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Background and ObjectivesIt is uncertain whether there is an association of carotid plaques (CPs) and flow velocities with peak width mean diffusivity (PSMD) and white matter hyperintensities (WMH) independent of shared risk factors. We aimed to study this association controlling for biomarkers of inflammation and cardiac dysfunction and typical cardiovascular risk factors and spatial distribution.MethodsWe included participants from the population-based Hamburg City Health Study, recruiting citizens between 45 and 74 years of age. Medical history was obtained from structured interviews and extended laboratory tests, physical examinations, MRI of the head, echocardiography, and abdominal and carotid ultrasound were performed. We performed multivariable regression analysis with PSMD and periventricular, deep, and total volume of WMH (pWMH, dWMH, tWMH) as dependent variables. PSMD was calculated as the difference between the 95th and 5th percentiles of MD values on the white skeleton in standard space. Volumes of WMH were determined by the application of a manually trained k-nearest neighbor segmentation algorithm. WMH measured within a distance of 1 cm from the surface of the lateral ventricles were defined as pWMH and above 1 cm as dWMH.ResultsTwo thousand six hundred twenty-three participants were included. The median age was 65 years, and 56% were women. Their median tWMH was 946 mm3(IQR:419, 2,164), PSMD 2.24 mm2/s × 10−4(IQR: 2.04, 2.47), peak systolic velocity (PSV) of internal carotid arteries 0.70m/second (IQR:0.60, 0.81), and 35% had CPs. Adjusted for age, sex, high-sensitive CRP, NT-proBNP, and commonly measured cardiovascular risk and systemic hemodynamic factors, both CPs (B = 0.15; CI: 0.04, 0.26;p= 0.006) and low PSV (B = −0.49; CI: −0.87, −0.11;p= 0.012) were significantly associated with a higher tWMH and PSMD. Low PSV (B = −0.48; CI: −0.87, −0.1;p= 0.013) was associated with pWMH and the presence of CP with pWMH (B = 0.15; CI: 0.04, 0.26;p= 0.008) and dWMH (B = 0.42; CI: 0.11, 0.74;p< 0.009).DiscussionLow PSV and CP are associated with WMH and PSMD independent of cardiovascular risk factors and biomarkers of inflammation and cardiac dysfunction. This points toward pathophysiologic pathways underlying both large and small vessel disease beyond the common cardiovascular risk profile.Trial Registration InformationThe trial was submitted atclinicaltrials.gov, underNCT03934957on January 4, 2019. The first participant was enrolled in February 2016.

Previously, the simultaneous presence of endocarditis (IE) has been reported in 3–30% of spondylodiscitis cases. The specific implications on therapy and outcome of a simultaneous presence of both diseases are not yet fully evaluated. Therefore, the aim of this study was to investigate the influence of a simultaneously present endocarditis on the course of therapy and outcome of spondylodiscitis. A prospective database analysis of 328 patients diagnosed with spontaneous spondylodiscitis (S) using statistical analysis with propensity score matching was conducted. Thirty-six patients (11.0%) were diagnosed with concurrent endocarditis (SIE) by means of transoesophageal echocardiography. In our cohort, the average age was 65.82 ± 4.12 years and 64.9% of patients were male. The incidence of prior cardiac or renal disease was significantly higher in the SIE group (coronary heart disease SIE n = 13/36 vs. S n = 57/292, p n = 11/36 vs. S n = 41/292, p n = 14/36 vs. S n = 55/292, p p

Background and aims: We aimed to determine the association of carotid intima media thickness (CIMT), carotid plaques, and heart function with peak systolic velocity (PSV) of the common (CCA) and internal carotid artery (ICA) in a cross-sectional study. Methods: In the population-based Hamburg-City-Health-Study participants between 45 and 74 years were recruited. Cardio-vascular risk factors were assessed by history, blood samples, and clinical examination. CIMT, plaques, and PSV were determined by carotid ultrasound. Serum N-terminal brain natriuretic peptide (NT-proBNP) was determined as a biomarker for cardiac dysfunction, and left ventricular ejection fraction (LVEF) was quantified by echocardiography. Participants with carotid stenosis were excluded. Data were analyzed by multivariate linear regression. Results: We included 8567 participants, median age was 62 years, 51.8% were women. Median CIMT was 0.75 mm, NT-proBNP 80 pg/ml, LVEF 58.5%, and 30.4% had carotid plaques. For women PSV decreased in decades from 89 to 73 cm/s in CCAs and 78 to 66 cm/s in ICAs, and for men from 91 to 76 cm/s in CCAs and from 70 to 66 cm/s in ICAs. Corrected for age, sex, red blood cell count, and blood pressure, in CCAs lower PSV was associated with carotid plaques (p

A significant proportion of patients presenting with acute coronary syndromes (ACS) have multivessel disease (MVD). Despite the abundance of clinical trials in this area, several questions regarding the procedure of complete coronary revascularisation remain unanswered. This state-of-the-art review summarises the latest evidence on complete revascularisation (CR) in this subset of patients and critically appraises clinical decision making based on non-culprit lesion (NCL) assessment. Future areas of research are put into perspective.

Background The recently updated European Society of Cardiology (ESC) dyslipidaemia guidelines recommend a lower low-density lipoprotein cholesterol (LDL-C) goal of 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 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.

Patients with atherosclerotic cardiovascular disease have a high risk for subsequent cardiovascular events despite optimal drug treatment including statins and ezetimibe. Dyslipidemia represents a central and direct cause of this, with a frequent failure to achieve the target values recommended in the guidelines. New lipid-lowering substances are increasingly becoming available for treatment of this residual risk. Due to their high cost, cost-effectiveness analyses are required in order to justify their use. Important variables when considering the cost-effectiveness of a drug are quality adjusted life years (QALY) and the incremental cost-effectiveness ratio (ICER). The lower bounds of the ICER determining the cost-effectiveness of a treatment vary between healthcare systems. The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab are deemed to be cost-effective particularly in patients with high levels of low-density lipoprotein cholesterol (LDL-C) prior to treatment or with a high cardiovascular risk as determined by the presence of defined risk criteria. Similar considerations apply to the PCSK9 small interfering RNA (siRNA) inclisiran. Administration of bempedoic acid is deemed cost-effective especially in patients with statin intolerance. Eicosapentaenoic acid is deemed cost-effective overall, although the data with respect to the exact placebo-controlled efficacy are still inconclusive.Trotz optimaler medikamentöser Therapie inklusive eines Statins und Ezetimib sind Patienten mit einer atherosklerotischen kardiovaskulären Erkrankung einem hohen Risiko für kardiovaskuläre Folgeereignisse ausgesetzt. Dyslipidämien stellen hierfür eine zentrale und kausale Ursache dar, mit einer häufigen Verfehlung der in Leitlinien empfohlenen Zielwerte. Zur Behandlung dieses residuellen Risikos stehen zunehmend neue lipidsenkende Substanzen zur Verfügung. Um ihre Anwendung angesichts teils hoher Therapiekosten zu rechtfertigen, sind Kosten-Nutzen-Analysen notwendig. Wichtige Kenngrößen in der Evaluation einer Kosteneffizienz sind QALY („quality adjusted life years“) und die ICER („incremental cost effectiveness ratio“). Grenzwerte der ICER, unter der eine Therapie als kosteneffektiv bewertet wird, variieren je nach Gesundheitssystem. Der Einsatz der PCSK9(Proproteinkonvertase Subtilisin/Kexin Typ 9)-Inhibitoren Alirocumab und Evolocumab wird als kosteneffektiv insbesondere bei den Patienten angesehen, die einen hohen LDL(„low-density lipoprotein“)-Cholesterin(LDL-C)-Wert vor Therapiebeginn oder ein hohes individuelles kardiovaskuläres Risiko gemäß dem Vorliegen definierter Risikokriterien aufweisen. Ähnliches gilt für die PCSK9-siRNA („small interfering RNA“) Inclisiran. Die Gabe von Bempedoinsäure wird insbesondere bei Patienten mit Statinintoleranz als kosteneffektiv gewertet. Die Gabe von Icosapent-Ethyl wird insgesamt als kosteneffektiv gewertet, die Datenlage hinsichtlich der genauen placebokontrollierten Wirksamkeit ist jedoch noch inkonklusiv.

Purpose Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly used treatment option for patients in need of mechanical cardiopulmonary support, while available outcome data is limited. The aim of this study was to identify predictors for 30-day in-hospital mortality. Material and methods We analyzed baseline characteristics and outcomes of 8351 VA-ECMO procedures performed in Germany from 2007 to 2015. Using a multivariable model, we identified the ten most important variables to allow for prediction of 30-day in-hospital mortality. Based on these variables, we created a mortality prediction score (ECMO-ACCEPTS score) to enhance decision making in patients considered for or treated with VA-ECMO support. Results Of 8351 patients (71.7% male) 3567 had prior CPR. Mean age was 62 years in the present cohort. The overall 30-day in-hospital mortality was 61%. The ECMO-ACCEPTS score, derived among randomly selected 4175 patients, included ten independent predictors for in-hospital mortality. Internal validation in the remaining 4176 patients confirmed strong differentiation between low and high risk of 30-day in-hospital mortality (r = 0.97 for correlation of predicted with observed mortality, p Conclusions The ECMO-ACCEPTS score might help clinicians to improve risk prediction among VA-ECMO patients for refractory cardiogenic shock.

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.

Background High-sensitivity Troponin T and I (hsTnT/I) concentration is independently associated with coronary artery disease (CAD) severity and cardiovascular outcome. Here we explored whether hsTnT/I blood levels add predictive information irrespective of CAD severity and further confounders in unselected stable patients with angiographically characterized CAD. Methods Between 2015 and 2020, 3,012 patients undergoing coronary angiography were included in the observational Hamburg INTERCATH study. In 2,209 consecutive patients Troponin levels were quantified for hsTnT (Roche Diagnostics Elecsys) and hsTnI (Abbott Diagnostics ARCHITECT STAT). Patients presenting with acute coronary syndromes and heart transplant recipients were excluded, leaving 1,841 patients for analyses. CAD severity was graded according to the Gensini score. Major adverse cardiac events (MACE) as a composite of cardiovascular death, stroke, myocardial infarction, and coronary revascularization were defined as endpoint. Kaplan-Meier analyses stratified by hsTnT/I quartiles were performed. Multivariable Cox models were computed for the association of hsTnT/I with MACE adjusting for age, gender, arterial hypertension, hyperlipoproteinemia, smoking, diabetes mellitus, body-mass index, eGFR and Gensini Score. Results Mean age was 68.5±10.9 years (27.9% female). 81.1% were diagnosed with CAD by coronary angiography. Gensini score was 21.0±30.2. Median follow-up time was 4.42 years. hsTnT quartiles differentiated MACE across all categories (Figure 1A). For hsTnI, cardiovascular risk was differentiated between the lowest and highest quartiles as well as the 1st and 2nd quartile particularly beyond 24 months of follow-up (Figure 1B). However, MACE after 3 years was not associated with hsTnT after adjustment for classical cardiovascular risk factors and CAD severity (Figure 1C), whereas the hazard of MACE was increased in the 3rd and 4th hsTnI quartiles compared to the 1st quartile (HR 1.3, IQR 1.1–1.6 for both categories; Figure 1D). Conclusion Increasing hsTn concentration was related to intermediate term cardiovascular outcome in unselected stable patients. Only hsTnI concentration remained as independent predictor after testing for most possible confounders, including CAD severity. This data underpins the role of hsTnI in outcome prediction. Funding Acknowledgement Type of funding sources: None.

Background The 2019 ESC dyslipidaemia guidelines recommend a more intense LDL-cholesterol (LDL-C) reduction for patients with coronary artery disease (CAD). As a result the need for PCSK9 inhibitors (PCSK9i) is projected to increase significantly, with a concomitant substantial impact on treatment cost. Adding the novel lipid lowering agent bempedoic acid (BA) to established oral lipid lowering therapy could provide an affordable alternative to PCSK9i to attain the LDL-C treatment target, particularly in patients with statin intolerance. Aims To quantify the target populations for BA and PCSK9i as well as the related treatment costs to achieve the LDL-C target of the 2019 ESC dyslipidaemia guidelines assuming addition of BA to lipid lowering medication. Methods We included 1922 patients (mean age 69.3 years) with angiographically documented CAD from an observational cohort study ongoing since 2015. A Monte Carlo simulation incorporating an algorithm for intensification of lipid lowering medication was applied in order to achieve the LDL-C treatment goal of Results Figure 1 displays the baseline LDL-C distribution (median LDL-C 86.0 mg/dL) and lipid lowering medications. The need for PCSK9i in scenario 1 would be 41.4% for a moderate and 46.1% for a high rate of statin intolerance. Addition of BA in scenario 2 would reduce the need for PCSK9i to 25.3% and 29.4%. Figure 2 displays the LDL-C distributions and lipid lowering medications for scenarios 1 and 2 assuming a moderate rate of statin intolerance. Use of BA would lower the annual overall treatment cost incurred through use of PCSK9i ± BA per 1,000,000 CAD patients by 13.3% and 10.5%. The cost per prevented event in the entire cohort would be lower (−5.0 and −6.3%), however at the price of less prevented cardiovascular events (−8.7% and −4.5%). Amongst patients with full statin intolerance, the cost per prevented event would be reduced (−6.8% for both rates of statin intolerance) whilst more cardiovascular events would be prevented (+7.5% and +6.9%). Conclusion Use of BA in patients with CAD would reduce the need for PCSK9i as well as the overall treatment cost for add-on lipid lowering therapy. The subpopulation of patients with full statin intolerance might profit particularly. Funding Acknowledgement Type of funding sources: None. Figure 1. Baseline LDL-C distribution and LLMFigure 2. LDL-C and LLM after LLM intensification

Background Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. Purpose The aim of the study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. Methods This study was conducted as part of the BiomarCaRE project using harmonised data from 12 population-based cohorts (n=40,212) from Europe. Cox proportional hazards models were used to determine hazard ratios (HRs) for the incidence of AF and HF in CKD and with competing mortality risk after adjusting for covariates. Results Mean age at baseline was 51.1 (standard deviation 11.9) years, and 49.3% were men. Overall, 3.5% had CKD at baseline. The rate for incident AF was 3.9 per 1000 person-years during follow-up. The HR for AF for those with CKD compared with those without was 1.23 (95% CI 1.00–1.52, p=0.0465) after adjustment for covariates. The rate for incident HF was 3.9 per 1000 person-years and the associated risk in the presence of CKD was HR 1.67 (95% CI 1.39–2.01). In subjects with CKD, N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed an association with AF, while NT-proBNP and C-reactive protein (CRP) showed an association with HF. Conclusion CKD is an independent risk factor for subsequent AF and even more so for HF. In patients with CKD, NT-proBNP was clearly associated with subsequent risk of AF. In addition to this marker, hs-CRP was also associated with risk of subsequent HF. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 7th framework programme collaborative project, grant agreement no. HEALTH-F2-2011_278913. Atrial Fibrillation and HF in CKD

Aims Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. The aim of this study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. We also included an assessment of baseline biomarkers of inflammation, myocardial injury, and left ventricular dysfunction with risk of AF and HF, respectively, to shed light on the potential underlying pathophysiology. Methods and results This study was conducted within the BiomarCaRE project using harmonized data from 12 European population‐based cohorts (n = 48 518 participants). Renal function was assessed by glomerular filtration rate estimated using the combined Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation with standardized serum creatinine (Cr) and non‐standardized serum cystatin C (CysC). Incidence of AF and HF respectively, during a median follow‐up of 8 years was recorded. Cox proportional hazards models were used to determine hazard ratios (HRs) for the incidence of AF and HF in CKD and the competing risk of mortality after adjustment for covariates. The mean age at baseline was 51.4 (standard deviation 12.1) years, 49% were men. Overall, 4.3% of subjects had CKD at baseline. The rate for AF was 3.8 per 1000 person‐years during follow‐up. The HR for AF in patients with CKD compared with patients without CKD was 1.28 (95% confidence interval 1.07–1.54) after adjustment for covariates. The rate for incident HF was 4.1 per 1000 person‐years and the HR of CKD for HF was 1.71 (95% confidence interval 1.45–2.01. In subjects with CKD, N‐terminal‐pro‐brain natriuretic peptide (NT‐proBNP) showed an association with AF, whereas NT‐proBNP and C‐reactive protein were associated with HF. Conclusions Chronic kidney disease is an independent risk factor for subsequent AF and is even more closely associated with HF. In these relatively young participants with CKD, NT‐proBNP was strongly associated with subsequent risk of AF. For HF, in addition, elevated levels of hs‐C‐reactive protein at baseline were related to incident events.

BackgroundStroke after a cardiovascular procedure (CVP) is a devastating complication adversely affecting outcome. Mechanical thrombectomy (MT) has not been investigated systematically in this population.ObjectiveTo 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.MethodsA 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).ResultsOverall 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 (ConclusionsUse 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.

Objectives: Peripheral arterial occlusive disease (PAOD) and periodontitis are common chronic diseases, which together affect almost 1 billion people worldwide. There is growing evidence suggesting a relationship between chronic inflammatory conditions such as periodontitis and PAOD. This study aims to determine an association between both entities using high quality research data and multiple phenotypes derived from an epidemiological cohort study. Design: This population-based cross-sectional cohort study included data from 3271 participants aged between 45 and 74 years enrolled in the Hamburg City Health Study (NCT03934957). Material &amp, Methods: An ankle-brachial-index below 0.9, color-coded ultrasound of the lower extremity arteries, and survey data was used to identify participants with either asymptomatic or symptomatic PAOD. Periodontitis data was collected at six sites per tooth and included the probing depth, gingival recession, clinical attachment loss, and bleeding on probing index. Multivariate analyses using logistic regression models were adjusted for variables including age, sex, smoking, education, diabetes, and hypertension. Results: The baseline characteristics differed widely between participants neither affected by periodontitis nor PAOD vs. the group where both PAOD and severe periodontitis were identified. A higher rate of males, higher age, lower education level, smoking, diabetes, and cardiovascular disease was observed in the group affected by both diseases. After adjusting, presence of severe periodontitis (odds ratio 1.265, 97.5% CI 1.006–1.591, p = 0.045) was independently associated with PAOD. Conclusion: In this cross-sectional analysis of a prospective cohort study, an independent association between periodontitis and PAOD was revealed. The results of the current study emphasize a potential for preventive medicine in an extremely sensitive target population. Future studies should determine the underlying factors modifying the relationship between both diseases.

Despite considerable advances in reducing the global burden of atherosclerotic cardiovascular disease by targeting conventional risk factors, significant residual risk remains, with low-grade inflammation being one of the strongest risk modifiers. Inflammatory processes within the arterial wall or systemic circulation, which are driven in a large part by modified lipoproteins but subsequently trigger a hypercoagulable state, are a hallmark of atherosclerotic cardiovascular disease and, in particular, its clinical complications. Extending conventional guideline-based clinical risk stratification algorithms by adding biomarkers of inflammation may refine phenotypic screening, improve risk stratification and guide treatment eligibility in cardiovascular disease prevention. The integration of interventions aimed at lowering the inflammatory burden, alone or in combination with aggressive lipid-modifying or even antithrombotic agents, for those at high cardiovascular risk may hold the potential to reduce the still substantial burden of cardiometabolic disease. This review provides perspectives on future clinical research in atherosclerosis addressing the tight interplay between inflammation, lipid metabolism and thrombosis, and its translation into clinical practice.

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.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 stenosis20% and Thrombolysis in Myocardial Infarction 3 flow. Follow-up angiography was performed at a median of 141.5 days.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.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.

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) Results Mean age was 72.9 ± 9.8 years (33.6% female). Median eGFR was 47.5 ml/min/1.73 m2 (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.

Background Coronary heart disease is a leading cause of mortality worldwide. Iron deficiency, a frequent comorbidity of coronary heart disease, causes an increased expression of transferrin receptor and soluble transferrin receptor levels (sTfR) levels, while iron repletion returns sTfR levels to the normal physiological range. Recently, sTfR levels were proposed as a potential new marker of iron metabolism in cardiovascular diseases. Therefore, we aimed to evaluate the prognostic value of circulating sTfR levels in a large cohort of patients with coronary heart disease. Methods and Results The disease cohort comprised 3423 subjects who had angiographically documented coronary heart disease and who participated in the AtheroGene study. Serum levels of sTfR were determined at baseline using an automated immunoassay (Roche Cobas Integra 400). Two main outcomes were considered: a combined end point of myocardial infarction and cardiovascular death and cardiovascular death alone. During a median follow‐up of 4.0 years, 10.3% of the patients experienced an end point. In Cox regression analyses for sTfR levels, the hazard ratio (HR) for future cardiovascular death and/or myocardial infarction was 1.27 (95% CI, 1.11–1.44, P P =0.02) after additional adjustment for body mass index, smoking status, hypertension, diabetes mellitus, dyslipidemia, C‐reactive protein, and surrogates of cardiac function, size of myocardial necrosis (hs‐Tnl), and hemoglobin levels. Conclusions In this large cohort study, sTfR levels were strongly associated with future myocardial infarction and cardiovascular death. This implicates a role for sTfR in secondary cardiovascular risk prediction.

Introduction Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) such as smoking, lack of physical activity (PA) and poor diet are associated with high inflammatory burden. An optimisation of modRF might significantly affect the target population for pharmacological anti-inflammatory treatment (AIT) as determined by a hsCRP ≥2 mg/l. Aim To analyse the influence of modRF on hsCRP in a contemporary CAD cohort and model the effect of modRF optimisation on hsCRP in a target population with high inflammatory burden. Methods We included all patients with angiographically documented CAD from an observational cohort study ongoing since 2015 and excluded patients with recent myocardial infarction, malignancy, infectious disease, and immunosuppressive medication. ModRF were assessed by questionnaire at enrolment. Lack of PA was defined as PA Results Of the 1003 patients (mean age 69 years, 72% male) included, 48% (N=479) had a hsCRP ≥2 mg/l. HsCRP increased with the incremental number of modRF (median hsCRP-values for 0–3 modRF: 1.1, 1.6, 2.1, 2.7 mg/l, p12, and smoking (Table 1). Recalculation of hsCRP levels identified 21% (N=102/479) of patients with hsCRP ≥2 mg/l who could achieve a hsCRP Table 1. Linear regression results Univariate Multivariate exp(β) (95% CI) p-value exp(β) (95% CI) p-value PA ≥1.5 h/week 0.63 (0.54, 0.72) 12 0.74 (0.65, 0.86) Conclusion Modifiable lifestyle risk factors are independently associated with hsCRP levels in CAD patients. A relevant portion of patients with high inflammatory burden might achieve a hsCRP

Introduction Chronic kidney disease (CKD) represents a global public health problem and affects a large proportion of the adult population worldwide. Early detection, adequate risk stratification and specific treatment can prevent or delay the adverse effects of CKD. Purpose To assess cardiovascular risk and total mortality of subjects with CKD using cystatin C based and Crea-based estimated glomerular filtration rate (eGFR) equations (CKDEpi) in the general population, in diseased cohorts, and in specific subgroups. Methods The present study has been conducted within the BiomarCaRE project, with harmonized data from 21 population-based cohorts from 6 European countries and 3 cardiovascular disease (CVD) cohorts from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for age, sex, cohort, smoking status, body mass index, history of diabetes, history of hypertension, and total cholesterol. Results 21 population-based cohorts (n=76,954, median age 51 years, 52.2% men, 4.4% diabetic) and 3 diseased cohorts (n=4,982, median age 63 years, 75.6% men, 18.7% diabetic) with an average follow-up between 2.8 and 23.5 years and between 0.5 and 9.4 years, respectively, were included in the analysis. Prevalence of CKD-stage 3–5 by CKD-EPIcrea and CKD-EPIcys eGFR respectively, was 3.4% and 7.3% in the population-based cohorts and 13.9% and 14.4% in the diseased cohorts. In the population-based cohorts the incidence (per 1000 person years) of a non-fatal or fatal CVD event and total mortality respectively, was 10.0 and 11.8, whereas it was 21.2 and 17.8 in the diseased cohorts. In the population-based cohorts the HR for a CVD-event was 1.32 (95% CI 1.21–1.44) for the population with CKD-EPIcrea stage 3–5 and it was 1.47 (95% CI 1.35–1.60) based on CKD-EPIcys after adjustment for covariates. The HR for total mortality for those with CKD-EPIcrea stage 3–5 was 1.31 (1.21–1.41) and for CKD-EPIcys it was 1.86 (95% CI 1.73–2.00). Discrepancies between CKD-EPIcrea and CKD-EPIcys were even more striking across subgroups with and without diabetes or across specific age groups. Conclusion CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of CKD-EPIcrea and CKD-EPIcys eGFR differ considerably between specific risk groups. Therefore, the clinical utility of both equations in different risk groups has to be considered and should be evaluated further. Acknowledgement/Funding 7th framework programme collaborative project, grant agreement no. HEALTH-F2-2011-278913

Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for treatment of patients with critical cardiopulmonary failure. However, utilization of VA-ECMO support must be carefully weighed against possible complications. Therefore, we investigated the incidence and impact of complications on VA-ECMO support in one of the largest datasets of VA-ECMO therapy. Material and methods We analyzed complications and outcomes of all VA-ECMO procedures performed in Germany from 2007 to 2015 by using administrative data from the German Federal Health Monitoring System. For the present analyses all cases treated with VA-ECMO between 2007 and 2015 were identified and selected by the primary procedural code (OPS) for VA-ECMO (OPS code 8852.3). Results Among 8,351 patients undergoing VA-ECMO between 2007 and 2015, there were significant changes in complication rates over time such as increase in acute kidney injury (from 35.9% in 2007–2012 to 44.6% in 2013–2015), major bleeding (from 11.3% in 2007–2012 to 19.5% in 2013–2015 and abdominal ischemia (from 4.5% in 2007–2009 to 7.2% in 2013–2015). The incidence of stroke and limb ischemia did not differ over time. Procedure-related and ischemic complications were more frequently observed in non-survivors as compared to survivors (12.2% versus 15.3%, p Conclusion In one of the largest registries, major bleeding and ischemic events are the most common complications on VA-ECMO support. Ischemic complications seem to influence outcome more than bleeding complications. However, only stroke and acute kidney injury were independently associated with higher mortality rates. These findings should be incorporated in risk-benefit stratification when initiation of VA-ECMO and in prevention of complications to avoid additional morbidity and mortality in these critically ill patients.

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. 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). Twelve months after RDN LV mass decreased from 80 ± 21 g/m2 to 74 ± 20 g/m2 (P

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

Intrinsic iron release is discussed to have favorable effects in coronary artery disease (CAD). The aim of this study was to evaluate the prognostic relevance of intrinsic iron release in patients with CAD. Intrinsic iron release was based on a definition including hepcidin and soluble transferrin receptor (sTfR). In a cohort of 811 patients with angiographically documented CAD levels of hepcidin and sTfR were measured at baseline. Systemic body iron release was defined as low levels of hepcidin (&lt, 24 ng/mL) and high levels of sTfR (&ge, 2 mg/L). A commercially available ELISA (DRG) was used for measurements of serum hepcidin. Serum sTfR was determined by using an automated immunoassay (). Cardiovascular mortality was the main outcome measure. The criteria of intrinsic iron release were fulfilled in 32.6% of all patients. Significantly lower cardiovascular mortality rates were observed in CAD patients with systemic iron release. After adjustment for body mass index, smoking status, hypertension, diabetes, dyslipidemia, sex, and age, the hazard ratio for future cardiovascular death was 0.41. After an additional adjustment for surrogates of the size of myocardial necrosis (troponin I), anemia (hemoglobin), and cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide), this association did not change (Hazard ratio 0.37 (95% confidence interval 0.14&ndash, 0.99), p = 0.047). In conclusion, significantly lower cardiovascular mortality rates were observed in CAD patients with intrinsic iron release shown during follow-up.

Patients with established cardiovascular (CV) disease remain at dramatic residual risk for subsequent events, despite growing evidence in secondary prevention and wider dissemination of intensive treatment. This review focuses on new options in secondary risk prevention as presented by these five major randomized controlled trials (RCT): PEGASUS-TIMI 54, COMPASS, FOURIER, ODYSSEY and CANTOS. Three main therapeutic targets are addressed: residual cholesterol, residual inflammatory and residual thrombotic risk. All of the trials reviewed included patients with stable CV disease on optimal medical treatment with a surprising similar mortality. As of now, evolocumab, alirocumab and ticagrelor are on the market, while rivaroxaban and canakinumab are not yet licensed for the treatment of secondary prevention in CV disease. Although life-style modifications and better utilization of established medical treatment options will remain first-line strategy, new medication is just about to enter the market. Secondary prevention in coronary artery disease (CAD) holds a strong potential to reduce subsequent CV events, even CV death. It seems that a combination of an aggressive lipid-lowering treatment in combination with antithrombotic therapy could improve prognosis significantly (at least for distinct subgroups). Against this background, individual efficacy, risk, and costs have to be considered when identifying patients for each new regime.

Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear. We aimed to evaluate the prognostic value of iron deficiency in the acute coronary syndrome (ACS). Levels of ferritin, iron, and transferrin were measured at baseline in 836 patients with ACS. A total of 29.1% was categorized as iron deficient. The prevalence of iron deficiency was clearly higher in women (42.8%), and in patients with anemia (42.5%). During a median follow-up of 4.0 years, 111 subjects (13.3%) experienced non-fatal myocardial infarction (MI) and cardiovascular mortality as combined endpoint. Iron deficiency strongly predicted non-fatal MI and cardiovascular mortality with a hazard ratio (HR) of 1.52 (95% confidence interval (CI) 1.03-2.26, p = 0.037) adjusted for age, sex, hypertension, smoking status, diabetes, hyperlipidemia, body-mass-index (BMI) This association remained significant (HR 1.73 (95% CI 1.07&ndash, 2.81, p = 0.026)) after an additional adjustment for surrogates of cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide, NT-proBNP), for the size of myocardial necrosis (troponin), and for anemia (hemoglobin). Survival analyses for cardiovascular mortality and MI provided further evidence for the prognostic relevance of iron deficiency (HR 1.50 (95% CI 1.02&ndash, 2.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome.

Iron is essential in terms of oxygen utilization and mitochondrial function. The liver-derived peptide hepcidin has been recognized as a key regulator of iron homeostasis. Since iron metabolism is crucially linked to cardiovascular health, and low hepcidin was proposed as potential new marker of iron metabolism, we aimed to evaluate the prognostic value of hepcidin in a large cohort of patients with coronary heart disease (CHD). Serum levels of hepcidin were determined at baseline in patients with angiographically documented CHD. The main outcome measure was non-fatal myocardial infarction (MI) or cardiovascular death. During a median follow-up of 4.1 years, 10.3% experienced an endpoint. In Cox regression analyses for hepcidin the hazard ratio for future cardiovascular death or MI was 1.03 (95% confidence interval (CI) 0.91&ndash, 1.18, p = 0.63) after adjustment for sex and age. This association virtually did not change after additional adjustment for body mass index (BMI), smoking status, hypertension, diabetes, dyslipidemia, and surrogates of cardiac function (NT-proBNP), size of myocardial necrosis (troponin I), and anemia (hemoglobin). In this study, by far the largest evaluating the predictive value of hepcidin, hepcidin levels were not associated with future MI or cardiovascular death. This implicates a limited, if any, role for hepcidin in secondary cardiovascular risk prediction.