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Abstract Background Platelets play a key role in the natural history of aortic stenosis (AS) and after transcatheter aortic valve implantation (TAVI). An echo-based staging system stratifies patients with severe AS into 5 groups according to the associated cardiac damage phenotype. We aimed to correlate these AS stages with platelet indices in post-TAVI patients. Methods Patients with severe AS who underwent TAVI and were admitted to intensive cardiac care unit (ICCU) were prospectively identified and divided into 5 groups according to extra-valvular cardiac damage [no extravalvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage (Stage 4)]. Baseline characteristics and complete blood count including mean platelet volume (MPV) and immature platelet fraction (IPF) were collected within 2 h after the procedure and analyzed in relation to aortic stenosis staging. Results A total of 220 patients were included. The mean age was 81 years old and 112 (50.9%) were female. Two (1%) patients were classified in stage 0; 34 (15%) in stage 1; 48 (22%) in stage 2; 49 (22%) in stage 3 and 87 (40%) in stage 4. Higher mean MPV values were correlated with higher AS staging (10.8 fL, 11 fL, 11.3 fL and 10.8 fL in stages 1, 2, 3 and 4, respectively, P = 0.02) as well as lower hemoglobin values (12 mg/dl, 11.6 mg/dl, 11 mg/dl and 11.3 mg/dl in stages 1, 2, 3 and 4, respectively P = 0.04). Mean IPF values were 5.3%, 5.58%, 5.57% and 4.83% in stage 1, 2, 3 and 4, respectively (P = 0.4). In a multivariate logistic regression model only MPV (OR = 2.6, P = 0.03) and body mass index (BMI) (OR = 1.17, P = 0.004) were correlated with higher staging (0–3) of AS. Conclusions Although IPF and MPV levels increased in stages 0–3, there was a decrease in indices in stage 4, (probably due to bone marrow dysfunction) in this end-stage population. Higher levels of MPV and lower levels of hemoglobin were independently correlated with higher stages (0–3) of AS.

There is a number of conflicting data regarding electrocardiographic predictors of atrial fibrillation, among which extrasystoles (ES) stand out, but there is no reliable data on which extrasystoles variants may be considered as a risk factor. To identify the relationship between extrasystoles and atrial fibrillation, we have analyzed 3927 publications, from which we identified 46 works relevant for the topic. The data obtained allows us to consider extrasystole as one of the main predictors of the development of atrial fibrillation. An increase in the number of supraventricular and ventricular ES in the anamnesis of patients with atrial fibrillation indicates their relationship.

Chronic coronary syndromes (CCS) comprehend a wide spectrum of conditions related to coronary artery disease (CAD). CCS definition includes either those patients who experienced an acute coronary syndrome such as myocardial infarction (MI) or unstable angina (UA), and the ones in which CAD has been detected through screening. This aspect creates a potential issue in differentiating medical treatments and modalities and timing for follow up. Another critical aspect is represented by the gap between American and European guidelines, which have been most recently updated respectively in 2023 and 2019. Furthermore, it is not clear what kind of patient must be screened for the detection for CAD and how to manage the eventual follow-up. Lastly, the latest guidelines are not clear for the choice of medical therapy and which are the patients who benefit the most from the eventual revascularization. The aim of this review is to analyze the issues related to the incongruities about CCS and propose potential options for adequate treatment and follow up.

Background Minimally invasive mitral valve repair has a favorable risk–benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge‐to‐edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR). Methods and Results We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naïve patients from those with prior TEER or (SMVR). Inhospital and long‐term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naïve to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow‐up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P>0.05). Propensity score–adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09–0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naïve, TEER, and SMVR groups (all P>0.05). Conclusions In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR.

Abstract Background and aims Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia. Methods PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867). Results Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79–0.95), myocardial infarction (OR 0.76, 95% CI 0.64–0.88) and unstable angina (OR 0.69, 95% CI 0.54–0.88) compared to control, over a median follow up of 87 (15–162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]–22.42,95% CI − 24.02% to − 20.82%), total cholesterol (− 16.50%,95% − 19.21% to − 13.79%), Apo-B lipoprotein (− 19.55%, − 22.68% to − 16.42%) and high-sensitivity CRP (− 27.83%, − 31.71% to − 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27–1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy. Conclusions The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.

Abstract Aims Interleukin‐1 (IL‐1) blockade may improve exercise capacity in patients with heart failure (HF) patients. The extent of the improvement and its persistence beyond discontinuation of IL‐1 blockade is unknown. Methods and results The primary objective was to determine changes in cardiorespiratory fitness and cardiac function on‐treatment with IL‐1 blocker, anakinra, and off‐treatment, after treatment cessation. We performed cardiopulmonary exercise testing, Doppler echocardiography, and biomarkers in 73 patients with HF, 37 (51%) females, 52 (71%) Black–African–American, before and after treatment with anakinra 100 mg daily. In a subset of 46 patients, testing was also repeated after treatment cessation. Quality of life was assessed in each patient using standardized questionnaires. Data are presented as median and interquartile range. Treatment with anakinra for 4 [2–12] weeks was associated with a significant improvement in high‐sensitivity C‐reactive protein (from 6.2 [3.3–15.4] to 1.4 [0.8–3.4] mg/L, P

Psychiatric conditions, such as depression, anxiety, bipolar disorder, and schizophrenia, are increasingly recognized as significant risk factors for cardiovascular disease (CVD). This review systematically analyzes evidence from various databases to provide a comprehensive understanding of the impact of psychiatric illnesses on the incidence, management, and prognosis of CVD. Key findings suggest a bidirectional relationship between psychiatric disorders and CVD, indicating that mental health conditions can predispose individuals to CVD, while CVD can exacerbate or trigger psychiatric symptoms. The review explores the underlying mechanisms of these associations, including behavioral factors, stress responses, and medication side effects. It also examines the challenges in managing CVD patients with comorbid psychiatric conditions, emphasizing the importance for integrated care approaches. This review underscores the necessity of considering mental health as an integral component of cardiovascular care and calls for further research to develop tailored management strategies for these complex conditions, ultimately aiming to improve patient outcomes and quality of life. This comprehensive analysis provides valuable insights for future investigations and guides clinicians in optimizing care for patients with both psychiatric and cardiovascular conditions.

Abstract Cangrelor, the first intravenous P2Y12 inhibitor (P2Y12-I), has been approved on the basis of three large RCTs from the CHAMPION program which nevertheless have been criticized for the low bleeding risk of the enrolled patients, the large quote of chronic coronary syndromes, and the use of Clopidogrel as control arm even in the setting of acute coronary syndromes (ACS). We sought to investigate, in the setting of ACS, the comparative performance of Cangrelor in terms of in-hospital ischemic and haemorrhagic outcomes compared with the current gold-standard of oral P2Y12-I. The study retrospectively enrolled 686 consecutive patients admitted to the Divisions of Cardiology of Policlinico of Bari and L. Bonomo Hospital of Andria for ACS and treated with percutaneous coronary intervention. The study population was divided according to the P2Y12-I treatment strategy in two groups: patients given an oral P2Y12-I and patients receiving Cangrelor in the cath lab followed by an oral P2Y12-I. Clinical endpoints included death, ischemic and bleeding events occurring during hospital stay. Cangrelor treated patients presented higher clinical risk profile at presentation and faced higher death rate. However, after PS matching, in-hospital mortality resulted comparable between the groups and Cangrelor use was associated with reduced in-hospital definite stent thrombosis (p = 0.03). Data from our real-world registry highlight that, in the setting of ACS, Cangrelor is prevalently used in patients with very challenging clinical presentations. The adjusted analysis provides for the first time promising data on stent thrombosis reduction associated with Cangrelor use.

In the recently published clinical practice guidelines by the American Heart Association/American College of Cardiology, a central part has been dedicated to the revascularization, as new evidence came up increasing our knowledge on this relevant topic. Providing symptom relief, preventing major adverse cardiovascular events and improving long-term survival is ultimately the aim of coronary revascularization. Such ambitious goals should be actively pursued, as suggested thoroughly in the text, sharing the clinical decision making with the patient. Aim of this commentary is to highlight critical messages from the recent guideline, especially in complex clinical scenarios such as angiographically intermediate coronary artery stenoses, significant left main disease and multivessel disease with severe left ventricular dysfunction.

Aortic stenosis (AS) is the most frequent form of valvular heart disease in developed countries, and severe AS is a major cause of morbidity and mortality in the elderly. Since many of these patients often have a high or prohibitive risk for surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI) has emerged as an established therapy and is now becoming a common practice, even in low-risk patients. As severe AS and coronary artery disease (CAD) are often concomitant, a matter of debate is whether, how, and when to treat coexisting CAD. The aim of this commentary is to analyze the rationale for the diagnostic evaluation and management of CAD in TAVI candidates, as proposed by the recent EAPCI/ESC consensus statement.

Background Postoperative atrial fibrillation (POAF) is the most frequent complication of cardiac surgery. Despite clinical and economic implications, ample variability in POAF assessment method and definition exist across studies. We performed a study‐level meta‐analysis to evaluate the influence of POAF assessment method and definition on its incidence and association with clinical outcomes. Methods and Results A systematic literature search was conducted to identify studies comparing the outcomes of patients with and without POAF after cardiac surgery that also reported POAF assessment method. The primary outcome was POAF incidence. The secondary outcomes were in‐hospital mortality, stroke, intensive care unit length of stay, and postoperative length of stay. Fifty‐nine studies totaling 197 774 patients were included. POAF cumulative incidence was 26% (range: 7.3%–53.1%). There were no differences in POAF incidence among assessment methods (27%, [range: 7.3%–53.1%] for continuous telemetry, 27% [range: 7.9%–50%] for telemetry plus daily ECG, and 19% [range: 7.8%–42.4%] for daily ECG only; P>0.05 for all comparisons). No differences in in‐hospital mortality, stroke, intensive care unit length of stay, and postoperative length of stay were found between assessment methods. No differences in POAF incidence or any other outcomes were found between POAF definitions. Continuous telemetry and telemetry plus daily ECG were associated with higher POAF incidence compared with daily ECG in studies including only patients undergoing isolated coronary artery bypass grafting. Conclusions POAF incidence after cardiac surgery remains high, and detection rates are variable among studies. POAF incidence and its association with adverse outcomes are not influenced by the assessment method and definition used, except in patients undergoing isolated coronary artery bypass grafting.

Background There is little evidence about the prognostic role of mitral regurgitation (MR) in patients with low‐flow, low‐gradient aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the prevalence and outcome implications of MR severity in patients with low‐flow, low‐gradient aortic stenosis undergoing TAVR, and to evaluate whether MR improvement after TAVR could influence clinical outcome. Methods and Results This study included consecutive patients with low‐flow, low‐gradient aortic stenosis undergoing TAVR at 2 Italian high‐volume centers. The study population was categorized according to the baseline MR severity and to the presence of MR improvement at discharge. The primary outcome was the composite of all‐cause death and hospitalization for worsening heart failure up to 1 year. The study included 268 patients; 57 (21%) patients showed MR >2+. Patients with MR >2+ showed a lower 1‐year survival free from the primary outcome (P2+ was an independent predictor of the primary outcome (P2+, MR improvement was reported in 24 (44%) cases after TAVR. The persistence of MR was associated with a significantly reduced survival free from the primary outcome, all‐cause death, and heart failure hospitalization up to 1 year. Conclusions In this study, the presence of moderately severe to severe MR in patients with low‐flow, low‐gradient aortic stenosis undergoing TAVR portends a worse clinical outcome at 1 year. TAVR may improve MR severity in nearly half of the patients, resulting in a potential outcome benefit after discharge.

Abstract Background Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF. Method We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes. Discussion The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF. Trial registration: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.

Introduction Long-term follow-up after an acute coronary syndrome (ACS) presents a crucial challenge due to the high residual cardiovascular risk and the potential for major bleeding events. Although several treatment strategies are available, this article focuses on patients who have undergone percutaneous coronary intervention (PCI) for ACS, which represent a frequent clinical situation. This position paper aims to support physicians in daily practice to improve the management of ACS patients. Material and methods A group of recognized international and French experts in the field, provides an overview of current evidence-based recommendations − supplemented by expert opinion where such evidence is lacking − and a practical guide for the management of patients with ACS after hospital discharge. Results The International Collaborative Group underlines the need of a shared collaborative approach, and a care plan individualized to the patient’s risk profile for both ischemia and bleeding. Each follow-up appointment should be viewed as an opportunity to optimize the personalized approach, to reduce adverse clinical outcomes and improve quality of life. As risks – both ischaemic and haemorrhagic – evolve over time, the risk–benefit balance should be assessed in an ongoing dynamic process to ensure that patients are given the most suitable treatment at each time point. Conclusions This Expert Opinion aims to help clinicians with a practical guide underlying the proven strategies and the remaining gaps of evidence to optimize the management of coronary patients.

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease. Patients who have undergone surgical repair of ToF constitute one of the largest groups of congenital heart disease patients surviving into adulthood. The history of ToF surgical techniques has evolved through the years, starting from the early 1930s. In this context, many leading figures are acknowledged as pioneers in cardiothoracic surgery. There is one who has struggled to obtain fair recognition of his work: Vivien T. Thomas. This young Afro-American man, because of his origin and economic possibilities, had to wait more than 30 years before being recognized his pivotal role in the groundbreaking first open-heart pediatric surgery of ToF.

Abstract Transcatheter aortic valve implantation (TAVI) requires thorough preprocedural planning with non-invasive imaging, including computed tomography (CT). The plethora of details obtained with thoraco-abdominal CT represents a challenge for accurate and synthetic decision-making. We devised and tested a comprehensive score suitable to summarize CT exams when planning TAVI. An original comprehensive scoring system (TAVI-CT score) was devised, including details on cardiac, aortic, iliac and femoral artery features. The score was applied to a prospectively collected series of patients undergoing TAVI at our institution, driving decision making on access and prosthesis choice. Different TAVI-CT score groups were compared in terms of procedural success, acute complications, and early clinical outcomes. We included a total of 200 undergoing TAVI between February 2020 and May 2021, with 74 (37.0%) having a low (0–2) TAVI-CT score, 50 (25.0%) having a moderate (3) TAVI-CT score, and 76 (38.0%) having a high (≥ 4) TAVI-CT score. Male gender was the only non-CT variable significantly associated with the TAVI-CT score (p = 0.001). As expected, access choice differed significantly across TAVI-CT scores (p = 0.009), as was device choice, with Portico more favored and Allegra less favored in the highest TAVI-CT score group (p = 0.036). Acute outcomes were similar in the 3 groups, including device and procedural success rates (respectively p = 0.717 and p = 1). One-month follow-up showed similar rates of death, myocardial infarction, stroke, and bleeding, as well as of a composite safety endpoint (all p > 0.05). However, vascular complications were significantly more common in the highest TAVI-CT score group (p = 0.041). The TAVI-CT score is a simple scoring system that could be routinely applied to CT imaging for TAVI planning, if the present hypothesis-generating findings are confirmed in larger prospective studies.

Abstract Non-ST-elevation acute coronary syndrome (NSTE-ACS) affects millions of patients. Although an invasive strategy can improve survival, the optimal treatment [i.e., percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] is not clear. We performed a meta-analysis of studies reporting outcomes between PCI and CABG in patients with NSTE-ACS. MEDLINE, EMBASE and Cochrane Library were assessed. The primary outcome was long-term mortality. Inverse variance method and random model were performed. We identified 13 observational studies (48,891 patients). No significant difference was found in the primary endpoint [CABG vs. PCI, incidence rate ratio (IRR) 0.93, 95% confidence interval (CI) 0.70; 1.23]. CABG was associated with lower long-term major adverse cardiovascular events (MACE) (IRR 0.64, 95% CI 0.54; 0.76) and lower long-term re-revascularization (IRR 0.37, 95% CI 0.30; 0.47). There was no significant difference in long-term myocardial infarction (CABG vs. PCI, IRR 0.96, 95% CI 0.50; 1.84) and peri-operative mortality (CABG vs. PCI, odds ratio 1.36, 95% CI 0.94; 1.95). For the treatment of NSTE-ACS, CABG and PCI are associated with similar rates of long-term mortality and myocardial infarction. CABG is associated with lower rates of long-term MACE and re-revascularization. Randomized comparisons in this setting are necessary.

Purpose: The purpose of this review is to evaluate the effect of resistance training (RT) as a unique intervention on muscle strength, body composition, and immune-inflammatory markers in people living with HIV (PLHIV). Methods: The searches were conducted in seven databases and included published randomized clinical trials that assessed the effect of RT vs. no exercise on muscle strength, body composition, and immune-inflammatory markers in PLHIV until June 2021. Random effects meta-analyses of mean differences (MD) and their 95% confidence intervals (CI) were performed, and the effect size was estimated by Hedges’ g test. Results: Seven RCTs were included (n= 258 PLHIV) and the study duration lasted between six and 24 weeks. In comparison to no exercise, RT improved muscle strength in bench press (MD 10.69 kg, 95%IC 3.44 to 17.93, p= 0.004, g =2.42) and squat (MD 22.66 kg, 95%IC 7.82 to 37.50, p= 0.003, g = 3.8) exercises, lean body mass (MD 2.96 kg, 95%CI 0.98 to 4.94, p= 0.003, g = 1.99), fat body mass(MD −2.67 kg; 95%CI −4.95 to −0.39, p= 0.02, g=-0.99), body fat percentage (MD −3.66%, 95%CI −6.04 to −1.29, p= 0.003, g=-1.99) and CD4+ cells count(MD 100.15 cells/mm3, 95%CI 12.21 to 188.08, p = 0.03, g = 2.91) in PLHIV. There was no effect of RT on IL-6 (MD −1.18 pg/mL, 95%CI −3.71 to 1.35, p = 0.36, g = 0.001) and TNF-α (MD −4.76 pg/mL, 95%CI −10.81 to 1.29, p = 0.12, g=-1.3) concentrations in PLHIV. Conclusions: RT as a unique intervention improves muscle strength, body composition and CD4+ count cells in PLHIV.

BackgroundA severe prosthesis-patient mismatch (PPM) is associated with adverse outcomes following transcatheter aortic valve replacement (TAVR) for de novo aortic stenosis or a failed surgical bioprosthesis. The impact of severe PPM in patients undergoing TAV-in-TAVR is unknown.AimWe sought to investigate the incidence and 1-year outcomes of different grades of PPM in patients undergoing TAV-in-TAVR.Materials and methodsThe TRANSIT-PPM is an international registry, including cases of degenerated TAVR treated with a second TAVR. PPM severity, as well as in-hospital, 30-day, and 1-year outcomes were defined according to the Valve Academic Research Consortium-3 (VARC-3) criteria.ResultsAmong 28 centers, 155 patients were included. Severe PPM was found in 6.5% of patients, whereas moderate PPM was found in 14.2% of patients. The rate of severe PPM was higher in patients who underwent TAV-in-TAVR with a second supra-annular self-expanding (S-SE) TAVR (10%, p = 0.04). Specifically, the rate of severe PPM was significantly higher among cases of a SE TAVR implanted into a balloon-expandable (BE) device (19%, p = 0.003). At 1-year follow-up, the rate of all-cause mortality, and the rate of patients in the New York Heart Association (NYHA) class III/IV were significantly higher in the cohort of patients with severe PPM (p = 0.016 and p = 0.0001, respectively). Almost all the patients with a severe PPM after the first TAVR had a failed < 23 mm BE transcatheter heart valve (THV): the treatment with an S-SE resolved the severe PPM in the majority of the cases.ConclusionAfter TAV-in-TAVR, in a fifth of the cases, a moderate or severe PPM occurred. A severe PPM is associated with an increased 1-year all-cause mortality.Clinical trial registration[https://clinicaltrials.gov], identifier [NCT04500964].

IntroductionVery limited data exist on normal age-related ECG variations in adolescents and no data have been published regarding the ECG anomalies induced by intensive training, which are relevant in pre-participation screening for sudden cardiac death prevention in the adolescent athletic population. The purpose of this study was to establish normal age-related electrocardiographic measurements (P wave duration, PR interval, QRS duration, QT, and QTc interval) grouped according to 2-year age intervals.MethodsA total of 2,151 consecutive healthy adolescent Soccer athletes (trained for a mean of 7.2 ± 1.1 h per week, 100% male Caucasians, mean age 12.4 ± 1.4 years, range 7–18) underwent pre-participation screening, which included ECG and transthoracic echocardiography in a single referral center.ResultsTheir heart rate progressively slowed as age increased (p < 0.001, ranging from 80.8 ± 13.2 to 59.5 ± 10.2 bpm), as expected. The P wave, PR interval, and QRS duration significantly increased in older age classes (p = 0.019, p = 0.001, and p < 0.001, respectively), and after Bonferroni's correction, the difference remained significant in all age classes for QRS duration. The QTc interval diminished progressively with increasing age (p = 0.003) while the QT interval increased progressively (p < 0.001).ConclusionsSignificant variations in the normal ECG characteristics of young athletes exist between different age groups related to increasing age and training burden, thus, age-specific reference values could be adopted, as already done for echocardiographic measurements, and may help to further discriminate potentially pathologic conditions.

Cardiotoxic therapies, whether chemotherapeutic or antibiotic, represent a burden for patients who may need to interrupt life-saving treatment because of serious complications. Cardiotoxicity is a broad term, spanning from forms of heart failure induction, particularly left ventricular systolic dysfunction, to induction of arrhythmias. Nanotechnologies emerged decades ago. They offer the possibility to modify the profiles of potentially toxic drugs and to abolish off-target side effects thanks to more favorable pharmacokinetics and dynamics. This relatively modern science encompasses nanocarriers (e.g., liposomes, niosomes, and dendrimers) and other delivery systems applicable to real-life clinical settings. We here review selected applications of nanotechnology to the fields of pharmacology and cardio-oncology. Heart tissue-sparing co-administration of nanocarriers bound to chemotherapeutics (such as anthracyclines and platinum agents) are discussed based on recent studies. Nanotechnology applications supporting the administration of potentially cardiotoxic oncological target therapies, antibiotics (especially macrolides and fluoroquinolones), or neuroactive agents are also summarized. The future of nanotechnologies includes studies to improve therapeutic safety and to encompass a broader range of pharmacological agents. The field merits investments and research, as testified by its exponential growth.

Background Quality of the peer‐review process has been tested only in small studies. We describe and summarize the randomized trials that investigated interventions aimed at improving peer‐review process of biomedical manuscripts. Methods and Results All randomized trials comparing different peer‐review interventions at author‐, reviewer‐, and/or editor‐level were included. Differences between traditional and intervention‐modified peer‐review processes were pooled as standardized mean difference (SMD) in quality based on the definitions used in the individual studies. Main outcomes assessed were quality and duration of the peer‐review process. Five‐hundred and seventy‐five studies were retrieved, eventually yielding 24 randomized trials. Eight studies evaluated the effect of interventions at author‐level, 16 at reviewer‐level, and 3 at editor‐level. Three studies investigated interventions at multiple levels. The effects of the interventions were reported as mean change in review quality, duration of the peer‐review process, acceptance/rejection rate, manuscript quality, and number of errors detected in 13, 11, 5, 4, and 3 studies, respectively. At network meta‐analysis, reviewer‐level interventions were associated with a significant improvement in review quality (SMD, 0.20 [0.06 to 0.33]), at the cost of increased duration of the review process (SMD, 0.15 [0.01 to 0.29]), except for reviewer blinding. Author‐ and editor‐level interventions did not significantly impact peer‐review quality and duration (respectively, SMD, 0.17 [−0.16 to 0.51] and SMD, 0.19 [−0.40 to 0.79] for quality, and SMD, 0.17 [−0.16 to 0.51] and SMD, 0.19 [−0.40 to 0.79] for duration). Conclusions Modifications of the traditional peer‐review process at reviewer‐level are associated with improved quality, at the price of longer duration. Further studies are needed. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020187910.

Smoking is still a major cardiovascular risk factor, despite many public awareness campaigns and dedicated interventions. Recently, modified risk products (MRP), e.g., heat-not-burn cigarettes (HNBCs), have been introduced as surrogates of traditional combustion cigarettes (TCCs). Although these products are promoted as healthier than TCCs, few studies have been conducted to assess it. This work is a sex-focused sub-study of a prospective observational study in which apparently healthy chronic TCC smokers were age-matched with regular HNBC users. Blood samples were collected for biochemical assays and blood pressure and flow-mediated dilation (FMD) were measured. Out of 60 subjects, 33 (55%) were women, and 27 (45%) men, with 11 (33%) vs. 9 (33%) non-smokers, respectively, 10 (30%) vs. 10 (37%) TCC smokers, and 12 (36%) vs. 8 (30%) HNBC smokers (p = 0.946). Bivariate and multivariable analyses showed no statistically significant between-sex differences in NO, H2O2, sCD40L, sNox2-dp, sP-selectin, platelet aggregation, cotinine or FMD, overall, in non-smokers, in TCC smokers, or in HNBC smokers (all p > 0.05). HNBCs appeared safer than TCCs when focusing on Nox2-dp (p = 0.026) and sP-selectin (p = 0.050) but had similar levels of the other measured markers. In conclusion, HNBCs have similar detrimental effects on women and men’s oxidative stress (H2O2: p = 0.49; sNox2-dp: p = 0.31) and platelet activation (sP-selectin: p = 0.33; platelet aggregation p = 0.87).

Epicardial adipose tissue (EAT) is correlated with endothelial dysfunction, metabolic syndrome, increased mortality and recent studies showed a possible association with the increased risk of stroke. We performed a systematic review of studies evaluating the association between EAT and stroke. Eighty studies met the inclusion criteria and were consequently analyzed. The review had Five main findings. First, the increased epicardial fat thickness (EFT) may be associated with the stroke episode. Second, regardless of the imaging method (echocardiography, MRI, and CT) this association remains. Third, the association of metabolic syndrome and atrial fibrillation seems to increase the risk of stroke. Fourth, this systematic review was considered as low risk of bias. Despite being unable to establish a clear association between EAT and stroke, we have organized and assessed all the research papers on this topic, analyzing their limitations, suggesting improvements in future pieces of research and pointing out gaps in the literature. Furthermore, the mechanistic links between increased EAT and stroke incidence remains unclear, thus, further research is warranted.

Background Several randomized trials have compared the patency of coronary artery bypass conduits. All of the published studies, however, have performed pairwise comparisons and a comprehensive evaluation of the patency rates of all conduits has yet to be published. We set out to investigate the angiographic patency rates of all conduits used in coronary bypass surgery by performing a network meta‐analysis of the current available randomized evidence. Methods and Results A systematic literature search was conducted for randomized controlled trials comparing the angiographic patency rate of the conventionally harvested saphenous vein, the no‐touch saphenous vein, the radial artery (RA), the right internal thoracic artery, or the gastroepiploic artery. The primary outcome was graft occlusion. A total of 4160 studies were retrieved of which 14 were included with 3651 grafts analyzed. The weighted mean angiographic follow‐up was 5.1 years. Compared with the conventionally harvested saphenous vein, both the RA (incidence rate ratio [IRR] 0.54; 95% CI, 0.35–0.82) and the no‐touch saphenous vein (IRR 0.55; 95% CI, 0.39–0.78) were associated with lower graft occlusion. The RA ranked as the best conduit (rank score for RA 0.87 versus 0.85 for no‐touch saphenous vein, 0.23 for right internal thoracic artery, 0.29 for gastroepiploic artery, and 0.25 for the conventionally harvested saphenous vein). Conclusions Compared with the conventionally harvested saphenous vein, only the RA and no‐touch saphenous vein grafts are associated with significantly lower graft occlusion rates. The RA ranks as the best conduit. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020164492.

Background The role of microRNAs dysregulation in tobacco cigarette smoking–induced vascular damage still needs to be clarified. We assessed the acute effects of tobacco cigarette smoking on endothelial cell‐related circulating microRNAs in healthy subjects. In addition, we investigated the potential role of microRNAs in smoking‐dependent endothelial cell damage. Methods and Results A panel of endothelial‐related microRNAs was quantified in healthy subjects before and after smoking 1 tobacco cigarette. Serum levels of miR‐155 were found to be significantly increased shortly after smoking. We also observed a progressive and significant miR‐155 accumulation in culture media of human endothelial cells after 30 minutes and up to 4 hours of cigarette smoke condensate treatment in vitro without evidence of cell death, indicating that miR‐155 can be released by endothelial cells in response to smoking stress. Cigarette smoke condensate appeared to enhance oxidative stress and impair cell survival, angiogenesis, and NO metabolism in human endothelial cells. Notably, these effects were abrogated by miR‐155 inhibition. We also observed that miR‐155 inhibition rescued the deleterious effects of cigarette smoke condensate on endothelial‐mediated vascular relaxation and oxidative stress in isolated mouse mesenteric arteries. Finally, we found that exogenous miR‐155 overexpression mimics the effects of smoking stress by inducing the upregulation of inflammatory markers, impairing angiogenesis and reducing cell survival. These deleterious effects were associated with downregulation of vascular endothelial growth factor and endothelial NO synthetase. Conclusions Our results suggest that miR‐155 dysregulation may contribute to the deleterious vascular effects of tobacco smoking.

Background The ART (Arterial Revascularization Trial) showed no difference in survival at 10 years between patients assigned to the single versus bilateral internal thoracic artery grafting strategies. This finding is in contrast with the results of most observational studies, where the use of 2 internal thoracic arteries has been associated with improved survival. Methods and Results We selected propensity‐matched studies from the most comprehensive observational meta‐analysis on the long‐term outcomes of patients receiving 1 versus 2 internal thoracic arteries. Individual participant survival data from each study and the ART were reconstructed using an iterative algorithm that was applied to solve the Kaplan‐Meier equations. The reconstructed individual participant survival data were aggregated to obtain combined survival curves and Cox regression hazard ratios with 95% CIs. Individual participant survival data were obtained from 14 matched observational studies (24 123 patients) and the ART. The 10‐year survival of the control group of ART was significantly higher than that of the matched observational studies (hazard ratio, 0.86; 95% CI, 0.80–0.93). The 10‐year survival of the experimental group of ART was significantly lower than that of the bilateral internal thoracic artery group of the observational studies (hazard ratio, 1.11; 95% CI, 1.03–1.20). Conclusions Both the improved outcome of the control arm and the lower beneficial effect of the intervention had played a role in the difference between observational evidence and ART.

The treatment of acute myocardial infarction is early revascularization. Heart failure and cardiogenic shock may complicate acute myocardial infarction despite applying the best available strategy. Levosimendan is a relatively new drug to treat heart failure with a peculiar mechanism of action: calcium sensitization of myocardial fibres. Levosimendan has a direct inotropic effect but also pleiotropic effects; through the K+ATP channel’s opening, it also has a vasodilator effect which may participate concretely in the global effects of the drug. The focus of the literature is on the anti-heart failure and anti-cardiogenic shock properties of Levosimendan, but it may have effects also preventing the development of myocardial insufficiency in acute myocardial infarction. The aim of the meta-analysis is to evaluate the effect of Levosimendan on acute myocardial infarction in placebo-controlled trials. Based on the eight studies selected, we found a beneficial effect of Levosimendan on acute and long-term mortality of patients affected by acute myocardial infarction. With caution in interpreting the results of this meta-analysis, our data support the idea that Levosimendan may already have a role in the treatment of acute ischemic heart disease. Further studies specifically designed to investigate the early role in the treatment of ischemic heart failure are needed.

Background Crossover dilutes treatment effect and reduces statistical power of intention‐to‐treat analysis. We examined incidence and impact on cardiac surgery randomized controlled trial (RCT) outcomes of crossover from experimental to control interventions, or vice versa. Methods and Results MEDLINE, EMBASE, and Cochrane Library were searched, and RCTs (≥100 patients) comparing ≥2 adult cardiac surgical interventions were included. Crossover from the initial treatment assignment and relative risks (RRs) for each trial's primary end point and mortality at longest available follow‐up were extracted. All RRs were calculated as >1 favored control group and

Background Transcatheter aortic valve replacement (TAVR) is the standard of care for many patients with severe symptomatic aortic stenosis and relies on accurate sizing of the aortic annulus. It has been suggested that 3‐dimensional transesophageal echocardiography (3D TEE) may be used instead of multidetector computed tomography (MDCT) for TAVR planning. This systematic review and meta‐analysis compared 3D TEE and MDCT for pre‐TAVR measurements. Methods and Results A systematic literature search was performed. The primary outcome was the correlation coefficient between 3D TEE– and MDCT‐measured annular area. Secondary outcomes were correlation coefficients for mean annular diameter, annular perimeter, and left ventricular outflow tract area; interobserver and intraobserver agreements; mean differences between 3D TEE and MDCT measurements; and pooled sensitivities, specificities, and receiver operating characteristic area under curve values of 3D TEE and MDCT for discriminating post‐TAVR paravalvular aortic regurgitation. A random effects model was used. Meta‐regression and leave‐one‐out analysis for the primary outcome were performed. Nineteen studies with a total of 1599 patients were included. Correlations between 3D TEE and MDCT annular area, annular perimeter, annular diameter, and left ventricular outflow tract area measurements were strong (0.86 [95% CI, 0.80–0.90]; 0.89 [CI, 0.82–0.93]; 0.80 [CI, 0.70–0.87]; and 0.78 [CI, 0.61–0.88], respectively). Mean differences between 3D TEE and MDCT between measurements were small and nonsignificant. Interobserver and intraobserver agreement and discriminatory abilities for paravalvular aortic regurgitation were good for both 3D TEE and MDCT. Conclusions For pre‐TAVR planning, 3D TEE is comparable to MDCT. In patients with renal dysfunction, 3D TEE may be potentially advantageous for TAVR measurements because of the lack of contrast exposure.

Background Little clinical research on new‐generation heat‐not‐burn cigarettes (HNBC) in comparison with electronic vaping cigarettes (EVC) and traditional tobacco combustion cigarettes (TC) has been reported. We aimed to appraise the acute effects of single use of HNBC, EVC, and TC in healthy smokers. Methods and Results This was an independent, cross‐over, randomized trial in 20 TC smokers, with allocation to different cycles of HNBC, EVC, and TC. All participants used all types of products, with an intercycle washout of 1 week. End points were oxidative stress, antioxidant reserve, platelet activation, flow‐mediated dilation, blood pressure, and satisfaction scores. Single use of any product led to an adverse impact on oxidative stress, antioxidant reserve, platelet function, flow‐mediated dilation, and blood pressure. HNBC had less impact than EVC and TC on soluble Nox2‐derived peptide (respectively, P=0.004 and 0.001), 8‐iso‐prostaglandin F2α‐III (P=0.004 and