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Aims: Cardiac magnetic resonance (CMR) has a growing role in evaluating athletes' hearts. Mapping techniques provide added value for tissue characterization, but data on athletes and sports disciplines are lacking. To describe native mapping values in a cohort of Olympic athletes and evaluate the influence of sports discipline and sex., Methods and Results: A group of 300 Olympic athletes (13% skill, 20% power, 25% mixed, 42% endurance, 58% male) with unremarkable cardiovascular screening and a control group of 42 sedentary subjects (52% male) underwent CMR without contrast administration. Athletes were divided based on sex and sports categories according to the ESC classification. Among athletes of different sports categories and controls, endurance presented the lowest value of T1 mapping (P < 0.001). No differences in T2 mapping were observed (P = 0.472). Female athletes had higher values of T1 native myocardial mapping compared with males (P = 0.001), while there were no differences in T2 mapping (P = 0.817). Male athletes with higher left ventricular mass indexed (LV-Massi) had lower values of T1 mapping (P = 0.006) and slightly higher values of T2 mapping, even if not significant (P = 0.150). Female athletes with higher LV-Massi did not show significant differences in T1 and T2 mapping (P = 0.053 and P = 0.438)., Conclusion: T1 native myocardial mapping showed significant differences related to sports disciplines and gender. Athletes with the largest LV remodelling, mostly endurance and mixed, showed the lowest values of T1 mapping. Male athletes showed lower values of T1 mapping than females. No significant differences were observed in T2 mapping related to sports disciplines and gender., Competing Interests: Conflict of interest: The authors have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Elderly patients are often under-represented in studies about coronary revascularization in acute coronary syndromes (ACS) and undertreated in clinical practice. We sought to evaluate differences in outcomes between an initial invasive or conservative strategy in this subset of patients, METHODS: The analysis was performed following PRISMA guidelines. Randomized controlled trials (RCTs) and adjusted observational studies comparing an invasive and conservative strategy in old patients with ACS were systematically identified. Random or fixed effect model was used accordingly to heterogeneity testing results. Short-term mortality was the primary outcome. 30-day and longer-term re-infarction, MACE and all-cause mortality were secondary endpoints. Sensitivity analysis including RCTs only were performed for the primary endpoint and 1 year mortality and another analysis, stratifying NSTEMI and STEMI studies, was performed for short-term mortality., Results: Invasive management was associated with lower short and long-term mortality (30 days OR 0.64, 95 % CI 0.54-0.76, p < 0.001; 1 year HR 0.60, 95 % CI 0.52-0.78, p < 0.001; Long-term HR 0.62, 95 % CI 0.55-0.71, p < 0.001) compared to a conservative strategy. In the short-term follow-up, the benefit was preserved when differentiating for NSTEMI or STEMI studies but not when considering only RCTs. Major bleedings were more frequent in the invasive group (30 days OR 1.61, 95 % CI 1.39-1.87, p < 0.001). The mean difference in length of stay was not significantly different between the two strategies (mean difference in days 0.14, 95 % CI -0.79 to 1.06, p = 0.77)., Conclusion: An initial invasive strategy might lead to reduced short and long-term mortality in elderly patients presenting with acute coronary syndrome but it is associated with increased bleeding events rate. No difference in hospital stay length was observed. Results were mainly driven by non-randomized studies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background : Celiac disease (CD) is associated with an increased risk of cardiovascular (CV) events, especially inflammatory heart diseases. We aimed to gather evidence on the association between CD and inflammatory CV diseases, including pericarditis and myocarditis, and the underlying pathophysiological mechanisms. Methods : The PubMed, Scopus, and Google Scholar databases were searched for studies assessing the prevalence and the long-term outcomes of patients with CD and inflammatory CV diseases. Result : Ten studies (nine case series/reports and one prospective observational study) covering a total of 22 patients, including 9 women (41%) and 13 men (59%), were evaluated. The median age was 23 (IQR, 12-41) years. A total of 6 patients had recurrent pericarditis, while 16 patients had celiac-related myocarditis (11 patients presented with heart failure and 5 with arrhythmia). A strict gluten-free diet (GFD) alone was effective in 87.5% of cases (4/6 for pericarditis and 10/16 for myocarditis). All patients with pericarditis achieved complete resolution of symptoms. Conversely, heart function was restored in 81% of patients with myocarditis. Only one patient died. Conclusions : Myocarditis and/or pericarditis, especially if recurrent, may complicate CD in pediatric and adult subjects due to an autoimmune reaction involving the pericardium/myocardium and the small intestine.

Background: COVID-19 vaccines reduced mortality, hospitalizations and ICUs admissions. Conversely, the impact of vaccination on Long COVID-19 syndrome is still unclear. This study compared the prevalence of post-acute sequelae at short and long-term follow-up among hospitalized unvaccinated and vaccinated COVID-19 survivors through a multidisciplinary approach., Methods: After 2 months from discharge, unvaccinated and vaccinated COVID-19 survivors underwent a follow-up visit at a dedicated "post-COVID-19 Outpatient Clinic". The follow-up visit included a cardiovascular evaluation, blood tests, chest computed tomography, 6-min walking test (6MWT), spirometry. A one-year telephone follow-up was performed to assess re-hospitalizations, death and long-lasting symptoms. An additional 1:1 case-control matching analysis adjusted for baseline characteristics was performed., Results: Between June 2020 and June 2022, a total of 458 unvaccinated and vaccinated patients (229 per group) underwent the follow-up visit. Vaccinated patients had lower rates of ICU admissions (1.7 % vs 9.6 %, p= <0.001) and severe respiratory complications requiring intubation (1.3 % vs 7 %, p = 0.002) or non-invasive ventilation such as high-flow nasal oxygen therapy (1.7 % vs 7.9 %, p = 0.02), CPAP (1.3 % vs 20.1 %, p= < 0.001), and low-flow oxygen therapy (3.5 % vs 63.3 %, p= <0.001) compared to unvaccinated ones. At 2-month follow-up, vaccinated patients had fewer persistent ground-glass opacities (2.6 % vs 52.8 %, p= <0.001) or consolidations (0.9 % vs 8.3 %, p= <0.001). Additionally, unvaccinated patients experienced more frequent myocarditis (4.8 % vs 0.9 %, p = 0.013) and pulmonary embolism (1.8 % vs 0 %, p = 0.042) and exhibited more significant respiratory impairment as evidenced by desaturation during the 6MWT(10.2 % vs 3.5 %, p = 0.005) and altered spirometry (14 % vs 8.7 %, p = 0.043) compared to vaccinated ones. At one-year, unvaccinated patients reported more symptoms such as dyspnea (20.5 % vs 10 %, p = 0.002), psychological symptoms (10 % vs 3.5 %, p = 0.005) and chronic rhinosinusitis/cough (6,6 % vs 2,6 %, p = 0.04) as compared to vaccinated ones. The 1:1 case-control matching analysis also confirmed these results., Conclusions: COVID-19 vaccines improve short-term outcomes and may reduce Long COVID-19 prevalence., Competing Interests: 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., (© 2024 The Authors.)

There is a need to address the evidence gap regarding the in-hospital administration of sacubitril/valsartan in acute myocardial infarction patients. After searching MEDLINE, Google Scholars and Scopus, a random-effects meta-analysis of randomized controlled trials comparing the in-hospital administration of the angiotensin receptor-neprilysin inhibitors (ARNis) versus the standard therapy in patients with reduced heart failure due to myocardial infarction was performed. The primary outcome was major adverse cardiovascular events. All-cause mortality, cardiac death, rehospitalization for heart failure, non-fatal myocardial infarction (MI), changes in left ventricular ejection fraction, left ventricular volumes, N terminal pro brain natriuretic peptide and adverse events were the secondary endpoints. Nine studies (eight randomized controlled trials and one echo-substudy) with a total 6597 individuals (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: 3300 patients vs. ARNis: 3297 patients) were included for quantitative analysis. Median follow-up was 6 months. Patients receiving an in-hospital coadministration of ARNi had a lower risk of major cardiovascular event [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.32-0.63, P < 0.0001] and lower rate of repeat rehospitalization for heart failure (OR 0.40, 95% CI 0.26-0.62, P < 0.0001), compared with a standard regimen. Additionally, left ventricle volumes were significantly lower in the ARNi group [left ventricular end-diastolic volume, mean difference (MD) 11.48 mL, 95% CI 6.10-16.85, P < 0.0001; left ventricular end-systolic volume, MD 7.09 mL, 95% CI 2.89-11.29, P = 0.0009] with a significant change in left ventricular ejection fraction (MD 3.07, 95% CI 1.61-4.53, P < 0.0001), compared with standard therapy. No significant differences were observed in terms of cardiac death, all cause of mortality, non-fatal myocardial infarction and N terminal pro brain natriuretic peptide. Higher rates of iatrogenic hypotensive events were observed in the ARNi group compared with the standard therapy (OR 1.42, 95% CI 1.26-1.60, P value < 0.00001). In patients with acute myocardial infarction related heart failure, the in-hospital administration of ARNis was associated with a reduced risk of major cardiovascular events and re-hospitalization for heart failure, as well as cardiac remodelling, but higher rates of hypotensive events compared with standard therapy., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

A metanalysis of available randomized controlled trials and observational studies comparing self-expanding (SE) and balloon-expandable (BE) bioprostheses in patients with small aortic annulus and aortic stenosis for short- and midterm hemodynamic and clinical outcomes was performed. A total of 21 studies with a total 8,647 patients (SE: n = 4,336 patients vs BE: n = 4,311 patients) were included. SE bioprostheses had a lower postoperative mean gradient at 30 days (Mean Difference [MD] -5.16, 95% confidence interval [CI] 4.7 to 5.5, p <0.001) and at 1 year (MD -6.6, 95%CI 6.1 to 7.03, p <0.001), with a larger indexed effective orifice area (0.17, 95% CI 0.13 to 0.22, p <0.001 and 0.17, 95% CI 0.08 to 0.27, p <0.001) at both time intervals. BE bioprostheses had a higher risk of 30-day and 1-year severe prosthesis-patient mismatch (risk ratio [RR] 1.07, 95% CI 1.04 to 1.09, p <0.001; RR 1.07, 95% CI 1.04 to 1.11, p <0.001). The 30-day and 1 year paravalvular leaks (RR 0.99, 95% CI 0.98 to 0.99, p <0.001; RR 0.89, 95% CI 0.82 to 0.95, p <0.001) and permanent pacemaker implantation (RR 0.97, 95% CI 0.94 to 0.99, p 0.01, I2 = 40%,) were lower in the BE group. BE bioprostheses were associated with a lower risk of in-hospital stroke (RR 0.99, 95% CI 0.98 to 1, p = 0.01). In conclusion, in patients with small aortic annulus and aortic stenosis, SE bioprostheses have superior hemodynamic performance but higher rates of paravalvular leak, permanent pacemaker implantation, and in-hospital stroke. BE bioprostheses were associated with a higher risk of severe prosthesis-patient mismatch., Competing Interests: Declaration of competing interest Dr. Thomas Pilgrim reports research, travel or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens; speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife. Dr. Kay Woon Ho received speaker fees from Edwards Lifesciences, Medtronic, and Abbott Vascular. The remaining authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

BTC overall incidence is globally increasing. CCA, including its subtypes, is a form of BTC. MetS, obesity, MASLD, and diabetes are all linked to CCA in interconnected ways. The link between obesity and CCA is less well-defined in Eastern countries as compared to Western. Although more research is needed to determine the relationship between MASLD and extrahepatic CCA (eCCA), MASLD may be a concurrent risk factor for intrahepatic CCA, particularly in populations with established or unidentified underlying liver disease. Interestingly, the risk of biliary tract cancer (BTC) seemed to be higher in patients with shorter diabetes durations who were not treated with insulin. Therefore, early detection and prevention of chronic liver disease, as well as additional intervention studies, will undoubtedly be required to determine whether improvements to MetS, weight loss, and diabetes therapy can reduce the risk and progression of BTC. However, further studies are needed to understand how reproductive hormones are involved in causing BTC and to develop consistent treatment for patients. Finally, it is critical to carefully assess the cardiological risk in BTC patients due to their increased intrinsic cardiovascular risk, putting them at risk for thrombotic complications, cardiovascular death, cardiac metastasis, and nonbacterial thrombotic endocarditis. This review aimed to provide an updated summary of the relation between the abovementioned cardio-metabolic conditions and BTC.

Background: The long-term symptomatology of COVID-19 has yet to be comprehensively described. The aim of the study was to describe persistent COVID-19 symptoms in a cohort of hospitalized and home-isolated patients., Methods: A retrospective cohort study was conducted on long COVID patients. Long COVID symptoms were identified, and patients were divided into hospitalized (in-patients) and home-isolated (out-patients), as well as according to the number of symptoms. Patients were examined by a multidisciplinary medical team. Blood tests, high resolution chest computed tomography (CT), and physical and infectious examinations were performed. Finally, in-patients were evaluated at 2 time-points: on hospital admission (T0) and 3 months after discharge (Tpost)., Results: There were 364 COVID-19 patients enrolled; 82% of patients reported one or more symptoms. The most reported symptom was fatigue. Chest CT showed alteration in 76% of patients, and pulmonary function alterations were observed in 44.7% of patients. A higher risk of presenting at least one symptom was seen in patients treated with corticosteroid, and a higher risk of presenting chest CT residual lesion was observed in hospitalized patients and in patients that received hydroxychloroquine treatment. Moreover, a higher risk of altered pulmonary function was observed in older patients., Conclusion: Long-term sequelae are present in a remarkable number of long COVID patients and pose a new challenge to the health care system to identify long-lasting effects and improve patients' well-being. Multidisciplinary teams are crucial to develop preventive measures, and clinical management strategies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with an increased risk of coronary artery disease. Computed Tomography Coronary Angiography (CTCA) can assess both the extent and the features of coronary plaques. We aimed to gather evidence about the prevalence and features of coronary plaques among MASLD patients., Methods: PubMed, Scopus, and Google Scholar databases were searched for randomized controlled trials and adjusted observational studies assessing the prevalence and features of coronary plaques by means of CTCA in MASLD patients as compared with a control group. The prevalence of coronary stenosis (defined as >30% and >50% diameter of stenosis), of increasing coronary artery calcium (CAC) score and of high-risk features (namely low-attenuation plaques, napkin ring sign, spotty calcification and positive remodelling) in MASLD patients were the endpoints of interest., Results: Twenty-four observational studies were included. MASLD was associated with an increased prevalence of critical coronary stenosis compared with controls (odds ratio [OR] 1.54, 95%CI 1.23-1.93). Increased values of CAC score were observed in MASLD patients (OR 1.35, 95%CI 1.02-1.78 and OR 2.26, 95%CI 1.57-3.23 for CAC score 0-100 and >100, respectively). An increased risk of 'high-risk' coronary plaques was observed in MASLD patients (OR 2.13, 95%CI 1.42-3.19). As high-risk features plaques, a higher prevalence of positive remodelling and spotty calcification characterize MASLD patients (OR 2.92, 95%CI 1.79-4.77 and OR 2.96, 95%CI 1.22-7.20)., Conclusions: Patients with MASLD are at increased risk of developing critical coronary stenosis and coronary plaques characterized by high-risk features as detected by CTCA., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Introduction: The 2021 European Society of Cardiology (ESC) Guidelines recommend the use of four different classes of drugs for heart failure with reduced ejection fraction (HFrEF): beta blockers (BB), sodium-glucose cotransporter-2 inhibitors (SGLT2i), angiotensin receptor/neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRAs). Moreover, the 2023 ESC updated Guidelines suggest an intensive strategy of initiation and rapid up-titration of evidence-based treatment before discharge, based on trials not using the four-pillars. We hypothesized that an early concomitantly administration and up-titration of four-pillars, compared with a conventional stepwise approach, may impact the vulnerable phase after hospitalization owing to HF., Methods: This prospective, single center, observational study included consecutive in-hospital patients with HFrEF. After performing propensity score matching, they were divided according to treatment strategy into group 1 (G1), with predischarge start of all four-pillars, with their up-titration within 1 month, and group 2 (G2) with the pre Guidelines update stepwise four-pillars introduction. HF hospitalization, cardiovascular (CV) death, and the composite of both were evaluated between the two groups at 6-month follow-up., Results: The study included a total of 278 patients who completed 6-month follow-up (139 for both groups). There were no differences in terms of baseline features between the two groups. At survival analysis, HF hospitalization risk was significantly lower in G1 compared with G2 (p < 0.001), while no significant differences were observed regarding CV death (p = 0.642) or the composite of CV death and HF hospitalization (p = 0.135)., Conclusions: In our real-world population, patients with HF treated with a predischarge and simultaneous use of four-pillars showed a reduced risk of HF hospitalization during the vulnerable phase after discharge, compared with  a conventional stepwise approach., (© 2024. The Author(s).)

Background/Objectives : Constrictive pericarditis very rarely causes protein-losing enteropathy (PLE) induced by secondary intestinal lymphangiectasia. This study thoroughly reviewed the literature to shed light on the clinical management of PLE provoked by intestinal lymphangiectasia following constrictive pericarditis. Methods : We performed a PubMed search using the keywords enteropathy, protein-losing enteropathy, pericarditis, acute pericarditis, pericardial effusion, recurrent pericarditis, constrictive pericarditis, noninfectious pericarditis, idiopathic pericarditis, and infective pericarditis, with only English-language publications included. Results : Although constrictive pericarditis is primarily idiopathic, less common causes include infectious etiologies, connective/autoimmune tissue disorders, previous cardiac surgery, congenital syndromes, and cancer. On the one hand, PLE secondary to intestinal lymphangiectasia may cause a severe cellular immune deficiency that could raise infection hazards due to lymphocytopenia and hypogammaglobulinemia. On the other hand, lymphocytopenia may cause anergy and mask an underlying tuberculous etiology of constrictive pericarditis. Cardiac catheterization is the most useful diagnostic tool for constrictive pericarditis, though it may be misdiagnosed in rare cases. The videocapsule endoscopy and double-balloon enteroscopy techniques can detect small bowel lymphangiectasias distal to the Treitz ligament. MRI or a CT scan helps confirm constrictive pericarditis, visualize lymphangiectasias, and reveal features specific to the underlying etiology of PLE. Radioisotopic techniques may ensure PLE diagnosis in challenging cases, whereas fecal alpha1-antitrypsin can estimate gastrointestinal protein loss. Conclusions : Constrictive pericarditis is rarely associated with PLE. The cardio-intestinal abnormalities of PLE caused by constrictive pericarditis are frequently reversed following a complete pericardiectomy, though its ability to invert severe hypoalbuminemia is currently unknown.

The long-term safety and effectiveness of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) in low surgical risk has not been evaluated in a pooled analysis. An electronic database search was conducted for randomized controlled trials with a maximal 5 years clinical and echocardiographic follow-up including low surgical risk patients who underwent TAVR or SAVR. We calculated odds ratio (OR) and 95% confidence intervals (CIs) using a random-effects model. Subgroups analysis was performed for permanent pacemaker implantation and paravalvular leaks. Three randomized controlled trials were included with a total of 2,611 low surgical risk patients (Society of Thoracic Surgeons score <4%). Compared with SAVR, the TAVR group had similar rates of all-cause mortality (OR 0.94,95% CI 0.65 to 1.37, p = 0.75) and disabling stroke (OR 0.84, 95% CI 0.52 to 1.36, p = 0.48). No significant differences were registered in the TAVR group in terms of major cardiovascular events (OR 0.96, 95% CI 0.67 to 1.38, p = 0.83), myocardial infarction (OR 0.69, 95% CI 0.34 to 1.40, p = 0.31), valve thrombosis (OR 3.11, 95% CI 0.29 to 33.47, p = 0.35), endocarditis (OR 0.71,95% CI 0.35 to 1.48, p = 0.36), aortic valve reintervention (OR 0.93, 95% CI 0.52 to 1.66, p = 0.80), and rehospitalization (OR 0.80, 95% CI 0.52 to 1.02, p = 0.07) compared with SAVR. However, TAVR patients had a higher risk of paravalvular leaks (OR 8.21, 95% CI 4.18 to 16.14, p <0.00001), but lower rates of new-onset atrial fibrillation (OR 0.27,95% CI 0.17 to 0.30, p <0.0001). The rates of permanent pacemaker implantation were comparable from 1 year up to a maximum of 5 years (OR 1.32, 95% CI 0.88 to 1.97, p = 0.18). Lastly, TAVR had a greater effective orifice area (0.10 cm 2 /m 2 , 95% CI 0.05 to 0.15, p = 0.0001), but similar transvalvular mean gradients (0.60, 95% CI 3.94 to 2.73, p = 0.72). In conclusion, TAVR patients had similar long-term outcomes compared with SAVR, except for an elevated risk of paravalvular leaks in the TAVR group and increased rates of atrial fibrillation in the SAVR cohort., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death ( p = 0.01) and CV death/HFH ( p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54-6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43-4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death ( p < 0.001) and CV death/HFH ( p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.

Objectives: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status., Materials and Methods: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications)., Results: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy., Conclusion: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers., Clinical Relevance Statement: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status., Trial Registration: ClinicalTrials.gov NCT02400229., Key Points: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Cardiac magnetic resonance (CMR) provides information on morpho-functional abnormalities and myocardial tissue characterisation. Appropriate indications for CMR in athletes are uncertain., Objective: To analyse the CMR performed at our Institute to evaluate variables associated with pathologic findings in a large cohort of athletes presenting with different clinical conditions., Methods: All the CMR performed at our Institute in athletes aged > 14 years were recruited. CMR indications were investigated. CMR was categorised as "positive" or "negative" based on the presence of morphological and/or functional abnormalities and/or the presence of late gadolinium enhancement (excluding the right ventricular insertion point), fat infiltration, or oedema. Variables associated with "positive" CMR were explored., Results: A total of 503 CMR were included in the analysis. "Negative" and "positive" CMR were 61% and 39%, respectively. Uncommon ventricular arrhythmias (VAs) were the most frequent indications for CMR, but the proportion of positive results was low (37%), and only polymorphic ventricular patterns were associated with positive CMR (p = 0.006). T-wave inversion at 12-lead ECG, particularly on lateral and inferolateral leads, was associated with positive CMR in 34% of athletes (p = 0.05). Echocardiography abnormalities resulted in a large proportion (58%) of positive CMR, mostly cardiomyopathies., Conclusion: CMR is more efficient in identifying a pathologic cardiac substrate in athletes in case of VAs (i.e., polymorphic beats), abnormal ECG repolarisation (negative T-waves in inferolateral leads), and borderline echocardiographic findings (LV hypertrophy, mildly depressed LV function). On the other hand, CMR is associated with a large proportion of negative results. Therefore, a careful clinical selection is needed to indicate CMR in athletes appropriately., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background & Aims: Echocardiographic findings may provide valuable information about the cardiac conditions in cirrhotic patients waiting for liver transplantation (LT). However, data on the ability of the different echocardiographic parameters to predict post-transplant risk of mortality are scarce and heterogeneous. This systematic review evaluates the role of different echocardiographic features as predictors of post-LT mortality. A meta-analysis was also performed according to the observed results., Methods: A systematic review was conducted according to PRISMA guidelines. Medline (PubMed) database was searched through February 2023 for relevant published original articles reporting the prognostic value of echocardiographic findings associated with outcomes of adult LT recipients. The risk of bias in included articles was assessed using ROBINS-E tool. Methodological quality varied from low to high across the risk of bias domains., Results: Twenty-three studies were identified after the selection process; ten were enrollable for the meta-analyses. According to the results observed, the E/A ratio fashioned as a continuous value (HR = 0.43, 95%CI = 0.25-0.76; P = 0.003), and tricuspid regurgitation (HR = 2.36, 95%CI = 1.05-5.31; P = 0.04) were relevant predicting variables for post-LT death. Other echocardiographic findings failed to merge with statistical relevance., Conclusion: Tricuspid regurgitation and left ventricular diastolic dysfunction play a role in the prediction of post-LT death. More studies are needed to clarify further the impact of these echocardiographic features in the transplantation setting., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: The multi-systemic effects of heart failure (HF) resemble the spread observed during cancer. We propose a new score, named HLM, analogous to the TNM classification used in oncology, to assess the prognosis of HF. HLM refers to H: heart damage, L: lung involvement, and M: systemic multiorgan involvement. The aim was to compare the HLM score to the conventional New York Heart Association (NYHA) classification, American College of Cardiology/American Heart Association (ACC/AHA) stages, and left ventricular ejection fraction (LVEF), to assess the most accurate prognostic tool for HF patients., Methods and Results: We performed a multicentre, observational, prospective study of consecutive patients admitted for HF. Heart, lung, and other organ function parameters were collected. Each patient was classified according to the HLM score, NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography. The follow-up period was 12 months. The primary endpoint was a composite of all-cause death and rehospitalization due to HF. A total of 1720 patients who completed the 12 month follow-up period have been enrolled in the study. 520 (30.2%) patients experienced the composite endpoint of all-cause death and rehospitalization due to HF. 540 (31.4%) patients were female. The mean age of the study population was 70.5 ± 12.9. The mean LVEF at admission was 42.5 ± 13%. Regarding the population distribution across the spectrum of HLM score stages, 373 (21.7%) patients were included in the HLM-1, 507 (29.5%) in the HLM-2, 587 (34.1%) in the HLM-3, and 253 (14.7%) in the HLM-4. HLM was the most accurate score to predict the primary endpoint at 12 months. The area under the receiver operating characteristic curve (AUC) was greater for the HLM score compared with the NYHA classification, ACC/AHA stages, or LVEF, regarding the composite endpoint (HLM = 0.645; NYHA = 0.580; ACC/AHA = 0.589; LVEF = 0.572). The AUC of the HLM score was significantly better compared with the LVEF (P = 0.002), ACC/AHA (P = 0.029), and NYHA (P = 0.009) AUC., Conclusions: The HLM score has a greater prognostic power compared with the NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography in terms of the composite endpoint of all-cause death and rehospitalization due to HF at 12 months of follow-up., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: To provide a comprehensive analysis of the current literature comparing the outcomes of surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (BAS), with particular attention to BAV morphology in patients undergoing TAVR., Methods: Following PRISMA guidelines, all relevant articles with no design restrictions from PubMed, CCTR (Cochrane Controlled Trials Register), and Google Scholar were screened for inclusion. Studies were included if they reported clinical endpoints for SAVR and TAVR or, in BAS treated with TAVR, for type 1 and non-type 1 morphology. Odds ratio and Cohen's D were considered as effect size measurements for qualitative and quantitative variables, respectively., Results: A total of eight studies comparing short-term outcomes between SAVR and TAVR and nine studies with outcomes data between type 1 and non-type 1 BAS treated with TAVR were considered for the final analysis. No statistically significant difference was found for what concerns the rates of death, stroke, and acute kidney injury between SAVR and TAVR. In comparison to patients undergoing SAVR, the incidence of PPI (permanent pacemaker implantation) was greater in the TAVR group (OR 0.35, 95% CI 0.15-0.79, p = 0.01), and the frequency of bleeding events was found to be higher among patients undergoing SAVR (OR 4.3, 95% CI 2.9-6.4, p < 0.001). The probabilities of 30-day mortality, stroke, and any bleeding were not significantly affected by bicuspid valve morphology in TAVR patients. PPI or development of new conduction anomalies was found to be more frequent in type 1 anatomies (OR 0.46, 95% CI 0.30-0.70, p <0.001). Mildly lower post-procedural transprothesic gradients were found in patients with type 1 morphology., Conclusions: In BAS patients, TAVR has comparable short-term outcomes rates with SAVR, but higher PPI rates and lower incidence of bleeding events. In patients undergoing TAVR, type 1 BAS is associated with lower postoperative transvalvular gradients but higher PPI rates and conduction abnormalities.

Purpose: The purpose of this review is to explore the benefits and controversies that telemedicine (TM), applied to patients with heart failure (HF), can provide in terms of diagnosis, therapeutic management, and prognosis improvement. During the coronavirus disease 19 (COVID-19) outbreak, TM emerged as the most effective and feasible method available to ensure continuous care for chronic diseases. Among these, HF, characterized by high mortality, morbidity, and the need for frequent visits, may benefit of the TM role. HF patients are affected by frequent exacerbations undergoing a progressive prognosis impoverishment, strongly depending on the disease's management. A precise clinical handling is always required, with a constant optimization of the therapy, a continuous control of risk factors, and a sensitive attention to any change in symptoms, clinical signs, and laboratory tests. In this context, TM has shown to improve therapy adherence and HF: patients' self-care, impacting the prognosis even if specific results are controversial. Major evidence shows that TM may allow an adequate primary prevention, reducing the impact of the main cardiovascular risk factors. TM can also be useful for the secondary prevention, early detecting a likely HF exacerbation before it becomes clinically manifest, thereby lowering the need for hospitalization. Moreover, an optimal up-titration of the therapy and an increase in treatment adherence are feasible by using TM. However, some studies did not show unambiguous results, and uncertainties still remain., (© 2023. The Author(s).)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), or gliflozins, have recently been shown to reduce cardiovascular death and hospitalization in patients with heart failure, representing a revolutionary therapeutic tool. The purpose of this review is to explore their multifaceted mechanisms of actions, beyond their known glucose reduction power. The cardioprotective effects of gliflozins seem to be linked to the maintenance of cellular homeostasis and to an action on the main metabolic pathways. They improve the oxygen supply for cardiomyocytes with a considerable impact on both functional and morphological myocardial aspects. Moreover, multiple molecular actions of SGLT2i are being discovered, such as the reduction of both inflammation, oxidative stress and cellular apoptosis, all responsible for myocardial damage. Various studies showed controversial results concerning the role of SGLT2i in reverse cardiac remodeling and the lowering of natriuretic peptides, suggesting that their overall effect has yet to be fully understood. In addition to this, advanced imaging studies evaluating the effect on all four cardiac chambers are lacking. Further studies will be needed to better understand the real impact of their administration, their use in daily practice and how they can contribute to benefits in terms of reverse cardiac remodeling.

Among the most common causes of death worldwide, ischemic heart disease (IHD) is recognized to rank first. Even if atherosclerotic disease of the epicardial arteries is known as the leading cause of IHD, the presence of myocardial infarction with non-obstructive coronary artery disease (MINOCA) is increasingly recognized. Notwithstanding the increasing interest, MINOCA remains a puzzling clinical entity that can be classified by distinguishing different underlying mechanisms, which can be divided into atherosclerotic and non-atherosclerotic. In particular, coronary microvascular dysfunction (CMD), classifiable in non-atherosclerotic mechanisms, is a leading factor for the pathophysiology and prognosis of patients with MINOCA. Genetic susceptibility may have a role in primum movens in CMD. However, few results have been obtained for understanding the genetic mechanisms underlying CMD. Future studies are essential in order to find a deeper understanding of the role of multiple genetic variants in the genesis of microcirculation dysfunction. Progress in research would allow early identification of high-risk patients and the development of pharmacological, patient-tailored strategies. The aim of this review is to revise the pathophysiology and underlying mechanisms of MINOCA, focusing on CMD and actual knowledge about genetic predisposition to it.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially born as anti-diabetic drugs, have shown many beneficial effects on the cardiovascular system, in particular against heart failure (HF). HF is a complex and multifaceted disease that requires a comprehensive approach. It should not be considered as a simplistic cardiac disease, but a systemic disease that leads to multisystemic organ failure and death. Exploiting their pleiotropic effects, SGLT2i are a very valid tool for HF treatment. Beyond the indication to reduce HF hospitalization and death risk, in patients with diabetes mellitus at high cardiovascular risk or with established cardiovascular event, SGLT2i administration reported beneficial effects regarding the wide spectrum of HF manifestations and stages, independently by diabetes mellitus presence. Recent evidence focuses on HF rehospitalization, cardiac and all-cause death reduction, as well as symptoms and quality of life improvement, in patients with chronic HF or with a recent HF decompensation episode. Given the recent finding about the SGLT2i usefulness in HF patients, further studies are needed to define the best administration timing to maximize the SGLT2i-derived beneficial effects., (© 2021. The Author(s).)

Genetic susceptibility may influence ischemic heart disease (IHD) predisposition and affect coronary blood flow (CBF) regulation mechanisms. The aim of this study was to investigate the association among single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in CBF regulation and IHD. A total of 468 consecutive patients were enrolled and divided into three groups according to coronary angiography and intracoronary functional tests results: G1, patients with coronary artery disease (CAD); G2, patients with coronary microvascular dysfunction (CMD); and G3, patients with angiographic and functionally normal coronary arteries. A genetic analysis of the SNPs rs5215 of the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene and rs1799983 of the nitric oxide synthase 3 (NOS3) gene, respectively encoding for the Kir6.2 subunit of ATP sensitive potassium (K ATP ) channels and nitric oxide synthase (eNOS), was performed on peripheral whole blood samples. A significant association of rs5215&#95;G/G of KCNJ11 and rs1799983&#95;T/T of NOS3 genes was detected in healthy controls compared with CAD and CMD patients. Based on univariable and multivariable analyses, the co-presence of rs5215&#95;G/G of KCNJ11 and rs1799983&#95;T/T of NOS3 may represent an independent protective factor against IHD, regardless of cardiovascular risk factors. This study supports the hypothesis that SNP association may influence the crosstalk between eNOS and the K ATP channel that provides a potential protective effect against IHD.

Objective: to evaluate the prevalence of cardiac involvement after COVID-19 in competitive athletes at return-to-play (RTP) evaluation, following the recommended Italian protocol including cardiopulmonary exercise test (CPET) and 24-Hour Holter monitoring., Design and Methods: this is a single centre observational, cross-sectional study. Since October 2020, all competitive athletes (age ≥ 14 years) evaluated in our Institute after COVID-19, prior RTP were enrolled. The protocol dictated by the Italian governing bodies included: 12‑lead ECG, blood test, CPET, 24-h ECG monitoring, spirometry. Cardiovascular Magnetic Resonance (CMR) was performed based on clinical indication., Results: 219 consecutive athletes were examined (59% male), age 23 years (IQR 19-27), 21% asymptomatic, 77% mildly symptomatic, 2% with previous pneumonia. The evaluation was performed after a median of 10 (6-17) days from negative SARS-CoV-2 swab. All athletes showed a good exercise capacity at CPET without cardiovascular and respiratory limitations. Uncommon premature ventricular contractions (PVCs) were found in 9.5% (n = 21) at CPET/Holter ECG monitoring. Two athletes (0.9%) were diagnosed with acute myocarditis (by CMR) and another one with new pericardial effusion. All the three athletes were temporally restricted from sport participation., Conclusions: Myocarditis in competitive athletes screened after COVID-19 resolution was detected in a low minority of the cases (0.9%). However, a non-negligible prevalence of uncommon PVCs (9%) was observed, either at CPET and/or Holter ECG monitoring, including all athletes with COVID-19 related cardiovascular abnormalities., (Copyright © 2022 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Micronutrients are ions and vitamins humbly required by the human body. They play a main role in several physiological mechanisms and their imbalance is strongly associated with potentially-fatal complications. Micronutrient imbalance is associated with many cardiovascular diseases, such as arrythmias, heart failure, and ischemic heart disease. It has been also observed in coronavirus disease 2019 (COVID-19), particularly in most severe patients. The relationship between cardiovascular diseases and COVID-19 is mutual: the latter triggers cardiovascular disease onset and worsening while patients with previous cardiovascular disease may develop a more severe form of COVID-19. In addition to the well-known pathophysiological mechanisms binding COVID-19 and cardiovascular diseases together, increasing importance is being given to the impact of micronutrient alterations, often present during COVID-19 and able to affect the balance responsible for a good functioning of the cardiovascular system. In particular, hypokalemia, hypomagnesemia, hyponatremia, and hypocalcemia are strongly associated with worse outcome, while vitamin A and D deficiency are associated with thromboembolic events in COVID-19. Thus, considering how frequent the cardiovascular involvement is in patients with COVID-19, and how it majorly affects their prognosis, this manuscript provides a comprehensive review on the role of micronutrient imbalance in the interconnection between COVID-19 and cardiovascular diseases.

Conflicting results on the cardiovascular involvement after SARS-CoV-2 infection generated concerns on the safety of return-to-play (RTP) in athletes. The aim of this study was to evaluate the prevalence of cardiac involvement after COVID-19 in Olympic athletes, who had previously been screened in our pre-participation program. Since November 2020, all consecutive Olympic athletes presented to our Institute after COVID-19 prior to RTP were enrolled. The protocol was dictated by the Italian governing bodies and comprised: 12-lead ECG, blood test, cardiopulmonary exercise test (CPET), 24-h ECG monitoring, and spirometry. Cardiovascular Magnetic Resonance (CMR) was also performed. All Athletes were previously screened in our Institute as part of their periodical pre-participation evaluation. Forty-seven Italian Olympic athletes were enrolled: 83% asymptomatic, 13% mildly asymptomatic, and 4% had pneumonia. Uncommon premature ventricular contractions (PVCs) were found in 13% athletes; however, only 6% ( n = 3) were newly detected. All newly diagnosed uncommon PVCs were detected by CPET. One of these three athletes had evidence for acute myocarditis by CMR, along with Troponin raise; another had pericardial effusion. No one of the remaining athletes had abnormalities detected by CMR. Cardiac abnormalities in Olympic athletes screened after COVID-19 resolution were detected in a minority, and were associated with new ventricular arrhythmias. Only one had evidence for acute myocarditis (in the presence of symptoms and elevated biomarkers). Our data support the efficacy of the clinical assessment including exercise-ECG to raise suspicion for cardiovascular abnormalities after COVID-19. Instead, the routine use of CMR as a screening tool appears unjustified.

Aims: Systemic inflammatory response syndrome (SIRS) could affect mortality after transcatheter aortic valve implantation (TAVI) up to 12 months of follow-up. The aim of this study was to evaluate the prevalence of SIRS after TAVI and its impact on all-cause mortality up to 24 months follow-up., Methods: We retrospectively enrolled 132 patients with symptomatic severe aortic stenosis undergoing TAVI. SIRS development during the first 72 h after the intervention was evaluated. Other postoperative complications were defined according to the Valve Academic Research Consortium 2 (VARC2). All patients underwent follow-up at 30 days and 24 months. Endpoints were 30-days and 24-months mortality., Results: Post-TAVI SIRS developed in 27 patients (20%). At 30-day follow-up, all-cause death occurred in 10 (8%) patients and SIRS occurred more frequently in patients with adverse short-term outcome (60 vs. 17%; P = 0.001). Twenty-four months all-cause death occurred in 25 (19%) patients. SIRS resulted as an independent predictor of long-term outcome [hazard ratio 3.7; 95% confidence interval (95% CI) 1.5-9; P = 0.004], along with major vascular complications (hazard ratio 4; 95% CI 1.6-9.9; P = 0.003), relevant bleedings (hazard ratio 6.4; 95% CI 1.5-28; P = 0.013) and baseline pulmonary hypertension (hazard ratio 2.4; 95% CI 1.05-5.6; P = 0.039)., Conclusion: Postoperative SIRS was more frequent in patients who died at 30 days follow-up. Moreover, SIRS resulted as a predictor of 24-month mortality along with vascular complications, relevant bleedings and baseline pulmonary hypertension., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Effects of Sacubitril/Valsartan (S/V) on left ventricular (LV) mechanics and ventricular-arterial coupling in patients with heart failure with reduced ejection fraction (HFrEF) are not completely understood. The aim of this study was to evaluate both cardiac and vascular remodeling in a group of HFrEF patients undergoing S/V therapy., Methods: Fifty HFrEF patients eligible to start a therapy with S/V were enrolled. Echocardiographic evaluation was performed at baseline and after 6 months of follow-up (FU). Beside standard evaluation, including global longitudinal strain (GLS), estimated hemodynamic forces (HDFs) and non-invasive pressure-volume curves (PV loop) were assessed using dedicated softwares. HDFs were evaluated over the entire cardiac cycle, in systole and diastole, both in apex to base (A-B) and latero-septal (L-S) directions. The distribution of LV HDFs was evaluated by L-S over A-B HDFs ratio (L-S/A-B HDFs ratio). Parameters derived from estimated PV loop curves were left ventricular end-systolic elastance (E es ), arterial elastance (E a ), and ventricular-arterial coupling (VAC)., Results: At 6 months of FU indexed left ventricular end-diastolic and end-systolic volumes decreased (EDVi: 101 ± 28 mL vs. 86 ± 30 mL, p < 0.001; ESVi: 72 ± 23 mL vs. 55 ± 24 mL, p < 0.001), ejection fraction and GLS significantly improved (EF: 29 ± 6% vs. 37 ± 7%, p < 0.001; GLS: -9 ± 3% vs. -13 ± 4%, p < 0.001). A reduction of E a (2.11 ± 0.91 mmHg/mL vs. 1.72 ± 0.44 mmHg/mL, p = 0.008) and an improvement of E es (1.01 ± 0.37 mmHg/mL vs. 1.35 ± 0.6 mmHg/mL, p < 0.001) and VAC (2.3 ± 1.1 vs. 1.5 ± 0.7, p < 0.001) were observed. Re-alignment of HDFs occurred, with a reduction of diastolic L-S/A-B HDFs ratio [23 (20-35)% vs. 20 (11-28) %, p < 0.001]., Conclusion: S/V therapy leads to a complex phenomenon of reverse remodeling involving increased myocardial contractility, HDFs distribution improvement, and afterload reduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Monosilio, Filomena, Luongo, Sannino, Cimino, Neccia, Mariani, Birtolo, Benedetti, Tonti, Pedrizzetti, Vizza, Maestrini and Agati.)

Aim: There is lack of evidence regarding the screening role of ECG for sudden cardiac death (SCD) prevention. Our aim was to evaluate the prevalence of ECG abnormalities among teenagers according to sport participation and competitive status., Methods: Eleven thousand nine hundred and forty-nine Italian pupils from 179 secondary schools (13-19 years) were consecutively enrolled. ECG abnormalities were divided into minor and major. Medical history, clinical examination and sport activity information were acquired. Further evaluations were suggested in case of major ECG abnormalities. Follow-up was performed at 2 years., Results: N = 1945 (16%) pupils had ECG abnormalities. Major ECG abnormalities were detected in 13% of the cohort, minor in 34%. ECG abnormalities were more common in nonathletes compared with athletes. A diagnosis of cardiac disease was reached in 25 (1.6%) of the pupils with major ECG abnormalities., Conclusion: ECG abnormalities are common among young populations and more prevalent in nonathletes. Among pupils with major ECG abnormalities 1.6% had a cardiac disease diagnosis. Our results are in line with the data supporting ECG screening in the general young population., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: The impact of percutaneous mitral valve repair (PMVr) on long-term prognosis in patients with functional mitral regurgitation (FMR) is still unclear. Recently, a new conceptual framework classifying FMR as proportionate (P-MR) and disproportionate (D-MR) was proposed, according to the effective regurgitant orifice area/left ventricular end-diastolic volume (EROA/LVEDV) ratio. The aim was to assess its possible influence on PMVr efficacy., Methods: A total of 56 patients were enrolled. MV annulus, LV volumes and function were assessed. Global longitudinal strain (GLS) was also calculated. Patients were divided into two groups, according to the EROA/LVEDV ratio. Echocardiographic follow-up was performed after 6 months, and adverse events were collected after 12 months., Results: D-MR patients (n = 28, 50%) had a significantly more elliptical MV annulus ( p = 0.048), lower tenting volume ( p = 0.01), higher LV ejection fraction (LVEF: 32 ± 7 vs. 26 ± 5%, p = 0.003), lower LVEDV, LV end-systolic volume (LVESV) and mass (LVEDV/i: 80 ± 20 vs. 126 ± 27 mL, p = 0.001; LVESV/i: 60 ± 20 vs. 94 ± 23 mL, p < 0.001; LV mass: 249 ± 63 vs. 301 ± 69 gr, p = 0.035). GLS was more impaired in P-MR ( p = 0.048). After 6 months, P-MR patients showed a higher rate of MR recurrence. After 12 months, the rate of CV death and rehospitalization due to HF was significantly higher in P-MR patients (46% vs. 7%, p < 0.001). P-MR status was strongly associated with CV death/rehospitalization (HR = 3.4, CI 95% = 1.3-8.6, p = 0.009)., Conclusions: Patients with P-MR seem to have worse outcomes after PVMr than D-MR patients. Our study confirms the importance of the EROA/LVEDV ratio in defining different subsets of FMR based on the anatomical characteristic of MV and LV.

Aims: Ischaemic heart disease is classically associated with coronary artery disease. Recent evidences showed the correlation between coronary microvascular dysfunction and ischaemic heart disease, even independently of coronary artery disease. Ion channels represent the final effectors of blood flow regulation mechanisms and their genetic variants, in particular of Kir6.2 subunit of the ATP-sensitive potassium channel (KATP), are reported to be involved in ischaemic heart disease susceptibility. The aim of the present study is to evaluate the role of KATP channel and its genetic variants in patients with ischaemic heart disease and evaluate whether differences exist between coronary artery disease and coronary microvascular dysfunction., Methods: A total of 603 consecutive patients with indication for coronary angiography due to suspected myocardial ischaemia were enrolled. Patients were divided into three groups: coronary artery disease (G1), coronary microvascular dysfunction (G2) and normal coronary arteries (G3). Analysis of four single nucleotide polymorphisms (rs5215, rs5216, rs5218 and rs5219) of the KCNJ11 gene encoding for Kir6.2 subunit of the KATP channel was performed., Results: rs5215 A/A and G/A were significantly more represented in G1, while rs5215 G/G was significantly more represented in G3, rs5216 G/G and C/C were both more represented in G3, rs5218 C/C was more represented in G1 and rs5219 G/A was more represented in G1, while rs5219 G/G was significantly more represented in G2. At multivariate analysis, single nucleotide polymorphism rs5215&#95;G/G seems to represent an ischaemic heart disease independent protective factor., Conclusions: These results suggest the potential role of KATP genetic variants in ischaemic heart disease susceptibility, as an independent protective factor. They may lead to a future perspective for gene therapy against ischaemic heart disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983&#95;GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983&#95;GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD.

Background: Cardiovascular disease (CVD) can occur in COVID-19 and has impact on clinical course. Data on CVD prevalence in hospitalized COVID-19 patients and sequelae in survivors is limited. Aim of this prospective study carried out on consecutive unselected COVID-19 population, was to assess: 1) CVD occurrence among hospitalized COVID-19 patients, 2) persistence or new onset of CVD at one-month and one-year follow-up., Methods: Over 30 days n = 152 COVID-19 patients underwent cardiovascular evaluation. Standard electrocardiogram (ECG), Troponin and echocardiography were integrated by further tests when indicated. Medical history, arterial blood gas, blood tests, chest computed tomography and treatment were recorded. CVD was defined as the occurrence of a new condition during the hospitalization for COVID-19. Survivors attended a one-month follow-up visit and a one-year telephone follow-up., Results: Forty-two patients (28%) experienced a wide spectrum of CVD with acute myocarditis being the most frequent. Death occurred in 32 patients (21%) and more frequently in patients who developed CVD (p = 0.032). After adjustment for confounders, CVD was independently associated with death occurrence. At one-month follow-up visit, 7 patients (9%) presented persistent or delayed CVD. At one-year telephone follow-up, 57 patients (48%) reported persistent symptoms., Conclusion: Cardiovascular evaluation in COVID-19 patients is crucial since the occurrence of CVD in hospitalized COVID-19 patients is common (28%), requires specific treatment and increases the risk of in-hospital mortality. Persistence or delayed presentation of CVD at 1-month (9%) and persistent symptoms at 1-year follow-up (48%) suggest the need for monitoring COVID-19 survivors., (Copyright © 2021. Published by Elsevier B.V.)

Recent reports based on cardiovascular magnetic resonance (CMR) showed a wide range of prevalence of inflammatory heart diseases in COVID-19 convalescent athletes ranging from 0.4 up to 15%. These observations had an important impact in the field of sport cardiology opening an intense debate around the best possible screening strategy before the return-to-play. The diagnostic yield of CMR for detecting acute inflammatory disease is undebatable. However, the opportunity to use it in the screening protocol after COVID-19 has been questioned. Current evidence does not seem to support the routine use of CMR and the prescription of CMR should be based upon clinical indication.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome responsible for high mortality and morbidity rates. It has an ever growing social and economic impact and a deeper knowledge of molecular and pathophysiological basis is essential for the ideal management of HFpEF patients. The association between HFpEF and traditional cardiovascular risk factors is known. However, myocardial alterations, as well as pathophysiological mechanisms involved are not completely defined. Under the definition of HFpEF there is a wide spectrum of different myocardial structural alterations. Myocardial hypertrophy and fibrosis, coronary microvascular dysfunction, oxidative stress and inflammation are only some of the main pathological detectable processes. Furthermore, there is a lack of effective pharmacological targets to improve HFpEF patients' outcomes and risk factors control is the primary and unique approach to treat those patients. Myocardial tissue characterization, through invasive and non-invasive techniques, such as endomyocardial biopsy and cardiac magnetic resonance respectively, may represent the starting point to understand the genetic, molecular and pathophysiological mechanisms underlying this complex syndrome. The correlation between histopathological findings and imaging aspects may be the future challenge for the earlier and large-scale HFpEF diagnosis, in order to plan a specific and effective treatment able to modify the disease's natural course.

Background: Early detection of myocardial involvement can be relevant in coronavirus disease 2019 (COVID-19) patients to timely target symptomatic treatment and decrease the occurrence of the cardiac sequelae of the infection. The aim of the present study was to assess the clinical value of cardiovascular magnetic resonance (CMR) in characterizing myocardial damage in active COVID-19 patients, through the correlation between qualitative and quantitative imaging biomarkers with clinical and laboratory evidence of myocardial injury., Methods: In this retrospective observational cohort study, we enrolled 27 patients with diagnosis of active COVID-19 and suspected cardiac involvement, referred to our institution for CMR between March 2020 and January 2021. Clinical and laboratory characteristics, including high sensitivity troponin T (hs-cTnT), and CMR imaging data were obtained. Relationships between CMR parameters, clinical and laboratory findings were explored. Comparisons were made with age-, sex- and risk factor-matched control group of 27 individuals, including healthy controls and patients without other signs or history of myocardial disease, who underwent CMR examination between January 2020 and January 2021., Results: The median (IQR) time interval between COVID-19 diagnosis and CMR examination was 20 (13.5-31.5) days. Hs-cTnT values were collected within 24 h prior to CMR and resulted abnormally increased in 18 patients (66.6%). A total of 20 cases (74%) presented tissue signal abnormalities, including increased myocardial native T1 (n = 11), myocardial T2 (n = 14) and extracellular volume fraction (ECV) (n = 10), late gadolinium enhancement (LGE) (n = 12) or pericardial enhancement (n = 2). A CMR diagnosis of myocarditis was established in 9 (33.3%), pericarditis in 2 (7.4%) and myocardial infarction with non-obstructive coronary arteries in 3 (11.11%) patients. T2 mapping values showed a moderate positive linear correlation with Hs-cTnT (r = 0.58; p = 0.002). A high degree positive linear correlation between ECV and Hs-cTnT was also found (r 0.77; p < 0.001)., Conclusions: CMR allows in vivo recognition and characterization of myocardial damage in a cohort of selected COVID-19 individuals by means of a multiparametric scanning protocol including conventional imaging and T1-T2 mapping sequences. Abnormal T2 mapping was the most commonly abnormality observed in our cohort and positively correlated with hs-cTnT values, reflecting the predominant edematous changes characterizing the active phase of disease.

Patent foramen ovale (PFO) is the most common congenital cardiac abnormality found approximately in 25% of the adult population The pathophysiological role of paradoxical embolization through the PFO in ischemic stroke is well established. "Self-expanding double disk" and, more recently, suture-based "deviceless" systems are used for PFO closure in the setting of secondary prevention after ischemic stroke likely related to paradoxical embolization. Ultrasound plays a significant role in PFO assessment, indication to treatment, intra-procedural guidance, and follow-up for those undergoing PFO closure. Three different techniques are frequently used for these purposes: transesophageal echocardiography, transthoracic echocardiogram, and transcranial Doppler. In this review, advantages and limits of these techniques are discussed in detail to improve our skills in detection and treatment of this important condition by using ultrasound., (© 2021 Wiley Periodicals LLC.)

Aim of the present study was to describe the left ventricular longitudinal strain (LS) in all myocardial layers in patients with severe aortic stenosis (AS), preserved left ventricular ejection fraction (LVEF) in different LV geometry and to compare LS analysis before and early after acute LV unloading provided by transcatheter aortic valve implantation (TAVI). 68 patients were enrolled. LS was measured from the endocardial layer (Endo-LS), epicardial layer (Epi-LS) and full thickness of myocardium (Transmural-LS) before and after TAVI. Patients were divided in two groups accordingly with relative wall thickness (RWT): concentric LV hypertrophy (cLVH) vs eccentric LV hypertrophy (eLVH). Less impaired values of LS at baseline were observed, in all layers, in patients with cLVHas compared to patients with eLVH (Endo-LS was - 13.2 ± 2 vs - 11.1±3 %, p = 0.041; Epi-LS was - 11.8 ± 1.8 vs - 9.9 ± 3 %, p = 0.043; Transmural-LS was - 12.3 ± 1.8 vs - 10.49 ± 3.3 %, p = 0.02, respectively). A significant improvement in endocardial LS (Endo-LS) after TAVI was detected only in cLVH(- 13 ± 2 vs - 14 ± 2, p = 0.011). Our findings documented that concentric LVH had better basal strain function and showed a better myocardial recovery after TAVI compared to eLVH.

Ischemic heart disease still represents a large burden on individuals and health care resources worldwide. By conventions, it is equated with atherosclerotic plaque due to flow-limiting obstruction in large-medium sized coronary arteries. However, clinical, angiographic and autoptic findings suggest a multifaceted pathophysiology for ischemic heart disease and just some cases are caused by severe or complicated atherosclerotic plaques. Currently there is no well-defined assessment of ischemic heart disease pathophysiology that satisfies all the observations and sometimes the underlying mechanism to everyday ischemic heart disease ward cases is misleading. In order to better examine this complicated disease and to provide future perspectives, it is important to know and analyze the pathophysiological mechanisms that underline it, because ischemic heart disease is not always determined by atherosclerotic plaque complication. Therefore, in order to have a more complete comprehension of ischemic heart disease we propose an overview of the available pathophysiological paradigms, from plaque activation to microvascular dysfunction.

Objectives: To describe patients according to the maximum degree of respiratory support received and report their inpatient mortality due to coronavirus disease 2019., Design: Analysis of patients in the Coracle registry from February 22, 2020, to April 1, 2020., Setting: Hospitals in the Piedmont, Lombardy, Tuscany, and Lazio regions of Italy., Patients: Nine-hundred forty-eight patients hospitalized for coronavirus disease 2019., Interventions: None., Measurements and Main Results: Among 948 patients, 122 (12.87%) received invasive ventilation, 637 (67.19%) received supplemental oxygen only, and 189 (19.94%) received no respiratory support. The median (quartile 1-quartile 3) age was 65 years (54-76.59 yr), and there was evidence of differential respiratory treatment by decade of life ( p = 0.0046); patients greater than 80 years old were generally not intubated. There were 606 men (63.9%) in this study, and they were more likely to receive respiratory support than women ( p < 0.0001). The rate of in-hospital death for invasive ventilation recipients was 22.95%, 12.87% for supplemental oxygen recipients, and 7.41% for those who received neither ( p = 0.0004). A sensitivity analysis of the 770 patients less than 80 years old revealed a lower, but similar mortality trend (18.02%, 8.10%, 5.23%; p = 0.0008) among the 14.42%, 65.71%, and 19.87% of patients treated with mechanical ventilation, supplemental oxygen only, or neither. Overall, invasive ventilation recipients who died were significantly older than those who survived (median age: 68.5 yr [60-81.36 yr] vs 62.5 yr [55.52-71 yr]; p = 0.0145)., Conclusions: Among patients hospitalized for coronavirus disease 2019, 13% received mechanical ventilation, which was associated with a mortality rate of 23%., Competing Interests: Dr. Mojoli received funding from GE Healthcare (fee for lectures), Hamilton Medical (fee for lectures), and Seda Spa (fee for lecture) and disclosed a consultancy agreement between University of Pavia and Hamilton Medical. On behalf of the Coracle registry, for the purpose of this study, no ICU data were retrieved by Drs. Corcione or Palazzo. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: Despite a successful percutaneous coronary intervention (PCI), several studies reported that the recurrence of angina after revascularization, even complete, is a particularly frequent occurrence in the first year after PCI., Methods: The aim was to evaluate the efficacy of treatment with ranolazine in addition to conventional anti-ischemic therapy in patients who underwent coronary angiography for persistent/recurrent angina after PCI and residual ischemia only due to small branches not suitable for further revascularization. Forty-nine consecutive patients were included in our registry, adding the ranolazine (375 mg b.i.d) to optimal medical therapy (OMT). The Exercise ECG Test (EET) was performed in all patients before to start the therapy (baseline BL) and at 30 days (T1) after enrollment., Results: The average duration of the exercise was increased after the therapy with ranolazine comparing to baseline (RG 9'1'' ± 2' versus BL 8'10'' ± 2', p = 0.01). Seven (14.3%) patients after receiving ranolazine had not crossed the threshold of six minutes (75 watts) compared to 20 (40.8%) of BL ( p = 0.0003). Stress angina appeared more frequently at BL than at 30 days (T1 4.1% versus BL 16.3%, p = 0.04) as well as exercise-induced arrhythmias (BL 30.6% versus T1 14.3%, p = 0.05)., Conclusions: The addition of ranolazine to standard anti-ischemic therapy showed a significant improvement in EET results after one month of therapy, including reduced exercise angina, increased exercise tolerance, and reduced exercise arrhythmias., Competing Interests: The authors declare no conflicts of interest.

Heart failure is a complex syndrome responsible for high rates of death and hospitalization. Ischemic heart disease is one of the most frequent causes of heart failure and it is normally attributed to coronary artery disease, defined by the presence of one or more obstructive plaques, which determine a reduced coronary blood flow, causing myocardial ischemia and consequent heart failure. However, coronary obstruction is only an element of a complex pathophysiological process that leads to myocardial ischemia. In the literature, attention paid to the role of microcirculation, in the pathophysiology of ischemic heart disease and heart failure, is growing. Coronary microvascular dysfunction determines an inability of coronary circulation to satisfy myocardial metabolic demands, due to the imbalance of coronary blood flow regulatory mechanisms, including ion channels, leading to the development of hypoxia, fibrosis and tissue death, which may determine a loss of myocardial function, even beyond the presence of atherosclerotic epicardial plaques. For this reason, ion channels may represent the link among coronary microvascular dysfunction, ischemic heart disease and consequent heart failure.

Heart failure is a multifaceted syndrome addressing for a high rate of death among the general population. The common approach to this disease has been always based on the evaluation of the left ventricular ejection fraction by two-dimensional echocardiography with Simpson's method. Mounting evidences have demonstrated the pitfalls of this method and have suggested that the management of heart failure requires a deep knowledge of the pathophysiological insights of the disease and cannot rely only on the evaluation of the left ventricular ejection fraction. Several advanced imaging technologies overwhelm the evaluation of ejection fraction and could provide a better understanding of the myocardial abnormalities underlying heart failure. Considering the limitation of left ventricular ejection fraction and the systemic involvement of heart failure, classifications of heart failure based on ejection fraction should be substituted with a comprehensive "staging" of multiorgan damage, not only considering the heart but also the lungs, kidneys, and liver, such as the HLM staging system. Such a holistic approach based on the HLM staging system and multimodality imaging can provide a global assessment of patient features allowing for targeted therapies and better heart failure management.

The original version of this article unfortunately contained a mistake.

Advanced heart failure (AdHF) represents a challenging aspect of heart failure patients. Because of worsening clinical symptoms, high rates of re-hospitalization and mortality, AdHF represents an unstable condition where standard treatments are inadequate and additional interventions must be applied. A heart transplant is considered the optimal therapy for AdHF, but the great problem linked to the scarcity of organs and long waiting lists have led to the use of mechanical circulatory support with ventricular-assist device (VAD) as a destination therapy. VAD placement improves the prognosis, functional status, and quality of life of AdHF patients, with high rates of survival at 1 year, similar to transplant. However, the key element is to select the right patient at the right moment. The complete assessment must include a careful clinical evaluation, but also take into account psychosocial factors that are of crucial importance in the out-of-hospital management. It is important to distinguish between AdHF and end-stage HF, for which advanced therapy interventions would be unreasonable due to severe and irreversible organ damage and, instead, palliative care should be preferred to improve quality of life and relief of suffering. The correct selection of patients represents a great issue to solve, both ethically and economically., Competing Interests: The authors declare no conflict of interests.

Purpose: To describe clinical and echocardiographic characteristics associated with reverse left ventricular (LV) remodeling after 6 months of cardiac resynchronization therapy (CRT) in patients with nonischemic dilated cardiomyopathy., Methods: Twenty-four consecutive patients underwent 2D and 3D echocardiography before and after 6 months of CRT implant. Several echocardiographic parameters including global longitudinal strain (GLS) and 3D mechanical dyssynchrony (MD) index were calculated. CRT response was defined as a decrease in LV end-systolic volume (LVESV) of at least 10% at follow-up. Patients were divided in two groups according to CRT response., Results: Cardiac resynchronization therapy responder (CRTR+) rate was 50%. Nonresponder (CRTR-) patients showed a less significant improvement in NYHA class at follow-up. At baseline, CRTR- presented with higher LV end-diastolic volume (LVEDV) (P = 0.031), LVESV (P = 0.024), lower left ventricular ejection fraction (LVEF) (P = 0.002) and less negative GLS (P = 0.03), and with higher diastolic dysfunction, more impaired right ventricle (RV), and higher pulmonary artery systolic pressure (PASP) (P = 0.002). No significant differences in echocardiographic parameters of MD were found. Univariate determinants of CRTR+ were LVEF (OR = 1.59, CI 95% = 1.13-2.22, P = 0.007) and TAPSE (OR 1.21, CI 95% = 1.024-1.429, P = 0.025). A ROC curve analysis showed a cutoff value of LVEF of 22.15% significantly related to CRTR+ (SE 80%, SP 50%)., Conclusions: Our findings suggest that end-stage HF patients, presenting before CRT with LVEF <22.15%, may not benefit from the procedure after 6 months. Mechanical dyssyncronicity did not provide additional information to improve candidate selection., (© 2019 Wiley Periodicals, Inc.)