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Background & Aim: The extent and composition of coronary plaque, and its progression differ with patients' age. The interplay of patient's age with respect to risk factor control, upon atheroma progression has not been evaluated. We tested the hypothesis that risk factor control modulates the association between age and coronary atheroma progression., Method: We performed a posthoc pooled analysis of data from 10 prospective, randomised trials involving serial coronary intravascular ultrasonography (IVUS) (n=5,823). The percent atheroma volume (PAV) was calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque., Results: Mean overall age was 58±9 years (28% women). In a fully adjusted multivariable analysis (following adjustment of sex, body mass index, systolic blood pressure [SBP], smoking, high-density lipoprotein and low-density lipoprotein [LDL]-cholesterol, triglyceride levels, peripheral vascular disease, diabetes mellitus, trial, region, and baseline PAV), an increase in age by one standard deviation was linked with PAV progression (β-estimate 0.097; 95% confidence interval 0.048-0.15; p<0.001). In patients with good risk factor control (LDL-cholesterol <1.8 mmol/L and SBP <130 mmHg), increasing age remained associated with PAV progression (0.123; 0.014-0.23; p=0.027). Lower effect sizes for the association of age with PAV progression were observed for patients with partial control of LDL-cholesterol and SBP and were not significantly associated with PAV progression when both LDL-cholesterol and SBP were not controlled (0.099; 0.032-0.167; p=0.004 and 0.042; -0.056 to 0.14; p=0.40, respectively)., Conclusions: Patient age is directly associated with coronary atheroma progression independently of traditional cardiovascular risk factors. In the setting of poor risk factor control, the influence of age on coronary artery disease progression is attenuated., Competing Interests: Conflicts of Interest S.E.N. reported receiving grants from AstraZeneca, Novartis, AbbVie, Silence Therapeutics, Medtronic, MyoKardia, Esperion, Eli Lilly, Amgen, Novo Nordisk, Pfizer, Cerenis, and The Medicines Company. S.J.N. reported receiving grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience and receiving personal fees from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. All other authors report no conflict of interest with regard to this work., (Copyright © 2024. Published by Elsevier B.V.)

Background: Smoking has conflicting results on outcomes following acute myocardial infarction (AMI). We evaluated the independent influence of smoking status on patient outcomes., Methods: We included patients with AMI undergoing invasive coronary angiography with available self-reported smoking status. The incidence of death of any cause was evaluated during a median follow-up of 1.14 years (range 0.36-3.40 years). Association between smoking status and long-term mortality was evaluated using multivariable adjusted Cox regression analysis., Results: From 1612 AMI patients (aged 65.7 ± 13.3 years, 72.1 % male), 378 patients (23.4 %) were current-smokers, 311 (19.3 %) ex-smokers, and 923 (57.3 %) non-smokers. Compared with non-smokers, current-smokers were younger (68.5 ± 13.0 vs. 58.6 ± 12.5, p < 0.0001) and more frequently presented with STEMI (21.6 % vs. 35,4 %, p < 0.0001), while ex-smokers with similar frequency of STEMI-manifestation as non-smokers (22.5 %, p = 0.79) constituted an intermediate-group in terms of age (65.8 ± 11,6 years). Although smoking status was not significantly associated with long-term survival in unadjusted-analysis, active-smokers had 56 % higher long-term mortality than non-smokers when adjusting for age, gender, medications and other traditional risk factors, whereas ex-smokers possessed comparable survival probability (current-smokers: 1.56[1.14-2.14], p = 0.006, ex-smokers 1.16[0.84-1.59], p = 0.37). Current-smokers had unadjusted lower NT-proBNP and modestly higher absolute in-hospital left ventricular global longitudinal strain (LV GLS) values that did not differ among groups after the same adjustments (NT-proBNP: -0.08[-0.31; 0.15], p = 0.5, LV GLS: 0.65[-0.26; 1.55], p = 0.16)., Conclusion: Active smoking is associated with increased adjusted long-term mortality, earlier onset and more frequent manifestation as STEMI, compared to non-smoking. Comparable adjusted results for LV GLS and NT-proBNP between groups support the presence of the pseudoparadox., Competing Interests: None., (© 2024 The Authors.)

Background and Aims: Current ESC guidelines on the management of patients after acute myocardial infarction only include the evaluation of left ventricular (LV) function by assessment of the ejection fraction in addition to clinical risk scores to estimate the patient's prognosis. We aimed to determine, whether comprehensive evaluation of cardiac function using LV and right ventricular (RV) global longitudinal strain (GLS) and left atrial (LA) reservoir strain improves the prediction of survival in patients with acute myocardial infarction., Methods: In patients with non-ST segment elevation or ST segment elevation myocardial infarction receiving echocardiography within 1 year after revascularisation, LV-GLS, RV-GLS and LA reservoir strain were quantified. In multivariable Cox regression analysis, HRs and 95% CIs were calculated per 1 SD increase in strain measure, adjusting for age, sex, systolic blood pressure, low-density lipoprotein cholesterol, smoking, diabetes and family history of premature coronary artery disease., Results: During a median follow-up of 1.5 (0.5-4.2) years, 157 (11.1%) out of 1409 patients (64.4±13.5 years, 24.7% female) died. LV-GLS (1.68 (1.37-2.06), p<0.001), RV-GLS (1.39 (1.16-1.67), p<0.001) and LA reservoir strain (0.57 (0.47-0.69), p<0.001) were associated with mortality. Adding LV ejection fraction, tricuspid annular plane systolic excursion (TAPSE) or LA volume index to these models did not alter the association of strain measures of the LV (1.41 (1.06-1.89), p=0.02), RV (1.48 (1.03-2.13), p=0.04) or LA (0.61 (0.49-0.76), p<0.001). In receiver operating characteristics, combining the three strain measures improved the prediction of mortality above risk factors (AUC: 0.67 (0.63-0.71) to 0.75 (0.70-0.80)), while further addition of LV ejection fraction, TAPSE and LA volume index did not (0.75 (0.70-0.81))., Conclusion: The comprehensive evaluation of contractility of various cardiac chambers via transthoracic echocardiography using myocardial strain analysis, when routinely performed after acute myocardial infarction, may help to detect patients at increased mortality risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We evaluated the ability of the assessment of regional wall motion abnormalities (RWMA) detected via transthoracic echocardiography to predict the presence of obstructive coronary artery disease (CAD) in patients presenting with acute chest pain to the emergency department., Design: Prospective single-centre observational study., Setting: Tertiary care university hospital emergency unit., Participants: Patients presenting to the emergency department with acute chest pain suggestive of obstructive CAD., Primary Outcome Measure: The primary endpoint was defined as the presence of obstructive CAD, requiring revascularisation therapy., Results: Overall, 657 patients (age 58.1±18.0 years, 53% men) were included in our study. RWMA were detected in 76 patients (11.6%). RWMA were significantly more frequent in patients reaching the primary endpoint (26.2% vs 7.6%, p<0.001). In multivariable regression analysis, the presence of RWMA was associated with threefold increased odds of the presence of obstructive CAD (3.41 (95% CI 1.99 to 5.86), p<0.001). Adding RWMA to a multivariable model of the Thrombolysis in Myocardial Infarction (TIMI) risk score, cardiac biomarkers and traditional risk factors significantly improved the area under the curve for prediction of obstructive CAD (95% CI 0.777 to 0.804, p=0.0092)., Conclusion: RWMA strongly and independently predicts the presence of obstructive CAD in patients presenting with acute chest pain to the emergency department., Trial Registration: The study has been registered online (NCT03787797)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute total occlusion (ATO) is diagnosed in a substantial proportion of patients with non-ST-elevation myocardial infarction (NSTEMI). We compared procedural outcomes and long-term mortality in patients with STEMI with NSTEMI with vs. without ATO., Methods and Results: We included patients with acute myocardial infarction (AMI) undergoing invasive coronary angiography between 2004 and 2019 at our centre. Acute total occlusion was defined as thrombolysis in myocardial infarction (TIMI) 0-1 flow in the infarct-related artery or TIMI 2-3 flow with highly elevated peak troponin (>100-folds the upper reference limit). Association between presentation and long-term mortality was evaluated using multivariable adjusted Cox regression analysis. From 2269 AMI patients (mean age 66 ± 13.2 years, 74% male), 664 patients with STEMI and 1605 patients with NSTEMI (471 [29.3%] with ATO) were included. ATO(+)NSTEMI patients had a higher frequency of cardiogenic shock and no reflow than ATO(-)NSTEMI with similar rates compared with STEMI patients (cardiogenic shock: 2.76 vs. 0.27 vs. 2.86%, P < 0.0001, P = 1; no reflow: 4.03 vs. 0.18 vs. 3.17%, P < 0.0001, P = 0.54). ATO(+)NSTEMI and STEMI were associated with 60 and 55% increased incident mortality, respectively, as compared with ATO(-)NSTEMI (ATO(+)NSTEMI: 1.60 [1.27-2.02], P < 0.0001, STEMI: 1.55 [1.24-1.94], P < 0.0001). Likewise, left ventricular ejection fraction (48.5 ± 12.7 vs. 49.1±11 vs. 50.6 ± 11.8%, P = 0.5, P = 0.018) and global longitudinal strain (-15.2 ± -5.74 vs. -15.5 ± -4.84 vs. -16.3 ± -5.30%, P = 0.48, P = 0.016) in ATO(+)NSTEMI were comparable to STEMI but significantly worse than in ATO(-)NSTEMI., Conclusion: Non-ST-elevation myocardial infarction patients with ATO have unfavourable procedural outcomes, resulting in increased long-term mortality, resembling STEMI. Our findings suggest that the occlusion perspective provides a more appropriate classification of AMI than differentiation into STEMI vs. NSTEMI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: In transcatheter aortic valve replacement (TAVR) recipients, the optimal management of concomitant chronic obstructive coronary artery disease (CAD) remains unknown. Some advocate for pre-TAVR percutaneous coronary intervention, while others manage it expectantly. The aim of this study was to assess the impact of varying degrees and extent of untreated chronic obstructive CAD on TAVR and longer-term outcomes., Methods: The authors conducted a retrospective cohort study of TAVR recipients from January 2015 to November 2021, separating patients into stable non-obstructive or varying degrees of obstructive CAD. The major outcomes of interest were procedural all-cause mortality and complications, major adverse cardiovascular events, and post-TAVR unplanned coronary revascularization., Results: Of the 1911 patients meeting inclusion, 75%, 6%, 10%, and 9% had non-obstructive, intermediate-risk, high-risk, and extreme-risk CAD, respectively. Procedural complication rates overall were low (death 0.4%, shock 0.1%, extracorporeal membrane oxygenation 0.1%), with no difference across groups. At a median follow-up of 21 months, rates of acute coronary syndrome and unplanned coronary revascularization were 0.7% and 0.5%, respectively, in the non-obstructive population, rising in incidence with increasing severity of CAD (P < .001 for acute coronary syndrome/unplanned coronary revascularization). Multivariable analysis did not yield a significantly greater risk of all-cause mortality or major adverse cardiovascular events across groups. One-year acute coronary syndrome and unplanned coronary revascularization rates in time-to-event analyses were significantly greater in the non-obstructive (98%) vs. obstructive (94%) subsets (Plog-rank< .001)., Conclusions: Transcatheter aortic valve replacement can be performed safely in patients with untreated chronic obstructive CAD, without portending higher procedural complication rates and with relatively low rates of unplanned coronary revascularization and acute coronary syndrome at 1 year., (© The Author(s) 2024. 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: Cardiac troponin I (cTnI) above the 99 th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99 th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99 th percentile in patients undergoing coronary angiography., Methods: The study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99 th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint., Results: Detectable cTnI below the 99 th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99 th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45-1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39-1.90) for the first tertile to 2.02 (95 % CI 1.74-2.35) for the third tertile., Conclusions: Detectable cTnI below the 99 th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.T. and T.R. report personal fees and others from Edwards, Novartis, Bristol Myers Squibb, Bayer, Daiichi Sankyo und AstraZeneca and Pfizer outside the submitted work. T.R. is a co-founder of Bimyo, a company focusing on the development of cardioprotective peptides. L.M. reports personal fees from Bayer, Alnylam, AstraZeneca, IFFM e. V. and from Bund der Niedergelassenen Kardiologen (BNK) outside the submitted work. M.S.A. reports personal fees from Servier, outside the submitted work. P.F. is the founder and CEO of Pharmahungary Group, a group of R&D companies. All other authors report no conflict of interest. D.D. obtained honoraria for educational lectures from Daiichi Sankyo, all unrelated to this work., (© 2024 The Authors. Published by Elsevier B.V.)

Aims: Conduction abnormalities necessitating permanent pacemaker (PPM) implantation remain the most frequent complication post-transcatheter aortic valve implantation (TAVI), yet reliance on PPM function varies. We evaluated the association of right-ventricular (RV)-stimulation rate post-TAVI with 1-year major adverse cardiovascular events (MACE) (all-cause mortality and heart failure hospitalization)., Methods and Results: This retrospective cohort study of patients undergoing TAVI in two high-volume centers included patients with existing PPM pre-TAVI or new PPM post-TAVI. There was a bimodal distribution of RV-stimulation rates stratifying patients into two groups of either low [≤10%: 1.0 (0.0, 3.6)] or high [>10%: 96.0 (54.0, 99.9)] RV-stimulation rate post-TAVI. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated comparing MACE in patients with high vs. low RV-stimulation rates post-TAVI. Of 4659 patients, 408 patients (8.6%) had an existing PPM pre-TAVI and 361 patients (7.7%) underwent PPM implantation post-TAVI. Mean age was 82.3 ± 8.1 years, 39% were women. A high RV-stimulation rate (>10%) development post-TAVI is associated with a two-fold increased risk for MACE [1.97 (1.20, 3.25), P = 0.008]. Valve implantation depth was an independent predictor of high RV-stimulation rate [odds ratio (95% CI): 1.58 (1.21, 2.06), P =<0.001] and itself associated with MACE [1.27 (1.00, 1.59), P = 0.047]., Conclusion: Greater RV-stimulation rates post-TAVI correlate with increased 1-year MACE in patients with new PPM post-TAVI or in those with existing PPM but low RV-stimulation rates pre-TAVI. A shallower valve implantation depth reduces the risk of greater RV-stimulation rates post-TAVI, correlating with improved patient outcomes. These data highlight the importance of a meticulous implant technique even in TAVI recipients with pre-existing PPMs., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Brain natriuretic peptide (BNP)/N-terminal-pro hormone brain natriuretic peptides (NT-proBNP) enable risk stratification, diagnosing, and monitoring of heart failure patients. An additional prognostic value for BNP/NT-proBNP in nonheart failure patients and general population cohorts is described in the literature, but specific cut-off levels are only described for heart failure patients., Objectives: This study aimed to determine thresholds for risk stratification in nonheart failure patients., Methods: Based on the Essen Coronary Artery Disease registry we excluded patients with known heart failure or elevated BNP/NT-pro BNP levels. The resulting cohort was divided into a derivation and validation cohort using random sampling. The prognostic value of BNP/NT-proBNP of incident mortality was evaluated in the derivation cohort using univariate and multivariable cox regression analysis. In receiver operating characteristic analysis and corresponding area under the curve the optimal threshold was determined using Youdens J index. The findings were verified in the validation cohort., Results: A total of 3,690 patients (age 62.9 ± 12.5 years, 71% male, 68% patients with coronary artery disease) were included. During a mean follow-up of 2.6 ± 3.4 years (median 1.2 [IQR: 0.4-2.88]), 169 deaths of any cause occurred. Based on Youden's J index, BNP-thresholds of 9.6 and 29pg/ml and NT-proBNP thresholds of 65 and 77pg/ml for men and women, respectively, were determined. BNP/NT-proBNP levels above these thresholds were associated with increased mortality in the derivation cohort (HR: 2.44 [95% CI: 1.32-4.53], P  = 0.005). The predictive value was confirmed in the validation cohort (HR: 2.78 [95% CI: 1.26-6.14], P  = 0.01)., Conclusions: We here describe sex-specific BNP/NT-proBNP thresholds that allow prediction of impaired survival in patients without heart failure, independent of traditional cardiovascular risk factors., Competing Interests: Dr Jehn was supported as a Junior Clinician Scientist within the University Medicine Essen Academy (UMEA) funded by the Faculty of Medicine, 10.13039/501100008349University of Duisburg-Essen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Bicuspid aortic valve (BAV) is a common congenital valvular malformation, which may lead to early aortic valve disease and bicuspid-associated aortopathy. A novel BAV classification system was recently proposed to coincide with transcatheter aortic valve replacement being increasingly considered in younger patients with symptomatic BAV, with good clinical results, yet without randomized trial evidence. Procedural technique, along with clinical outcomes, have considerably improved in BAV patients compared with tricuspid aortic stenosis patients undergoing transcatheter aortic valve replacement. The present review summarizes the novel BAV classification systems and examines contemporary surgical and transcatheter approaches., Competing Interests: Dr Josep Rodes-Cabau has reported institutional research grants from 10.13039/100006520Edwards Lifesciences, 10.13039/100004374Medtronic, and 10.13039/100000046Abbott. Dr Michael J. Reardon has received consultation fees from Medtronic, Boston Scientific, Gore Medical, and Abbott medical paid to his department. Dr Rishi Puri is a consultant to Medtronic, Boston Scientific, Philips, Shockwave Medical, Products & Features, V-Dyne, VahatiCor, Advanced NanoTherapies, NuevoSono, TherOx, Bioventrix and Centerline Biomedical. No other disclosures were reported., (© 2023 The Author(s).)

Background: Lipid-lowering therapy (LLT) in patients with cardiovascular disease (CVD) is insufficient despite clear guideline recommendations. Lipid clinics have specialized in patients with dyslipidemia, but the magnitude and reduction of low-density lipoprotein cholesterol (LDL-C) in lipid clinics has not yet been studied in depth., Objective: To assess LDL-C reduction in very high-risk CVD patients achieved in a lipid clinic through different forms of LLT in comparison to standard care without the initiation of PSCK9 inhibitors., Methods: Data from 96 lipid clinic patients were analyzed retrospectively and compared to 84 standard care patients. Very high-risk patients were defined according to the European Society of Cardiology (ESC). Different combinations of LLT focusing on statins and ezetimibe were investigated. Achievement of LDL-C treatment goals according to ESC guidelines as well as LDL-C reduction were assessed., Results: Baseline and follow-up data of 180 very high-risk CVD patients (mean age 67.7 (±9.8) y; 60.6% male) were used. Achievement of the LDL-C goal in lipid clinic patients increased significantly from 14.6% at baseline to 41.7% at the latest visit (p<0.001) while standard care patients improved from 21.4% to 33.3% (p=0.08). The largest relative LDL-C reduction via an adjustment in LLT was achieved by initiation of high-intensity statins (50.8 ± 4.9%, n = 5, p < 0.05)., Conclusion: Treatment in a lipid clinic leads to a superior LDL-C goal achievement in very high-risk CVD patients as compared to standard care with the highest reduction under LLT with high-intensity statins and ezetimibe. Referral algorithms have to be established for high-risk patients., (Copyright © 2023. Published by Elsevier Inc.)

Background: Although the prognosis and management of severe aortic stenosis has been extensively studied, the risk stratification and outcomes of patients with moderate aortic stenosis remain elusive., Methods: This study included 674 patients from the Cleveland Clinic Health System with moderate aortic stenosis (aortic valve area, 1-1.5 cm 2 ; mean gradient, 20-40 mm Hg; and peak velocity <4 m/s) and an NT-proBNP (N-terminal pro-B-type natriuretic peptide) level within 3 months of index diagnosis. The primary outcome of major adverse cardiovascular events (defined as the composite outcome of progression to severe aortic stenosis requiring aortic valve replacement, heart failure hospitalization, or death) was extracted from the electronic medical record., Results: The mean age was 75.3±12 years, and 57% were men. During a median follow-up of 316 days, the composite end point occurred in 305 patients. There were 132 (19.6%) deaths, 144 (21.4%) heart failure hospitalizations, and 114 (16.9%) patients underwent aortic valve replacement. Elevated NT-proBNP (1.41 [95% CI, 1.01-1.95]; P =0.048), diabetes (1.46 [95% CI, 1.08-1.96]; P =0.01), elevated averaged mitral valve E/e' ratio (hazard ratio, 1.57 [95% CI, 1.18-2.10]; P <0.01), and presence atrial fibrillation at the time of index echocardiogram (hazard ratio, 1.83 [95% CI, 1.15-2.91]; P =0.01) were each independently associated with an increased hazard for the composite outcome and when taken collectively, each of these factors incrementally increased risk., Conclusions: These results further elucidate the relatively poor short-medium term outcomes and risk stratification of patients with moderate aortic stenosis, supporting randomized trials assessing the efficacy of transcatheter aortic valve replacement in this population., Competing Interests: Disclosures None.

Aims: We tested the hypothesis that epicardial adipose tissue (EAT) quantification improves the prediction of the presence of obstructive coronary artery disease (CAD) in patients presenting with acute chest pain to the emergency department., Methods and Results: Within this prospective observational cohort study, we included 657 consecutive patients (mean age 58.06 ± 18.04 years, 53% male) presenting to the emergency department with acute chest pain suggestive of acute coronary syndrome between December 2018 and August 2020. Patients with ST-elevation myocardial infarction, haemodynamic instability, or known CAD were excluded. As part of the initial workup, we performed bedside echocardiography for quantification of EAT thickness by a dedicated study physician, blinded to all patient characteristics. Treating physicians remained unaware of the results of the EAT assessment. The primary endpoint was defined as the presence of obstructive CAD, as detected in subsequent invasive coronary angiography. Patients reaching the primary endpoint had significantly more EAT than patients without obstructive CAD (7.90 ± 2.56 mm vs. 3.96 ± 1.91 mm, P < 0.0001). In a multivariable regression analysis, a 1 mm increase in EAT thickness was associated with a nearby two-fold increased odds of the presence of obstructive CAD [1.87 (1.64-2.12), P < 0.0001]. Adding EAT to a multivariable model of the GRACE score, cardiac biomarkers and traditional risk factors significantly improved the area under the receiver operating characteristic curve (0.759-0.901, P < 0.0001)., Conclusion: Epicardial adipose tissue strongly and independently predicts the presence of obstructive CAD in patients presenting with acute chest pain to the emergency department. Our results suggest that the assessment of EAT may improve diagnostic algorithms of patients with acute chest pain., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: T he COVID-19 pandemic led to an alteration of algorithms in emergency medicine, which may influence the management of patients with similar symptoms but underlying cardiovascular diseases. We evaluated key differential diagnoses to acute COVID-19 infection and the prevalence and the prognosis of myocardial injury in patients presenting for suspected COIVD-19 infection., Methods: This prospective observational study includes patients presenting with symptoms suggestive of COVID-19 infection during the pandemic. In patients without COVID-19, leading diagnoses was classified according to ICD-10. Myocardial injury was defined as elevated high-sensitivity Troponin I with at least one value above the 99th percentile upper reference limit and its prevalence together with 90-days mortality rate was compared in patients with vs without COVID-infection., Results: From 497 included patients (age 62.9 ± 17.2 years, 56 % male), 314 (63 %) were tested positive on COVID-19 based on PCR-testing, while another cause of symptom was detected in 183 patients (37 %). Cardiovascular diseases were the most frequent differential diagnoses (40 % of patients without COVID-19), followed by bacterial infection (24 %) and malignancies (16 %). Myocardial injury was present in 91 patients (COVID-19 positive: n = 34, COVID-19 negative: n = 57). 90-day mortality rate was higher in patients with myocardial injury (13.4 vs 4.6 %, p = 0.009)., Conclusion: Cardiovascular diseases represent the most frequent differential diagnoses in patients presenting to a tertiary care emergency department with symptoms suggestive of an acute infection. Screening for cardiovascular disease is crucial in the initial evaluation of symptomatic patients during the COVID pandemic to identify patients at increased risk. Trial Registration: Clinicaltrials.gov Identifier: NCT04327479., 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.)

Background: Statin therapy promotes the progression of coronary artery calcification (CAC). Comparing patients on high (HIST) vs. low-to-intermediate intensity statin therapy (LIST), randomized controlled trials with a one-year follow-up failed to document a relevant difference in the Agatston score and CAC volume. We evaluated whether statin intensity modifies CAC density at one year. Methods: We performed a pooled analysis of two randomized-controlled trials (BELLES, EBEAT), comparing the effects of HIST (Atorvastatin 80 mg) vs. LIST (Pravastatin 40 mg, Atorvastatin 10 mg) on CAC measures after one year. The differences in CAC density and its change were compared using the two-sided t-test. Results: Data from 852 patients (66.7% female) with available baseline and follow-up CT were evaluated from both trials. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: −45.8 ± 38.5 vs. −72.9 ± 46.0 mg/dL, p < 0.001). Mean CAC density increased from 228.8 ± 35.4 HU to 232.6 ± 37.0 HU (p < 0.0001) at one-year follow-up. Comparing patients on HIST vs. LIST, CAC density at follow-up (HIST: 231.9 ± 36.1 HU vs. LIST: 233.3 ± 37.7 HU, p = 0.59) and its change from baseline (HIST: 4.0 ± 19.1 HU vs. LIST: 3.6 ± 19.6 HU, p = 0.73) did not differ. Subgroup analyses, stratifying by LDL reduction (

Background: Patients undergoing transcatheter aortic valve implantation (TAVI) often have multiple comorbidities, such as anaemia and chronic inflammatory disorders. We sought to investigate the association between preoperative and postoperative haematological parameters and clinical outcomes in TAVI patients at mid-term follow-up., Methods: In the present study, consecutive patients (N=908) who underwent TAVI at the Cleveland Clinic between 2017 and 2019 with available complete blood counts were studied. Data were collected on preoperative and postoperative anaemia and elevations in neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Survival analysis was used to study the association of haematologic parameters with all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE)., Results: We found that preoperative anaemia and elevated NLR were significantly associated with a higher risk of all-cause mortality (aHR=1.6 (95% CI: 1.1 to 2.0) and 1.4 (95% CI: 1.1 to 1.6), respectively) and MACCE (aHR=1.9 (95% CI: 1.3 to 2.8) and 1.6 (95% CI: 1.1 to 2.4), respectively). While an elevated preoperative PLR was not associated with increased mortality risk, it had a significant association with MACCE risk (aHR: 1.6 (95% CI: 1.1 to 2.4)). Further, postoperative anaemia, elevated NLR and PLR were associated with increased risks of all-cause mortality and MACCE., Conclusion: Pathological alterations in haematological parameters were associated with higher risks of post-TAVI mortality and MACCE at mid-term follow-up. Our findings advocate for further incorporating haematological parameters in the preoperative evaluation of TAVI candidates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The relation between serial high-sensitivity C-reactive protein (hsCRP) and long-term major cardiovascular events (MACEs; cardiovascular death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) has not been explored in optimally-treated patients with atherosclerotic cardiovascular disease. We tested the hypothesis that longitudinal follow-up hsCRP (repeated measures over time) would associate with 30-month MACE rates. We performed a post hoc analysis of ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibitor with Evacetrapib in Patients with High-Risk for Vascular Outcomes), involving optimally-treated patients with high-risk vascular disease, with available baseline and at least 1 follow-up hsCRP level. Using multivariable Cox proportional hazard models, we determined the association of longitudinal follow-up hsCRP with MACE at 30 months among 8,563 patients (aged 64.6 ± 9 years, 22% women). Patients with incident MACE (n = 961) had higher baseline hsCRP levels (1.77 vs 1.46 mg/L, p &lt;0.0001 for patients with and without MACE, respectively) and showed an upward trajectory during follow-up, whereas median hsCRP levels remained &lt;2 mg/L at all time points (1.83 vs 1.53 mg/L, 1.91 vs 1.53 mg/L, 1.76 vs 1.37 mg/L, at 3, 12, and 24 months, respectively). In a multivariable analysis, higher longitudinal hsCRP levels were independently associated with MACE (hazard ratio [95% confidence interval] per SD 1.19 [1.10 to 1.29], p &lt;0.001), the majority of its individual components and all-cause death. Multivariable models containing longitudinal hsCRP provided improved predictive ability of MACE over baseline hsCRP. In the setting of established medical therapies, longitudinal follow-up hsCRP was independently associated with long-term MACE. In conclusion, these findings suggest that longitudinal hsCRP represents a novel approach of residual cardiovascular risk even when on-treatment hsCRP levels remain &lt;2 mg/L., Competing Interests: Disclosures Dr. Nissen reported receiving grants from AstraZeneca, Novartis, AbbVie, Silence Therapeutics, Medtronic, MyoKardia, Esperion, Eli Lilly, Amgen, Novo Nordisk, Pfizer, Cerenis, and The Medicines Company. Dr. Lincoff reports receiving grants from AstraZeneca, Esperion, Novartis, CSL, and AbbVie and personal fees from Novo Nordisk and Eli Lilly. Dr. Nicholls reported receiving grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, the Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience and receiving personal fees from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: The initial and dynamic levels of B-type natriuretic peptide (BNP) and N-terminal-prohormone BNP (NT-proBNP) are routinely used in clinical practice to identify patients with acute and chronic heart failure. In addition, BNP/NT-proBNP levels might be useful for risk stratification in patients with and without heart failure. We performed a meta-analysis to investigate, whether the value of BNP/NT-proBNP as predictors of long-term prognosis differentiates in cohorts with and without heart failure., Methods and Results: We systematically searched established scientific databases for studies evaluating the prognostic value of BNP or NT-proBNP. Random effect models were constructed. Data from 66 studies with overall 83 846 patients (38 studies with 46 099 patients with heart failure and 28 studies with 37 747 patients without heart failure) were included. In the analysis of the log-transformed BNP/NT-proBNP levels, an increase in natriuretic peptides by one standard deviation was associated with a 1.7-fold higher MACE rate (hazard ratio [95% confidence interval]: 1.74[1.58-1.91], P < 0.0001). The effect sizes were comparable, with a substantial overlap in the confidence intervals, when comparing studies involving patients with and without heart failure (1.75[1.54-2.0], P < 0.0001 vs. 1.74[1.47-2.06], P < 0.0001). Similar results were observed when stratifying by quartiles of BNP/NT-proBNP. In studies using pre-defined cut-off-values for BNP/NT-proBNP, elevated levels were associated with the long-term prognosis, independent of the specific cut-off value used., Conclusions: BNP/NT-proBNP levels are predictors for adverse long-term outcome in patients with and without known heart failure. Further research is necessary to establish appropriate thresholds, especially in non-heart failure cohorts., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: We aimed to determine, whether epicardial adipose tissue (EAT) as local source of inflammation, as well as its change over time, associates with the development of heart failure with preserved ejection fraction (HFpEF) in patients with coronary artery disease., Methods and Results: We retrospectively included 379patients (aged 65.2 ± 11.7 years, 70.2%male) with coronary artery disease but without heart failure at baseline, undergoing clinical and echocardiographic assessment in 2010-2013 and receiving a second assessment in 2014-2018. EAT thickness was defined as space between the myocardium and the pericardium and indexed (EATi) by body surface area. Change in EATi was calculated as the difference of follow-up and baseline EATi. HFpEF was defined according to presence of dyspnea, elevated natriuretic peptides, and structural and/or functional alterations on echocardiography in accordance with current European Society of Cardiology guidelines. During a median follow-up of 4.3 years, 142patients (37.5%) developed HFpEF. Patients with onset of HFpEF had higher EATi at baseline (2.4 ± 1.3 vs. 1.9 ± 0.9 mm/m 2 , p = 0.001). In multivariable regression analysis, EATi associated with onset of HFpEF (1.25 [1.01-1.54], p = 0.04). Likewise, an increase in EATi over time was linked HFpEF development, independent of other risk factors and baseline EATi (1.39 [1.04-1.87], p = 0.03). EATi was significantly associated with follow-up b-type natriuretic peptide (BNP) levels (4.31[0.58-8.05], p = 0.024), but not with baseline BNP (2.24[-0.27-4.76], p = 0.08)., Conclusion: EATi is associated with the development of HFpEF. The finding of changes in EATi altering the risk of HFpEF manifestation support the rationale for further research on epicardial fat modulation as a treatment target for HFpEF., (Copyright © 2022 Elsevier B.V. All rights reserved.)

New-onset left bundle branch block (LBBB) is common after transcatheter aortic valve implantation (TAVI) but can resolve in the post-TAVI period. We sought to examine the incidence, predictors, and outcomes of early resolution of new-onset LBBB among TAVI recipients with a SAPIEN 3 (S3) valve. Among 1,203 S3-TAVI recipients without a pre-existing pacemaker or wide QRS complex at our institution between 2016 and 2019, we identified 143 patients who developed new-onset LBBB during TAVI and divided them according to the resolution or persistence of LBBB by the next day post-TAVI to compare high-degree atrioventricular block (HAVB) and permanent pacemaker (PPM) rates. Patients with resolved LBBB (n = 74, 52%), compared with those with persistent LBBB, were more often women and had a shorter QRS duration at baseline and post-TAVI, with a smaller S3 size and a shallower implantation depth. A multivariable logistic regression model demonstrated significant associations of post-TAVI QRS duration (per 10 ms increase, odds ratio = 0.60 [95% confidence interval = 0.44 to 0.82]) and implantation depth (per 1-mm-depth-increase, 0.77 [0.61 to 0.97]) with a lower likelihood of LBBB resolution. No patient with resolved LBBB developed HAVB within 30 days post-TAVI. Meanwhile, 8 patients (11.6%) with persistent LBBB developed HAVB. The 2-year PPM rate was significantly higher after persistent LBBB than after resolved LBBB (30.3% vs 4.5%, log-rank p <0.001), mainly driven by higher 30-day PPM rate (18.8% vs 0.0%). In conclusion, about half of new-onset LBBBs that occurred during S3-TAVI resolved by the next day post-TAVI without HAVB. In contrast, new-onset persistent LBBB may need follow-up with ambulatory monitoring within 30 days because of the HAVB risk., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Pre-existing right bundle branch block (RBBB) is a strong predictor of increased need for a permanent pacemaker (PPM) following transcatheter aortic valve implantation (TAVI). Yet, further risk stratification and management remain challenging in patients with pre-existing RBBB owing to limited data. Therefore, we sought to investigate the incidence, predictors, and management of advanced conduction disturbances after TAVI in patients with pre-existing RBBB., Methods: We retrospectively reviewed 261 consecutive patients with pre-existing RBBB (median age 81 years; 28.0% female; 95.0% received a balloon-expandable valve) without a pre-existing PPM who underwent TAVI at our institution in 2015-2019. Outcomes were high-degree atrioventricular block/complete heart block (HAVB/CHB) and PPM requirement., Results: Overall, the 30-day HAVB/CHB rate was 28.0%, of which 76.7% occurred during the TAVI procedure. The delayed HAVB/CHB rate was 8.3%. Implantation depth below aortic annulus (per 1-mm increase) was significantly associated with increased risk of procedural HAVB/CHB (adjusted odds ratio = 1.25, 95% confidence interval = 1.07-1.46), delayed HAVB/CHB (1.34 [1.01-1.79]), and 30-day PPM (1.32 [1.11-1.55]). Predilation was associated with delayed HAVB/CHB (4.02 [1.22-13.23]). The combination of no predilation and implantation depth of ≤2.0 mm had lower rates of procedural HAVB/CHB (11.2% vs. 26.7%-30.4%, p = 0.011), delayed HAVB/CHB (2.1% vs. 7.6%-28.1%, p < 0.001), and 30-day PPM (10.3% vs. 20.0%-43.5%, p < 0.001) than the other strategies of valve deployment. Complete HAVB/CHB recovery after PPM implantation was uncommon at 7.1%., Conclusions: In patients with pre-existing RBBB, the majority of HAVB/CHB events occurred during the TAVI procedure. Avoidance of predilation coupled with high valve deployment may result in relatively low rates of procedural and delayed HAVB/CHB, along with 30-day PPM rates., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Aims: The 2021 European Society of Cardiology guidelines recommend early pacemaker implantation in pre-existing right bundle branch block (RBBB) patients who develop PR prolongation or QRS axis change after transcatheter aortic valve implantation (TAVI). We aimed to evaluate this recommendation in TAVI recipients with a balloon-expandable valve (BEV)., Methods and Results: We retrospectively reviewed 188 pre-existing RBBB patients without pre-existing permanent pacemaker (PPM) who underwent TAVI with a BEV at our institution in 2015-19. Patients who developed high-degree atrioventricular block (HAVB) during TAVI or within 24 h post-TAVI were excluded. Eligible patients were divided according to the guideline-directed criteria (ΔPR interval ≥20 ms and/or QRS axis change). Patients who met the criteria ( n = 102, 54.3%), compared with those who did not ( n = 86), had a higher prevalence of baseline right axis deviation and were more likely to have received a larger valve with greater oversizing. The 30-day delayed HAVB rate did not differ significantly between the groups (3.9% vs. 4.7%, P = 1.00; odds ratio = 0.84, 95% confidence interval = 0.20-3.45). There was also no significant difference in terms of death (5.0% vs. 8.4% at 1 year; overall log-rank P = 0.94) or a composite of death or PPM implantation (14.8% vs. 16.6% at 1 year; overall log-rank P = 0.94) during follow-up post-TAVI. The majority of PR prolongations (79.4%) and QRS axis changes (52.0%) regressed within the following 24 h., Conclusion: The present data did not demonstrate an association of significant changes in PR interval or QRS axis with heightened delayed HAVB risk in BEV recipients with pre-existing RBBB. Prospective studies are warranted to confirm these findings., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: We tested the hypothesis that on-treatment HbA1c levels independently associate with coronary atheroma progression and major adverse cardiovascular events (MACE: death, myocardial infarction, cerebrovascular accident, coronary revascularization, or hospitalization for unstable angina) rates., Methods: We performed a post-hoc pooled analysis of data from seven prospective, randomized trials involving serial coronary intravascular ultrasonography (IVUS). The percent atheroma volume (PAV) was calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque. Using multivariable mixed modeling, we determined the association of on-treatment HbA1c with annualized change in PAV. Cox proportional hazard models were used to assess the association of HbA1c with incidence of MACE., Results: Among 3,312 patients (mean age 58.6±9years, 28.4%women) average on-treatment HbA1c was 6.2±1.1%. Overall, there was no net significant annualized change in PAV (0.12±0.19%, p  = 0.52). In a fully adjusted multivariable analysis (following adjustment of age, sex, body mass index, systolic blood pressure, smoking, low- and high-density lipoprotein cholesterol, triglyceride levels, peripheral vascular disease, trial, region, and baseline PAV), higher on-treatment HbA1c levels were independently associated with annualized changes in PAV [beta-estimate (95% confidence interval): 0.13(0.08, 0.19), p  < 0.001]. On-treatment HbA1c levels were independently associated with MACE [hazard ratio (95% confidence interval): 1.13(1.04, 1.23), p =  0.005]., Conclusions: Independent of achieved cardiovascular risk factor control, greater HbA1c levels significantly associate with coronary atheroma progression rates and clinical outcomes. These results support the notion of a direct, specific effect of glycemic control upon coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to directly modulate it., 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., (© 2022 The Author(s).)

Background: Epicardial adipose tissue (EAT) surrounds the heart and the coronary vessels. EAT produces pro- and anti-inflammatory cytokines. Several studies have already documented the association of EAT and cardiovascular risk factors as well as coronary artery disease manifestations. Currently computed tomography (CT) is considered the gold standard for measurement of 3-dimensional volume of EAT. In addition, echocardiography might be an easy accessible alternative in particular in an emergency setting., Methods: We performed a metaanalysis of existing studies describing the differences of EAT in patients with and without myocardial infarction. We used established databases and were searching for "epicardial adipose tissue" or "pericardial adipose tissue" and "myocardial infarction", "coronary events", or "acute coronary syndrome". We included over 6600 patients from 7 studies. Random effect models were calculated and all analyses were performed by using the Review Manager 5.3., Results: Patients with myocardial infarction had 37% (confidence interval [0.21-0.54], P value <.001)] higher measures of EAT compared to patients without myocardial infarction. Comparing studies using echocardiography vs CT for assessment of EAT thickness, similar relative differences in EAT with wide overlap of confidence intervals were observed (for echocardiography: 0.4 [0.04-0.76], for CT: 0.36 [0.16-0.57], P value <.001 for both)., Conclusions: Patients with myocardial infarction have more EAT as compared to patients without myocardial infarction independently of the used imaging modality. Further prospective studies are needed to evaluate, how quantification of EAT in clinical routine can improve patients management., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background/objectives: Coronary microvascular dysfunction (CMD) is a common disorder, leading to symptoms similar to obstructive coronary artery disease and bears important prognostic implications. Local inflammation is suggested to promote development of CMD. Epicardial adipose tissue (EAT) is a local visceral fat depot surrounding the heart and the coronary arteries, modifying the inflammatory environment of the heart. We compared EAT in patients with and without CMD., Methods: We retrospectively included consecutive patients undergoing diagnostic coronary angiography as well as transthoracic echocardiography between March and October 2016. EAT thickness was defined as space between the epicardial wall of the myocardium and the visceral layer of the pericardium and EAT index was calculated as EAT thickness/body surface area. Logistic regression analysis was used to determine the association of EAT index with the presence of CMD., Results: Overall, 399 patients (mean age 60.2 ± 14.0 years, 46% male) were included. EAT thickness was significantly higher in patients with CMD compared to patients without CMD (EAT thickness 4.4 ± 1.8 vs. 4.9 ± 2.4 mm, p = 0,048 for patients without and with CMD, respectively). In univariate regression analysis, EAT index was associated with a 30% higher frequency of CMD (odds ratio [95% confidence interval]: 1.30 [1.001-1.69], p = 0.049). Effect sizes remained stable upon adjustment for body mass index (BMI, 1.30 [1.003-1.70], p = 0.048), but were attenuated when ancillary adjusting for age and gender (1.17 [0.90-1.54, p = 0.25). The effect was more pronounced in patients >65 years of age and independent of BMI and sex (1.85 [1.14-3.00], p = 0.013)., Conclusion: EAT thickness is independently associated with CMD and can differentiate between patients with and without CMD especially in older age groups. Our results support the hypothesis that modulation of local inflammation by epicardial fat is involved in the development of CMD., (© 2021. The Author(s).)