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Introduction: The aim of this study was to investigate changes in echocardiographic right ventricular (RV) indices in relation to the degree of fluid accumulation between hemodialysis sessions, evaluated according to the recommended threshold of interdialytic-weight-gain corrected for dry weight (IDWG%)., Methods: A post-hoc analysis was performed using data from 41 maintenance hemodialysis patients. Patients were divided into a higher (>4.5%) and a lower (<4.5%) IDWG% group and underwent an echocardiographic assessment at the start and the end of the 3-day and the 2-day interdialytic interval., Results: RV systolic pressure (RVSP) increments were more pronounced in the higher compared to the lower IDWG% group (16.43 ± 5.37 vs. 14.11 ± 13.38 mm Hg respectively, p = 0.015) over the 3-day interval, while changes in RV filling pressures, did not differ significantly between the groups (p = 0.84)., Conclusions: During the 3-day interdialytic interval, pulmonary circulation is particularly overloaded in patients with fluid accumulation higher than the recommended thresholds, as evidenced by higher RVSP elevations., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Background: This study sought to explore the prevalence and clinical utility of different patterns of multiorgan venous congestion as assessed by the venous excess ultrasound (VExUS) score in hospitalized patients with acute heart failure (HF)., Methods: Consecutive patients admitted for acute HF were prospectively enrolled. Inferior vena cava diameter, hepatic vein, portal vein, and renal vein Doppler waveforms were assessed at admission, and patients were stratified based on VExUS score from 0 to 3, with higher values indicating worse congestion. The clinical score Get with the Guidelines (GWTG)-HF for predicting in-hospital mortality in HF was evaluated. In-hospital mortality was recorded., Results: Two hundred ninety patients admitted with acute HF were included, and 114 (39%) of them were classified as VExUS score 3, which was the most prevalent group. Patients with VExUS score 3 suffered more frequently from chronic atrial fibrillation, chronic kidney disease, and anemia. Parameters independently associated with VExUS score 3 were higher mean E/e' ratio, larger right ventricular size, severe tricuspid regurgitation, and impaired right atrial function. A VExUS score of 3 was associated with in-hospital mortality (odds ratio, 8.03; 95% CI [2.25-28.61], P = .001). The addition of VExUS score on top of the GWTG-HF score improved the predictability of the model (Δx 2 = +8.44, P = .03) for in-hospital mortality, whereas other indices of venous congestion (right atrial function, inferior vena cava size) did not., Conclusions: Patients admitted with acute HF commonly had severe venous congestion based on the VExUS score. The VExUS score improved the prediction of in-hospital mortality compared with other indices of venous congestion., Competing Interests: Disclosures V.D. received speaker fees from Edwards Lifesciences, GE Healthcare, Abbott Vascular, Medtronic, Novartis, and Philips and consulting fees from Edwards Lifesciences, MSD, and Novo Nordisk. The remaining authors have nothing to declare., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: To systematically evaluate the prognostic utility of estimated plasma volume status (ePVS) on the outcomes of patients undergoing transcatheter aortic valve implantation (TAVI)., Methods: The exposure variable of interest was the ePVS, enumerating the percentage change of the actual plasma volume from the ideal plasma volume, and being calculated on the basis of weight and hematocrit using sex-specific constants. A random-effects meta-analysis was performed after a systematic literature search in PubMed, Scopus and Web Of Science., Results: The systematic literature search yielded 5 eligible observational cohort studies encompassing a total of 7,121 patients undergoing TAVI. The meta-analysis suggested that "high ePVS" status was independently associated with increased risk for 1-year all-cause mortality (pooled adjusted hazard ratio: 1.63, 95 % confidence intervals: 1.36-1.95) compared to "low ePVS". Also, the pooled unadjusted odds for 1-year mortality, 30-day mortality, peri-procedural stroke, major bleeding, and acute kidney injury were significantly increased in the "high ePVS" group of patients. Conversely, the unadjusted risk of pacemaker implantation and major vascular complications did not differ significantly between the 2 groups., Conclusions: Plasma volume expansion appears to be linked with a worse peri-procedural and long-term prognostic course in TAVI. Its use in clinical practice could refine risk stratification and candidate selection practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Evidence on the relative impact of diverse genetic backgrounds associated with non-ischaemic dilated cardiomyopathy (DCM) remains contradictory. This study sought to synthesize the available data regarding long-term outcomes of different gene groups in DCM., Methods and Results: Electronic databases were systematically screened to identify studies reporting prognostic data on pre-specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C variants (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), malignant ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). A total of 26 studies (n = 7255) were included in the meta-analysis and 6791 patients with genotyped DCM were analysed. Patients with P/LP variants had a higher risk for CAEs (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.67-2.65), MVAEs (OR 1.86, 95% CI 1.52-2.26), and HFEs (OR 2.01, 95% CI 1.08-3.73) than genotype-negative patients. The presence of TTNtv was linked to a higher risk for CAEs (OR 1.78, 95% CI 1.20-2.63), but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non-LMNA and non-desmosomal groups, respectively. When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harboured a higher risk for MVAEs compared to TTNtv., Conclusions: Different genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: In acute heart failure (HF), low cardiac output and venous congestion are pathophysiological mechanisms that contribute to renal function impairment. This study investigated the association between advanced echocardiographic measures of right ventricular and atrial function and renal impairment in patients with acute HF., Methods and Results: A total of 377 patients hospitalized for acute HF were prospectively evaluated. Estimated glomerular filtration rate (eGFR) on admission was measured using the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Advanced echocardiographic assessment was performed on admission. Patients with eGFR < 45 mL/min/1.73 m 2 were more likely to have chronic heart failure, chronic atrial fibrillation, and type 2 diabetes mellitus compared to patients with eGFR ≥ 45 mL/min/1.73 m 2 . Patients with lower eGFR had lower cardiac output, higher mean E/e' ratio, larger right ventricular (RV) size, worse RV free wall longitudinal strain, more impaired right atrial (RA) reservoir strain, and more frequent severe tricuspid regurgitation. RV free wall longitudinal strain and RA reservoir strain were the only independent echocardiographic associates of low eGFR, whereas cardiac output was not., Conclusions: Impaired RV and RA longitudinal strain were independently associated with eGFR < 45 mL/min/1.73 m 2 in acute HF, while reduced cardiac output was not. This suggests that RV and RA dysfunction underlying venous congestion and increased renal afterload are more important pathophysiological determinants of renal impairment in acute HF than reduced cardiac output.

Context: Prolactin (PRL) is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data have outlined the potential prognostic value of PRL in various clinical settings., Objective: This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum PRL levels and risk of mortality in adults without prolactinoma., Methods: A systematic literature search was conducted up to June 10, 2023, to identify studies reporting the association of serum PRL levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death (CVD) during follow-up., Results: Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum PRL levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23 596 individuals. Each unit of PRL increase was independently associated with increased risk of all-cause (pooled aHR = 1.17 [1.08-1.27]; I2 = 48%) and CV mortality (pooled aHR = 1.54 [1.14-2.09]; I2 = 89%). Individuals belonging to the highest PRL category had significantly higher risk for all-cause (pooled aHR = 1.81 [1.43-2.30]; I2 = 65%) and CV (pooled aHR = 1.59 [1.04-2.42]; I2 = 82%) mortality compared to their lowest-PRL category counterparts. The association between PRL levels and in-hospital death did not reach statistical significance., Conclusion: PRL levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk-stratification tool can be delineated in clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate for right ventricular-pulmonary arterial (RV-PA) coupling, studied in chronic RV pressure overload syndromes. However, its prognostic utility in patients with acute myocardial infarction (AMI), which may cause acute RV pressure overload, remains unexplored., Objective: This study aimed to determine predictors of RV-PA uncoupling in patients with first AMI and examine whether it could improve risk stratification for cardiovascular in-hospital mortality after revascularization., Methods: Three-hundred consecutive patients with first AMI were prospectively studied (age 61.2 ± 11.8, 24% females). Echocardiography was performed 24 h after successful revascularization, and TAPSE/PASP was evaluated. Cardiovascular in-hospital mortality was recorded., Results: The optimal cutoff value of TAPSE/PASP to determine cardiovascular in-hospital mortality was 0.49 mm/mmHg. RV-PA uncoupling was considered for patients with TAPSE/PASP ≤0.49 mm/mmHg. Left ventricular ejection fraction (LVEF) was independently associated with RV-PA uncoupling. A total of 23 (7.7%) patients died in hospital despite successful revascularization. TAPSE/PASP was independently associated with in-hospital mortality after adjustment for Global Registry of Acute Coronary Events (GRACE) risk score and LVEF (odds ratio 0.14 [95% confidence interval 0.03-0.56], P = 0.007). The prognostic value of a baseline model including the GRACE risk score and NT-pro-BNP (χ 2 26.55) was significantly improved by adding LVEF ≤40% (χ 2 44.71, P < 0.001), TAPSE ≤ 17 mm (χ 2 75.42, P < 0.001) and TAPSE/PASP ≤ 0.49 mm/mmHg (χ 2 101.74, P < 0.001) for predicting cardiovascular in-hospital mortality., Conclusion: RV-PA uncoupling, assessed by echocardiographic TAPSE/PASP ≤ 0.49 mm/mmHg 24 h after revascularization, may improve risk stratification for cardiovascular in-hospital mortality after first AMI., Competing Interests: Conflict of interest None relevant to this work., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Background: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA., Methods: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding., Results: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, P non-inferiority  < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48)., Conclusion: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background/Objectives : Contradictory results have been reported regarding the influence of obesity on the prognosis of atrial fibrillation (AF). The present study aimed to explore the potential association of body mass index (BMI) with the clinical outcomes of hospitalized patients with AF. Methods : In this retrospective, post hoc analysis of the MISOAC-AF randomized trial, 1113 AF patients were included and stratified as the following: underweight (BMI < 18 kg/m 2 ), normal weight (BMI 18-24.9 kg/m 2 ), overweight (BMI 25-29.9 kg/m 2 ), and obese (BMI ≥ 30 kg/m 2 ). The primary outcome was all-cause mortality; the secondary composite outcome was any hospitalization related to AF, heart failure (HF), or stroke. Cox regression analysis, survival analysis, and spline curve models were utilized. Results : Of the patients (median age: 76 years (IQR: 13), male: 54.6%), the majority were overweight (41.4%), followed by obese (33%), normal weight (24%), and underweight (1.6%). During a median 31-month follow-up, 436 (39.2%) patients died and 657 (59%) were hospitalized due to AF, HF, or stroke. Underweight, overweight, and obesity groups were significantly associated with an increased risk of all-cause mortality ( p -values 0.02, 0.001, and <0.001, respectively), while overweight and obesity were significantly associated with the composite endpoint ( p -values 0.01, <0.001, respectively) compared to normal weight. The spline curve analyses yielded that BMIs > 26.3 and > 25 were incrementally associated with all-cause mortality and the composite endpoint, respectively. A J-shaped relationship between BMI and AF prognosis was deduced. Conclusions : In conclusion, in recently hospitalized AF patients, BMI values outside the normal range were independently associated with poorer prognosis; therefore, it is essential that AF patients maintain a normal weight.

Background/Objectives : Radial artery occlusion (RAO) is the most common complication of transradial coronary catheterization. In this study, we aimed to evaluate the incidence of RAO and identify the risk factors that predispose patients to it. Methods : We conducted an investigator-initiated, prospective, multicenter, open-label study involving 1357 patients who underwent cardiac catheterization via the transradial route for angiography and/or a percutaneous coronary intervention (PCI). Univariate and multivariate logistic regression analyses were performed to identify potential predictors of RAO occurrence. Additionally, a subgroup analysis only for patients undergoing PCIs was performed. Results : The incidence of RAO was 9.5% overall, 10.6% in the angiography-only group and 6.2% in the PCI group. Independent predictors of RAO were as follows: (i) the female gender (aOR = 1.72 (1.05-2.83)), (ii) access site cross-over (aOR = 4.33 (1.02-18.39)), (iii) increased total time of the sheath in the artery (aOR = 1.01 (1.00-1.02)), (iv) radial artery spasms (aOR = 2.47 (1.40-4.36)), (v) the presence of a hematoma (aOR = 2.28 (1.28-4.06)), (vi) post-catheterization dabigatran use (aOR = 5.15 (1.29-20.55)), (vii) manual hemostasis (aOR = 1.94 (1.01-3.72)) and (viii) numbness at radial artery ultrasound (aOR = 8.25 (1.70-40)). Contrariwise, two variables were independently associated with increased odds for radial artery patency (RAP): (i) PCI performance (aOR = 0.19 (0.06-0.63)), and (ii) a higher dosage of intravenous heparin per patient weight (aOR = 0.98 (0.96-0.99)), particularly, a dosage of >50 IU/kg (aOR = 0.56 (0.31-1.00)). In the PCI subgroup, independent predictors of RAO were as follows: (i) radial artery spasms (aOR = 4.48 (1.42-14.16)), (ii) the use of intra-arterial nitroglycerin as a vasodilator (aOR = 7.40 (1.67-32.79)) and (iii) the presence of symptoms at echo (aOR = 3.80 (1.46-9.87)), either pain (aOR = 2.93 (1.05-8.15)) or numbness (aOR = 4.66 (1.17-18.57)). On the other hand, the use of intra-arterial verapamil as a vasodilator (aOR = 0.17 (0.04-0.76)) was independently associated with a greater frequency of RAP. Conclusions : The incidence of RAO in an unselected, all-comers European population after transradial coronary catheterization for angiography and/or PCIs is similar to that reported in the international literature. Several RAO prognostic factors have been confirmed, and new ones are described. The female gender, radial artery trauma and manual hemostasis are the strongest predictors of RAO. Our results could help in the future identification of patients at higher risk of RAO, for whom less invasive diagnostic procedures maybe preferred, if possible.

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., (© 2023. The Author(s).)

The increasing prevalence of atrial fibrillation (AF) in adults with congenital heart disease raises significant questions regarding its management. The unique underlying anatomic and physiological background further adds to the difficulty in eliminating the AF burden in these patients. Herein, we provide an overview of the current knowledge on the pathophysiology and risk factors for AF in adult congenital heart disease, with a special focus on the existing challenges in AF ablation. Emerging imaging modalities and ablation techniques might have a role to play. Evidence regarding the safety and efficacy of AF ablation in adult congenital heart disease is summarized, especially for patients with an atrial septal defect, Ebstein anomaly of the tricuspid valve, tetralogy of Fallot, and Fontan circulation. Finally, any remaining gaps in knowledge and potential areas of future research are highlighted.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The P wave, representing the electrical fingerprint of atrial depolarization, contains information regarding spatial and temporal aspects of atrial electrical-and potentially structural-properties. However, technical and biological reasons, including-but not limited to-the low amplitude of the P wave and large interindividual variations in normal or pathologic atrial electrical activity, make gathering and utilizing this information for clinical purposes a rather cumbersome task. However, even crude ECG descriptors, such as P-wave dispersion, have been shown to be of predictive value for assessing the probability that a patient already has or will shortly present with AF. More sophisticated methods of analyzing the ECG signal, on a single- or multi- beat basis, along with novel approaches to data handling, namely machine learning, seem to be leading up to more accurate and robust ways to obtain clinically useful information from the humble P wave., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling which corresponds well with the respective invasively derived index. Recently, a wealth of observational data has arisen, outlining its prognostic value in heart failure (HF) patients. To systematically appraise and quantitatively synthesize the evidence of the prognostic value of TAPSE/PASP ratio in left-sided HF regardless of etiology or left ventricular ejection fraction. A systematic literature review was conducted in electronic databases to identify studies reporting the association of TAPSE/PASP ratio with outcomes in patients with HF and, when appropriate, a random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome of all-cause death or HF hospitalization. Eighteen studies were deemed eligible encompassing 8,699 HF patients. The applied cut-off value for RV-PA uncoupling varied substantially from 0.27 to 0.58 mm/mmHg, and in most studies values lower than the applied cutoff conveyed dismal prognosis. Eleven studies reported appropriate data for meta-analysis. TAPSE/PASP reduction by 1 mm/mmHg was independently associated with all-cause death (pooled aHR=1.32 [1.06-1.65]; p=0.01; I 2 =56%) and the composite outcome (pooled aHR=3.48 [1.67-7.25]; p<0.001; I 2 =0%). When a TAPSE/PASP cutoff value of 0.36 mm/mmHg was applied it yielded independent association with all-cause death (pooled aHR=2.84 [2.22-3.64]; p<0.001; I 2 =82%). RV-PA coupling assessed by echocardiographic TAPSE/PASP ratio appears to be an independent outcome predictor for HF patients., (© 2023. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Right ventricular (RV) dysfunction is a well-recognized adverse prognostic feature in patients with heart failure (HF). Recently, many single-center studies have demonstrated that RV longitudinal strain assessed using speckle tracking echocardiography might be a powerful prognosticator in HF., Objectives: To systematically appraise and quantitatively synthesize the evidence of the prognostic value of echocardiographic RV longitudinal strain, across the entire spectrum of left ventricular ejection function (LVEF) in HF., Methods: A systematic literature review was conducted in electronic databases to identify every study reporting the predictive role of RV global longitudinal strain (RV GLS) and RV free wall longitudinal strain (RV FWLS) in HF subjects. A random-effects meta-analysis was conducted to quantify the adjusted and unadjusted hazard ratios [(a)HRs] for all-cause-mortality and for the composite outcome of all-cause mortality or HF-related hospitalization for both indices., Results: Twenty-four studies were deemed eligible and 15 of these provided appropriate quantitative data for the meta-analysis, encompassing 8,738 patients. Each 1% worsening in RV GLS and RV FWLS was independently associated with increased risk of all-cause mortality (pooled aHR = 1.08 [1.03-1.13]; p < 0.01; I 2  = 76% and 1.05 [1.05-1.06]; p < 0.01; I 2  = 0%, respectively) and the composite outcome (pooled aHR = 1.10 [1.06-1.15]; p < 0.01; I 2  = 0% and 1.06 [1.02-1.10]; p < 0.01; I 2  = 69%, respectively) for patients with HF. The subgroup analysis of HF patients with LVEF < 45% yielded similar results, with worsening in RV GLS and RV FWLS retaining strong association with the two outcomes., Conclusion: Echocardiographic RV GLS and RV FWLS appear to have powerful prognostic value across the range of HF., (© 2023. The Author(s).)

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, I 2  = 87%). Major or clinically relevant non-major bleeding (pOR 1.65, 95% CI 1.35-2.02, I 2  = 98%) and all-cause death (pOR 2.17, 95% CI 1.83-2.56, I 2  = 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., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Right ventricular (RV) dysfunction after acute myocardial infarction (AMI) is a recognized predictor of dismal prognosis. However, the most reliable RV index to predict mortality early after revascularization remains undetermined. This study aimed to explore the ability of RV global longitudinal strain (GLS) to predict inhospital mortality in patients with first AMI. All consecutive patients with first AMI were prospectively enrolled from March 2022 until February 2023. An echocardiogram was performed 24 hours after successful revascularization and RV GLS alongside conventional echocardiographic indexes were measured. Inhospital mortality was recorded. A total of 300 patients (age 61.2 ± 11.8 years, 74% male) were included in the study. RV GLS was the only RV performance index that differed significantly between anterior and inferior ST-segment-elevation patients with AMI (14.5 ± 5.2% vs 17.4 ± 5.1% respectively, p <0.001). After revascularization, 23 patients (7.7%) died in hospital. The model of Global Registry of Acute Coronary Event risk score and left ventricular ejection fraction, built for predicting inhospital mortality, significantly improved its prognostic performance only by the addition of RV GLS (chi-square value increase by 7.485, p = 0.006) compared with the other RV function indexes. RV GLS was independently associated with inhospital mortality (odds ratio 0.83, 95% confidence interval 0.71 to 0.97, p = 0.017) after adjustment for Global Registry of Acute Coronary Event risk score and left ventricular ejection fraction. Echocardiographic RV GLS measured 24 hours after revascularization in patients with first AMI outperformed conventional RV function indexes in predicting inhospital mortality., Competing Interests: Declaration of Competing Interest Dr. Delgado received speaker fees from Edwards Lifesciences, Medtronic, Novartis, and Philips and consulting fees from Edwards Lifesciences and Novo Nordisk. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: The CHA 2 DS 2 -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 CHA 2 DS 2 -VASc score over time (Delta CHA 2 DS 2 -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 CHA 2 DS 2 -VASc scores were used to extract the Delta CHA 2 DS 2 -VASc score. The stroke predicting accuracies of the baseline, follow-up, and Delta CHA 2 DS 2 -VASc scores were assessed through regression analyses., Results: The mean baseline, follow-up, and Delta CHA 2 DS 2 -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 CHA 2 DS 2 -VASc score ≥1, contrary to 40.1% of the stroke-free group. The stroke risk per 1-point increase of the CHA 2 DS 2 -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 CHA 2 DS 2 -VASc scores were more potent predictors of ischemic stroke compared to baseline., Conclusion: In atrial fibrillation patients, changes in CHA 2 DS 2 -VASc score over time were associated with the incidence of stroke. The improved predictability of follow-up and Delta CHA 2 DS 2 -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)., (© 2023. The Author(s).)

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.

Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease that has been long overlooked, but lately its independent association with adverse cardiovascular outcomes was recognized. The time point to intervene and repair the tricuspid valve is defined by the right ventricular (RV) dilation and dysfunction that comes up at a later stage. While guidelines favor tricuspid valve repair before severe RV dysfunction ensues, the definition of RV dysfunction in a universal manner remains vague. As a result, the candidates for transcatheter or surgical TR procedures are often referred late, when advanced RV dysfunction is established, and any derived procedural survival benefit is attenuated. Thus, it is of paramount importance to establish a universal means of RV function assessment in patients with TR. Conventional echocardiographic indices of RV function routinely applied have fundamental flaws that limit the precise characterization of RV performance. More recently, novel echocardiographic indices such as strain via speckle-tracking have emerged, demonstrating promising results in the identification of early RV damage. Additionally, evidence of the role of alternative imaging modalities such as cardiac computed tomography and cardiac magnetic resonance, for RV functional assessment in TR, has recently arisen. This review provides a systematic appraisal of traditional and novel multimodality indices of RV function in severe TR and aims to refine RV function assessment, designate future directions, and ultimately, to improve the outcome of patients suffering from severe TR.

Coronary artery disease (CAD) is multifactorial and strongly affected by genetic, epigenetic and environmental factors. Several studies have reported development of concomitant CAD in identical twins. We report a case in which a pair of Caucasian male monozygotic twins presented almost concomitantly with acute coronary syndrome (ACS) and had concordant coronary anatomy and identical site of occlusion. We performed a systematic literature review of PubMed, Web Of Science and Scopus databases from inception until 28 February 2023 of case reports/case series reporting the concomitant development of CAD in monozygotic twins. We found 25 eligible case reports with a total of 31 monozygotic twin pairs (including the case from our center) suffering from CAD and presenting (most of them simultaneously) with ACS (mean age of presentation: 45 ± 12 years, males: 81%). Coronary angiograms demonstrated lesion and anatomy concordance in 77% and 79% of the twin pairs, respectively. Screening for disease-related genetic mutations was performed in six twin pairs leading to the identification of five CAD-related genetic polymorphisms. This is the first systematic literature review of studies reporting identical twin pairs suffering from CAD. In summary, there is high concordance of coronary anatomy and clinical presentation between monozygotic twins. Future monozygotic twin studies-unbiased by age effects-can provide insights into CAD heritability being able to disentangle the traditional dyad of genetic and environmental factors and investigate the within-pair epigenetic drift.

Background: Acute myocardial infarction (AMI) remains a major cause of death worldwide. Survivors of AMI are particularly at high risk for additional cardiovascular events. Consequently, a comprehensive approach to secondary prevention is necessary to mitigate the occurrence of downstream complications. This may be achieved through a multiparametric tailored risk stratification by incorporating clinical, laboratory and echocardiographic parameters., Methods: The ''CLEAR-AMI Study'' (ClinicalTrials.gov Identifier: NCT05791916) is a non-interventional, prospective study including consecutive patients with AMI without a known history of coronary artery disease. All patients satisfying these inclusion criteria are enrolled in the present study. The rationale of this study is to refine risk stratification by using clinical, laboratory and novel echocardiographic biomarkers. All the patients undergo a comprehensive transthoracic echocardiographic assessment, including strain and myocardial work analysis of the left and right heart chambers, within 48 h of admission after coronary angiography. Their laboratory profile focusing on systemic inflammation is captured during the first 24 h upon admission, and their demographic characteristics, past medical history, and therapeutic management are recorded. The angioplasty details are documented, the non-culprit coronary lesions are archived, and the SYNTAX score is employed to evaluate the complexity of coronary artery disease. A 24-month follow-up period will be recorded for all patients recruited., Conclusion: The ''CLEAR-AMI" study is an ongoing prospective registry endeavoring to refine risk assessment in patients with AMI without a known history of coronary artery disease, by incorporating echocardiographic parameters, biochemical indices, and clinical and coronary characteristics in the acute phase of AMI.

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 age‑dependent diseases associated with higher thromboembolic and bleeding risks. The very elderly are under‑represented in oral anticoagulation (OAC) clinical trials. However, real‑world 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 DOAC‑treated 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 randomized‑level 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.

Objective: Temporal artery biopsy (TAB) remains the standard criterion for the diagnosis of giant cell arteritis (GCA). Temporal artery biopsy is suggested to be performed within 2 weeks from the initiation of corticosteroids. However, the effects of TAB timing on the sensitivity of its findings still warrant further investigation., Methods: We reviewed the medical records of patients with GCA from a tertiary medical center in Germany over an 8-year period., Results: We analyzed data from 109 patients with a median age of 76 years and a median time from glucocorticoid treatment to TAB of 4 days. Approximately 60% of biopsies were positive. Our analysis yielded a nonsignificant trend toward shorter duration of corticosteroid treatment in the TAB(+) group ( p = 0.06). A more than 7 days' duration of steroid treatment was independently linked with lower rates of positive TAB (adjusted odds ratio, 0.33; 95% confidence interval, 0.11-1.00)., Conclusion: We conclude that the duration of corticosteroid treatment seems to affect the positivity of TAB in patients with suspected GCA. Further larger studies are required to confirm the generalizability of our findings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Adverse ventricular remodeling is an inflexion point of disease progression in aortic stenosis (AS) and a major determinant of prognosis. Intervention before irreversible myocardial damage is of paramount importance to sustain favorable post-operative outcomes. Current guidelines recommend a left ventricular ejection fraction (LVEF)-based strategy to determine the threshold for intervention in AS. However, LVEF has several pitfalls: it denotes the left ventricular cavity volumetric changes and it is not suited to detecting subtle signs of myocardial damage. Strain has emerged as a contemporary imaging biomarker that describes intramyocardial contractile force, providing information on subclinical myocardial dysfunction due to fibrosis. A large body of evidence advocates its use to determine the switch from adaptive to maladaptive myocardial changes in AS, and to refine thresholds for intervention. Although mainly studied in echocardiography, studies exploring the role of strain in multi-detector row computed tomography and cardiac magnetic resonance are emerging. This review, therefore, summarizes contemporary evidence on the role of LVEF and strain imaging in AS prognosis, aiming to move from an LVEF-based to a strain-based approach for risk stratification and therapeutic decision-making in AS.

Magnetic nanoparticles (MNs) are typically used as contrast agents for magnetic resonance imaging or as drug carriers with a remotely controlled delivery to the tumor. However, they can also potentiate the action of anticancer drugs under the influence of applied constant magnetic (CMFs) and electromagnetic fields (EMFs). This review demonstrates the role of magneto-mechanochemical effects produced by MNs alone and loaded with anticancer agents (MNCs) in response to CMFs and EMFs for modulation of tumor redox state. The combined treatment is suggested to act by two mechanisms: spin-dependent electron transport propagates free radical chain reactions, while magnetomechanical interactions cause conformational changes in drug molecules loaded onto MNs and generate reactive oxygen species (ROS). By adjusting the parameters of CMFs and EMFs during the magneto-mechanochemical synthesis and subsequent treatment, it is possible to modulate ROS production and switch redox signaling involved in ERK1/2 and NF-κB pathways from initiation of tumor growth to inhibition. Observations of tumor volume in different animal models and treatment combinations reported a 6%-70% reduction as compared with conventional drugs. Despite these results, there is a general lack of research in magnetic nanotheranostics that link redox changes across multiple levels of organization in the tumor-bearing host. Further multidisciplinary studies with more focus on the relationship between the electron transport processes in biomolecules and their effects on the tumor-host interaction should accelerate the clinical translation of magnetic nanotheranostics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology., (© 2022 Wiley Periodicals LLC.)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Acute myocardial infarction (AMI) remains the leading cause of mortality worldwide. The majority of patients who suffer an AMI have a history of at least one of the standard modifiable risk factors (SMuRFs): smoking, hypertension, dyslipidemia, and diabetes mellitus. However, emerging scientific evidence recognizes a clinically significant and increasing proportion of patients presenting with AMI without any SMuRF (SMuRF-less patients). To date, there are no adequate data to define specific risk factors or biomarkers associated with the development of AMIs in these patients., Methods: The ''Beyond-SMuRFs Study'' is a prospective, non-interventional cohort trial designed to enroll patients with AMI and no previous coronary intervention history, who undergo coronary angiography in two academic hospitals in Thessaloniki, Greece. The rationale of the study is to investigate potential relations between SMuRF-less AMIs and the clinical, laboratory and imaging profile of patients, by comparing parameters between patients with and without SMuRFs. Complete demographic and comprehensive clinical data will be recorded, Venous blood samples will be collected before coronary angiography and the following parameters will be measured: total blood count, standard biochemistry parameters, coagulation tests, hormone levels, glycosylated hemoglobin, N- terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels- as well as serum levels of novel atherosclerosis indicators and pro-inflammatory biomarkers. Furthermore, all participants will undergo a complete and comprehensive transthoracic echocardiographic assessment according to a pre-specified protocol within 24 h from admission. Among others, 2D-speckle-tracking echocardiographic analysis of cardiac chambers and non-invasive calculation of myocardial work indices for the left ventricle will be performed. Moreover, all patients will be assessed for angiographic parameters and the complexity of coronary artery disease using the SYNTAX score. Multivariable linear and logistic regression models will be used to phenotypically characterize SMuRF-less patients and investigate independent clinical, laboratory, echocardiographic and angiographic biomarkers-predictors of SMuRF-less status in AMI.The first patient was enrolled in March 2022 and completion of enrollment is expected until December 2023., Discussion: The ''Beyond-SmuRFs'' study is an ongoing prospective trial aiming to investigate potential clinical, laboratory and imaging biomarkers associated with the occurrence of AMIs in SMuRF-less patients. The configuration of these patients' profiles could lead to the development of personalized risk-stratification models predicting the occurrence of cardiovascular events in SΜuRF-less individuals., Trial Registration: ClinicalTrials.gov Identifier: NCT05535582 / September 10, 2022., (© 2023. The Author(s).)

Background: Despite ongoing treatment advancements in chronic heart failure (HF), mortality and readmission rates remain high for patients hospitalized for decompensated acute HF. These patients represent a distinct HF group, which requires emergent echocardiographic evaluation in an attempt to provide optimal and individualized acute care. The role of serial advanced echocardiographic assessment in acute HF for risk stratification and treatment guidance has not been thoroughly explored., Methods: The "Beyond Myo-HF Study" is a prospective, non-interventional cohort trial designed to enroll acutely admitted patients with symptoms and/or signs of HF. The aim of this study is to investigate whether intrahospital changes of conventional and novel echocardiographic indices of myocardial function and congestion-related markers can predict early mortality, late mortality, and HF rehospitalization. As per the protocol, all patients undergo a pair of state-of-the-art echocardiographic assessments, with a rigorous protocol including speckle tracking analysis of all cardiac chambers and myocardial work analysis for the left and right ventricle, upon admission and pre-discharge. Their laboratory profile is captured at those two time-points, and their therapeutic management is recorded. Patients will be followed-up for a median period of 12 months after enrollment., Conclusions: The "Beyond Myo-HF" study is an ongoing, prospective trial aspiring to provide deep insight into the pathophysiology of acute HF, to enlighten the reverse cardiac functional and anatomical remodeling during hospitalization, and to recognize echocardiographic patterns capable of predicting adverse outcomes during and post decompensation of acute HF.

Objectives: Micro-computed tomography (micro-CT) is a novel, nondestructive, slide-free digital imaging modality that enables the acquisition of high-resolution, volumetric images of intact surgical tissue specimens. The aim of this systematic mapping review is to provide a comprehensive overview of the available literature on clinical applications of micro-CT tissue imaging and to assess its relevance and readiness for pathology practice., Methods: A computerized literature search was performed in the PubMed, Scopus, Web of Science, and CENTRAL databases. To gain insight into regulatory and financial considerations for performing and examining micro-CT imaging procedures in a clinical setting, additional searches were performed in medical device databases., Results: Our search identified 141 scientific articles published between 2000 and 2021 that described clinical applications of micro-CT tissue imaging. The number of relevant publications is progressively increasing, with the specialties of pulmonology, cardiology, otolaryngology, and oncology being most commonly concerned. The included studies were mostly performed in pathology departments. Current micro-CT devices have already been cleared for clinical use, and a Current Procedural Terminology (CPT) code exists for reimbursement of micro-CT imaging procedures., Conclusions: Micro-CT tissue imaging enables accurate volumetric measurements and evaluations of entire surgical specimens at microscopic resolution across a wide range of clinical applications., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 β = 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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The use of technological and chemical means aiming to achieve favorable weather conditions or reduce the risk of weather extremes is known as Weather Modification (WM). The United States of America, the People's Republic of China, Thailand, the United Arab Emirates, and Europe have employed WM in an effort to prevent hurricanes and storms, control precipitations, mitigate deforestation and drought, and enhance agriculture. Recently, the use of WM has been expanded toward decreasing air pollution and creating favorable weather conditions for major political and athletic events. The increasing significance and use of WM call for consideration upon its positive and negative effects on human health, close collaboration among health experts and WM decision makers, and relevant public health emergency contingency planning.

Abstract: Patients with atrial fibrillation (AF) often receive multiple medications daily. The purpose of this study was to examine the prognostic implications of polypharmacy in patients with AF. This is a retrospective post hoc analysis of 1113 AF patients, enrolled in a randomized trial during an acute hospitalization (MISOAC-AF, NCT02941978). The presence of polypharmacy (use of >4 drugs daily) was assessed at hospital discharge. Regression analyses were performed to identify clinical predictors of polypharmacy and compare the outcomes of patients with or without confirmed polypharmacy. The coprimary outcomes were all-cause and cardiovascular (CV) mortality. Among patients with polypharmacy, the difference in the risk of mortality was also assessed per each added drug as a numeric variable. Polypharmacy was found in 36.9% of participants. Dyslipidemia, coronary artery disease, lower left ventricular ejection fraction, and higher glomerular filtration rates were independent predictors of polypharmacy. Polypharmacy was an independent predictor for all-cause death (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.01-1.64) and CV death (aHR: 1.39, 95% CI: 1.05-1.84). Among patients with polypharmacy, each additional concomitant medication was independently associated with a 4% increased risk of all-cause mortality (aHR = 1.04, 95% CI: 1.00-1.08) and a 5% increased risk of CV mortality (aHR = 1.05, 95% CI: 1.00-1.10). Polypharmacy was common among patients with AF hospitalized in a tertiary hospital and was incrementally associated with higher rates of mortality., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Maternal pregestational diabetes mellitus (PGDM), type 1 or type 2, has been established as a potential risk factor for congenital heart disease (CHD). At the same time, the correlation between gestational diabetes mellitus (GDM) and increased risk of CHD has not been yet fully elucidated. The objective of this systematic review and meta-analysis (PROSPERO number: CRD42020182390) was to analyze the existing evidence on PGDM and to attempt to fill, to the best of our ability, the remaining knowledge gap in the association of GDM with CHD., Materials and Methods: Two authors have independently searched the Pubmed/Medline, Scopus, Cochrane, Web of Science, and Theses Global databases with keywords and Boolean operators. The search yielded 9333 relevant articles, which were later screened for eligibility. Original peer-reviewed (case-control or cohort) studies were included if they were published in English between 1997 and 2020. Thirteen studies on mothers with PGDM and seven studies on mothers with GDM were finally included in our meta-analysis to investigate the association of maternal diabetes with the risk of delivering a child with CHD. The selected studies were all assessed for their methodological quality using the Newcastle-Ottawa scale. Associations with p < .05 were considered statistically significant., Results: Our meta-analysis ( I 2 > 75%, total population: n  = 12,461,586) of 79,476 women with PGDM and 160,893 with GDM produced an odds ratio of 3.48 (2.36-4.61) and 1.55 (1.48-1.61), respectively. Additionally, we did not find any noticeable difference in the risk for CHD among diabetic women living in the USA and Europe. Nevertheless, it still needs to be clarified, whether or not the gestational diabetic population includes undiagnosed women with preexisting diabetes, which might account for the increased risk of delivering a child with CHD in women classified as suffering from GDM., Conclusion: While both GDM and PGDM seem to significantly increase the risk of CHD in comparison with the general population, PDGM appears to have a greater association with CHD, being correlated with a 3.5-fold increase in the risk of malformation. Preconceptional and gestational diabetes care are, therefore, essential to mitigate the adverse effect of hyperglycemia on fetal heart formation during pregnancy.

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), β-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 β-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 β-blockers and DAPT., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Digoxin is widely used in atrial fibrillation (AF) and heart failure (HF). However, current evidence regarding its association with clinical outcomes is conflicting., Aim: To investigate the relationship between digoxin therapy and adverse outcomes in patients with AF, with or without HF, in a contemporary AF cohort., Methods: We performed a retrospective analysis of data from 698 patients, who were followed over a median of 2.5 years. The primary outcome was all-cause mortality and the secondary outcome was all-cause hospitalization, in a time-to-event analysis. Propensity scores were used to derive matched populations, balanced on key baseline covariates. To limit potential confounding, inverse probability of treatment weighting (IPTW) analysis was performed., Results: Among patients with HF, 39 (10.5%) were administered digoxin at baseline, whereas 331 (89.5%) were not. Digoxin administration was not associated with an increased risk of death (hazard ratio (HR) in the digoxin group, 1.21; 95% Confidence Interval (CI), 0.69 to 2.13, p = 0.50) or hospitalization of any cause (HR 1.15; 95% CI, 0.67 to 1.96; p = 0.60). Among patients without HF, 11 (3.5%) were administered digoxin, with neutral effects on all-cause mortality (HR: 3.25; 95% CI, 0.98 to 10.70), p = 0.06) and all-cause hospitalization (HR, 1.15; 95% CI, 0.67 to 1.96, p = 0.60). Qualitatively, consistent results were observed using IPTW., Conclusions: Among patients with AF, digoxin administration was not associated with an increased risk of death and hospitalization for any cause, irrespective of HF status., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

The prognostic value of health status metrics in patients with adult congenital heart disease (ACHD) and atrial arrhythmias is unclear. In this retrospective cohort study of an ongoing national, multicenter registry (PROTECT-AR, NCT03854149), ACHD patients with atrial arrhythmias on apixaban are included. At baseline, health metrics were assessed using the physical component summary (PCS), the mental component summary (MCS) of the Short-Form-36 (SF-36) Health Survey, and the modified European Heart Rhythm Association (mEHRA) score. Patients were divided into groups according to their SF-36 PCS and MCS scores, using the normalized population mean of 50 on the PCS and MCS as a threshold. The primary outcome was the composite of mortality from any cause, major thromboembolic events, major/clinically relevant non-major bleedings, or hospitalizations. Multivariable Cox-regression analyses using clinically relevant parameters (age greater than 60 years, anatomic complexity, ejection fraction of the systemic ventricle, and CHA₂DS₂-VASc and HAS-BLED scores) were performed to examine the association of health metrics with the composite outcome. Over a median follow-up period of 20 months, the composite outcome occurred in 50 of 158 (32%) patients. The risk of the outcome was significantly higher in patients with SF-36 PCS ≤ 50 compared with those with PCS > 50 (adjusted hazard ratio (aHR), 1.98; 95% confidence interval [CI], 1.02−3.84; p = 0.04) after adjusting for possible confounders. The SF-36 MCS ≤ 50 was not associated with the outcome. The mEHRA score was incrementally associated with a higher risk of the composite outcome (aHR = 1.44 per 1 unit increase in score; 95% CI, 1.03−2.00; p = 0.03) in multivariable analysis. In ACHD patients with atrial arrhythmias, the SF-36 PCS ≤ 50 and mEHRA scores predicted an increased risk of adverse events.

Background: There is limited "real-world" data on the prognostic role of gender in comorbid atrial fibrillation (AF) and coronary artery disease (CAD)., Methods: In this post-hoc analysis of the MISOAC-AF randomized trial (NCT: 02941978), consecutive patients with AF and CAD who were discharged from the cardiology ward between 2015 and 2018 were included. Multivariable Cox-regression analysis was performed for all-cause mortality and cardiovascular (CV) mortality. Competing-risk analysis was performed for the outcomes of stroke or systemic embolism, major bleeding, AF- or heart failure (HF)-related hospitalization, adjusted for the competing risk of all-cause death., Results: Of 1098 patients with AF, 461 patients with comorbid CAD were analyzed. Women were older and more likely to have a history of diabetes mellitus and valvular heart disease, while men were more likely to have a history of smoking or myocardial infarction. Over a median follow-up of 31 months, 143 (43.4%) men and 71 (53.7%) women died. Women were at a higher risk for all-cause mortality (adjusted hazard ration [aHR] 1.65; 95% confidence interval [CI] 1.14-2.38) and stroke or systemic embolism (aHR 3.52; 95% CI 1.46-8.49) compared to men. The risks of CV mortality, major bleeding, AF-related hospitalization, and HF-related hospitalization were similar between genders., Conclusions: In recently hospitalized patients with AF and comorbid CAD, the female gender was independently associated with increased all-cause mortality and thromboembolic events.