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Aims: We aimed to investigate the association between the burden of modifiable lifestyle risk factors (modLRF) with high-sensitivity cardiac troponins T and I (hsTnT/I) and clinical outcomes in a contemporary cohort., Methods: Patients undergoing coronary angiography with available hsTnT/I concentrations and information about modLRF were included in the current single-centre study. The modLRF investigated were overweight, lack of physical activity, poor adherence to a Mediterranean diet and current smoking. To evaluate the impact of modLRF on hsTnT/I levels, a linear regression model was used. A Cox regression analysis was computed to investigate the association of hsTnT/I levels with clinical outcomes, stratified by the burden of modLRF, and a C-Index was calculated to investigate the additive predictive benefit of the integration of hsTn on top of a base model containing modLRF only. Outcomes of interest were all-cause mortality and major adverse cardiovascular events (MACE)., Results: In the overall study population of n=1,716 patients median troponin levels were 15.0 ng/l (IQR 8.0, 29.0) and 7.6 ng/l (IQR 3.3, 18.6) for hsTnT and I, respectively. An increasing number of modLRF was independently associated with elevated hsTnT and I concentrations. Moreover, hsTnT and hsTnI were independently associated with all-cause mortality in patients with 1-2 and ≥3 modLRF, and an incremental value of the integration of hsTnT and hsTnI was noted, especially in the prediction of all-cause mortality was noted. Lastly, an independent association of hsTnI with MACE was documented in patients with 1-2 modLRF, which was not the case for hsTnT., Conclusion: Increasing numbers of modLRF are associated with elevated concentrations of hsTnT and I, whilst the predictive capability of troponins varied according to the presence of modLRF. Further prospective studies are needed to investigate, whether targeting modLRF might result in lower hsTn concentrations and improved outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Acute ischaemic stroke (AIS) after percutaneous coronary intervention (PCI) is a rare, but debilitating, complication. However, contemporary data from real-world unselected patients are scarce., Aims: We aimed to explore the temporal trends, outcomes and variables associated with AIS as well as in-hospital all-cause mortality in a nationwide cohort., Methods: A retrospective analysis of healthcare records from 2006-2021 was implemented. Patients were stratified according to the occurrence of AIS in the setting of PCI. The temporal trends of AIS were analysed. A stepwise regression model was used to identify variables associated with AIS and in-hospital all-cause mortality., Results: A total of 4,910,430 PCIs were included for the current analysis. AIS occurred in 4,098 cases (0.08%). An incremental increase in the incidence of AIS after PCI from 0.03% to 0.14% per year was observed from 2006-2021. The strongest associations with AIS after PCI included carotid artery disease, medical history of stroke, atrial fibrillation, presentation with an ST-segment elevation myocardial infarction (STEMI) or non-STEMI and coronary thrombectomy. For patients with AIS, a higher in-hospital all-cause mortality (18.11% vs 3.29%; p<0.001) was documented. With regard to all-cause mortality, the strongest correlations in the stroke cohort were found for cardiogenic shock, dialysis and clinical presentation with a STEMI., Conclusions: In an unselected nationwide cohort of patients hospitalised for PCI, a gradual increase in AIS incidence was noted. We identified several variables associated with AIS as well as with in-hospital mortality. Hereby, clinicians might identify the patient population at risk for a peri-interventional AIS as well as those at risk for an adverse in-hospital outcome after PCI.

The prevalence of cardiovascular diseases increases with age. Common symptoms such as dyspnea, chest pain, dizziness, or syncope can impact driving fitness. Due to a growing number of private drivers aged 65 and older and an increasing prevalence of cardiovascular diseases, questions regarding driving fitness restrictions for cardiological patients are gaining prominence in clinical settings. This article aims to summarize current recommendations for driving fitness in the context of cardiovascular diseases. The basis for the guidelines includes the Driving License Ordinance, the expert assessment guidelines of the Federal Highway Research Institute, and the guidelines of the German Society of Cardiology on driving fitness. Original literature on this topic is limited.Emphasizing an individualized assessment, clear guidelines for driving fitness in cardiac diseases or their symptoms and treatments are formulated. Regardless of the cardiac condition, the symptoms and likelihood of sudden loss of consciousness play a leading role in driving fitness assessment. Resulting impairments can range from a few weeks to a complete revocation of driving fitness. Regular examinations and differentiated assessments by medical professionals are prerequisites for maintaining driving fitness.The driving fitness of older private drivers is a significant and practical topic in cardiology. Current guidelines support the treating physicians in providing appropriate recommendations., (© 2024. The Author(s).)

Background: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities., Objectives: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDL Lp(a)corr ) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events., Methods: Among 68,748 CHD-free subjects at baseline LDL Lp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDL Lp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile)., Results: Similar risk estimates for incident CHD were found for LDL-C and LDL-C Lp(a)corr30 or LDL-C Lp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; P interaction 0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (P interaction 0.49)., Conclusions: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels., Competing Interests: Funding Support and Author Disclosures The BiomarCaRE Project is funded by the European Union Seventh Framework Programme Collaborative Project (FP7/2007–2013) under grant agreement no. HEALTHF2-2011–278913. The MORGAM Project has received funding from European Union projects MORGAM (Biomed, BMH4-CT98-3183), GenomEUtwin (Fifth Framework Programme FP5, QLG2-CT-2002-01254), BiomarCaRE (FP7, HEALTH-F2-2011-278913), European Network for Genetic and Genomic Epidemiology (ENGAGE) (FP7, HEALTH-F4-2007-201413), Consortium on Health and Ageing: Network of cohorts in Europe and the United States (CHANCES) (FP7, HEALTH-F3-2010-242244), euCanSHare (Horizon 2020, No. 825903), Digital, Risk-Based Screening for Atrial Fibrillation in the European Community project - European Union (AFFECT-EU) (Horizon 2020, no. 847770), and Medical Research Council, London (G0601463, no. 80983: Biomarkers in the MORGAM Populations). This funding has supported central coordination, workshops, and part of the activities of the MORGAM Data Centre, the MORGAM Laboratories, and the MORGAM Participating Centres; MORGAM Participating Centres are funded by regional and national governments, research councils, charities, and other local sources. Dr Schnabel has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 648131), German Ministry of Research and Education (BMBF 01ZX1408A), and German Center for Cardiovascular Research (DZHK e.V.; grant no. 81Z1710103); and has received personal fees from BMS/Pfizer. Dr Kee has received funding from the National Institute of Health Research United Kingdom. Dr Salomaa was supported by the Finnish Foundation for Cardiovascular Research and the Juho Vainio Foundation; and has received grants from Bayer AG. Dr Zeller was supported by the German Center of Cardiovascular Research (DZHK e.V.; DZHK, 81Z0710102). Dr Blankenberg has received a grant from Abbott Diagnostics during the conduct of the study; has received grants and personal fees from Abbott Diagnostics, Bayer, SIEMENS, and Thermo Fisher; has received grants from Singulex; and has received personal fees from AstraZeneca, AMGEN, Medtronic, Pfizer, Roche, Siemens Diagnostic, and Novartis. Dr Söderberg has been supported by the Swedish Heart-Lung Foundation (20140799, 20120631, and 20100635), the County Council of Västerbotten (ALF, VLL- RV-967561, RV-841381548791), and Umeå University; and has received grants and personal fees from Actelion Ltd. All funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Outside the scope of the present work, Dr Arnold has received consulting fees and grant support from Novartis. Dr Brunner has received grant supports from Daiichi-Sankyo, Novartis, Pfizer, and Sanofi; has received nonfinancial support from Abbott, ASAHI INTECC, and Inari Medical; and has received personal fees from Amgen and Novartis. Dr Bay is supported by a grant from the German Heart Foundation (grant no. S/06/23). Dr Koenig has received consulting fees and lecture fees from AstraZeneca, Novartis, and Amgen; has received consulting fees from Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, Esperion, Genentech, OMEICOS, Novo Nordisk, LIB Therapeutics, TenSixteen Bio, New Amsterdam Pharma, and Daiichi-Sankyo; has received lecture fees from Berlin-Chemie, Bristol Myers Squibb, and Sanofi; and has received grant support and provision of reagents from Singulex, Abbott, Roche Diagnostics, and Dr Beckmann Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex., Methods: From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out., Results: A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup., Conclusions: We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men., Registration: https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438., (© 2024. The Author(s).)

Background and Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population., Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L)., Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024)., Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds., (© 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: Mortality in cardiogenic shock (CS) remains high even when mechanical circulatory support (MCS) restores adequate circulation. To detect a potential contribution of systemic inflammation to shock severity, this study determined associations between C-reactive protein (CRP) concentrations and outcomes in patients with CS., Methods: Unselected, consecutive patients with CS and CRP measurements treated at a single large cardiovascular center between 2009 and 2019 were analyzed. Adjusted regression models were fitted to evaluate the association of CRP with shock severity, 30-day in-hospital mortality and treatment response to MCS., Results: The analysis included 1116 patients [median age: 70 (IQR 58-79) years, 795 (71.3%) male, lactate 4.6 (IQR 2.2-9.5) mmol/l, CRP 17 (IQR 5-71) mg/l]. The cause of CS was acute myocardial infarction in 530 (48%) patients, 648 (58%) patients presented with cardiac arrest. Plasma CRP concentrations were equally distributed across shock severities (SCAI stage B-E). Higher CRP concentrations were associated with 30-day in-hospital mortality (8% relative risk increase per 50 mg/l increase in CRP, range 3-13%; p < 0.001), even after adjustment for CS severity and other potential confounders. Higher CRP concentrations were only associated with higher mortality in patients not treated with MCS [hazard ratio (HR) for CRP > median 1.50; 95%-CI 1.21-1.86; p < 0.001], but not in those treated with MCS (HR for CRP > median 0.92; 95%-CI 0.67-1.26; p = 0.59; p-interaction = 0.01)., Conclusion: Elevated CRP concentrations are associated with increased 30-day in-hospital mortality in unselected patients with cardiogenic shock. The use of mechanical circulatory support attenuates this association., (© 2023. The Author(s).)

Background: Despite advances in cardiovascular medicine, coronary artery disease (CAD) remains a leading cause of mortality. Among the pathophysiological features of this condition, platelet-leukocyte aggregates (PLAs) require further attention, either as diagnostic/prognostic disease markers or as potential interventional targets., Objectives: In this study, we characterized PLAs in patients with CAD. Primarily, we investigated the association of PLA levels with CAD diagnosis. In addition, the basal levels of platelet activation and degranulation were assessed in patients with CAD and controls, and their correlation with PLA levels was analyzed. Finally, the effect of antiplatelet treatments on circulating PLA numbers, basal platelet activation, and degranulation was studied in patients with CAD., Methods: Participants were recruited at the Department of Cardiology of the University Heart and Vascular Centre Hamburg Eppendorf. Among patients admitted with severe chest pain, the diagnosis of CAD was made angiographically, and patients without CAD were used as controls. PLAs, platelet activation, and platelet degranulation were assessed by flow cytometry., Results: Circulating PLAs and basal platelet degranulation levels were significantly higher in patients with CAD than in controls. Surprisingly, there was no significant correlation between PLA levels and platelet degranulation (or any other measured parameter). In addition, patients with CAD on antiplatelet therapy did not display lower PLA or platelet degranulation levels compared with those in controls., Conclusion: Overall, these data suggest a mechanism of PLA formation that is independent of platelet activation or degranulation and highlights the inefficiency of current antiplatelet treatments for the prevention of basal platelet degranulation and PLA formation., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Robotic-assisted percutaneous coronary intervention (rPCI) has proven to be feasible and safe. Comparative analyses of rPCI versus manual PCI (mPCI) are scarce., Aims: We aimed to investigate procedural aspects and outcomes of rPCI using the second-generation CorPath GRX Vascular Robotic System compared with mPCI in patients with chronic coronary syndrome and non-ST-segment elevation myocardial infarction acute coronary syndrome., Methods: From January to April 2021, 70 patients underwent rPCI at the University Heart & Vascular Center Hamburg-Eppendorf and were recruited into the INTERCATH study. By propensity score matching, a control cohort of 210 patients who underwent mPCI from 2015-2021 was identified. Co-primary endpoints were one-year all-cause mortality and major adverse cardiovascular events (MACE) as a composite of cardiovascular death, unplanned target lesion revascularisation, myocardial infarction, and stroke., Results: The median age of the patients (n=280) was 70.7 (25th percentile-75th percentile: 62.0-78.0) years, and 24.6% were female. The Gensini score (28.5 [16.2-48.1] vs 28.0 [15.5-47.0]; p=0.78) was comparable between rPCI versus mPCI. During the PCI procedure, total contrast fluid volume did not differ, whilst longer fluoroscopy times (20.4 min [13.8-27.2] vs 14.4 min [10.4-24.3]; p=0.001) were documented in the rPCI versus mPCI cohort. After 12 months of follow-up, neither all-cause mortality (p=0.22) nor MACE (p=0.25) differed between the groups., Conclusions: rPCI was associated with longer fluoroscopy times compared with mPCI, though without increased use of contrast medium. One-year follow-up revealed no differences in all-cause mortality or MACE, supporting the safety of a robotic-assisted approach.

The inflammatory burden as measured by high-sensitivity C-reactive Protein (hsCRP) is recognized as a cardiovascular risk factor, which can however be affected by lifestyle-related risk factors (LRF). Up-to-date the interplay between hsCRP, LRF and presence and extent of atherosclerotic disease is still largely unknown, which we therefore sought to investigate in a contemporary population-based cohort. We included participants from the cross-sectional population-based Hamburg City Health Study. Affected vascular beds were defined as coronary, peripheral, and cerebrovascular arteries. LRF considered were lack of physical activity, overweight, active smoking and poor adherence to a Mediterranean diet. We computed multivariable analyses with hsCRP as the dependent variable and LRF as covariates according to the number of vascular beds affected. In the 6765 individuals available for analysis, we found a stepwise increase of hsCRP concentration both according to the number of LRF present as well as the number of vascular beds affected. Adjusted regression analyses showed an independent association between increasing numbers of LRF with hsCRP levels across the extent of atherosclerosis. We demonstrate increasing hsCRP concentrations according to both the number of LRF as well as the extent of atherosclerosis, emphasizing the necessity of lifestyle-related risk factor optimization., (© 2023. The Author(s).)

Background: Stroke after a cardiovascular procedure (CVP) is a devastating complication adversely affecting outcome. Mechanical thrombectomy (MT) has not been investigated systematically in this population., Objective: To carry out a retrospective study in patients undergoing MT for early stroke after CVP, aiming to further characterize this cohort of patients, and to evaluate the efficacy, safety, procedural characteristics, and outcome of MT., Methods: A single-center stroke registry of patients who received MT was analyzed. Baseline and procedural parameters, mortality, functional outcome, recanalization rates, and complications were evaluated. Propensity score matching was carried out, identifying a control cohort with non-periprocedural large vessel occlusion (LVO)., Results: Overall 913 patients were included (mean age 73.0 (±13.0) years, 52.5% female, median National Institutes of Health Stroke Scale score 15 (10-19)). Eleven patients with a LVO after a recent (<30 days postoperatively) CVP were identified (n=3 transcatheter aortic valve and n=1 surgical aortic valve replacements (SAVR), n=3 coronary bypass grafting (CABG) surgeries, n=2 SAVR+CABG, and n=2 aortic surgeries). After matching, 8 patients in the CVP group were compared with 16 patients in the matched cohort. Comparable rates of reperfusion were achieved. Time from symptom onset to groin puncture (171.5 min (136.3, 178.3) vs 284.0 min (215.0, 490.5); p=0.039), as well as recanalization (195.0 min (146.0, 201.0) vs 419.0 min (274.0, 613.0); p=0.028) was faster in the CVP group. However, this was not reflected by an improved outcome (modified Rankin Scale score after 90 days: 5.5 (3.3, 6.0) vs 5.0 (4.0, 6.0), mortality after 90 days 50.0% vs 37.5%). Complications did not differ between the groups., Conclusions: Use of MT for LVO stroke in patients after a recent CVP is a safe and efficient treatment in comparison with patients with a non-periprocedural LVO undergoing MT., Competing Interests: Competing interests: GT reports receiving consulting fees from Acandis, grant support and lecture fees from Bayer; lecture fees from Boehringer Ingelheim, BristolMyersSquibb/Pfizer, and Daiichi Sankyo; and consulting fees and lecture fees from Portola and Stryker. JF research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions-/Förderbank (IFB), Medtronic, Microvention, Philips, Stryker; consultancy appointments; Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Covidien, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, Microvention, Penumbra, Route92, Stryker, Transverse Medical; stock holdings for Tegus; and serves on the editorial board of JNIS., (© 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.)

Objectives: The study aimed to investigate the alterations of myocardial deformation responding to long-standing pressure overload and the effects of focal myocardial fibrosis using feature-tracking cardiac magnetic resonance (FT-CMR) in patients with resistant hypertension (RH)., Methods: Consecutive RH patients were prospectively recruited and underwent CMR at a single institution. FT-CMR analyses based on cine images were applied to measure left ventricular (LV) peak systolic global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). Functional and morphological CMR variables, and late gadolinium enhancement (LGE) imaging were also obtained., Results: A total of 50 RH patients (63 ± 12 years, 32 men) and 18 normotensive controls (57 ± 8 years, 12 men) were studied. RH patients had a higher average systolic blood pressure than controls (166 ± 21 mmHg vs. 116 ± 8 mmHg, p < 0.001) with the intake of 5 ± 1 antihypertensive drugs. RH patients showed increased LV mass index (78 ± 15 g/m 2 vs. 61 ± 9 g/m 2 , p < 0.001), decreased GLS (- 16 ± 3% vs. - 19 ± 2%, p = 0.001) and GRS (41 ± 12% vs. 48 ± 8%, p = 0.037), and GCS was reduced by trend (- 17 ± 4% vs. - 19 ± 4%, p = 0.078). Twenty-one (42%) RH patients demonstrated a LV focal myocardial fibrosis (LGE +). LGE + RH patients had higher LV mass index (85 ± 14 g/m 2 vs. 73 ± 15 g/m 2 , p = 0.007) and attenuated GRS (37 ± 12% vs. 44 ± 12%, p = 0.048) compared to LGE - RH patients, whereas GLS (p = 0.146) and GCS (p = 0.961) were similar., Conclusion: Attenuation of LV GLS and GRS, and GCS decline by tendency, might be adaptative changes responding to chronic pressure overload. There is a high incidence of focal myocardial fibrosis in RH patients, which is associated with reduced LV GRS., Clinical Relevance Statement: Feature-tracking CMR-derived myocardial strain offers insights into the influence of long-standing pressure overload and of a myocardial fibrotic process on cardiac deformation in patients with resistant hypertension., Key Points: • Variations of left ventricular strain are attributable to the degree of myocardial impairment in resistant hypertensive patients. • Focal myocardial fibrosis of the left ventricle is associated with attenuated global radial strain. • Feature-tracking CMR provides additional information on the attenuation of myocardial deformation responding to long-standing high blood pressure., (© 2023. The Author(s).)

Robotic-assisted percutaneous coronary interventions (rPCI) have proven feasible and safe while reducing radiation exposure for the operator. Recently, rPCI systems have been refined to facilitate the treatment of complex lesions. The aim of the current study was to evaluate challenges and opportunities of establishing an rPCI program at a tertiary referral center. rPCI was performed using the CorPath GRX Vascular Robotic System (Corindus Inc., a Siemens Healthineers Company, Waltham, USA). Baseline, procedural, and in-hospital follow-up data were prospectively assessed. rPCI success was defined as completion of the PCI without or with partial manual assistance. The safety endpoint was the composite of missing angiographic success or procedure-related adverse events during hospital stay. Overall, 86 coronary lesions were treated in 71 patients (28.2% female) from January to April 2021. Median age was 71.0 years (IQR 60.3; 79.8). Indications for rPCI were stable angina pectoris (71.8%), unstable angina (12.7%) and non-ST elevation myocardial infarction (15.5%). Most lesions were complex (type B2/C: 88.4%) and included 7 cases of rPCI for chronic total occlusions. Angiographic and rPCI success were achieved in 100.0% and 94.2%, respectively. Partial manual assistance was used in 25.6%. Conversion to manual PCI was required in 5.8%. The safety endpoint occurred in 7.0% of patients. rPCI when applied as clinical routine for complex coronary lesions is effective with good immediate angiographic and clinical results. Future investigations should focus on the identification of patients that particularly benefit from robotic-assisted vs. manual PCI despite higher resource utilization., (© 2022. The Author(s).)

Background The association between high-sensitivity troponin T (hsTnT) and high-sensitivity troponin I (hsTnI) and outcome when adjusted for confounders including the angiographical severity of coronary artery disease (CAD) remains largely unknown. We therefore aimed to explore whether hsTnT and hsTnI blood levels increase with CAD severity and add independent predictive information for future major adverse cardiovascular events and all-cause mortality in stable patients. Methods and Results Patients from the INTERCATH cohort with available coronary angiography and hsTnT and hsTnI concentrations were included. Troponin concentrations were quantified via hsTnT (Roche Elecsys) and hsTnI (Abbott ARCHITECT STAT). To investigate the association of hsTnT and hsTnI with outcome, a multivariable analysis adjusting for classical cardiovascular risk factors, low-density lipoprotein cholesterol, estimated glomerular filtration rate, hs-CRP (high-sensitivity C-reactive protein), NT-proBNP (N-terminal pro-brain natriuretic peptide), and Gensini score was carried out. Of 1829 patients, 27.9% were women, and the mean age was 68.6±10.9 years. Troponin blood concentrations were higher in patients with diagnosed CAD compared with those without. Using a linear regression model current smoking, arterial hypertension, estimated glomerular filtration rate, hs-CRP, NT-proBNP, and CAD severity as graded by the Gensini and SYNTAX scores were associated with high-sensitivity troponin levels. Patients were followed for 4.4 years (25th and 75th percentiles: 4.3, 4.4). After multivariable adjustment, all-cause mortality was predicted by hsTnT (hazard ratio [HR], 1.7 [95% CI, 1.5-2.2], P <0.001) as well as hsTnI (HR, 1.5 [95% CI, 1.2-1.8], P <0.001). However, only hsTnI (HR, 1.2 [95% CI, 1.0-1.4], P =0.032) remained as an independent predictor of major adverse cardiovascular events after adjusting for most possible confounders, including CAD severity (hsTnT: HR, 1.0 [95% CI, 0.9-1.2], P =0.95). Conclusions After adjusting for classical cardiovascular risk factors, low-density lipoprotein cholesterol, estimated glomerular filtration rate, hs-CRP, NT-proBNP, and CAD severity, hsTnT and hsTnI were independently associated with all-cause mortality, but only hsTnI was associated with major adverse cardiovascular events in stable patients undergoing coronary angiography. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT04936438.

Purpose: Implanting stents to re-open stenotic lesions during percutaneous coronary interventions is considered a standard treatment for acute or chronic coronary syndrome. Intravascular ultrasound (IVUS) can be used to guide and assess the technical success of these interventions. Automatically segmenting stent struts in IVUS sequences improves workflow efficiency but is non-trivial due to a challenging image appearance entailing manifold ambiguities with other structures. Manual, ungated IVUS pullbacks constitute a challenge in this context. We propose a fully data-driven strategy to first longitudinally detect and subsequently segment stent struts in IVUS frames. Approach: A cascaded deep learning approach is presented. It first trains an encoder model to classify frames as "stent," "no stent," or "no use." A segmentation model then delineates stent struts on a pixel level only in frames with a stent label. The first stage of the cascade acts as a gateway to reduce the risk for false positives in the second stage, the segmentation, which is trained on a smaller and difficult-to-annotate dataset. Training of the classification and segmentation model was based on 49,888 and 1826 frames of 74 sequences from 35 patients, respectively. Results: The longitudinal classification yielded Dice scores of 92.96%, 82.35%, and 94.03% for the classes stent, no stent, and no use, respectively. The segmentation achieved a Dice score of 65.1% on the stent ground truth (intra-observer performance: 75.5%) and 43.5% on all frames (including frames without stent, with guidewires, calcium, or without clinical use). The latter improved to 49.5% when gating the frames by the classification decision and further increased to 57.4% with a heuristic on the plausible stent strut area. Conclusions: A data-driven strategy for segmenting stents in ungated, manual pullbacks was presented-the most common and practical scenario in the time-critical clinical workflow. We demonstrated a mitigated risk for ambiguities and false positive predictions., (© 2022 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting in inflammation and thrombosis. The present study found that homozygous deletion of the CFHR1 gene, which encodes the plasma complement protein factor H-related protein 1 (FHR-1), was protective in two cohorts of patients with ACVD, suggesting that FHR-1 accelerates inflammation and exacerbates the disease. To test this hypothesis, FHR-1 was isolated from human plasma and was found to circulate on extracellular vesicles and to be deposited in atherosclerotic plaques. Surface-bound FHR-1 induced the expression of pro-inflammatory cytokines and tissue factor in both monocytes and neutrophils. Notably, plasma concentrations of FHR-1, but not of factor H, were significantly (p < 0.001) elevated in patients with ACVD, and correlated with the expression of the inflammation markers C-reactive protein, apolipoprotein serum amyloid protein A, and neopterin. FHR-1 expression also significantly correlated with plasma concentrations of low-density lipoprotein (LDL) (p < 0.0001) but not high-density lipoprotein (HDL). Taken together, these findings suggest that FHR-1 is associated with ACVD., (© 2021. The Author(s).)

Purpose: The lowered LDL-C treatment goal of the 2019 European Society of Cardiology dyslipidemia guidelines results in a significant increase in the projected need for cost-intensive proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Addition of bempedoic acid (BA) to established oral lipid-lowering medication (LLM) has the potential to enable affordable LDL-C goal attainment, particularly in patients with statin intolerance (SI). The goal of this study was to quantify the target populations for BA and PCSK9 inhibitors as well as the related treatment costs to achieve the LDL-C goal of <55 mg/dL and a ≥50% reduction assuming the addition of BA to LLM., Methods: This study included 1922 patients with coronary artery disease (CAD) from the contemporary observational cohort study INTERCATH. A Monte Carlo simulation incorporating an algorithm adding sequentially a statin, ezetimibe, optionally BA, and a PCSK9 inhibitor was applied to achieve the LDL-C treatment goal, with consideration of both partial and total SI. Two scenarios were simulated for both a moderate (2% full and 10% partial) and a high (12% full) rate of SI: (1) without BA; and (2) with BA., Findings: Patients' mean age was 69.3 years, and the median baseline LDL-C level was 86.0 mg/dL. The need for a PCSK9 inhibitor would be 41.4% for a moderate rate of SI and 46.1% for a high rate of SI. Addition of BA would: (1) reduce the need for a PCSK9 inhibitor to 25.3% and 29.4%, thus lowering the annual overall treatment cost incurred through PCSK9 inhibitor ± BA per 1 million patients with CAD by 13.3% and 10.5%; (2) lower the cost per prevented event in the entire cohort (-5.0% and -6.3%), although at the price of fewer prevented events (-8.7% and -4.5%); and (3) reduce the cost per prevented event (-6.8% for both rates of SI) while preventing more events (7.6% and 6.9%) in the subpopulation of patients with full SI., Implications: Use of BA is projected to reduce the need for PCSK9 inhibitors as well as the treatment cost for add-on LLM. The subpopulation of patients with full SI might profit particularly., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV) remains a major long-term complication in heart transplant (HT) recipients related to increased mortality. We aimed to identify non-immune recipient- and donor-related risk factors for the development of CAV in HT patients., Methods: 40,647 recipients, prospectively enrolled from April 1995 to January 2019 in the Organ Procurement and Transplantation Network (OPTN), were analyzed after exclusion of pediatric patients, those with missing information on CAV, and re-transplantation. Multivariable-adjusted Cox regression analyses were performed to identify recipient- and donor-related risk factors for CAV. 5-year population attributable risk for classical cardiovascular risk factors was calculated to estimate the recipients' CAV risk. Analyses were based on OPTN data (June 30, 2019)., Results: Of 40,647 post-transplant patients, 14,698 (36.2%) developed CAV with a higher incidence in males (37.3%) than in females (32.6%) (p < 0.001). The mean follow-up time was 68.2 months. In recipients, male sex, African American and Asian ethnicity, ischemic cardiomyopathy, body mass index and smoking were associated with CAV occurrence. In donors, older age, male sex, smoking, diabetes and arterial hypertension were related to CAV. Results remained fairly stable after analysis of different time periods. 5-year attributable CAV risk for classical cardiovascular risk factors was 9.1%., Conclusions: In this large registry with known limitations concerning data completeness, CAV incidence was higher in males than in females. Next to male sex and donor age, the classical cardiovascular risk factors were related to incident CAV. Classical cardiovascular risk factors played only a minor role for the 5-year attributable CAV risk., Competing Interests: Declaration of Competing Interest AMB has received honoraria from Abbott, Abiomed, AstraZeneca, BerlinHeart, Medtronic and Novartis (unrelated to the submitted work). BS has received speakers fee from AstraZeneca and Abiomed (unrelated to the submitted work). CM reports speaker fees from AstraZeneca, Novartis and Loewenstein Medical (unrelated to the current work). RBS has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239)(unrelated to the submitted work). RSP has received honoraria from the Abiomed Advisory Board and the Medtronic Advisory Board (unrelated to the submitted work). SB has received received speaker fees from Medtronic, Pfizer, Roche, Novartis and Siemens Diagnostics (unrelated to the submitted work)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) are associated with increased inflammation represented by elevated C-reactive protein (CRP) levels. Lifestyle changes may influence the inflammatory burden in patients with CAD, relevantly modifying the target population for emerging anti-inflammatory compounds., Aims: The aims of this study were to analyse the association of modRF and CRP levels in CAD patients, and to define a potential target population for anti-inflammatory treatment with and without the optimisation of modRF., Methods: We included all patients with angiographically documented CAD from the observational cohort study INTERCATH. Patients with recent myocardial infarction, malignancy, infectious disease, and pre-existing immunosuppressive medication including a history of solid organ transplantation were excluded. Overweight (body mass index (BMI) ≥ 25 kg/m2), smoking, lack of physical activity (PA; <1.5 h/week), and poor diet (≤12 points of an established Mediterranean diet score (MDS), range 0-28 points) were considered as modRF. CRP was measured by a high-sensitivity assay (hsCRP) at baseline. We performed multivariable linear regressions with log-transformed hsCRP as the dependent variable. Based on these associations, we calculated potential hsCRP levels for each patient, assuming optimisation of the individual modRF., Results: Of 1014 patients, 737 (73%) were male, the mean age was 69 years, and 483 (48%) had an hsCRP ≥ 2 mg/l. ModRF were significantly overrepresented in patients with hsCRP ≥ 2 mg/l compared to patients with an hsCRP < 2 mg/l (BMI ≥ 25 kg/m2: 76% vs 61%; PA < 1.5 h/week: 69% vs 57%; MDS ≤ 12: 46% vs 37%; smoking: 61% vs 54%; p < 0.05 for all). hsCRP increased with the incremental number of modRF present (median hsCRP values for N = 0, 1, 2, 3, and 4 modRF: 1.1, 1.0, 1.6, 2.4, 2.8 mg/l, p < 0.001). Multivariable linear regression adjusting for age, sex, intake of lipid-lowering medication, and diabetes mellitus revealed independent associations between log-transformed hsCRP and all modRF (BMI ≥ 25 kg/m2: exp(ß) = 1.55, p < 0.001; PA < 1.5 h/week: exp(ß) = 1.33, p < 0.001; MDS ≤ 12: exp(ß) = 1.18, p = 0.018; smoking: exp(ß) = 1.18, p = 0.019). Individual recalculation of hsCRP levels assuming optimisation of modRF identified 183 out of 483 (38%) patients with hsCRP ≥ 2 mg/l who could achieve an hsCRP < 2 mg/l via lifestyle changes., Conclusion: modRF are strongly and independently associated with CRP levels in patients with CAD. A relevant portion of CAD patients with high inflammatory burden could achieve an hsCRP < 2 mg/l by lifestyle changes alone. This should be considered both in view of the cost and side-effects of pharmacological anti-inflammatory treatment and for the design of future clinical trials in this field., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The recently updated European Society of Cardiology (ESC) dyslipidaemia guidelines recommend a lower low-density lipoprotein cholesterol (LDL-C) goal of <55 mg/dL for patients with atherosclerotic cardiovascular disease (ASCVD), with a concomitant Class IA upgrade for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) for patients not reaching their LDL-C goal under conventional lipid-lowering therapy., Aims: We aim to quantify the need for PCSK9i and the related costs to achieve the revised LDL-C goal in ASCVD patients compared to former ESC recommendations, in particular the risk-based 2017 ESC consensus update., Methods and Results: We included patients with ASCVD from an observational cohort study ongoing since 2015. A Monte Carlo simulation incorporating a treatment algorithm adding sequentially a statin, ezetimibe, and a PCSK9i was applied with consideration of partial and total statin intolerance. The need for PCSK9i was calculated for three different ESC recommendations (2019 guidelines, 2016 guidelines, 2017 consensus update). Preventable events and treatment costs due to PCSK9i were calculated for a range of annual event rates from 2% to 8% and annual treatment costs of ca. 6050 €. We included 1780 patients (mean age 69.5 years). Median LDL-C at baseline was 85.0 mg/dL, with 61% of patients taking lipid-lowering medication. The need for PCSK9i was simulated to be 42.0% (ESC 2019), 31.9% (ESC 2016), and 5.0% (ESC 2017). The LDL-C goals were achieved in 97.9%, 99.1%, and 60.9% of patients, respectively. Annual treatment cost for PCSK9i per 1 000 000 ASCVD patients would be 2.54 billion € (ESC 2019) compared to 0.30 billion € (ESC 2017). Costs per prevented event due to PCSK9i initiation differed widely, e.g. 887 000 € for an event rate of 3% and a treatment goal of <55 mg/dL compared to 205 000 € for an event rate of 7% and risk-based use of PCSK9i., Conclusion: The revised LDL-C treatment goals increase the projected need for PCSK9i with a substantial increase in associated treatment cost. An allocation strategy based on residual LDL-C and clinical or angiographic risk factors leads to a more tailored target population for PCSK9i with a reasonable benefit/cost ratio., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Coronary intravascular lithotripsy (IVL) has recently been evaluated for the treatment of severely calcified native coronary lesions. Evidence for its use in in-stent restenosis is sparse and is still an off-label indication. Therefore, we aimed to evaluate the feasibility, safety, and acute and mid-term angiographic outcomes after IVL for the treatment of calcium-mediated coronary in-stent restenosis., Methods: A retrospective, single-center analysis was performed for 6 cases with undilatable instent restenosis due to calcium-mediated stent underexpansion and/ or calcified neointima from January to November 2019. Lesions were treated with IVL (Shockwave Medical) and subsequent drug-eluting stent or drug-coated balloon. Angiographic success was defined as residual lumen stenosis <20% and Thrombolysis in Myocardial Infarction 3 flow. Follow-up angiography was performed at a median of 141.5 days., Results: Six patients presented with symptomatic in-stent restenoses (65.8% to 87.9%) at 11 to 175 months after implantation. Intravascular and angiographic imaging detected calcium-mediated stent underexpansion (n = 2), calcified neointima (n = 2), or a combination of both (n = 2) as cause of restenosis. In-stent IVL, subsequent high-pressure balloon dilation, and drug-eluting stent or drug-coated balloon implantation were performed successfully in all cases. Acute angiographic success and angina relief were achieved in 5 of 6 cases and sustained during follow-up. No major acute cardiovascular events occurred., Conclusions: The application of IVL for the treatment of calcium-mediated coronary in-stent restenosis was feasible and safe, and yielded promising short- and mid-term results in the majority of cases.

Aims: The first reports of declining hospital admissions for major cardiovascular emergencies during the COVID-19 pandemic attracted public attention. However, systematic evidence on this subject is sparse. We aimed to investigate the rate of emergent hospital admissions, subsequent invasive treatments and comorbidities during the COVID-19 pandemic in Germany., Methods and Results: This was a retrospective analysis of health insurance claims data from the second largest insurance fund in Germany, BARMER. Patients hospitalized for acute myocardial infarction, acute limb ischemia, aortic rupture, stroke or transient ischemic attack (TIA) between January 1, 2019, and May 31, 2020, were included. Admission rates per 100,000 insured, invasive treatments and comorbidities were compared from January-May 2019 (pre-COVID) to January-May 2020 (COVID). A total of 115,720 hospitalizations were included in the current analysis (51.3% females, mean age 72.9 years). Monthly admission rates declined from 78.6/100,000 insured (pre-COVID) to 70.6/100,000 (COVID). The lowest admission rate was observed in April 2020 (61.6/100,000). Administration rates for ST-segment elevation myocardial infarction (7.3-6.6), non-ST-segment elevation myocardial infarction (16.8-14.6), acute limb ischemia (5.1-4.6), stroke (35.0-32.5) and TIA (13.7-11.9) decreased from pre-COVID to COVID. Baseline comorbidities and the percentage of these patients treated with interventional or open-surgical procedures remained similar over time across all entities. In-hospital mortality in hospitalizations for stroke increased from pre-COVID to COVID (8.5-9.8%)., Conclusions: Admission rates for cardiovascular and cerebrovascular emergencies declined during the pandemic in Germany, while patients' comorbidities and treatment allocations remained unchanged. Further investigation is warranted to identify underlying reasons and potential implications on patients' outcomes.

Background and Aims: Cardiac troponin blood levels are frequently elevated in patients with impaired renal function. Their predictive value for the severity of stable coronary artery disease (CAD) remains unclear in these cases. Therefore, we aimed to evaluate the blood levels of high-sensitivity troponin T and I (hsTnT/I) and their association with the severity of stable CAD in patients with chronic kidney disease., Methods: Overall, 2209 patients with suspected stable CAD undergoing invasive coronary angiography were included in an ongoing prospective cohort study. We identified 595 patients with impaired renal function defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2 . Coronary morphology was assessed by the number of affected major coronary vessels (CAD classification), SYNTAX, and Gensini scores. hsTnT/I blood levels were measured by three latest-generation assays (Roche Diagnostics Elecsys, Abbott ARCHITECT STAT, and Singulex Clarity). Ordinal logistic regression for the severity of CAD adjusted by classical cardiovascular risk factors and eGFR were performed with each troponin assay as an independent variable., Results: Mean age was 72.9 ± 9.8 years (33.6% female). Median eGFR was 47.5 ml/min/1.73 m 2 (interquartile range [IQR] 34.9, 54.1). For the association of Roche-hsTnT, Abbott-hsTnI, and Singulex-hsTnI with the CAD classification, odds ratios per standard deviation (OR) were 1.27 (95% confidence interval [CI] 1.07-1.51), 1.21 (CI 1.02-1.44), and 1.24 (CI 1.04-1.47), respectively. The associations for the investigated assays with SYNTAX and Gensini scores, respectively, were OR 1.40, CI 1.11-1.78 and OR 1.24, CI 1.01-1.51 (Roche-hsTnT), OR 1.42, CI 1.12-1.78 and OR 1.25, CI 1.02-1.52 (Abbott-hsTnI), OR 1.38, CI 1.09-1.74 and OR 1.25, CI 1.02-1.53 (Singulex-hsTnI)., Conclusions: In patients with impaired renal function, blood levels of hsTnT/I were significantly associated with the severity of stable CAD. These findings may help clinicians guide further diagnostic assessment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The purpose of this prospective study was to analyze the relationship between ventricular morphology and parameters of cardiac function in two different athletic groups and controls, using feature tracking cardiac magnetic resonance (FT-CMR). Twenty-three professional soccer players (22 ± 4 years), 19 competitive triathletes (28 ± 6 years) and 16 controls (26 ± 3 years) were included in the study. CMR was performed using a 1.5 T scanner. Cardiac chamber volumes, mass and biventricular global myocardial strain were obtained and compared. In comparison to the control subjects, athletes were characterized by a higher cardiac volume (p < 0.0001), higher cardiac mass (p < 0.001), reduced longitudinal strain of the left and right ventricle (p < 0.05 and p < 0.01 respectively) and reduced left ventricular radial strain (p < 0.05). Soccer players revealed higher amounts of left ventricular mass (87 ± 15 vs. 75 ± 13 g/m 2 , p < 0.05) than triathletes. Moreover, they showed a greater decrease in left and right ventricular longitudinal strain (p < 0.05 and p < 0.05) as well as in radial left ventricular strain (p < 0.05) in comparison to triathletes. An increase in left ventricular mass correlated significantly with a decrease in longitudinal (r = 0.47, p < 0.001) and radial (r =  - 0.28, p < 0.05) strain. In athletes, attenuation of strain values is associated with cardiac hypertrophy and differ between soccer players and triathletes. Further studies are needed to investigate whether it is an adaptive or maladaptive change of the heart induced by intense athletic training.

Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment., Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol., Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced., Interpretation: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies., Funding: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the effects of renal denervation (RDN) on left ventricular (LV) mass, myocardial strain and diastolic function in patients with treatment-resistant arterial hypertension by cardiac magnet resonance imaging on a 12-month follow-up., Materials and Methods: Sixteen patients (38% female) were examined before and 12 months after RDN. LV morphology and strain were analyzed. Diastolic function was determined by early (EPFR) and atrial peak filling rates (APFR) derived from differential volume-time-curve analysis. Clinical visits included 24-h ambulant blood pressure monitoring (ABPM)., Results: Twelve months after RDN LV mass decreased from 80 ± 21 g/m 2 to 74 ± 20 g/m 2 (P < 0.05). Global radial (35 ± 12% vs. 41 ± 10%, P < 0.05) and longitudinal strain improved (- 15 ± 4% vs. - 17 ± 3%, P < 0.05). Global circumferential strain (- 16 ± 5% vs. - 18 ± 4%, P = 0.12) remained unchanged. The parameter of diastolic LV function PFRR (EPFR/APFR) improved following RDN (0.9 ± 0.4 vs. 1.1 ± 0.5, P < 0.05). Individual changes of LV mass were associated with an increase of EPFR (r = - 0.54, P < 0.05) and a reduction of APFR by trend (r = 0.45, P = 0.08). Systolic ABPM showed a decrease by trend (152 mmHg vs. 148 mmHg, P = 0.08)., Conclusions: After RDN we observed a reduction of LV mass, improvement of global strain and diastolic function.

Background and Aims: Guidelines recommend a healthy diet as a cornerstone of cardiovascular disease (CVD) prevention. Although the Mediterranean diet (MD) is the best studied dietary pattern for CV outcomes, data on association between MD and severity of CAD are limited. Therefore, we analysed dietary data in association with the SYNTAX score in coronary artery disease (CAD) patients from the INTERCATH study., Methods: The INTERCATH study is an observational study in patients undergoing coronary angiography at the University Heart Center Hamburg. Coronary morphology is assessed by the SYNTAX score. A lifestyle questionnaire collects dietary data with food frequency questions at baseline. Based on seven dietary characteristics, we calculated an established Mediterranean diet score (MDS) with a range of 0-28 points at which 28 points reflect maximal adherence to MD. To investigate the association of MD with severity of CAD, we performed logistic regression analysis after adjustment for confounding factors., Results: Of 1121 patients, 27% were women. The median age was 70.7 years (interquartile range (IQR) 61.1,77.0). CV risk factors were distributed as expected for a CAD cohort (31.3% diabetes, 81.1% arterial hypertension, 34.0% smoking, median BMI 26.6 kg/m 2 (IQR 24.1, 30.3), median LDL-C 87 mg/dL (IQR 65.0,116,6). Of all variables included, the strongest correlation with MDS was found for log (hs-CRP) (r = -0.21, p < 0.001). Adherence to MD represented by a higher MDS was significantly associated with a reduced probability for a medium/high risk SYNTAX score of ≥23 with an odds ratio (OR) of 0.923 per point increase of MDS (95% confidence interval 0.869-0.979; p = 0.0079). This association remained significant after adjustment for cardiovascular risk factors (OR 0.934, 95% CI 0.877-0.995, p = 0.035). After further adjustment for log (hs-CRP), the association remained no longer significant (OR 0.955 (0.893-1.022, p = 0.19)., Conclusions: In this contemporary data set, we found an independent association of adherence to MD with a less complex CAD. Hs-CRP correlated significantly with adherence to MD and may be a marker of the vasoprotective effects of MD. These results strengthen the evidence for the protective effect of an MD pattern in CVD prevention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Although the efficacy of lipid-lowering medication (LLM) in patients with coronary artery disease (CAD) is well established, the majority of patients fail to achieve their LDL-C goals. The evidence for measurement of LDL-C to achieve these goals is limited. The goal of the present study, therefore, was to analyze ambulatory LLM management in relation to performance of LDL-C measurements and achieved LDL-C levels after the initial diagnosis of CAD., Methods: The study followed up a subcohort of 200 patients with newly diagnosed CAD of the INTERCATH trial, an observational study including patients undergoing coronary angiography. In addition to baseline information, data were collected on LLM, performance of lipid measurements, and laboratory results at a minimum of 6 months' postdischarge., Findings: The mean age of the sample was 67.9 years, and 36.0% were women. In 34.5% of all patients, no measurement of LDL-C levels was performed during follow-up. We found no differences in baseline characteristics between patients with and without LDL-C measurements during follow-up. In patients with measurement of LDL-C levels, the frequency of intensification of statin medication according to LDL-C reduction was higher compared with those patients without LDL-C measurement (23.6% vs 4.3%; P < 0.001); all other categories of intensity adjustment were comparable. In patients with 3 LDL-C measurements, achieved LDL-C levels were significantly lower (mean, 81 mg/dL), and a higher proportion reached an LDL-C level <70 mg/dL (44.7%) compared with patients with 1 (95 mg/dL [P = 0.013]; 21.8%) or 2 (91 mg/dL [P = 0.037]; 28.9%) LDL-C measurements despite comparable LDL-C levels at baseline. Ezetimibe was used in 3.5% of the entire study cohort., Implications: We found no differences in patient characteristics between patients with and without LDL-C measurements after being newly diagnosed with CAD. Performance and frequency of LDL-C measurements were clearly associated with better, higher frequency of intensification of statin medication, lower achieved LDL-C levels, and a higher proportion of patients achieving the LDL-C goal of <70 mg/dL. These results suggest an important role of LDL-C measurements for secondary prevention after the initial diagnosis of CAD., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Coronary artery disease (CAD) has a complex etiology involving numerous environmental and genetic factors of disease risk. To date, the genetic 9p21 locus represents the most robust genetic finding for prevalent and incident CAD. However, limited information is available on the genetic background of the severity and distribution of CAD. CAD manifests itself as stable CAD or acute coronary syndrome. The Gensini score quantifies the extent CAD but requires coronary angiography. Here, we aimed to identify novel genetic variants associated with Gensini score severity and distribution of CAD. A two-stage approach including a discovery and a replication stage was used to assess genetic variants. In the discovery phase, a meta-analysis of genome-wide association data of 4,930 CAD-subjects assessed by the Gensini score was performed. Selected single nucleotide polymorphisms (SNPs) were replicated in 2,283 CAD-subjects by de novo genotyping. We identified genetic loci located on chromosome 2 and 9 to be associated with Gensini score severity and distribution of CAD in the discovery stage. Although the loci on chromosome 2 could not be replicated in the second stage, the known CAD-locus on chromosome 9p21, represented by rs133349, was identified and, thus, was confirmed as risk locus for CAD severity.

Aims: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations., Methods and Results: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years. All Lp(a) measurements were performed in the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott Diagnostics). The three endpoints considered were incident major coronary events (MCE), incident cardiovascular disease (CVD) events, and total mortality. We found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL) (Jonckheere-Terpstra test P < 0.001). Kaplan-Meier curves showed the highest event rate of MCE and CVD events for Lp(a) levels ≥90th percentile (log-rank test: P < 0.001 for MCE and CVD). Cox regression models adjusted for age, sex, and cardiovascular risk factors revealed a significant association of Lp(a) levels with MCE and CVD with a hazard ratio (HR) of 1.30 for MCE [95% confidence interval (CI) 1.15‒1.46] and of 1.25 for CVD (95% CI 1.12‒1.39) for Lp(a) levels in the 67‒89th percentile and a HR of 1.49 for MCE (95% CI 1.29‒1.73) and of 1.44 for CVD (95% CI 1.25‒1.65) for Lp(a) levels ≥ 90th percentile vs. Lp(a) levels in the lowest third (P < 0.001 for all). There was no significant association between Lp(a) levels and total mortality. Subgroup analysis for a continuous version of cube root transformed Lp(a) identified the highest Lp(a)-associated risk in individuals with diabetes [HR for MCE 1.31 (95% CI 1.15‒1.50)] and for CVD 1.22 (95% CI 1.08‒1.38) compared to those without diabetes [HR for MCE 1.15 (95% CI 1.08‒1.21; HR for CVD 1.13 (1.07-1.19)] while no difference of the Lp(a)- associated risk were seen for other cardiovascular high risk states. The addition of Lp(a) levels to a prognostic model for MCE and CVD revealed only a marginal but significant C-index discrimination measure increase (0.001 for MCE and CVD; P < 0.05) and net reclassification improvement (0.010 for MCE and 0.011 for CVD)., Conclusion: In this large dataset on harmonized Lp(a) determination, we observed regional differences within the European population. Elevated Lp(a) was robustly associated with an increased risk for MCE and CVD in particular among individuals with diabetes. These results may lead to better identification of target populations who might benefit from future Lp(a)-lowering therapies., (© The Author 2017. Published on behalf of the European Society of Cardiology.)

Background: The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date., Methods: The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction. The troponin I concentration was determined on admission (0 hours) and 3 hours later. The diagnostic algorithm incorporated troponin I elevation above the gender-specific 99th percentile as well as predefined relative or absolute 3-hour changes in the troponin I concentration (delta)., Results: The diagnostic criterion of troponin I above the 99th percentile resulted in a negative predictive value of 98.0% and 98.2% in men and women, respectively. For rule-in of non-ST-segment elevation myocardial infarction, the use of absolute deltas yielded higher positive predictive values and sensitivities compared to relative deltas. With detection rates of about 85% and 82% in men and women, respectively, non-ST-segment elevation myocardial infarction was diagnosed with a positive predictive value close to 84% in men and 80% in women., Conclusions: The investigational troponin I assay provides an excellent non-ST-segment elevation myocardial infarction rule out. With gender-specific differences, the application of absolute changes in troponin concentration was superior to relative changes to rule in patients with non-ST-segment elevation myocardial infarction.

Rationale: Phosphodiesterase 2 is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyzes cAMP. Myocardial phosphodiesterase 2 is upregulated in human heart failure, but its role in the heart is unknown., Objective: To explore the role of phosphodiesterase 2 in cardiac function, propensity to arrhythmia, and myocardial infarction., Methods and Results: Pharmacological inhibition of phosphodiesterase 2 (BAY 60-7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor activation in healthy mice. Under pathological conditions induced by chronic catecholamine infusions, BAY reversed both the attenuated β-adrenoceptor-mediated inotropy and chronotropy. Conversely, ECG telemetry in heart-specific phosphodiesterase 2-transgenic (TG) mice showed a marked reduction in resting and in maximal heart rate, whereas cardiac output was completely preserved because of greater cardiac contraction. This well-tolerated phenotype persisted in elderly TG with no indications of cardiac pathology or premature death. During arrhythmia provocation induced by catecholamine injections, TG animals were resistant to triggered ventricular arrhythmias. Accordingly, Ca 2+ -spark analysis in isolated TG cardiomyocytes revealed remarkably reduced Ca 2+ leakage and lower basal phosphorylation levels of Ca 2+ -cycling proteins including ryanodine receptor type 2. Moreover, TG demonstrated improved cardiac function after myocardial infarction., Conclusions: Endogenous phosphodiesterase 2 contributes to heart rate regulation. Greater phosphodiesterase 2 abundance protects against arrhythmias and improves contraction force after severe ischemic insult. Activating myocardial phosphodiesterase 2 may, thus, represent a novel intracellular antiadrenergic therapeutic strategy protecting the heart from arrhythmia and contractile dysfunction., (© 2016 American Heart Association, Inc.)

Background: The 99th percentile of cardiac troponin levels, determined in a reference population, is accepted as threshold for diagnosis of acute myocardial infarction (AMI). However, there is no common consensus of how to define the reference population. The aim of the present study was to determine 99th percentile reference values, determined by a high-sensitivity assay (hsTnI), according to different health status and cardiovascular risk factor prevalence in a large population-based sample., Methods: Troponin I was determined using the Abbott ARCHITECT STAT highly sensitive troponin I immunoassay in 4138 participants of the Gutenberg Health Study., Results: hsTnI was detectable in 81.6% of all individuals. The 99th percentile of the overall population was 27 ng/L. Age and gender had a prominent influence on these values. Exclusion of individuals with elevated natriuretic peptide levels or cardiac abnormalities resulted in lower 99th percentile values, whereas exclusion of individuals with an impaired estimated glomerular filtration rate (eGFR) or with prevalent coronary artery disease/myocardial infarction (CAD/MI) did not result in a meaningful change., Conclusions: Troponin I, measured by a high-sensitivity assay, can be reliably detected in the vast majority of the general population. hsTnI values were dependent on age, gender as well as structural and functional cardiac abnormalities.