Newly detected diabetes mellitus patients with acute coronary syndrome have an adverse cardiometabolic profile similar to patients with prior diabetes and a more extensive ischemic myocardial insult.

AIMS: The impact of newly detected diabetes mellitus (NDDM) on metabolic parameters and extent of myocardial necrosis in patients with acute coronary syndrome (ACS) is not fully explored. We examined the impact of NDDM on cardiometabolic characteristics and myocardial necrosis in ACS patients. METHODS: CALLINICUS-Hellas Registry is an ongoing prospective multicenter observational study evaluating the adherence to lipid-lowering therapy (LLT) among ACS patients in Greece. Three groups were created: a) patients with NDDM (abnormal fasting glucose, HbA1c ≥ 6.5 % and no previous history of DM), b) patients without known DM and HbA1c < 6.5 % (non-DM) and c) patients with prior DM. RESULTS: The prevalence of NDDM among 1084 patients was 6.9 %. NDDM patients had lower HDL-C [38 (32-45) vs 42 (36-50) mg/dL] and higher triglycerides levels [144 (104-231) vs 115 (87-152) mg/dL] compared to non-DM patients (p < 0.05). NDDM patients featured both higher body mass index [29.5 (26.4-34.3) vs 27.1 (24.9-29.9) kg/m2] and waist circumference [107 (100-114) vs 98 (91-106) cm] compared to non-DM patients (p < 0.05). In addition, NDDM patients had more extensive myocardial necrosis than patients with prior DM. CONCLUSIONS: ACS patients with NDDM have an adverse cardiometabolic profile similar to patients with prior DM and have more extensive myocardial insult.

The Prognostic Role of Spot Urinary Sodium and Chloride in a Cohort of Hospitalized Advanced Heart Failure Patients: A Pilot Study.

Recent studies have demonstrated the prognostic value of spot urinary sodium (UNa+) in acutely decompensated chronic HF (ADCHF) patients. However, data on the prognostic role of UNa+ and spot urinary chloride (UCl-) in patients with advanced HF are limited. In the present prospective pilot study, we examined the predictive value of UNa+ and UCl- concentration at baseline, at 2 h and at 24 h after admission for all-cause mortality and HF rehospitalization up to 3 months post-discharge. Consecutive advanced HF patients (n = 30) admitted with ADCHF and aged > 18 years were included in the study. Loop diuretics were administered based on the natriuresis-guided algorithm recommended by the recent HF guidelines. Exclusion criteria were cardiogenic shock, acute coronary syndrome, estimated glomerular filtration rate < 15 mL/min/1.73 m2, severe hepatic dysfunction (Child-Pugh category C), and sepsis. UNa+ at baseline (Area Under the Curve (AUC) = 0.75, 95% Confidence Interval (CI) (0.58-0.93), p = 0.019) and at 2 h after admission (AUC = 0.80, 95% CI: 0.64-0.96, p = 0.005) showed good and excellent discrimination, respectively. UCl- at 2 h after admission (AUC = 0.75, 95%CI (0.57-0.93), p = 0.017) demonstrated good discrimination. In the multivariate logistic regression analysis, UNa+ at 2 h (p = 0.02) and dose of loop diuretics at admission (p = 0.03) were the only factors independently associated with the study outcome. In conclusion, UNa+ and UCl- may have a prognostic role in hospitalized advanced HF patients.

COVID-19 and the heart.

An outbreak of coronavirus disease 2019 (COVID-19) occurred in December 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a strain of SARS-CoV. Patients infected with the virus present a wide spectrum of manifestations ranging from mild flu-like symptoms, cough, fever and fatigue to severe lung injury, appearing as bilateral interstitial pneumonia or acute respiratory failure. Although SARS-CoV-2 infection predominantly offends the respiratory system, it has been associated with several cardiovascular complications as well. For example, patients with COVID-19 may either develop type 2 myocardial infarction due to myocardial oxygen demand and supply imbalance or acute coronary syndrome resulting from excessive inflammatory response to the primary infection. The incidence of COVID-19 related myocarditis is estimated to be accountable for an average of 7% of all COVID-19 related fatal cases, whereas heart failure (HF) may develop due to infiltration of the heart by inflammatory cells, destructive action of pro-inflammatory cytokines, micro-thrombosis and new onset or aggravated endothelial and respiratory failure. Lastly, SARS-CoV-2 can engender arrhythmias through direct myocardial damage causing acute myocarditis or through HF decompensation or secondary, through respiratory failure or severe respiratory distress syndrome. In this comprehensive review we summarize the COVID-19 related cardiovascular complications (acute coronary syndromes, myocarditis, HF, arrhythmias) and discuss the main underlying pathophysiological mechanisms.

Acute Myopericarditis after the Second Dose of mRNA COVID-19 Vaccine Mimicking Acute Coronary Syndrome.

Myocarditis is a rare adverse event of vaccination. Recently, mRNA vaccines for COVID-19 have been reported to correlate with myocarditis, specifically in adolescents and young men. We report a rare case of a 50-year-old man who presented with symptoms of myocardial infarction 3 days after the second dose of vaccination for COVID-19. Cardiac magnetic resonance (CMR) imaging revealed acute myopericarditis. Clinicians should be aware of that rare side effect of mRNA vaccines for COVID-19 that can affect not only younger recipients but also middle-aged patients presenting with symptoms mimicking acute coronary syndrome.

Adherence to oral anticoagulation in ischemic stroke patients with atrial fibrillation.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved. AIMS: We sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF). METHODS: We recruited hospitalised patients (2013-2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA2DS2-VASc and SAMe-TT2R2 scores with poor adherence. RESULTS: Among 396 patients (median age 75.0 years, interquartile range [IQR] 70-80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12-33]; median ARMS score 17 [IQR 17-19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA2DS2-VASc and SAMe-TT2R2 scores were not associated with poor adherence. CONCLUSIONS: Adherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients.KEY MESSAGESAdherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke.Independent patient-related factors rather than composite scores were associated with poor adherence.The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.

Statin treatment and outcomes after embolic stroke of undetermined source.

The association of low-density lipoprotein cholesterol lowering with outcomes in embolic stroke of undetermined source (ESUS) patients is unclear. In these patients we aimed to assess the effect of statin on stroke recurrence, major adverse cardiovascular events (MACE) and death rates. Consecutive ESUS patients in the Athens Stroke Registry were prospectively followed-up to 10 years for stroke recurrence, MACE, and death. The Nelson-Aalen estimator was used to estimate the cumulative probability by statin allocation at discharge and cox-regression analyses to investigate whether statin at discharge was a predictor of outcomes. Among 264 ESUS patients who were discharged and followed for 4 years, 89 (33.7%) were treated with statin at discharge. Patients who were discharged on statin had lower rates of stroke recurrence (3.58 vs. 7.23/100 patient-years, HR: 0.48; 95% CI 0.26-0.90), MACE (4.98 vs. 9.89/100 patient-years, HR: 0.49; 95% CI 0.29-0.85), and death (3.93 vs. 8.21/100 patient-years, HR: 0.50; 95% CI: 0.28-0.89). In the multivariate analysis, statin treatment at discharge was an independent predictor of stroke recurrence (adjusted HR: 0.48; 95% CI 0.26-0.91), MACE (adjusted HR: 0.48; 95% CI 0.28-0.82), and death (adjusted HR: 0.50; 95% CI 0.27-0.93). Patients with ESUS discharged on statins have lower rates of stroke recurrence, MACE, and death compared to those not receiving statin therapy.

Atrial Cardiopathy and Likely Pathogenic Patent Foramen Ovale in Embolic Stroke of Undetermined Source.

BACKGROUND: Atrial cardiopathy and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. METHODS: Atrial cardiopathy was defined as increased left atrial diameter index (> 23 mm/m2) or left atrial volume index (> 34 mL/m2), or PR prolongation (≥ 200 ms), or presence of supraventricular extrasystoles in the electrocardiograms performed during hospitalization for the index stoke. The presence of PFO was assessed by transthoracic echocardiography with microbubble test or by transesophageal echocardiography. The presence of PFO was considered as likely pathogenic if the Risk of Paradoxical Embolism score was 7 to 10. RESULTS: Among 367 ESUS patients with available information about the presence of PFO and the presence of atrial cardiopathy (median age: 61 years, 40.6% women), likely pathogenic PFO was diagnosed in 62 (16.9%) and atrial cardiopathy in 122 (33.2%). Only 4 patients (1.1%) had both likely pathogenic PFO and atrial cardiopathy. The prevalence of atrial cardiopathy was lower in patients with likely pathogenic PFO (6.5%) compared with patients with likely incidental PFO (31.2%) or without PFO (40.6%) (Pearson's chi-square test: 26.08, p < 0.001; adjusted odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.09-0.86). The prevalence of likely pathogenic PFO was lower in patients with atrial cardiopathy compared with patients without atrial cardiopathy (3.3% vs. 23.7%, respectively [Pearson's chi-square test: 24.13, p < 0.001; adjusted OR: 0.2, 95% CI: 0.02-0.6]). CONCLUSION: The presence of atrial cardiopathy is inversely related to the presence of likely pathogenic PFO in patients with ESUS.

Antithrombotic treatment in patients with stroke and supracardiac atherosclerosis.

OBJECTIVE: To compare the efficacy and safety of oral anticoagulants vs antiplatelets in patients with stroke and atherosclerotic plaques in the aortic arch or cervical or intracranial arteries, collectively described as supracardiac atherosclerosis. METHODS: We searched PubMed and Scopus until August 28, 2019, for randomized trials comparing oral anticoagulants vs antiplatelets in patients with stroke and supracardiac atherosclerosis using the terms "anticoagulant or anticoagulation" and "antiplatelet or aspirin" and "randomized controlled trial or RCT" and "stroke or cerebral ischemia" and "aortic or carotid or vertebrobasilar or intracranial or atherosclerosis or stenosis or arterial." Four outcomes were assessed: recurrent ischemic stroke, major ischemic event or death, major bleeding, and intracranial bleeding. Treatment effects (relative risk [RR] and 95% confidence interval [CI]) were estimated by meta-analysis using random-effects models. RESULTS: Among 1,117 articles identified in the literature search, results from 10 randomized controlled trials involving 6,068 patients with stroke/TIA with supracardiac atherosclerosis were included in the meta-analysis. Recurrent ischemic stroke rates were 2.94 per 100 patient-years in the anticoagulant-assigned patients vs 3.30 per 100 patient-years in the antiplatelet-assigned patients (RR, 0.91; 95% CI, 0.70-1.18 for the SJ estimator, I2 = 26%). Major ischemic event or death rates were 4.39 per 100 patient-years in anticoagulant-assigned patients vs 4.32 in antiplatelet-assigned patients (RR, 1.03; 95% CI, 0.79-1.35; I2 = 54.5%). Major bleeding rates were 2.88 per 100 patient-years in anticoagulant-assigned patients vs 0.82 in antiplatelet-assigned patients (RR, 3.21; 95% CI, 1.96-5.24; I2 = 46%). CONCLUSION: This systematic review and meta-analysis showed that anticoagulant-assigned patients with stroke and supracardiac atherosclerosis were not at different risk of ischemic stroke recurrence and increased risk of major bleeding compared to antiplatelet-assigned patients.

Bleeding risk comparison between direct oral anticoagulants at doses approved for atrial fibrillation and aspirin: systematic review, meta-analysis and meta-regression.

BACKGROUND: A considerable proportion of patients with atrial fibrillation (AF) are still treated with aspirin despite current guidelines due to presumed favorable safety. AIM: We performed a systematic review and meta-analysis of bleeding outcomes in randomized controlled trials (RCTs) comparing direct oral anticoagulants (DOACs) at doses approved for AF vs. aspirin. METHODS: We searched PubMed and Scopus for phase-III RCTs of DOACs at AF-approved doses vs. aspirin. Outcomes assessed were major-, intracranial-, gastrointestinal-, clinically-relevant-non-major- and fatal bleeding. We performed two subgroup analyses: one per patient population i.e. those at high risk of arterial or venous thromboembolism, and one per DOAC. We also performed a meta-regression to assess the association with patient age. RESULTS: In 4 eligible trials (20,440 patients) comparing DOACs vs. aspirin, the ORs were: 1.52 (95%CI: 0.91-2.53) for major bleeding in patients at high risk of arterial thromboembolism and 1.55 (95%CI:0.99-2.45, relative-risk-increase:55%, absolute-risk-increase:0.6%, number-needed-to-harm:170) in the overall analysis; 1.39 (95%CI:0.62-3.14) for intracranial bleeding in patients at high risk of arterial thromboembolism which was similar for the overall analysis; 1.27 (95%CI: 0.84-1.92) for gastrointestinal bleeding in patients at high risk of arterial thromboembolism and 1.26 (95%CI:0.86-1.85) in the overall analysis. Patient age was not a predictor of the magnitude of ORs for all bleeding outcomes. CONCLUSION: The present meta-analysis does not support the use of aspirin over DOACs in AF. Accordingly, the level of evidence of the related recommendations should be upgraded, which in turn may reduce further the proportion of AF patients treated with antiplatelets.

Characteristics and outcomes of Embolic Stroke of Undetermined Source according to stroke severity.

BACKGROUND AND AIMS: Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. METHODS: In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan-Meier product limit method. RESULTS: In 772 patients (median NIHSS: 6 (interquartile range: 3-12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27-2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73-1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44-1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05-2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2-48.6) vs. 36.6% (27.8-47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5-50.0) vs. 34.0% (26.0-43.6) respectively; log-rank test: 4.54, p = 0.033). CONCLUSIONS: Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.

A novel antioxidant non-steroidal anti-inflammatory agent protects rat liver against ischemia-reperfusion injury.

Liver ischemia followed by reperfusion is an important and common clinical event. A major mechanism is leukocyte adhesion to endothelium followed by release of reactive oxygen metabolites. The aim of this study was to determine the effects of a novel antioxidant ethylenediamine derivative with anti-inflammatory properties (compound IA) on an imitated clinical setting of acute hepatic ischemia-reperfusion injury. Eight groups of rats were subjected to a model of hepatic ischemia that was produced by occluding for 30 min the portal vein and hepatic artery. At the end of ischemia, compound IA was administered intravenously and the clamps were removed allowing reperfusion for 60 min or 24 h. The effect of compound IA was evaluated by histopathological examination, lipid peroxidation and plasma levels of liver enzymes. Administration of compound IA resulted in significantly less histological damage in liver tissue after 30-min ischemia followed by 60-min and 24-h reperfusion. Ischemia followed by 60 min of reperfusion increased lipid peroxidation compared to the sham-operated and the non-ischemic group. This increase was attenuated in the group treated with compound IA. Serum enzyme levels were significantly higher in the reperfusion groups compared to the non-ischemic groups and diminished after treatment. Compound IA exerted a protective effect on hepatic reperfusion injury in rats. Compound IA is believed to act by means of its potent antioxidant and anti-inflammatory activities.