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Purpose To establish a COronary Risk Score in WOmen (CORSWO) to predict major adverse coronary events (MACE). Materials and Methods This retrospective analysis included 2226 female individuals (mean age, 66.7 years ± 11.6 [SD]) from a cohort of 25 943 consecutive patients referred for clinical gated SPECT myocardial perfusion imaging (gSPECT MPI). During the follow-up (mean, 4 years ± 2.7) after gSPECT MPI, occurrence of MACE (unstable angina requiring hospitalization, nonfatal myocardial infarction, coronary revascularization, cardiac death) was assessed. The patients were divided into training ( n = 1460) and validation ( n = 766) groups. To obtain the predictor model, multiple Cox regression analyses were performed. Results In the training group, 148 female individuals had MACE (2.6% per year). The best model (area under the receiver operating characteristic curve [AUC]: 0.80 [95% CI: 0.74, 0.83]; Brier score: 0.08) to predict MACE in female individuals included the following variables: age older than 69 years (hazard ratio [HR]: 1.58, P = .01), diabetes mellitus (HR: 1.47, P = .03), pharmacologic test (HR: 1.63, P = .01), ST-segment depression (≥1 mm) (HR: 2.02, P < .001), myocardial ischemia greater than 5% (HR: 2.21, P < .001), perfusion defect at rest greater than 9% (HR: 1.96, P = .009), perfusion defect at stress greater than 6% (HR: 1.63, P = .03), and end-systolic volume index greater than 15 mL (HR: 2.04, P < .001). During validation, the model achieved moderate performance (AUC: 0.78 [95% CI: 0.70, 0.83]). CORSWO obtained from these variables allowed for stratification of female individuals into four risk levels: low (score: 0-3, HR: 1), moderate (score: 4-6, HR: 1.58), high (score: 7-11, HR: 4.13), and very high (score: >11, HR: 13.87). The high and very high risk levels (HR: 5.29) predicted MACE in female individuals, with excellent performance (AUC: 0.78 [95% CI: 0.72, 0.80]). Conclusion With clinical, stress test, and gSPECT MPI variables, CORSWO effectively stratified female individuals according to coronary risk and was able to detect those with high and very high risk. Keywords: SPECT, Cardiac, Coronary Arteries, Women, Risk Stratification, Cardiac Event, CORSWO, MACE, Gated SPECT Supplemental material is available for this article. ©RSNA, 2024.

Cysteine proteases calpains contribute to heart failure (HF), but it remains unknown whether their inhibition provides any benefit compared to standard pharmacological treatment for HF. Here, we characterize the pharmacological properties of NPO-2270 (NPO) as a potent inhibitor of cysteine proteases. Then, we describe that acute administration of NPO in rodent models of transient ischemia at the time of reperfusion reduces myocardial infarction, while its chronic oral administration attenuates adverse remodeling and cardiac dysfunction induced by ischemic and non-ischemic pathological stimuli more effectively than enalapril when given at the same dose. Finally, we provide evidence showing that the effects of NPO correlate with calpain inhibition and the preservation of the T-tubule morphology, due at least in part to reduced cleavage of the calpain substrate junctophilin-2. Together, our data highlight the potential of cysteine protease inhibition with NPO as a therapeutic strategy for the treatment of heart failure., Competing Interests: Dr. J. Inserte received a grant from Landsteiner Genmed SL., (© 2024 The Author(s).)

Background: Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms remain unclear. This prospective, longitudinal study evaluates the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients., Methods: Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two time-resolved three-dimensional phase-contrast cardiovascular magnetic resonance (4D flow CMR) studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two matched cohorts of 40 healthy volunteers (HV) and 16 sHTAD patients without indication for aortic root replacement (sHTAD-NSx) with available 4D flow CMR were included for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV), and aortic strain were analyzed in the ascending (AscAo) and descending aorta (DescAo)., Results: All patients with sHTAD presented altered hemodynamics and increased stiffness (p < 0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9 m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3 m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm 2 /s in HV, p = 0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p = 0.002), and decreased WSS (0.36 vs 0.47 N/m 2 in HV, p = 0.004) in the proximal DescAo. After VSARR, proximal DescAo IRF (p = 0.010) and circumferential WSS increased (p = 0.011), no longer differing from HV, but SFRR, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3 cm 2 /s, p = 0.047). Most AscAo flow alterations were restored to physiological values after VSARR., Conclusion: In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arturo Evangelista and Gisela Teixido-Tura report financial support was provided by Carlos III Health Institute. Jose Rodriguez-Palomares and Ignacio Ferreira Gonzalez report financial support was provided by the Spanish Ministry of Science, Innovation and Universities. Jose Rodriguez-Palomares and Gisela Teixido-Tura report financial support was provided by the Spanish Society of Cardiology. Andrea Guala reports financial support was provided by La Caixa Foundation. Juan Garrido-Oliver reports financial support was provided by Secretaria d’Universitats i Recerca del Departament de Recerca i Universitats de la Generalitat de Catalunya i del Fons Europeu Social Plus. Kevin M. Johnson and Oliver Wieben report a relationship with General Electric Healthcare that includes non-financial support. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Longitudinal data on reverse cardiac remodeling and outcomes after transcatheter edge-to-edge repair (TEER) are limited., Methods: A total of 78 patients with severe mitral regurgitation (MR) were included retrospectively. All patients had echocardiography at baseline and again six months after TEER. They were monitored for a primary composite endpoint, consisting of heart failure hospitalization and cardiovascular death, over 13 months., Results: Significant decreases in the left ventricular ejection fraction (LVEF), all myocardial work indices (except global wasted work), and the left atrial reservoir were observed after TEER. Additionally, there was a decrease in the pulmonary artery systolic pressure and an increase in the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. A post-TEER TAPSE/PASP ratio of <0.47 (HR: 4.76, p -value = 0.039), and a post-TEER left atrial reservoir of <9.0% (HR: 2.77, p -value = 0.047) were associated with the primary endpoint., Conclusions: Echocardiography post-TEER reflects impairment in ventricular performance due to preload reduction and right ventricle and pulmonary artery coupling improvement. Short-term echocardiography after TEER identifies high-risk patients who could benefit from a close clinical follow-up. The prognostic significance of LA strain and the TAPSE/PASP ratio should be validated in subsequent large-scale prospective studies.

Introduction : Non-ischemic dilated cardiomyopathy (NIDCM) is characterized by a reduced left ventricular (LV) ejection fraction (LVEF, <50%) and a high risk for heart failure (HF) and death. Echocardiography-derived hemodynamic forces (HDFs) may provide important information on LV mechanics, but their prognostic value is unknown. Aim : To explore the features of echocardiography-derived HDFs in NIDCM and their association with clinical endpoints. Methods : Asymptomatic, non-hospitalized NIDCM patients free from coronary artery disease and moderate or severe valvular heart disease were included in this single-center observational retrospective longitudinal study. Those with atrial fibrillation and a follow-up <12 months were excluded. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death, HF hospitalization, and ambulatory intravenous diuretics administration. LV HDFs were analyzed with a prototype software. Apex-base (HDFs-ab), lateral-septal (HDFs-ls), and HDFs-angle were computed. Results : Ninety-seven patients were included, sixty-seven (69%) were males, mean age was 62 ± 14 years, and mean LVEF was 39.2 ± 8.6%. During a median follow-up of 4.2 (3.1-5.1) years, 19 (20%) patients experienced MACE. These patients had a higher HDFs-angle (71.0 (67.0-75.0) vs. 68.0 (63.0-71.0)°, p = 0.005), lower HDFs-ls (1.36 (1.01-1.85) vs. 1.66 ([1.28-2.04])%, p = 0.015), but similar HDFs-ab (5.02 (4.39-6.34) vs. 5.66 (4.53-6.78)%, p = 0.375) compared to those without MACE. in a Cox regression analysis, HDFs-angle (HR 1.16 (95%-CI 1.04-1.30), p = 0.007) was associated with MACE, while other conventional echocardiography parameters, including LVEF and LV longitudinal strain, were not. Conclusions : HDFs-angle is associated with clinical endpoints in NIDCM. A higher HDFs-angle may be a marker of impaired myocardial performance in patients with reduced LVEF.

Aims: Atrial fibrillation (AF) is a common comorbidity in non-ischaemic dilated cardiomyopathy (NIDCM) affecting conventional measures of left atrial (LA) function. We aimed to determine whether LA function analysis could identify patients at higher risk of major cardiovascular events (MACEs)., Methods and Results: A retrospective study of patients with NIDCM in AF referred to a single centre for transthoracic echocardiography (TTE) between 2015 and 2019. Peak atrial longitudinal strain (PALS) was measured along with LA emptying fraction and LA filling index (LAFI = E wave/PALS). Cox regression analysis was conducted. A total of 153 patients were included [median age 74 years, left ventricular ejection fraction (LVEF) 35%], and 57 (37.3%) had MACE after a median follow-up of 3.2 years. LAFI was the only independent TTE parameter associated with MACE after adjustment for age, diabetes, LVEF, left ventricular global longitudinal strain (LV-GLS), and LA volume index [adjusted hazard ratio (HR) = 1.02 per point increase, P = 0.024], with the best cut-off at ≥15. LAFI ≥15 predicted each of MACE components when separately analysed: MACE HR = 1.95, 95% confidence interval (CI) 1.16-3.30; cardiovascular death HR = 3.68, 95% CI 1.41-9.56, heart failure admission HR = 2.13, 95% CI 1.19-3.80, and ventricular arrhythmia HR = 4.72, 95% CI 1.52-14.67. Higher LAFI was associated with worsening LV-GLS, E / e ', systolic pulmonary artery (PA) pressure, tricuspid annular plane systolic excursion, and right ventricular to PA coupling., Conclusion: LA deformation analysis is feasible in patients with NIDCM presenting with AF. LAFI may identify patients at higher risk of MACE and correlates with higher pulmonary pressures and worse right ventricular function, suggesting an elevation of left-sided ventricular pressures in patients with higher LAFI., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The measurement of aortic dimensions and their evolution are key in the management of patients with aortic diseases. Manual assessment, the current guideline-recommended method and clinical standard, is subjective, poorly reproducible, and time-consuming, limiting the capacity to track aortic growth in everyday practice. Aortic geometry mapping (AGM) via image registration of serial computed tomography angiograms outperforms manual assessment, providing accurate and reproducible 3D maps of aortic diameter and growth rate. This observational study aimed to evaluate the accuracy and reproducibility of AGM on non-gated contrast-enhanced (CE-) and cardiac- and respiratory-gated (GN-) magnetic resonance angiographies (MRA)., Methods: Patients with thoracic aortic disease followed with serial CE-MRA (n = 30) or GN-MRA (n = 15) acquired at least 1 year apart were retrospectively and consecutively identified. Two independent observers measured aortic diameters and growth rates (GR) manually at several thoracic aorta reference levels and with AGM. Agreement between manual and AGM measurements and their inter-observer reproducibility were compared. Reproducibility for aortic diameter and GR maps assessed with AGM was obtained., Results: Mean follow-up was 3.8 ± 2.3 years for CE- and 2.7 ± 1.6 years for GN-MRA. AGM was feasible in the 93% of CE-MRA pairs and in the 100% of GN-MRA pairs. Manual and AGM diameters showed excellent agreement and inter-observer reproducibility (ICC>0.9) at all anatomical levels. Agreement between manual and AGM GR was more limited, both in the aortic root by GN-MRA (ICC=0.47) and in the thoracic aorta, where higher accuracy was obtained with GN- than with CE-MRA (ICC=0.55 vs 0.43). The inter-observer reproducibility of GR by AGM was superior compared to manual assessment, both with CE- (thoracic: ICC= 0.91 vs 0.51) and GN-MRA (root: ICC=0.84 vs 0.52; thoracic: ICC=0.93 vs 0.60). AGM-based 3D aortic size and growth maps were highly reproducible (median ICC >0.9 for diameters and >0.80 for GR)., Conclusion: Mapping aortic diameter and growth on MRA via 3D image registration is feasible, accurate and outperforms the current manual clinical standard. This technique could broaden the possibilities of clinical and research evaluation of patients with aortic thoracic diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 μL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion., Competing Interests: The authors declare no conflicts of interest.

TRPV4 channels, which respond to mechanical activation by permeating Ca 2+ into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 involvement in pathological and physiological remodeling through Ca 2+ -dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca 2+ dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4-/- mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4-/-, displayed significant TRPV4 overexpression, elevated Ca 2+ influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4-/- mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca 2+ -dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response.

Objectives: The aim of this study was to create a new Vall d'Hebron Risk Score-II (VH-RS-II) for non-fatal myocardial infarction (MI) and/or cardiac death (CD), excluding patients with coronary revascularisation (CR) during the follow-up., Methods: We analysed 5215 consecutive patients underwent gated single photon emission CT (SPECT); 2960 patients (age 64.2±11, male 58.1%) had no previous MI and/or CR, and 2255 patients (age 63.3±11, male 81.9%) had previous MI and/or CR. During a follow-up of 4.3±2.6 years, the cardiac event (MI and CD) was evaluated. This study was reviewed and approved by the ethics committee of our institution (number form trial register, PR(AG)168.2012). To obtain the predictor model, multivariate Cox regression analysis and multivariate logistic regression analysis were used. RS-VH-II was validated with 679 patients., Results: In patients without previous MI and/or CR, age (HR: 1.01; p<0.001), diabetes (HR: 2.1, p=0.001), metabolic equivalent (METs) (HR: 0.89, p=0.038), ST segment depression (HR: 1.4, p=0.011), ejection fraction (EF) (HR: 0.97, p<0.001) and summed stress score (HR: 1.2, p<0.001) were the independent predictors of CE (C-statistic: 0.8). In patients with previous MI and/or CR, age (HR: 1.06, p<0.001), male (HR: 1.9, p=0.047), smoker (HR: 1.5, p=0.047), METs (HR: 0.8, p<0.001), ST segment depression (HR: 1.4, p=0.002), EF (HR: 0.96; p<0.001) and summed difference score (HR: 1.03, p=0.06) were the independent predictors of CE (C-statistic:0.8)., Conclusion: The VH-RS-II obtained from different clinical exercise and gated SPECT variables allow the risk stratification for MI and CD in patients with or without previous MI and/or CR in due form., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes., Methods and Results: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS., Conclusion: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Infective endocarditis (IE) is a serious albeit relatively infrequent disease. Given the paucity of cases, particularly in non-referral centres, patient registries have progressively gained relevance to inform about the epidemiology, clinical presentation, and natural history of IE in the last two decades. Although they have become key to advancing knowledge of IE, registries also have shortcomings that lead to relevant consequences that are often overlooked., Objectives: We aimed to discuss the strengths and limitations of registries in IE., Sources: We conducted a PubMed search of relevant articles published between January 2000 and June 2022., Content: The backbone of the contemporary knowledge on IE has been built upon data collected in prospective registries, which has allowed us to collect data on relatively unknown aspects of the disease, identify knowledge gaps, and generate new hypotheses, serving as platforms for further research endeavours. Well-exploited registries can provide key information on how IE is distributed across populations and how it differentially impacts patients and subgroups. However, registries face several difficulties, such as the definition of IE, which includes subjective variables and changes over time. Other limitations include difficulty achieving a comprehensive collection of cases (which depends on both project funding and information systems), over-representation of the centres that created the registry, lack of inclusion of variables to assess endpoints that are relevant to patients in terms of quality of life and prognosis, and ethical issues., Implications: The review of the advantages and disadvantages of registries aims to improve the quality of the information collected, the viability of the registry itself, and the ability to answer questions that are relevant to both researchers and patients., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Succinate is enhanced during initial reperfusion in blood from the coronary sinus in ST-segment elevation myocardial infarction (STEMI) patients and in pigs submitted to transient coronary occlusion. Succinate levels might have a prognostic value, as they may correlate with edema volume or myocardial infarct size. However, blood from the coronary sinus is not routinely obtained in the CathLab. As succinate might be also increased in peripheral blood, we aimed to investigate whether peripheral plasma concentrations of succinate and other metabolites obtained during coronary revascularization correlate with edema volume or infarct size in STEMI patients. Plasma samples were obtained from peripheral blood within the first 10 min of revascularization in 102 STEMI patients included in the COMBAT-MI trial (initial TIMI 1) and from 9 additional patients with restituted coronary blood flow (TIMI 2). Metabolite concentrations were analyzed by 1 H-NMR. Succinate concentration averaged 0.069 ± 0.0073 mmol/L in patients with TIMI flow ≤ 1 and was significantly increased in those with TIMI 2 at admission (0.141 ± 0.058 mmol/L, p < 0.05). However, regression analysis did not detect any significant correlation between most metabolite concentrations and infarct size, extent of edema or other cardiac magnetic resonance (CMR) variables. In conclusion, spontaneous reperfusion in TIMI 2 patients associates with enhanced succinate levels in peripheral blood, suggesting that succinate release increases overtime following reperfusion. However, early plasma levels of succinate and other metabolites obtained from peripheral blood does not correlate with the degree of irreversible injury or area at risk in STEMI patients, and cannot be considered as predictors of CMR variables.Trial registration: Registered at www.clinicaltrials.gov (NCT02404376) on 31/03/2015. EudraCT number: 2015-001000-58., (© 2023. The Author(s).)

Background: Ischaemic cardiomyopathy is a leading cause of heart failure and is associated with a poor prognosis., Aim: To evaluate predictors of major adverse cardiovascular events (MACE) and to develop a risk score for the disease., Methods: All patients with ischaemic cardiomyopathy referred to a tertiary hospital between 2010 and 2018 for stress-rest gated single-photon emission computed tomography (SPECT) were included retrospectively (n=747). Clinical and gated SPECT-derived variables were analysed as predictors of MACE, a combined endpoint of cardiovascular mortality, heart failure hospitalization or myocardial infarction during follow-up. A multivariable Cox model using backwards stepwise regression with competing risks was used to select the best parsimonious model., Results: After a median follow-up of 4.7 years, 313 patients had MACE (41.9%). Independent predictors of MACE were previous heart failure admission, worsening angina or dyspnoea, estimated glomerular filtration rate ≤60mL/min/1.73 m 2 , age>73 years, diabetes, atrial fibrillation, end-diastolic volume index>83mL/m 2 and>12% of scarred myocardium. A risk score ranging from 0 to 12 classified patients as at intermediate risk (event rate of 4.0 MACE per 100 person-years), high risk (11.3 MACE per 100 person-years) or very high risk (27.8 MACE per 100 person-years). The internally validated area under the curve was 0.720 (95% confidence interval 0.660-0.740) and calibration was adequate (Hosmer-Lemeshow test P=0.28) for MACE., Conclusions: In patients with ischaemic cardiomyopathy, a simple risk score using dichotomic and readily available variables obtained from clinical assessment and gated SPECT accurately predicts the risk of MACE., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Myocardial injury after non-cardiac surgery (MINS) is a frequent complication caused by cardiac and non-cardiac pathophysiological mechanisms, but often it is subclinical. MINS is associated with increased morbidity and mortality, justifying the need to its diagnose and the investigation of their causes for its potential prevention., Methods: Prospective, observational, pilot study, aiming to detect MINS, its relationship with silent coronary artery disease and its effect on future adverse outcomes in patients undergoing major non-cardiac surgery and without postoperative signs or symptoms of myocardial ischemia. MINS was defined by a high-sensitive cardiac troponin T (hs-cTnT) concentration > 14 ng/L at 48-72 h after surgery and exceeding by 50% the preoperative value; controls were the operated patients without MINS. Within 1-month after discharge, cardiac computed tomography angiography (CCTA) and magnetic resonance imaging (MRI) studies were performed in MINS and control subjects. Significant coronary artery disease (CAD) was defined by a CAD-RADS category ≥ 3. The primary outcomes were prevalence of CAD among MINS and controls and incidence of major cardiovascular events (MACE) at 1-year after surgery. Secondary outcomes were the incidence of individual MACE components and mortality., Results: We included 52 MINS and 12 controls. The small number of included patients could be attributed to the study design complexity and the dates of later follow-ups (amid COVID-19 waves). Significant CAD by CCTA was equally found in 20 MINS and controls (30% vs 33%, respectively). Ischemic patterns (n = 5) and ischemic segments (n = 2) depicted by cardiac MRI were only observed in patients with MINS. One-year MACE were also only observed in MINS patients (15.4%)., Conclusion: This study with advanced imaging methods found a similar CAD frequency in MINS and control patients, but that cardiac ischemic findings by MRI and worse prognosis were only observed in MINS patients. Our results, obtained in a pilot study, suggest the need of further, extended studies that screened systematically MINS and evaluated its relationship with cardiac ischemia and poor outcomes. Trial registration Clinicaltrials.gov identifier: NCT03438448 (19/02/2018)., (© 2023. The Author(s).)

Background: The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the CE of major adverse cardiac events (MACE)., Methods: A systematic review and quantitative synthesis of trials that include MACE as the primary outcome through search strategies in MEDLINE and EMBASE electronic databases. We limited to articles published in journals indexed in the first quartile of the Cardiac & Cardiovascular Systems category (Journal Citation Reports, 2015-2020). The authors were contacted to estimate the DoA between death and AMI using joint probability and correlation. We analyzed the SSR variation using the DoA estimated from RCTs., Results: Sixty-three of 134 publications that reported event rates and the therapy effect in all component endpoints were included in the quantitative synthesis. The most frequent combination was death, AMI, and revascularization (n = 20; 31.8%). The correlation between death and AMI, estimated from 5 trials¸ oscillated between - 0.02 and 0.31. SSR varied from 14,602 in the scenario with the strongest correlation to 12,259 in the scenario with the weakest correlation; the relative impact was 16%., Conclusions: The DoA between death and AMI is highly variable and may lead to a considerable SSR variation in a trial including MACE., (© 2022. The Author(s).)

Aims: The burden of ischaemia is a risk factor for adverse outcomes in ischaemic cardiomyopathy (ICM) but is not systematically tested when deciding on revascularization. Limited data exists in patients with ICM regarding the interaction between ischaemia and early coronary revascularization (ECR). This study sought to determine if the burden of ischaemia modifies the outcomes of ECR in ICM., Methods and Results: Consecutive patients with ICM (left ventricular ejection fraction < 40%) with a stress-rest gated single-photon emission computed tomography (N = 747) were followed-up for ECR and major cardiovascular events (MACEs, cardiovascular death, myocardial infarction, or heart failure hospitalization). A 1:1 matched population was selected using a propensity score for ECR. The interaction between ischaemia and ECR was evaluated in the matched cohort. In the initial cohort, 131 patients underwent ECR. Of them, 109 were matched to non-ECR patients. After a median follow up of 4.1 years, 102 (46.8%) patients experienced a MACE. The effect of revascularization on MACE was dependent of the percent of ischaemia (P for the interaction at 10% ischaemia = 0.021), so that a trend towards a decreased risk of MACE was seen in patients with >10% of ischaemia [hazard ratio (HR) = 0.59 (0.30-1.18)], whereas a non-significant increase of MACE was observed in those with <10% ischaemia (HR = 1.67 [0.94-2.96])., Conclusions: In a contemporary cohort of patients with ICM, the beneficial effects of ECR may be mediated by the percent of ischaemia. This study supports stress testing in ICM and an ischaemia-guided approach for ECR., Competing Interests: Conflicts of interest: E.R.-A. has received non-conditioned grants from Biotronik, Micropport, Johnson&Johnson, Sanofi, and Sanofi Genzyme; none of them related to the current topic., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Diagnosis of prosthetic valve endocarditis (PVE) by positron emission computed tomography angiography (PET/CTA) is based on visual and quantitative morpho-metabolic features. However, the fluorodeoxyglucose (FDG) uptake pattern can be sometimes visually unclear and susceptible to subjectivity. This study aimed to validate a new parameter, the valve uptake index [VUI, maximum standardized uptake value (SUVmax)-mean standardized uptake value (SUVmean)/SUVmax], designed to provide a more objective indication of the distribution of metabolic activity. Secondly, to re-evaluate the utility of traditionally used PVE imaging criteria and determine the potential value of adding the VUI in the diagnostic algorithm of PVE., Methods and Results: Retrospective analysis of 122 patients (135 prosthetic valves) admitted for suspicion of endocarditis, with a conclusive diagnosis of definite (N = 57) or rejected (N = 65) PVE, and who had undergone a cardiac PET/CTA scan as part of the diagnostic evaluation. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern, and the presence of endocarditis-related anatomic lesions. The VUI, SUVmax, and SUVratio values were 0.54 ± 0.1 vs. 0.36 ± 0.08, 7.68 ± 3.07 vs. 3.72 ± 1.11, and 4.28 ± 1.93 vs. 2.16 ± 0.95 in the 'definite' PVE group vs. the 'rejected' group, respectively (mean ± SD; P < 0.001). A cut-off value of VUI > 0.45 showed a sensitivity, specificity, and diagnostic accuracy for PVE of 85%, 88%, and 86.7% and increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria., Conclusions: The VUI demonstrated good diagnostic accuracy for PVE, even increasing the diagnostic power of the traditionally used morphometabolic parameters, which also confirmed their own diagnostic performance. More research is needed to assess whether the integration of the VUI into the PVE diagnostic algorithm may clarify doubtful cases and thus improve the diagnostic yield of PET/CTA., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)