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Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD) have abnormal myocardial energy metabolism and reduced coronary functional capacity, even in the absence of risk factors for cardiovascular disease (CVD). We aimed to evaluate diastolic and systolic function in NAFLD individuals with preserved ejection fraction without overt CVD. We prospectively included 95 patients (median age 53.0 [IQR 44.5-62.5] years, male sex 44.6%) with ultrasound-diagnosed NAFLD undergoing echocardiographic evaluation, which included speckle tracking analysis with left ventricular global longitudinal strain (GLS) measurement (Philips, Andover, US). Diastolic dysfunction was defined by mitral E/E'>9 and systolic dysfunction was defined by GLS >-18. Significant liver fibrosis (SLF) was defined by Fibrosis-4 (FIB-4) score>1.3. Obesity, type 2 diabetes (T2D), arterial hypertension and dyslipidemia were present in 43.3%, 21.1%, 46.2% and 57.8% of cases, while median FIB-4 was 0.97 [0.67-1.24]. SLF, diastolic and systolic dysfunction were found in 20%, 17% and 18.3% of the total. Higher FIB-4 levels were found in both diastolic and systolic dysfunction (p=0.003 and p=0.001). SLF was associated with diastolic dysfunction (OR 6.8 [95%CI 1.8-25.5], p=0.004), showing an Area Under the Curve of 0.76 (Se 76.9%, Sp 72.2%, PPV 33.3%, NPV 94.5%). In a multiple stepwise logistic regression model including T2D, obesity, arterial hypertension, dyslipidemia, male sex and SLF, both SLF and T2D were significantly and independently associated with diastolic dysfunction (aOR of SLF 6.2 [95%CI 1.5-25.1, p=0.011). In the same regression model for systolic dysfunction, only T2D showed a significant association (aOR 4.6 [95%CI 1.3-16.8], p=0.021). In NAFLD patients with preserved ejection fraction, SLF by FIB-4 is associated with diastolic dysfunction independently of major risk factors for CVD. Screening echocardiography may be recommended in this population. Funding: the Italian Ministry for Education, University and Research (MIUR) under the programme "Dipartimenti di Eccellenza 2018-2022" Project code D15D18000410001. [ABSTRACT FROM AUTHOR]

Background: The clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non-flow-limiting lesions remains uncertain., Objectives: The authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE)., Methods: Thirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling., Results: CPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the prevalence of CPCs among plaques was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes., Conclusions: Characterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810)., Competing Interests: Funding Support and Author Disclosures In the past 2 years, Dr Porto has received speaker or advisor fees from GE, Terumo, Medtronic, Abbott, Philips, Sanofi, Amgen, and Daiichi-Sankyo, all outside of the scope of the submitted work; his laboratory has received support from Chiesi and Amgen. Dr Williams is supported by the British Heart Foundation (FS/ICRF/20/26002) and has given lectures for Canon Medical Systems and Siemens Healthineers. Dr Pontone has received speaker honoraria or research grants from GE Healthcare, Heartflow, Bracco, and Boehringer. Dr Libby is an unpaid consultant to or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Cartesian, Esperion, Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Novo Nordisk, Merck, Novartis, Pfizer, and Sanofi-Regeneron. Dr Libby is a member of scientific advisory boards for Amgen, Corvidia Therapeutics, Caristo, CSL Behring, DalCor Pharmaceuticals, Dewpoint, PlaqueTec, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, TenSixteen Bio, and XBiotech; his laboratory has received research funding in the last 2 years from Novartis; he is on the Board of Directors of and has a financial interest in Xbiotech, a company developing therapeutic human antibodies; his interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies; and he has received funding support from the National Heart, Lung, and Blood Institute (1R01HL134892), the American Heart Association (18CSA34080399), the RRM Charitable Fund, and the Simard Fund. Dr Stone has received speaker honoraria from Pulnovo and Infraredx; is a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; his daughter is an employee of Medtronic; and his employer, Mount Sinai Hospital, receives research support from Abbott, Bioventrix, Cardiovascular Systems, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, and V-wave. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In terms of pathophysiology, tricuspid regurgitation (TR), right ventricular function and pulmonary artery pressure are linked to each other. Our aim was to analyze whether the echocardiography-derived right ventricular free wall longitudinal strain/pulmonary artery systolic pressures (RVFWLS/PASP) ratio can improve risk stratification in patients with severe tricuspid regurgitation (TR)., Methods: In this single-center retrospective study, 250 consecutive patients with severe TR were enrolled from December 2015 to December 2018. Baseline clinical and echocardiographic parameters were collected. Echocardiography-derived TAPSE/PASP and RVFWLS/PASP were evaluated. The primary endpoint was all-cause mortality., Results: Out of 250 consecutive patients, 171 meet inclusion criteria. Patients were predominantly female, with several cardiovascular risk factors and comorbidities. RVFWLS/PASP ≤0.34%/mmHg (AUC 0.68, p < 0.001, sensitivity 70%, specificity 67%) was associated with baseline clinical RV heart failure (p = 0.03). After univariate and multivariate analyses, RVFWLS/PASP, but not TAPSE/PASP, independently correlated with all-cause mortality (HR 0.004, p = 0.02). Patients with RVFWLS/PASP >0.26%/mmHg (AUC 0.74, p < 0.001, sensitivity 77%, specificity 52%) showed higher survival rates (p = 0.02). In addition at 24 months follow-up, the Kaplan-Meyer curves showed patients with RVFWLS >14% & RVFWLS/PASP >0.26%/mmHg had the best survival rate compared to patients without., Conclusion: RVFWLS/PASP is independently associated with baseline RV heart failure and poor long-term prognosis in patients with severe TR., Competing Interests: Declaration of Competing Interest None. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Each author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Transventricular beating-heart mitral valve repair (TBMVR) with artificial chordae implantation is a technique to treat mitral valve prolapse. Two-dimensional (2D) echocardiography completed with simultaneous biplane view during surgeon finger pushing on the left ventricular (LV) wall (finger test [FT]) is currently used to localize the desired LV access, on the inferior-lateral wall, between the papillary muscles (PMs). We aimed to compare a new three-dimensional (3D) method with conventional FT in terms of safety and better localization of LV access., Methods: During TBMVR, conventional FT was completed using 3D transesophageal echocardiography by placing the sample box in the bicommissural view of the LV, including the PMs and the apex. The 3D volume was subsequently edited to visualize the LV from above (surgical view) to localize the bulge of the operator's finger pushing on the LV. We asked the first operator, the second operator, and the cardiac surgery fellow, separately, to evaluate the location of their finger pushing, both with the 2D method and the 3D method, to estimate the interoperator concordance., Results: From 2019 to 2021, 42 TBMVRs were performed without complications related to access using FT completed with the 3D method. Regarding the choice of the right and safe entry site, the operator's agreement was higher using 3D rendering compared with conventional FT (mean agreement 0.59 ± 0.29 for 2D vs 0.83 ± 0.20 for 3D), while full operator agreement was 10 of 42 for 2D and 23 of 42 for 3D ( P = 0.004)., Conclusions: Three-dimensional FT is easy to perform and facilitates surgeons choosing the best access for TBMVR in term of anatomical localization and safety.

The identification of heart failure (HF) patients at risk for arrhythmic sudden cardiac arrest (SCA) is a major challenge in the cardiovascular field. In addition to optimal medical treatment for HF, implantable cardioverter defibrillator (ICD) is currently recommended to prevent SCA in patients with reduced left ventricular ejection fraction (LVEF). The indication for an ICD implantation, in addition to HF etiology, New York Health Association (NYHA) class and life expectancy, mainly depends on LVEF value at echocardiography. However, the actual role of LVEF in the prediction of SCA has recently been debated, while newer multimodality imaging techniques with increased prognostic accuracy have been developed. Speckle tracking imaging allows the quantification of mechanical dispersion, a marker of electrophysiological heterogeneity predisposing to malignant arrhythmias, while advanced cardiac magnetic resonance techniques such as myocardial T1-mapping and extracellular volume fraction assessment allow the evaluation of interstitial diffuse fibrosis. Nuclear imaging is helpful for the appraisal of sympathetic nervous system dysfunction, while newer computed tomography techniques assessing myocardial delayed enhancement allow the identification of focal myocardial scar. This review will focus on the most modern advances in the field of cardiovascular imaging along with its applications for the prediction of SCA in patients with HF. Modern artificial intelligence applications in cardiovascular imaging will also be discussed., 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Background: Right ventricular dysfunction (RVD) is a major issue in patients with advanced heart failure because it precludes the implantation of left ventricular assist device, usually leaving heart transplantation (HTx) as the only available treatment option. The pulmonary artery pulsatility index (PAPi) is a hemodynamic parameter integrating information of right ventricular function and of pulmonary circulation. Our aim is to evaluate the association of preoperative RVD, hemodynamically defined as a low PAPi, with post-HTx survival., Methods and Results: Consecutive adult HTx recipient at 2 Italian transplant centers between 2000 and 2018 with available data on pre-HTx right heart catheterization were included retrospectively. RVD was defined as a value of PAPi lower than the 25th percentile of the study population. The association of RVD with the 1-year post-HTx mortality and other secondary end points were evaluated. Multivariate logistic regression was used to adjust for clinical and hemodynamic variables. Analyses stratified by pulmonary vascular resistance (PVR) status (≥3 Woods units vs <3 Woods units) were also performed. Among 657 HTx recipients (female 31.1%, age 53 ± 11 years), patients with pre-HTx RVD (PAPi of <1.68) had significantly lower 1-year survival rates (77.8% vs 87.1%, P = .005), also after adjusting for estimated glomerular filtration rate, total bilirubin, PVR, serum sodium, inotropes, and mechanical circulatory support at HTx (hazard ratio 2.0, 95% confidence interval, 1.3-3.1). RVD was also associated with post-HTx renal replacement therapy (hazard ratio 2.0, 95% confidence interval 1.05-3.30) and primary graft dysfunction (hazard ratio 1.7, , 95% confidence interval 1.02-3.30). When stratifying patients by estimated PVR status, RVD was associated with worse 1-year survival among patients with normal PVR (76.9% vs 88.3%, P = .003), but not in those with increased PVR (78.6% vs 83.2%, P = .49)., Conclusions: Preoperative RVD, evaluated through PAPi, is associated with mortality and morbidity after HTx, providing incremental prognostic value over traditional clinical and hemodynamic parameters., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cardiac implantable electronic device (CIED) implantation rates as well as the clinical and procedural characteristics and outcomes in patients with known active coronavirus disease 2019 (COVID-19) are unknown., Objective: The purpose of this study was to gather information regarding CIED procedures during active COVID-19, performed with personal protective equipment, based on an international survey., Methods: Fifty-three centers from 13 countries across 4 continents provided information on 166 patients with known active COVID-19 who underwent a CIED procedure., Results: The CIED procedure rate in 133,655 hospitalized COVID-19 patients ranged from 0 to 16.2 per 1000 patients (P <.001). Most devices were implanted due to high-degree/complete atrioventricular block (112 [67.5%]) or sick sinus syndrome (31 [18.7%]). Of the 166 patients in the study survey, the 30-day complication rate was 13.9% and the 180-day mortality rate was 9.6%. One patient had a fatal outcome as a direct result of the procedure. Differences in patient and procedural characteristics and outcomes were found between Europe and North America. An older population (76.6 vs 66 years; P <.001) with a nonsignificant higher complication rate (16.5% vs 7.7%; P = .2) was observed in Europe vs North America, whereas higher rates of critically ill patients (33.3% vs 3.3%; P <.001) and mortality (26.9% vs 5%; P = .002) were observed in North America vs Europe., Conclusion: CIED procedure rates during known active COVID-19 disease varied greatly, from 0 to 16.2 per 1000 hospitalized COVID-19 patients worldwide. Patients with active COVID-19 infection who underwent CIED implantation had high complication and mortality rates. Operators should take these risks into consideration before proceeding with CIED implantation in active COVID-19 patients., (Copyright © 2021 Heart Rhythm Society. All rights reserved.)

Background: The placebo effect is a well described phenomenon in blinded studies evaluating antianginal therapeutics, although its effect on clinical research metrics remains unknown. We conducted a systematic review and meta-analysis to quantify the effect of placebo on end points of symptoms, life quality, and functional outcomes in randomized placebo-controlled trials (RCTs) of symptomatic stable coronary artery disease., Methods: We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for double-blind RCTs of antiangina therapeutics. Patients randomized to the placebo arm were the study population. Main outcomes were the changes in exercise performance (exercise treadmill test [ETT] parameters), quality of life (Seattle Angina Questionnaire domains), symptoms (Canadian Cardiovascular Society angina class) and drug usage (nitroglycerin tablets per week) between baseline and after placebo treatment. The primary outcome was ETT total duration time. Data were pooled with a random effect model., Results: Seventy-eight RCTs (83% drug-controlled, 17% procedure-controlled) were included encompassing 4925 patients randomized to placebo. ETT total duration time was significantly improved after placebo treatment compared with baseline (mean, 29.2; 95% confidence interval, 20.6-37.8] seconds) with evidence of high heterogeneity (I 2  = 98%) At subgroup analysis, crossover design was associated with a smaller placebo effect on ETT performance than parallel study design (P for interaction = 0.001). A significant placebo effect was observed for all secondary outcomes with overall high heterogeneity., Conclusions: A substantial placebo effect was present in angina RCTs across a variety of functional and life quality metrics. High variability in placebo effect size was present, mostly unexplained by differences in study and patient characteristics., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with patent foramen ovale (PFO) and cryptogenic ischemic stroke (CS) are at risk for stroke recurrence. The optimal antithrombotic strategy in patients who undergo medical management is still debated., Methods: We systematically searched the literature for studies that reported on cerebrovascular event recurrences and/or death in patients with PFO treated with oral anticoagulation (OAC) or antiplatelet therapy (APT) for secondary prevention of CS. The efficacy endpoints were stroke recurrence and the composite of stroke, transient ischemic attack or all-cause death. Major bleedings represented the safety endpoint., Results: A total of 16 studies with 3953 patients (OAC = 1527, APT = 2426) were included. Weighted mean follow-up was 2.9 years. OAC was associated with a significant reduction in the risk of stroke compared with APT (RR 0.65; 95% CI 0.44-0.95; ARR 2%, NNT 49), while no difference was found regarding the composite outcome (RR 0.78; 95% CI 0.57-1.07) and the safety outcome (RR 1.57; 95% CI 0.85-2.90; p = 0.15)., Conclusions: OAC was more effective than APT in reducing the risk of stroke recurrence in patients with PFO and CS, without a significant increase in the risk of major bleedings. Our findings support the need for further randomized data focused on the comparison of antithrombotic strategies in this setting., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)