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Aims: While factors associated with adverse events are well elucidated in setting of isolated left ventricular dysfunction, clinical and imaging-based prognosticators of adverse outcomes are lacking in context of biventricular dysfunction. The purpose of this study was to establish role of clinical variables in prognosis of biventricular heart failure (HF), as assessed by cardiac magnetic resonance imaging., Methods: Study cohort consisted of 840 patients enrolled in DERIVATE registry with coexisting CMR-derived right ventricular (RV) and left ventricular (LV) dysfunction, as defined by RV and LV ejection fractions ≤45 % and ≤ 50 %, respectively. The primary objective was to identify factors associated with adverse long-term outcomes, defined as composite of all-cause death and HF hospitalizations (DHFH). Kaplan-Meir curves were plotted for survival analysis. Cox proportional hazard models were constructed to estimate adjusted hazard ratios (aHRs) and associated 95 % confidence intervals for clinical variables and their correlation with adverse events., Results: Mean age was 61.0 years; 83.1 % were male, 26.6 % had diabetes mellitus (DM), and 45.9 % had non-ischemic cardiomyopathy. At median follow-up of 2 years, DHFH occurred in 32.5 % of the cohort. Kaplan-Meir analysis showed higher rate of DHFH in patients with DM (35.2 % vs. 22.6 %, p < 0.001). Multivariate Cox regression analysis showed that DM was independently associated with DHFH (aHR 1.61 [95 % CI: 1.15-2.25]; p = 0.003). Importantly, ACE-inhibitor/ARB usage in patients with DM was associated with significant reduction in DHFH (aHR 0.53 [95 % CI: 0.31-0.90]; p = 0.02)., Conclusion: In patients with biventricular HF, DM was a strong predictor of DHFH, with ACE-inhibitor/ARB usage having cardioprotective effect., Competing Interests: Declaration of competing interest Subhi J. Al’Aref is supported by NIH: National Institutes of Health, USA 2R01 HL12766105 & 1R21 EB030654 and receives royalty fees from Elsevier. Carlo De Cecco received grant from Siemens. Gianluca Pontone received institutional fees by General Electric, Bracco, Heartflow, Medtronic, Bayer, Bhoeringher. Juerg Schwitter received research support by Bayer Healthcare Switzerland. U. Joseph Schoepf received grant by Astellas, Bayer, General Electric, and Siemens Healthcare, personal fees by Guerbet, speaking honorarium by Heartflow. Akos Varga-Szemes received grant from Siemens Healthcare and personal fees from Elucid Bioimaging. The other authors have no conficts of interestes relevant to this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated., Methods: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones., Results: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women., Conclusions: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Previous studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS., Methods and Results: CORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39-0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5-2.39 and HR 1.85,95%CI 1.6-2.14, respectively)., Conclusions: Incidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022. Published by Elsevier B.V.)

Background A new imaging metric using coronary computed tomography angiography (CCTA), addressing the peri-coronary adipose tissue (PCAT) computed tomography (CT) attenuation, has been clinically validated. This method provides information regarding coronary inflammation. It is unclear how coronary inflammation affects microvascular function. The non-invasive evaluation of coronary flow velocity reserve is widely used in clinical practice using Doppler measurement on the left anterior descending coronary artery (CFVR-lad) during stress-echocardiography (SE). We hypothesize that coronary inflammation affects CFVR-lad and, in the absence of overt CAD, they are significantly correlated. Methods We evaluated the relationship between coronary inflammation (by PCAT CT attenuation) and coronary microvascular function (by CFVR-lad) in subjects with no or non-obstructive (diameter stenosis <70%) coronary artery disease (CAD). Results Two-hundred and two subjects were enrolled in the study. The relationship between PCAT CT attenuation and CFVR-lad show a significant inverse relationship in the entire group of subjects enrolled in the study (r = -0.32, p < 0.001). Correlation between PCAT CT attenuation and CFVR-lad was significant in subjects with no or mild CAD-lad, while this was not the case in subjects with intermediate CAD-lad. The R and R 2 were respectively -0.40, -0.16 in subjects without CAD (p < 0.001) and - 0.35 and - 0.12 in subjects with mild CAD-lad (p = 0.001). Conclusions The main finding of the current study is the independent relationship between coronary microvascular function, by Doppler CFVR-lad during SE, in subjects without severely obstructive CAD in the left anterior descending coronary artery, and the level of local coronary inflammation, by PCAT attenuation measurement on CCTA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: The impact of Covid-19 on the survival of patients presenting with acute coronary syndrome (ACS) remains to be defined., Methods: Consecutive patients presenting with ACS at 18 Centers in Northern-Italy during the Covid-19 outbreak were included. In-hospital all-cause death was the primary outcome. In-hospital cardiovascular death along with mechanical and electrical complications were the secondary ones. A case period (February 20, 2020-May 3, 2020) was compared vs. same-year (January 1-February 19, 2020) and previous-year control periods (February 20-May 3, 2019). ACS patients with Covid-19 were further compared with those without., Results: Among 779 ACS patients admitted during the case period, 67 (8.6%) tested positive for Covid-19. In-hospital all-cause mortality was significantly higher during the case period compared to the control periods (6.4% vs. 3.5% vs. 4.4% respectively; p 0.026), but similar after excluding patients with COVID-19 (4.5% vs. 3.5% vs. 4.4%; p 0.73). Cardiovascular mortality was similar between the study groups. After multivariable adjustment, admission for ACS during the COVID-19 outbreak had no impact on in-hospital mortality. In the case period, patients with concomitant ACS and Covid-19 experienced significantly higher in-hospital mortality (25% vs. 5%, p < 0.001) compared to patients without. Moreover, higher rates of cardiovascular death, cardiogenic shock and sustained ventricular tachycardia were found in Covid-19 patients., Conclusion: ACS patients presenting during the Covid-19 pandemic experienced increased all-cause mortality, driven by Covid-19 positive status due to higher rates of cardiogenic shock and sustained ventricular tachycardia. No differences in cardiovascular mortality compared to non-pandemic scenarios were reported., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To determine whether calcifications of the coronary arteries (coronary artery calcium 0 to 4 score), or extending the assessment also to cardiac valves and thoracic aorta (overall calcium 0 to 8 score), as seen on computed tomography for attenuation correction during stress-scintigraphy (SPECT-CT), are associated with total mortality and non-fatal myocardial infarction. We aimed to assess whether these calcifications added to the prognostic value of SPECT imaging., Background: The presence/amount of calcium in the coronary arteries, but also in the heart valves and aorta, has been associated with cardiovascular (CV) and all-cause mortality. This information can be obtained during SPECT-CT examinations, where low resolution CT images are co-registered for attenuation correction of myocardial perfusion, but then discarded., Methods: Clinical data were collected on 353 consecutive patients submitted to stress SPECT-CT between Sept 2010 and Oct 2012, for suspected coronary artery disease (CAD). Follow-up data on outcomes were collected retrospectively., Results: Mean age was 72 and 58% were male. Mean follow-up was 6.4 years, during which 48 subjects died (15 from CV causes) and 10 had non-fatal myocardial infarction (MI). Reversible perfusion defects were detected in 55 patients (15.6%), 39 of whom (11%) had >mild defects. The presence of a calcium score > 1 in the attenuation correction images was the strongest univariate predictor of all-cause death or MI (hazard ratio 7.21, p < .001). On multivariate analysis, controlling for age, gender and myocardial perfusion defects an overall calcium score > 2 remained a predictor of all-cause death or non-fatal MI (hazard ratio 4.12, p < .001)., Conclusions: Visual assessment of coronary or overall coronary, cardiac and aortic calcium in the CT images used for attenuation correction during SPECT-CT is feasible and reproducible. It was strongly associated with all-cause death and MI, even after controlling for clinical variables and myocardial perfusion data. This simple visual calcium assessment does not add additional costs or radiation, and may significantly improve risk-assessment of patients with suspected CAD undergoing SPECT-CT., Condensed Abstract: Calcium in the coronary arteries, heart valves and aorta has been associated with worse prognosis. We sought to determine whether assessment of such calcifications on computed tomography images (co-registered for myocardial perfusion attenuation correction and then discarded) are independently associated with long-term outcome on top of available data. We enrolled 353 consecutive patients, referred for suspected coronary artery disease. An overall calcium score > 1 in the attenuation correction images was the strongest univariate (hazard ratio 7.21, p < .001) and multivariate predictor of all-cause death or non-fatal MI (hazard ratio 4.12, p < .001), even after controlling for clinical variables and myocardial perfusion data., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: We assessed whether the non-invasive measure of peak diastolic-systolic velocity ratio (rDSVR) at rest on the left anterior descending artery (LAD) using Doppler transthoracic echocardiography is associated with obstructive coronary artery disease (CAD) on the LAD and left main (LM) arteries. We compared rDSVR diagnostic accuracy with stress wall motion (WM) and coronary flow reserve (CFR-LAD), in a group of subjects who underwent contrast stress-echocardiography (cSE) and coronary angiography within 3 months., Methods: 286 patients selected with a clinical indication to cSE, in which CFR-LAD was measured during the test who also underwent coronary angiography within 3 months were selected and diagnostic performance compared., Results: Demographics and clinical variables were univariate predictors of LAD or LM >50% stenosis, but rDSVR < 1.7 outperformed other variables (OR 11.18, 95% CI 5.82-21.49, p < 0.001), comprising cSE variables such as reversible WM abnormalities (OR 1.53, 95% CI 0.94-2.49, p = 0.087) or CFR-LAD < 2 (OR 2.88, 95% CI 21.74-4.77, p < 0.001). The addition of rDSVR to multivariate logistic regression models (clinical or clinical + cSE variables) led to a marked increase in C-index (0.82, 95%CI 0.78-0.87) with significant improvement compared to all prior models (p < 0.001)., Conclusions: Our data suggest a strict association of reduced rDSVR with >50% coronary artery stenosis on the LM/LAD, superior to other standard clinical or cSE related indexes, such as WM assessment or CFR-LAD, and builds incrementally to them and clinical variables in multivariable logistic models for the prediction of CAD on LM and LAD coronaries., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Increasing evidence exists regarding calcium detected in aortic cusps and/or mitral annulus (AOC&#95;MAC) at transthoracic echocardiogram as a predictor of cardiovascular (CV) events and mortality., Purpose: To verify whether AOC&#95;MAC has a prognostic role in the setting of primary prevention independently of the presence of atrial fibrillation (AF)., Methods: All subjects consecutively referred from January 2011 to October 2014 to the Cardiovascular Centre for CV risk assessment in primary prevention were selected. AOC&#95;MAC was assessed by transthoracic echocardiography. Primary study endpoint was a composite of CV hospitalizations/all-cause death., Results: The 1389 study patients were 70 years old, 43% males, 24% had diabetes mellitus, 75% arterial hypertension, 56% dyslipidaemia. Of all, 997 (72%) were in sinus rhythm (SR), 392 (28%) in AF. Patients with AF were older and more frequently males, with larger atria than SR subjects. During a median follow-up of 32 months, 165 patients (12%) were hospitalized for CV cause, 68 (5%) died. The primary endpoint occurred more frequently in patients with than without AOC&#95;MAC (18% vs 11%, p < 0.001). AF patients showed higher event-rate compared with patients in SR (20% vs 10%, respectively; p < 0.01). AOC&#95;MAC emerged as an independent prognosticator of primary endpoint in SR patients (HR 1.74 [1.07-2.82], p = 0.02), together with increasing age and left ventricular hypertrophy, while AOC&#95;MAC had no prognostic relevance in AF patients., Conclusions: In subjects with multiple CV risk factors assessed in primary prevention, the presence of AF nullifies the prognostic power of AOC&#95;MAC, on the contrary robustly confirmed in SR patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The trial "Stress Echo (SE) 2020" evaluates novel applications of SE beyond coronary artery disease. The aim of the study was control quality and harmonize reading criteria., Methods: One reader from 78 centers of the SE 2020 network asked for credentials to read a set of 20 SE video-clips selected by the core lab. All aspiring centers met the pre-requisite of high-volume and the years of experience in SE ranged from 5 to 31years (mean value 18years). The diagnostic gold standard was a reading by the core lab. The a priori determined pass threshold was 18/20 (≥90%)., Results: Of the initial 78 who started, 57 completed the first attempt: individual readers' score on first attempt ranged from 07/20 to 20/20 (accuracy from 35% to 100%, mean 78.7±13%) and 44 readers passed it. There was a very poor correlation between years of experience and the reader's score on first attempt (r=-0.161, p=0.231). Of the 13 readers who failed the first attempt, 12 took it again after the web-based session and their accuracy improved (74% vs. 96%, p<0.001). The kappa inter-observer agreement before and after web-based training was 0.59 on first attempt and rose to 0.91 on the last attempt., Conclusions: In SE reading, the volume of activity or years of experience is not synonymous with diagnostic quality. Qualitative analysis and operator-dependence can become a limiting weakness in clinical practice, in the absence of strict pathways of learning, credentialing and audit., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Although it is well documented that an exaggerated sympathetic stimulation plays a role in the development of Takotsubo Syndrome (TS) during the acute phase, only few studies have focused on autonomic adaptations in stress-induced cardiomyopathy long after the acute phase. Aim of the study was to investigate whether an impairment of the autonomic function is still present long after a TS event. This was done by comparing the response to a maximal exercise test in TS patients after apparent recovery (>1-year after the acute event) with that obtained in healthy subjects and in post-myocardial infarction (post-MI) patients., Methods: To assess heart rate recovery (HRR) and chronotropic response (CR), 24 TS patients, 25 healthy subjects and 22 post-MI patients underwent maximal exercise test, after at least 3 days of β-blockers wash-out., Results: HRR in TS patients (19.2±9.7bpm) was lower than in healthy subjects (27.7±8.3, p=0.003), and similar to post-MI patients (19.3±8.4; p=0.99). A decreasing CR trend (p=0.06), higher in healthy subjects (72±13%) than in TS (65±22%) and post-MI (57±21%) patients, was also found., Conclusion: Compared to healthy subjects, TS patients showed a blunted parasympathetic reactivation after exercise, similar to that observed in post-MI patients, thereby suggesting that vagal control of heart rate after exercise is abnormal long after the acute presentation of TS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Unlabelled: There are no studies analyzing the association between aortic valve sclerosis (AVS) and coronary artery disease (CAD) in a large and multicenter patient population with an overall low prevalence of CAD. We hypothesized that AVS could predict the presence and degree of CAD in patients with severe organic mitral regurgitation., Methods: We retrospectively analyzed consecutive patients with flail mitral leaflet who had coronary angiography for pre-surgical screening and not because suspect of CAD. End-points were considered: 1) any degree of CAD (stenosis>20%) and 2) obstructive CAD (stenosis>75% of at least one coronary artery). AVS was defined as focal areas of increased echogenicity and thickening of the leaflets. Traditional clinical risk factors were considered: age, male gender, hypertension (>140/90 mmHg or medical therapy), hypercholesterolemia (total cholesterol>200 mg/dl or statin), diabetes, family history of CAD and smoking habit., Results: 675 patients (mean age: 64±12; 27% female) formed the study population. Among patients with AVS, 60% and 39% had any-CAD and ob-CAD respectively, on the opposite among patients without AVS 12% and 7% had any-CAD and ob-cad. After adjustment for clinical risk factors, AVS was associated with a 22.7 fold increased risk of any degree of CAD (95% CI 8.1 63.6 p<0.0001) and with a 21.8 fold increased risk of obstructive-CAD (95% CI 6.6 71.9; p<0.0001)., Conclusion: In a large and multicenter sample of patient with flail mitral leaflet, AVS was strongly associated with the presence and degree of CAD independently of clinical risk factors., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)