69 were eligible. Basal cortisol levels had a pooled effect of 88.7 ng mL-1 (n = 57), while post-acute stress levels were 385.9 ng mL-1 (n = 34). The average SMD between basal and post-stress was calculated to be 3.02 (n = 22). All analyses had a high between-study heterogeneity. Results for basal and post-stress levels were affected by the assay type and anesthesia prior to blood sampling. CONCLUSIONS: Cortisol levels in E. sea bass are higher than most studied fish species and display large heterogeneity. Application of stress led to elevated cortisol levels in all studies examined. In all cases, sources of between-studies heterogeneity were identified.

Artificial intelligence-based mining of electronic health record data to accelerate the digital transformation of the national cardiovascular ecosystem: design protocol of the CardioMining study.

INTRODUCTION: Mining of electronic health record (EHRs) data is increasingly being implemented all over the world but mainly focuses on structured data. The capabilities of artificial intelligence (AI) could reverse the underusage of unstructured EHR data and enhance the quality of medical research and clinical care. This study aims to develop an AI-based model to transform unstructured EHR data into an organised, interpretable dataset and form a national dataset of cardiac patients. METHODS AND ANALYSIS: CardioMining is a retrospective, multicentre study based on large, longitudinal data obtained from unstructured EHRs of the largest tertiary hospitals in Greece. Demographics, hospital administrative data, medical history, medications, laboratory examinations, imaging reports, therapeutic interventions, in-hospital management and postdischarge instructions will be collected, coupled with structured prognostic data from the National Institute of Health. The target number of included patients is 100 000. Natural language processing techniques will facilitate data mining from the unstructured EHRs. The accuracy of the automated model will be compared with the manual data extraction by study investigators. Machine learning tools will provide data analytics. CardioMining aims to cultivate the digital transformation of the national cardiovascular system and fill the gap in medical recording and big data analysis using validated AI techniques. ETHICS AND DISSEMINATION: This study will be conducted in keeping with the International Conference on Harmonisation Good Clinical Practice guidelines, the Declaration of Helsinki, the Data Protection Code of the European Data Protection Authority and the European General Data Protection Regulation. The Research Ethics Committee of the Aristotle University of Thessaloniki and Scientific and Ethics Council of the AHEPA University Hospital have approved this study. Study findings will be disseminated through peer-reviewed medical journals and international conferences. International collaborations with other cardiovascular registries will be attempted. TRIAL REGISTRATION NUMBER: NCT05176769.

Prescription Rates and Prognostic Implications of Optimally Targeted Guideline-Directed Medical Treatment in Heart Failure and Atrial Fibrillation: Insights From The MISOAC-AF Trial.

ABSTRACT: Heart failure (HF) and atrial fibrillation (AF) commonly coexist in real-life clinical practice. Among patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF), guidelines call for evidence-based target doses of renin-angiotensin-aldosterone system inhibitors and beta-blockers. However, target doses of guideline-directed medical treatment (GDMT) are often underused in real-world conditions, including HF-AF comorbidity. This retrospective cohort study of a randomized trial (Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with nonvalvular AF) included hospitalized patients with AF and HFrEF or HFmrEF. Optimally targeted GDMT was defined as intake of evidence-based target doses of renin-angiotensin-aldosterone system and beta-blockers at 3 months after discharge. Rates of optimally targeted GDMT achievement across the baseline estimated glomerular filtration rate (eGFR) were assessed. Independent predictors of nontargeted GDMT and its association with all-cause mortality and the composite of cardiovascular death or HF hospitalization were assessed by regression analyses. In total, 374 patients with AF and HFrEF or HFmrEF were studied. At 3 months after discharge, 30.7% received target doses of GDMT medications. The rate of optimally targeted GDMT was reduced by 11% for every 10 mg/min/1.73 m 2 decrease in baseline eGFR [adjusted ß = 0.99; 95% confidence interval (CI), 0.98-0.99] levels. After a median 31-month follow-up period, 37.8% patients in the optimally targeted GDMT group died, as compared with 67.8% (adjusted hazard ratio: 1.49; 95% CI, 1.05-2.13) in the nontargeted GDMT group. The risk of cardiovascular death or HF hospitalization was also higher in these patients (adjusted hazard ratio: 1.60; 95% CI, 1.17-2.20). Target doses of all HF drugs were reached in roughly one-third of patients with AF and HFrEF or HFmrEF 3 months after hospital discharge. Nontargeted GDMT was more frequent across lower eGFR levels and was associated with worse outcomes.

Prognostic implications of adherence to oral anticoagulants among patients with atrial fibrillation: Insights from MISOAC-AF trial.

OBJECTIVES: To explore the implications of adherence to oral anticoagulants (OACs) on all-cause mortality and cardiovascular outcomes in patients with atrial fibrillation (AF). METHODS: This post-hoc analysis of the MISOAC-AF trial included recently hospitalized patients with AF. Adherence to OACs was assessed by the proportion of days covered (PDC). Good adherence was defined as PDC >80 %. Cox regression models were used to associate PDC with clinical outcomes of all-cause death, cardiovascular death (CVD), stroke, and bleeding. A sub-analysis was performed among adherent patients to compare outcomes between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). RESULTS: During a median 31-month follow-up, 778 cardiac patients with comorbid AF who had been prescribed OACs upon hospital discharge were studied. The mean PDC was 0.78; 66 % of patients had good adherence (>80 %) which was associated with lower risk of all-cause death [adjusted hazard ratio (aHR): 0.64; 95 % confidence interval (CI): 0.46 to 0.84, p < 0.001] and CVD (aHR: 0.70; 95 % CI: 0.50 to 0.97, p = 0.03). The risk of stroke and major or non-major bleeding did not differ by adherence status. Among adherent patients to OACs, VKA use was associated with higher rates of all-cause death (p < 0.001), CVD (p < 0.001), and stroke (p = 0.01); no differences were found regarding major or non-major bleeding risk. CONCLUSIONS: In recently hospitalized patients with AF, good adherence to OACs was associated with a reduced risk of all-cause death and CVD. The rates of stroke or bleeding events were not significantly different. VKAs were associated with more adverse events compared to DOACs.

Fish Scales Produce Cortisol upon Stimulation with ACTH.

Cortisol concentration in fish scales is a novel and reliable indicator of chronic stress. However, until now cortisol in scales has been considered to be accumulated through the circulation and it has not yet been studied whether it can be de novo produced from cells found in the scales. In the current study, scales of European sea bass, Dicentrarchus labrax, were stimulated in-vitro with a range of concentrations of adrenocorticotropic hormone (ACTH) to investigate if they can produce and release cortisol. Moreover, scales were exposed to a combination of ACTH and metyrapone, an inhibitor of cortisol production, to examine whether cortisol was actually produced in the scales. Results from ACTH administration showed that scales increased their cortisol release in a dose-dependent manner. This effect was reversed when scales were co-incubated with ACTH and metyrapone, indicating that cortisol was produced de novo and not released only upon stimulation with ACTH.

Prognostic impact of secondary prevention medical therapy following myocardial infarction with non-obstructive coronary arteries: a Bayesian and frequentist meta-analysis.

Aims: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical entity with several causes and pathophysiologic mechanisms. Secondary prevention with medical therapy used in patients with obstructive coronary artery disease has unclear benefits in MINOCA patients. Methods and results: A literature search was conducted until 8 March 2022. Random-effect frequentist and hierarchical Bayesian meta-analyses were performed to assess the clinical impact of medical therapy [renin-angiotensin-aldosterone system (RAAS) inhibitors, statins, dual antiplatelet therapy (DAPT), ß-blockers] in MINOCA patients. Outcomes of interest were all-cause mortality and major adverse cardiovascular events (MACE). A total of 12 663 MINOCA patients among five observational studies were analysed. The mean follow-up ranged from 12 to 90 months across studies. In frequentist meta-analysis, statins and ß-blockers were associated with a lower risk of all-cause mortality [pooled adjusted hazard ratios (aHRs) 0.53 and 0.81, with 95% confidence intervals (CIs) (0.37-0.76) and (0.67-0.97), respectively]. Only RAAS inhibitors were associated with a lower risk of MACE [pooled aHR: 0.69, with 95% CI (0.53-0.90)]. Bayesian meta-analysis based on informative prior assumptions offered strong evidence only for the benefit of statins on decreasing the risk of all-cause death [Bayes factor (BF): 33.2] and moderate evidence for the benefit of RAAS inhibitors on decreasing the risk of MACE (BF: 9); assigning less informative prior distributions did not affect the results, yet it downgraded the level of evidence to anecdotal. Conclusion: In this meta-analysis, statins and RAAS inhibitors were consistently associated with a lower risk of all-cause mortality and MACE, respectively, in patients with MINOCA. Neutral prognostic evidence was demonstrated for ß-blockers and DAPT.

Intracoronary Thrombolysis in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: an Updated Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the standard reperfusion treatment in ST-segment elevation myocardial infarction (STEMI). Intracoronary thrombolysis (ICT) may reduce thrombotic burden in the infarct-related artery, which is often responsible for microvascular obstruction and no-reflow. METHODS: We conducted, according to the PRISMA statement, the largest meta-analysis to date of ICT as adjuvant therapy to PPCI. All relevant studies were identified by searching the PubMed, Scopus, Cochrane Library, and Web of Science. RESULTS: Thirteen randomized controlled trials (RCTs) involving a total of 1876 patients were included. Compared to the control group, STEMI ICT-treated patients had fewer major adverse cardiac events (MACE) (OR 0.65, 95% CI, 0.48-0.86, P = 0.003) and an improved 6-month left ventricular ejection fraction (MD 3.78, 95% CI, 1.53-6.02, P = 0.0010). Indices of enhanced myocardial microcirculation were better with ICT (Post-PCI corrected thrombolysis in myocardial infarction (TIMI) frame count (MD - 3.57; 95% CI, - 5.00 to - 2.14, P < 0.00001); myocardial blush grade (MBG) 2/3 (OR 1.76; 95% CI, 1.16-2.69, P = 0.008), and complete ST-segment resolution (OR 1.97; 95% CI, 1.33-2.91, P = 0.0007)). The odds for major bleeding were comparable between the 2 groups (OR 1.27; 95% CI, 0.61-2.63, P = 0.53). CONCLUSIONS: The present meta-analysis suggests that ICT was associated with improved MACE and myocardial microcirculation in STEMI patients undergoing PPCI, without significant increase in major bleeding. However, these findings necessitate confirmation in a contemporary large RCT.