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Background and aims: Available data suggest that the use of IVUS for guidance of percutaneous coronary interventions (PCIs) improves the prognosis of patients undergoing complex interventions. We aimed to examine how the utilization of intravascular ultrasound (IVUS) affects patient survival irrespective of procedure complexity. Methods: The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography between 2004 and 2019. The incidence of death due to any cause was evaluated during a mean follow-up of 3.4 years. Cox regression analysis was used to determine the association of IVUS utilization with incident mortality. Results: Overall, data from 30,814 coronary angiography exams (mean age 64.9 ± 12.5 years, 70.3% male) were included, among which 4991 procedures (16.2%) were guided by IVUS. Utilization of IVUS was associated with a 35% reduction in mortality, independent of traditional risk factors (0.64(0.58–0.71), p

Background Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients. Methods Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed. Results The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment. Conclusion Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term “real-world” conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs.

Background The use of transcatheter aortic valve replacement (TAVR) in cancer survivors and patients with active cancer (AC) in cancer survivors and patients with active cancer (AC) is expanding, suggesting a need to adjust the indications and risk assessment pre-TAVR. Objectives The purpose of this study was to determine the impact of cancer on peri-procedural complications and survival in a long-term, single-center cohort of patients treated with TAVR. Methods Patients treated with TAVR between January 2006 and December 2018 were grouped as follows: controls (patients without cancer), stable cancer (SC), and AC. The primary endpoints were peri-procedural complications and 30-day survival. A secondary endpoint was 10-year survival. Results A total of 1,088 patients (age 81 ± 5 years, 46.6% men) treated with transfemoral TAVR were selected: 839 controls, 196 SC, and 53 AC. Predominant malignancies were breast, gastrointestinal, and prostate cancer. No differences were observed between patients with cancer and controls regarding peri-procedural complications. Patients with AC had similar 30-day survival compared with controls and SC (94.3% vs. 93.3% vs. 96.9%, p = 0.161), but as expected, reduced 10-year survival. AC was associated with a 1.47 (95% CI 1.16 to 1.87) fold increased risk of all-cause 10-year mortality in multivariable adjusted models. Conclusions TAVR should be performed in patients with cancer when indicated, considering that patients with cancer have similar periprocedural complications and short-term survival compared with control patients. However, patients with AC have worse 10-year survival. Future studies are needed to define cancer-specific determinants of worse long-term survival.

Immune checkpoint inhibitor (ICI) therapy induces an immune response against cancer cells. Immune checkpoint inhibitor therapy has tremendously improved the prognosis for a large number of cancers, but is associated with considerable immune-related adverse events (irAEs). Cardiovascular complications from ICI therapy occur in a modest proportion of patients, but show the highest lethality rates of all ICI-related complications. While ICI-related myocarditis is the most dangerous complication, its clinical manifestation varies, e.g., asymptomatic reduction of left ventricular function, isolated increase in cardiac troponins, and arrhythmias. This review delineates current data on cardiovascular complications of ICI therapy. The effects of ICI therapy on the cardiovascular system are classified in the context of preclinical data on the biochemical and immunological function of the immune checkpoint signaling pathways in the heart and the vascular system. Incidence, suspected pathomechanisms, typical symptoms, as well as recommended diagnostics are summarized. Current therapy recommendations for ICI-related cardiotoxicity are outlined and innovative new approaches with high potential for improving outcome in ICI-related myocarditis are delineated. A better understanding of cardiovascular complications is essential for the best possible oncocardiology care of the growing number of patients undergoing ICI therapy.

Background Parameters that mark the timing of left ventricular (LV) reverse remodeling following transcatheter aortic valve replacement (TAVR) are incompletely defined. This study aims to identify the dynamics of LV strain derived from speckle tracking echocardiography in a cohort of patients with severe aortic stenosis (AS) who underwent TAVR and its correlation with postprocedural outcomes. Methods We selected 150 consecutive patients (82 ± 4 years old, STS score 6.4 ± 6.2) who underwent transfemoral TAVR between 07/2016 and 12/2017 at our tertiary care center. All patients were evaluated at baseline, 1 week after TAVR, and 3 months following TAVR. Results The global longitudinal strain (GLS) 1 week following TAVR was comparable to that at baseline (− 15,9 ± 4.3 vs − 16.8 ± 4.1; p = NS) but significantly improved at 3 months following TAVR (− 15.9 ± 4.3% vs. -19.5 ± 3.5%; p p = 0.005). The linear regression analysis showed that the main predictors of the improvement in the GLS at 3 months in our cohort were baseline GRS and GCS. Conclusion GLS improves at 3 months after TAVR, while LV ejection fraction does not show a substantial change, signaling an early recovery of LV longitudinal function after the intervention. Additionally, GLS has a direct correlation with the postprocedural outcomes. GLS improvement might emerge as a valuable parameter for a tailored follow-up in TAVR patients.

Introduction Lipid-lowering therapy of elderly patients with coronary artery disease (CAD) inherits a medical challenge, as these patients experience a higher absolute risk reduction but may be more prone to side effects. We aimed to evaluate the treatment patterns in lipid-lowering therapy, comparing CAD patients above versus below 75 years of age. Methods We retrospectively included patients with known CAD admitted to the West German Heart and Vascular Center. Low-density lipoprotein cholesterol (LDL-C) levels and intensity of statin therapy (based on dosage and type of statin) were assessed from all available hospital records. Results We included 1500 patients (mean age 68.4 ± 11.2 years, 75.7% male) from 813 referring treating primary care physicians in 98 cities of Germany in our analysis. A total of 982 patients were

The acute and long-lasting side effects of modern multimodal tumour therapy significantly impair quality of life and survival of patients afflicted with malignancies. The key components of this therapy include radiotherapy, conventional chemotherapy, immunotherapy and targeted therapies. In addition to established tumour therapy strategies, up to 30 new therapies are approved each year with only incompletely characterised side effects. This consensus paper discusses the risk factors that contribute to the development of a potentially adverse reaction to tumour therapy and, in addition, defines specific side effect profiles for different treatment groups. The focus is on novel therapeutics and recommendations for the surveillance and treatment of specific patient groups.

Aims Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio-oncology has not yet been systematically evaluated. This meta-analysis aims to determine whether cardiac troponins and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) predict cancer therapy-related left ventricular (LV) dysfunction. Methods and results Scientific databases were searched for studies that assessed troponins or BNP/NT-proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR) 14.3, 95% confidence interval (CI) 6.0-34.1; n = 3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR 11.9, 95% CI 4.4-32.1; n = 2163). Troponin had a negative predictive value of 93%. Mean BNP/NT-proBNP levels were increased in patients post-treatment (standardized mean difference 0.6, 95% CI 0.3-0.9; n = 912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR 1.7, 95% CI 0.7-4.2; n = 197). β-blocker and angiotensin-converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR 4.1, 95% CI 1.7-9.8; n = 466). Conclusion Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio-oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.

Background The improvement of anticancer-therapy results in a greater amount of long-term survivors after radiotherapy. Therefore, the understanding of cardiotoxicity after irradiation is of increasing importance. Long-term adverse cardiovascular events may become evident years or decades after radiotherapy. The relative contribution of irradiation in relation to other cancer treatments can often only be estimated. Recent experimental and clinical evidence suggests that cardiovascular symptoms, including exertional dyspnoea, may be caused by heart failure with preserved ejection fraction (HFpEF), which remains incompletely understood in patients after radiation therapy. Purpose We aim to characterize the development of radiation-induced cardiomyopathy and elucidate underlying patho-mechanisms. Methods Mice received a single dose of whole thorax irradiation (12.5 Gy) and were sacrificed at 1 and 3 days or 3, 6, 12, 16, 20 and 25–30 weeks. Endothelial cells and immune cells at different time points were quantified using flow cytometry (FACS). Structural changes and localization of endothelial cell damage was imaged using light-sheet fluorescence microscopy (LSFM) with CD31 staining. Development of fibrosis was determined using qRT-PCR (fibronectin and TGFβ), western blot (collagen-1,α-smooth muscle) and (immune-)histological analyses. Functional analyses were conducted using echocardiography and pressure-volume-(PV-)catheterization. Results Endothelial damage was determined by significant reduction of CD31 expression in mouse hearts 6 weeks after irradiation compared to sham-treated control mice using FACS analyses. LSFM showed structural changes especially in the edge zone of left ventricle presented as less densely CD31 stained regions. Additionally, we investigated cardiac immune cell response regarding innate and adaptive immunity, showing specific response to tissue damage at different time points. Invasion of monocytes started 6 weeks after irradiation and highest level of monocytes and macrophages was measured at 12 weeks. Regarding cardiac long-term damage, myocardial fibrosis was detected on RNA- and protein-level as well as in histological analyses with significant changes 20 weeks after chest irradiation. This could be correlated with echocardiographic parameters for diastolic dysfunction (elevated isovolumic relaxation time/mitral valve deceleration time). Also functional reserve of irradiated mice was reduced, investigated by measurement of cardiac output and stroke volume after dobutamine injection in PV-catheterization. Conclusion We described a novel time-dependent endothelial cell damage and immune cell response after thoracic irradiation in mice, which could also be imaged using LSFM. Characterization of long-term damage showed cardiac fibrosis correlating with diastolic dysfunction and reduced contractile reserve. Furthermore, therapeutic approaches will be investigated using the established mouse model. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Dr. S.M. Mrotzek acknowledges the following funding source: IFORES research grant from the Medical Faculty, University Duisburg-Essen, Germany.

Background Current ESC guidelines for non-ST-segment elevation myocardial infarction suggest the utilization of echocardiography in patients with inconclusive initial electrocardiography and cardiac enzymes. Besides detection of alternative pathologies associated with chest pain, echocardiography can screen for wall motion abnormalities (WMA) as sign of myocardial necrosis. Purpose We evaluated the ability of the assessment of regional WMA, detected via transthoracic echocardiography, to predict the presence of culprit lesions in patients presenting with acute chest pain to the emergency department. Methods In this prospective single-centre observational cohort study, we included consecutive patients presenting to the emergency department of our University Hospital with acute chest pain, suggestive of an acute coronary syndrome, between December 2018 and August 2020. Patients with ST-elevation myocardial infarction, hemodynamic instability, or known coronary artery disease were excluded. As part of initial workup, patients received bedside echocardiography for the assessment of regional WMA by a dedicated study physician, blinded to all patients' characteristics. The primary endpoint was defined as the presence of culprit lesions as detected in subsequent invasive coronary angiography, requiring coronary revascularization therapy. Logistic regression analysis was performed in different models adjusted for traditional cardiovascular risk factors, cardiac biomarkers as well as established risk scores. Area under the receiver operating characteristics curve (AUC) was calculated to assess a potential improvement in the prediction of culprit lesions. Results Overall, 657 patients (age 58.06±18.04 years, 53% male) were included in our study. WMA were detected in 76 patients (11.6%). Patients with WMA were older (66.92±13.85 vs. 56.90±18.21 years, p Conclusion WMA strongly and independently predict the presence of culprit lesions in patients presenting with acute chest pain to the emergency department. Our results suggest that routine bedside echocardiography for assessment of WMA in emergency department may improve diagnostic algorithms in suspected acute coronary syndrome. Funding Acknowledgement Type of funding sources: None.

Background The clinical value of positive family history of premature coronary artery disease (CAD) in risk prediction of cardiovascular diseases is controversial. While an association with risk factors and disease manifestation has been described in observational studies, it is not implemented in clinically established risk algorithms. Purpose We evaluated the association of positive family history of premature CAD with cardiovascular risk factors, presence of obstructive CAD, and long-term mortality. Methods The present analysis is based on the ECAD registry of patients undergoing invasive coronary angiography at the Department of Cardiology and Vascular Medicine at the University Clinic Essen between 2004 and 2019. For this analysis, we excluded all patients with missing follow-up information. Self-reported family history of premature CAD was categorized as positive, negative, or unknown. Baseline characteristics and presence of obstructive CAD were compared between patient with and without positive family history. Cox regression analysis was used to determine the association of positive family history with morality. Results Overall, data from 33,865 patient admissions (mean age: 65.0±13.1 years, 69% male) were included. Positive family history was present in 4,995 (14.8%) patients, negative family history in 17,806 patients (52.6%), while family history of premature CAD was unknown in 11,064 (32.7%) patients. Patients with positive family history were significantly younger (63.6±12.4 vs. 65.9±13.3 years, p Conclusion Positive family history of premature CAD is associated with younger age, higher rates of smoking and diabetes, and higher frequency of obstructive coronary artery disease, while long-term survival was improved as compared to patients without family history of premature CAD. In contrast, patients with unknown status regarding family history of CAD seem to represent a heterogeneous cohort and may qualify for intensified workup, as they have highest rates of obstructive CAD and poorest short- to intermediate survival. Funding Acknowledgement Type of funding sources: None. Figure 1. Survival by status of family history

Background High-density lipoprotein-cholesterol (HDL-C) has anti-atherogenic, anti-inflammatory, anti-oxidative, anti-apoptotic, and vasodilatory properties. While a linear inverse relationship between HDL-C levels and all-cause mortality is established, recent observational studies suggest a U-shaped association between HDL-C and outcome. Purpose We tested the hypothesis that both low and high HDL-C levels associate with long-term mortality. Methods The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography at the West German Heart and Vascular Center between 2004 and 2019. HDL-C was quantified at hospital admission using standardized enzymatic methods. The incidence of death due to any cause was evaluated during follow-up. Cox regression analysis was used to determine the association of HDL-C with incident mortality, adjusting for age, sex, systolic blood pressure, low-density lipoprotein cholesterol, smoking status, and family history of premature cardiovascular disease. In addition to the analysis on HDL-C as continuous variable, the association of HDL-groups ( Results Among 17,433 patients, mean age was 65.9±12.6 years and 70.1% were men. Mean HDL-C was 48.7±16.2 mg/dL. During a mean follow-up 3.38±2.10 years, 2,401 patients (13.8%) died. In multivariable analysis, higher HDL-C levels were independently associated with lower all-cause mortality [hazard ratio (95% confidence interval): 0.83 (0.76, 0.91) per 1 standard deviation change in HDL-C, p Conclusions In a large longitudinal registry cohort of patients undergoing invasive coronary angiography, only very low HDL-C levels were associated with increased long-term mortality. We found no signs of a U-shaped association between HDL-C and prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Iryna Dykun was supported by the German Research Foundation (DY 149/2-1)Stefanie Hendricks was supported by the Universitätsmedizin Essen Clinician Scientist Academy (UMEA)

Background: Anthracycline-based chemotherapy (ANT) remains among the most effective therapies for breast cancer. Cardiotoxicity from ANT represents a severe adverse event and may predominantly manifest as heart failure. While it is well-recognised that left ventricular systolic heart failure assessment is key in ANT-treated patients, less is known about the relevance of LV diastolic functional impairment and its characterisation. Methods: Studies reporting on echocardiographic diastolic function parameters before and after ANT in breast cancer patients without cardiac disease were included. We evaluated pulsed wave (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue Doppler (mean velocities of the mitral ring in the early diastole (e′) and E/e′ ratio) echocardiographic parameters. Results: A total of 892 patients from 13 studies were included. E/A ratio was significantly reduced at the end of ANT while EDT was not influenced by ANT. Additionally, e’ and E/e’ ratio showed no significant change after ANT. A modest reduction in LV ejection fraction and global longitudinal strain was observed at the end of ANT therapy. Conclusions: ANT had a modest early impact on E/A ratio, without changing EDT, e’, or E/e’ in patients with breast cancer without cardiac disease. Randomised studies on larger populations, using new parameters are required to define the role of diastolic dysfunction in the early diagnosis of ANT-induced cardiotoxicity.

ZusammenfassungDie aktuelle Leitlinie der europäischen Gesellschaft für Kardiologie (ESC) zur myokardialen Revaskularisierung adressiert Algorithmen und Qualitätsindikatoren für das gesamte Spektrum der koronaren Herzerkrankung. Die Empfehlungen für die Durchführung von Revaskularisierungs-Maßnahmen (Bypassoperation und perkutane Koronarintervention) beziehen sich auf das Vorliegen einer stabilen koronaren Herzerkrankung oder eines akutes Koronarsyndrom. Gerade bei letzterem ist die Einhaltung von Mindestzeitintervallen bis zur Koronardiagnostik und Intervention entscheidend und verbessert die Prognose von Patienten. Für die Revaskularisierungs-Algorithmen bei stabiler koronarer Herzerkrankung sind die Komplexität der Erkrankung im Kontext von Komorbiditäten und Operationsrisiken wichtige Einflussgrößen. Zur Qualitätssicherung sollten sowohl operative als auch interventionelle Eingriffe an Zentren mit Mindestvolumina durchgeführt werden. Gleiches gilt für die strukturierte Ausbildung von Sondeuren und Operateuren zur Durchführung von Routine- und Notfalleingriffen.

Current therapy of advanced cancers is based on several modalities including radiotherapy, cytotoxic chemotherapy, molecularly targeted inhibitors and antibodies targeting immune checkpoints. All of those these modalities can negatively impact the cardiovascular system, and there is considerable experience in relation to radiotherapy and chemotherapy. In contrast, the knowledge base on cardiovascular toxicities of novel agents targeting signal transduction pathways and immune regulation is quite limited. In particular, potential late effects are of concern as cardiovascular pathology can negatively impact quality of life and prognosis in cancer survivors, particularly when additional cardiovascular risk factors are present. Treatment-associated adverse events include hypertension, venous thromboembolism, coronary artery disease, valvular heart disease, heart failure and arrhythmias. Early diagnosis of subclinical cardiotoxic effects of cancer therapies remains challenging. Integrated care, as provided by multidisciplinary cardio-oncology teams is the best option for prevention, diagnosis and treatment of cardiovascular diseases associated with cancer therapy. This review considers the cardiotoxic effects of specific cancer therapies and discusses novel diagnostic and therapeutic approaches as a reference for optimizing the care of cancer patients receiving novel cancer therapies.

Patient: Male, 65 Final Diagnosis: Shunt vitium Symptoms: Dyspnea Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: The diagnostic work-up and treatment of pulmonary hypertension can be complex. Pulmonary arterial hypertension (PAH), pulmonary hypertension second to lung or heart diseases and thromboembolic pulmonary hypertension, and other rare causes of pulmonary hypertension such as congenital heart diseases must be considered in the differential diagnostic work-up. Case Report: We report on a patient who has been treated for PAH over many years. At the age of 65, progressive symptoms required a complete re-evaluation. Here, a complex shunt vitium with a partial anomalous pulmonary venous return (PAPVR) and a sinus venosus defect (SVD) was diagnosed. Conclusions: PAPVR is a rare congenital heart disease that is often associated with an SVD. It is usually diagnosed during childhood but may also be detected in adult patients who develop pulmonary hypertension and dyspnea as primary symptoms. The initial predominant left-to-right shunting associated with this disease may be undetected for years, with a slow development of right heart failure with right heart volume overload and pulmonary hypertension. Early detection is important, with a subsequent surgical intervention.

AIMS The aim of this retrospective analysis was to examine the pattern of cardiac 68Ga-fibroblast-activation protein-α inhibitor (FAPI) uptake in patients after acute myocardial infarction (AMI) using PET and to investigate its association with results of coronary angiography. We correlated FAPI uptake with biomarkers of myocardial damage including left ventricular function. METHODS AND RESULTS A cohort of 10 patients with no history of coronary artery disease underwent PET 18 ± 20.6 days after AMI (ST-segment elevation myocardial infarction [n = 5] and non-ST-segment elevation infarction [n = 5]), respectively. SUVmax, SUVmean, and SUVpeak of localized tracer uptake were calculated; tracer uptake volume was reported as fibroblast activation volume (FAV), with imaging data being correlated with clinical parameters. Focal FAPI uptake was observed in all patients. Average uptake at 10 minutes postinjection was 8.9 ± 4.4 (SUVmax), 7.6 ± 4.0 (SUVpeak), and 5.3 ± 2.8 (SUVmean), respectively. Affected myocardium showed a partial to complete match between tracer uptake and confirmed culprit lesion by coronary angiography in 44.4% and 55.6% of patients, respectively. A strong correlation between FAV and peak creatine kinase level (r = 0.90, P < 0.01) and inverse correlation of FAV with left ventricular function (r = -0.69, P < 0.05) was observed. CONCLUSIONS This analysis demonstrates in vivo visualization of fibroblast activation after AMI. The uptake area showed a very good agreement with the affected coronary territory. A strong correlation of the de novo established parameter FAV with left ventricular function and peak creatine kinase was observed. This imaging modality may provide important insights into mechanisms of structural remodeling after AMI at an early stage.

Summary Background SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin–angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. Methods ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596. Findings Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66–80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00–2·00) vs 1·00 (0·00–3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00–9·25] vs 3·50 [0·00–23·50]; p=0·040), mean SOFA score (0·00 [0·00–0·31] vs 0·12 [0·00–0·78]; p=0·040), and 30-day SOFA score (0·00 [10–90th percentile, 0·00–1·20] vs 0·00 [0·00–24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. Interpretation Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options. Funding Austrian Science Fund and German Center for Cardiovascular Research.

Background The amount of epicardial adipose tissue (EAT) is associated with prevalent and incident myocardial infarction. However, clinical studies, specifically designed to determine, how the assessment of EAT can affect patient management, are lacking. Within Epicardial adipose tissue thickness PredIcts obstructive Coronary artery disease in Acute Coronary Syndrome patients (EPIC-ACS) study we tested the hypothesis that EAT quantification improves the prediction of the presence of culprit lesions in patients presenting with acute chest pain to the emergency department. Methods In this observational cohort study, we prospectively included consecutive patients presenting to the emergency department with acute chest pain suggestive of acute coronary syndrome between December 2018 and August 2020. Patients with ST-elevation myocardial infarction, hemodynamic instability, or known coronary artery disease were excluded. As part of the initial workup, bedside echocardiography for quantification of EAT thickness was performed by a dedicated study physician, blinded to all patients' characteristics. Treating physicians remained unaware of the results of the EAT assessment. The primary endpoint was defined as presence of a culprit lesion, as detected in subsequent invasive coronary angiography within 90 days after initial presentation. Logistic regression analysis was performed in different models adjusted for traditional cardiovascular risk factors, cardiac biomarkers as well as established cardiovascular risk scores. Results Overall, 657 patients (mean age 58.06±18.04 years, 53% male) were included in our study. Patients reaching the primary endpoint had significantly more EAT than patients without culprit lesions (7.90±2.56mm vs. 3.96±1.91mm, p Conclusion EAT strongly and independently predicts the presence of culprit lesions in patients presenting with acute chest pain to the emergency department. Our results suggest that the bedside echocardiographic assessment including the quantification of EAT may improve diagnostic algorithms of patients with acute chest pain. Funding Acknowledgement Type of funding sources: None. Distribution of EAT thickness

Background The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. Methods This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. Results Both treatments resulted in substantial improvements at post (PeEx-I: d\(_{within}\) = 1.50, PeEx-S: d\(_{within}\) = 1.78) and follow-up (PeEx-I: d\(_{within}\) = 2.34; PeEx-S: d\(_{within}\) = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR\(_{PeEx-I}\)-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. Conclusions Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.

BACKGROUND: With the 2019 update of European Society of Cardiology (ESC) guidelines for chronic coronary syndromes, the pre-test probabilities (PTPs) based on age, sex, and symptoms have undergone major revisions. We aimed to determine implications of these alterations on diagnostic accuracy of dobutamine stress echocardiography (DSE). METHODS: We retrospectively included consecutive patients undergoing pharmacological stress-echocardiography for evaluation of suspected obstructive coronary artery disease. DSE was performed as non-invasive imaging test and was indicated by individual treating physician's decision. Sensitivity, specificity, positive and negative predictive value as well as accuracy were assessed for detection of obstructive coronary artery disease, defined as revascularization therapy following DSE. RESULTS: We included 206 patients (mean age 63.2 ± 12.4 years, 59.7% male). 51% of the cohort had a PTP of < 15% according to both scores. 9.2% of patients with PTP < 15% according to the original Diamond and Forrester score had a PTP > 15% according to 2019 ESC guidelines, predominantly due to the accountancy of dyspnea. In contrast, 13.6% of patient had a PTP ≥ 15% according to the original Diamond and Forrester score, while PTP was assessed below this threshold by updated guidelines. The differences in patient selection according to updated guidelines did not alter the diagnostic accuracy of DSE (68% for both). CONCLUSIONS: Changes in assessment of PTP according to updated ESC guidelines from 2019 led to a relevant reclassification of patients with suspected coronary artery disease, ultimately changing the group of patients appropriate for DSE for evaluation of myocardial ischemia. Comparing the diagnostic performance in appropriate PTP groups, however, led to similar results. OA platinum

Background The characterization of five different clinical types of acute myocardial infarction (MI) was recently updated in 2018. Type 1 MI is caused by plaque rupture leading to an acute atherothrombotic coronary event. Type 2 MI is an entity where a condition other than coronary artery disease leads to a critical imbalance between oxygen supply and demand. There exist controversial data about the prognosis of patients with type 2 MI. While some studies have shown that type 2 MI is associated with higher mortality rates compared to type 1 MI, other trials revealed comparable mortality rates after multivariate adjustment. Purpose The aim of the present study was to compare the mortality rates of patients without MI with patients, which presented with type 1 and type 2 MI. Methods The present analysis is a longitudinal registry analysis based on the Essen Registry of Coronary Artery Disease (ECAD registry) of patients undergoing coronary angiography at the West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, at the University Hospital Essen between 2004 and 2019. Type 1 MI was defined as a significant increased troponin level (Siemens Troponin I (Dimension) >0,1 ng/ml and Troponin I Ultra (Centaur) >40 ng/l) and coronary stenosis requiring intervention. Type 2 MI was defined as a significant troponin increase without percutaneous coronary intervention. During follow up, the all-cause mortality of patients without MI and patients with type 1 and 2 MI was investigated. Cox regression analysis was used to determine the association of type 1 and 2 MI with all-cause mortality. Multivariable adjustment was performed for age, sex, low-density lipoprotein cholesterol, systolic blood pressure, diabetes, family history of coronary artery disease and nicotine abuse. Results Overall, data from 18,286 coronary angiography exams (mean age 65.3±13.0 years, 71.6% male) were included in our analysis. 14,883 patients (81.3%) had no MI, 1,699 patients (9.3%) presented with type 1 MI and 1,704 patients (9.3%) presented with type 2 MI. During a mean follow-up of 3.4±3.6 years, 3321 deaths occurred (18.2%). Compared to patients without MI (16.1%), patients with type 1 MI (25.2%) and type 2 MI (29.1%) had significant higher mortality rates (p= Conclusion In this large longitudinal registry cohort of patients undergoing invasive coronary angiography, type 2 MI was associated with impaired long-term survival. Prospective studies are required to determine risk stratification for these high-risk populations. Funding Acknowledgement Type of funding sources: None. Figure 1

Intact endothelial function plays a fundamental role for the maintenance of cardiovascular (CV) health. The endothelium is also involved in remote signaling pathway-mediated protection against ischemia/reperfusion (I/R) injury. However, the transfer of these protective signals into clinical practice has been hampered by the complex metabolic alterations frequently observed in the cardiometabolic continuum, which affect redox balance and inflammatory pathways. Despite recent advances in determining the distinct roles of hyperglycemia, insulin resistance (InR), hyperinsulinemia, and ultimately diabetes mellitus (DM), which define the cardiometabolic continuum, our understanding of how these conditions modulate endothelial signaling remains challenging. It is widely accepted that endothelial cells (ECs) undergo functional changes within the cardiometabolic continuum. Beyond vascular tone and platelet-endothelium interaction, endothelial dysfunction may have profound negative effects on outcome during I/R. In this review, we summarize the current knowledge of the influence of hyperglycemia, InR, hyperinsulinemia, and DM on endothelial function and redox balance, their influence on remote protective signaling pathways, and their impact on potential therapeutic strategies to optimize protective heterocellular signaling.

Aims Cardiac immune-related adverse events (irAEs) from immune checkpoint inhibition (ICI) targeting programmed death 1 (PD1) are of growing concern. Once cardiac irAEs become clinically manifest, fatality rates are high. Cardio-oncology aims to prevent detrimental effects before manifestation of severe complications by targeting early pathological changes. We therefore aimed to investigate early consequences of PD1 inhibition for cardiac integrity to prevent the development of overt cardiac disease. Methods and results We investigated cardiac-specific consequences from anti-PD1 therapy in a combined biochemical and in vivo phenotyping approach. Mouse hearts showed broad expression of the ligand PDL1 on cardiac endothelial cells as a main mediator of immune-crosstalk. Using a novel melanoma mouse model, we assessed that anti-PD1 therapy promoted myocardial infiltration with CD4+ and CD8+ T cells, the latter being markedly activated. Left ventricular (LV) function was impaired during pharmacological stress, as shown by pressure–volume catheterization. This was associated with a dysregulated myocardial metabolism, including the proteome and the lipidome. Analogous to the experimental approach, in patients with metastatic melanoma (n = 7) receiving anti-PD1 therapy, LV function in response to stress was impaired under therapy. Finally, we identified that blockade of tumour necrosis factor alpha (TNFα) preserved LV function without attenuating the anti-cancer efficacy of anti-PD1 therapy. Conclusions Anti-PD1 therapy induces a disruption of cardiac immune homeostasis leading to early impairment of myocardial functional integrity, with potential prognostic effects on the growing number of treated patients. Blockade of TNFα may serve as an approach to prevent the manifestation of ICI-related cardiotoxicity.

Coronavirus disease 2019 (COVID-19) is challenging the care for cardiovascular patients, resulting in serious consequences with increasing mortality in pre-diseased heart failure patients. In the current state of the pandemic, the physiopathology of COVID-19 affecting pre-diseased hearts and the management of terminal heart failure in COVID-19 patients remain unclear. We outline the findings of a young COVID-19 patient suffering from idiopathic cardiomyopathy who was treated for acute multi-organ failure and required cardiac surgery with implantation of a temporary right ventricular and durable left ventricular assist device (LVAD). For deeper translational insights, we used in-depth tissue analysis by electron and light sheet fluorescence microscopy revealing evidence for spatial distribution of severe acute respiratory syndrome coronavirus 2 in the heart. This indicates that in-depth analysis may represent a valuable tool in understanding indistinct clinical cases. We conclude that COVID-19 directly affects pre-diseased hearts, but the consequences can be treated successfully with LVAD implantation. OA Förderung 2020

Background Immune checkpoint inhibitor (ICI) therapy has improved treatment of advanced cancers but is associated with yet incompletely characterized cardiotoxic side effects. While inflammatory cardiac complications were initially described as a rare phenomenon, emerging evidence indicates frequent cardiotoxicity, particularly latent left ventricular (LV) dysfunction. Distinct clinical characteristics and potential pathomechanisms are so far unknown. Purpose This study aims to investigate incidence and frequency of LV dysfunction in patients receiving ICI therapy for malignant melanoma. Using a suitable melanoma mouse model, ICI-related cardiotoxicity will be reenacted to identify potential underlying pathomechanisms. Methods Patients receiving ICI therapy for stage IV melanoma that presented in our cardio-oncology unit were evaluated at baseline and four weeks after initiation of therapy including echocardiography, cardiac biomarkers, and dobutamine stress echocardiography in the absence of contraindications. Patients with decreased LV ejection fraction (LVEF) were further evaluated by 18-fludeoxyglucose PET-MRI to assess manifest myocarditis. To elucidate underlying pathomechanisms, we established a melanoma mouse model that showed profound response to anti-programmed death 1 (PD1) ICI therapy. Immune cell infiltration was assessed by flow cytometry and light sheet fluorescence microscopy. Myocardial biochemical function was analyzed using a multi-omics mass spectrometry-based approach. Results Seven patients were included to the analysis. Six patients received a combination ICI therapy with ipilimumab and nivolumab, and one patient received nivolumab monotherapy. Echocardiography revealed significantly decreased 3D-LVEF after 4 weeks of therapy in treated patients (p=0.021). A reduced global longitudinal strain was found in six of seven patients. Remarkably, dobutamine stress echocardiography revealed a more pronounced LVEF-decrease (p=0.009) as a sign for impaired myocardial contractility with a mean decrease of 5 percentage points. Using the melanoma mouse model, we were able to recapitulate the disease phenotype as indicated by decreased LVEF and impaired response to inotropic stress during mouse pressure/volume catheterization. Increased concentrations of intramyocardial CD4+ and CD8+ T cells were found in mice treated with anti-PD1 ICI therapy compared to controls (p=0.01). Mass spectrometry revealed disrupted energy metabolism and calcium homeostasis as a putative underlying pathomechanism for impaired myocardial function. Conclusions ICI-related left ventricular dysfunction may affect a large proportion of patients and potentially increase cardiac morbidity and mortality. Preclinical data proposes myocardial lymphocyte infiltration and disruption of cardiomyocyte metabolism as the underlying pathomechanism. Prospective studies are now needed for a further characterization of this novel form of ICI-related cardiotoxicity. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): IFORES research grant, Medical Faculty, University Duisburg-Essen, Germany

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

5q-Associated spinal muscular atrophy is a hereditary neuromuscular disease leading to progressive muscle weakness in which fatigue occurs and affects quality of life. Treatment with the antisense oligonucleotide nusinersen has been shown to improve motor function. Fatigue can be measured within the Fatigue Severity Scale (FSS). FSS is a self-reported questionnaire consisting of nine items to quantify fatigue severity within the last week. Higher values indicating a higher severity. Using the FSS, fatigue was measured in 28 adult patients, subdivided into ambulatory and non-ambulatory, suffering from a genetically confirmed 5q-SMA under treatment with nusinersen in accordance with the label. Correlations were performed among FSS and motor scales, 6-minute walk test (6MWT) and Hammersmiths Functional Motor Scale Expanded (HFMSE). Evaluation was performed prior to treatment initiation and after 6 and 10 months. The mean FSS score for all 28 patients at baseline was 4.61 ± 1.44. After 6 months mean FSS score significantly reduced to 3.92 ± 1.35. After 10 months mean FSS score had not differed from baseline, 3.84 ± 1.25. A moderate negative correlation of the difference of FSS and 6MWT after 6 months compared to baseline conditions was measured. Nusinersen reduces fatigue as measured by the FSS in adult patients with 5q-SMA transiently after initiation of treatment. There was no reduction of FSS 10 months after the beginning of treatment when compared to baseline.

Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for cancer patients, it will be essential to set up specialized oncocardiology services. However, there is a lack of clinical studies to give evidence-based recommendations regarding cardiological diagnostic and therapeutic approaches for cancer patients. An oncocardiology service is a patient-centered structure that aims to integrate research and interdisciplinary patient care to bridge this gap. We discuss the current challenges in developing an oncocardiology service and review the literature on this topic. We further provide an overview of the essential diagnostic tools and upcoming ethical issues to be considered in the management of oncology patients.

Background: The long-term survival of cancer patients has significantly improved over the past years. Despite their therapeutic efficacy, various cancer therapies are associated with cardiotoxicity. Therefore, timely detection of cardiotoxic adverse events is crucial. However, the clinical assessment of myocardial damage caused by cancer therapy remains difficult. Methods: This retrospective study was performed to evaluate the diagnostic value of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for monitoring cancer therapy-induced cardiomyopathy. A total of 485 cancer patients referred to our cardio-oncology unit between July 2018 and January 2020 were selected from our Essen Cardio-oncology Registry (ECoR). We included patients with all types of cancer. Plasma concentrations of cTnI and NT-proBNP were measured by radioimmunoassay, and two-dimensional left ventricular ejection fraction (2D-LVEF), diastolic function, and global longitudinal strain (GLS) were measured by transthoracic echocardiography. In 116 patients, assessment was conducted before the induction of cancer therapy and during a short-term follow-up period; n = 42 of these were treated for malignant melanoma, and n = 42 with serial measurements were under treatment for breast cancer. Results: In cross-sectional data, elevated NT-proBNP was associated with reduced LVEF and pathological GLS in the total cohort. A total of 116 patients had serial LVEF and biomarker measurements, and changes in NT-proBNP and troponin correlated with changes in LVEF during follow-up investigations. Similar to the total cohort, a subgroup of patients treated for malignant melanoma showed a correlation between the change in cTnI and the change in LVEF. In a subgroup analysis of patients undergoing breast cancer therapy, a correlation between the change in NT-proBNP and the change in LVEF could be detected. Thirty patients presented with chemotherapy-induced cardiomyopathy, defined as a significant LVEF decrease (> 10%) to a value below 50%. The number of patients with increased cTnI and NT-proBNP was significantly higher in patients with chemotherapy-induced cardiomyopathy than in patients without cardiotoxicity. Patients with positive cTnI and NT-proBNP were more likely to have a history of coronary heart disease, atrial fibrillation, and arterial hypertension. Conclusion: Our data suggest that cardiac biomarkers play an important role in the detection of cancer therapy-induced cardiotoxicity. Larger systematic assessment in prospective cohorts is mandatory. CA - Rassaf

Background Immune checkpoint inhibitors (ICI) have tremendously improved survival in patients with melanoma. By unbalancing the immune system, ICI also generate immune-related adverse events (IRAEs) that could affect any tissue, including the heart. Early detection of IRAEs is essential to avoid life-threatening adverse events like myocarditis and to maintain patients under this effective therapy. Aim To identify whether patients treated with ICI that develop extra-cardiac IRAEs additionally show a subclinical impairment of the heart function. Methods We have analysed the patients with melanoma without established cardiac disease evaluated in our cardio-oncology unit between July 2018 and December 2019. Data was collected at two timepoints: before initiating the ICI therapy (baseline) and one month after ICI treatment begin (follow-up). Evaluation was performed using clinical data, laboratory parameter including biomarkers, electrocardiography, comprehensive 2D, 3D, tissue Doppler, and speckle tracking echocardiography assessment, and cardiac magnetic imaging. Results A total of 69 patients with melanoma (59±12 years old, 63% males, 93.8% metastatic disease), without known cardiovascular disease were included. Patients were divided in two groups: patients with extra-cardiac IRAEs (Group 1, n=22) and without IRAEs (Group 2, n=46) after one month of ICI therapy. One patient was diagnosed with immune-related myocarditis at follow-up and was excluded from the analysis. Patients in Group 1 developed colitis (n=10), thyroiditis/hypophysitis (n=8), hepatitis (n=2), and pneumonitis (n=2). There were no differences in age, gender distribution, cardiovascular risk factors, or proportion of metastatic disease between the two groups. The proportion of patients treated with combination ICI therapy (nivolumab plus ipilimumab) was significantly higher in Group 1 (72% vs. 33%, p=0.04). The left ventricular systolic and diastolic function were similar at baseline and after one month of therapy between the two groups, except for the global longitudinal strain (GLS), which showed a significant reduction at follow-up for patients in Group 1 vs. Group 2 (−18.8±2.6% vs. −21±1.2%, p=0.03). The radial and circumferential strain were similar. Follow-up GLS had a good correlation with the extra-cardiac IRAEs rate (r=0.43; p=0.03). Patients with combination ICI therapy had a 5 times higher risk to develop extra-cardiac IRAEs (OR 5.33, 95% CI (1.07–26.61), p=0.04). Troponin and NT-proBNP were not significantly different at follow-up between the two groups. Conclusion The abnormal function of the immune system triggered by ICI therapy in patients with extra-cardiac IRAEs seems to induce a subclinical left ventricular dysfunction, signalized by a reduction of the GLS. However, the diagnosis criteria for myocarditis were fulfilled in only one patient. The mechanism of these changes should be further investigated and addressed. Funding Acknowledgement Type of funding source: None

An increasing number of patients with coronary artery disease are at high operative risk due to advanced age, severe comorbidities, complex coronary anatomy, and reduced ejection fraction. Consequently, these high-risk patients are often offered percutaneous coronary intervention (PCI) as an alternative to coronary artery bypass grafting (CABG). We aimed to investigate the outcome of patients with diabetes mellitus (DM) undergoing high-risk PCI. We analyzed consecutive patients undergoing high-risk PCI (period 01/2016&ndash, 08/2018). In-hospital major adverse cardiac and cerebrovascular events (MACCEs), defined as in-hospital stroke, myocardial infarction and death, and the one-year incidence of death from any cause were assessed in patients with and without DM. There were 276 patients (age 70 years, 74% male) who underwent high-risk PCI. Eighty-six patients (31%) presented with DM (insulin-dependent DM: n = 24, non-insulin-dependent DM: n = 62). In-hospital MACCEs occurred in 9 patients (3%) with a non-significant higher rate in patients with DM (n = 5/86, 6% vs. n = 4/190 2%, p = 0.24). In patients without DM, the survival rate was insignificantly higher than in patients with DM (93.6% vs. 87.1%, p = 0.07). One-year survival was not significantly different in DM patients with more complex coronary artery disease (SYNTAX I-score &le, 22: 89.3% vs. &gt, 22: 84.5%, p = 0.51). In selected high-risk patients undergoing high-risk PCI, DM was not associated with an increased incidence of in-hospital MACCEs or a decreased one-year survival rate.

Background Increasing use of immune checkpoint inhibitor (ICI) therapy has recently been associated with latent left ventricular dysfunction as a common cardiotoxic side effect during early therapy. Considering the potential impact on morbidity and mortality, strategies to prevent ICI-related cardiotoxicity are urgently needed, but established immunosuppressive measures prevent the anti-tumor effect of the ICI therapy, thereby limiting its applicability to severe, life-threatening cases. Recently, tumor necrosis factor alpha (TNFα) blockade was shown to prevent ICI-related gut toxicity while preserving, or even enhancing, anti-tumor efficacy. Purpose This study aims to investigate a cardioprotective effect of TNFα blockade during anti programmed death 1 (PD1) ICI therapy in a preclinical model as a basis for a potential new, preventive therapeutic approach for ICI-related cardiotoxicity. Methods A melanoma mouse model was established as the basis to study PD1 blocking therapy and protective measures in a preclinical setting. Mice were subcutaneously transplanted with a syngeneic melanoma cell line and treated with anti-PD1 antibodies for 15 days. Response to therapy was monitored by assessment of tumor size. Cardiotoxicity was confirmed by mouse echocardiography. Mice were then simultaneously treated with anti-PD1 antibodies and TNFα-blocking antibodies. A cardioprotective effect was evaluated by echocardiography and flow cytometry was used to characterize myocardial immune cells. Results Mice receiving anti-PD1 showed smaller tumor sizes with increased immune cell infiltration compared to control littermates as a sign for a profound response to therapy. Cardiotoxicity was confirmed as demonstrated by reduced left ventricular ejection fraction and reduced global radial strain in anti-PD1-treated mice. Mice receiving anti-PD1 ICI therapy showed 2-fold elevated concentrations of CD4+ and CD8+ T-lymphocytes in the murine heart as determined by flow cytometry. CD44 expression was upregulated in cytotoxic T-cells as a marker of enhanced T-cell activity in anti-PD1 treated mice. Administration of TNFα-blocking antibodies did not alter tumor sizes during anti-PD1 treatment as a sign for a sustained response to therapy. Remarkably, mice receiving TNFα-blocking antibodies together with anti-PD1 ICI therapy showed increased left ventricular function compared to mice receiving anti-PD1 monotherapy. Flow cytometry revealed increased expression of T cell exhaustion markers in mice receiving TNFα blockade as a potential underlying mechanism. Conclusions ICI therapy targeting PD1 induces latent cardiotoxicity with left ventricular dysfunction. TNFα blockade may serve as a novel cardioprotective treatment without compromising the anti-tumor efficacy of ICI therapy. Prospective studies are needed to further characterize ICI-related cardiotoxicity in patients and to evaluate the cardioprotective effect of TNFα blockade. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): IFORES research grant, Medical Faculty, University Duisburg-Essen, Essen, Germany

Background Natriuretic peptides (BNP/NT-proBNP) are routinely used for the diagnosis of heart failure and predicts outcome in patients with both heart failure with preserved and reduced ejection fraction. In addition, natriuretic peptides are associated with incident cardiovascular disease manifestation in primary prevention cohorts. Whether the assessment of BNP/NT-proBNP is of value in patients with coronary artery disease but without heart failure has not been investigated in detail. We here evaluate the association of BNP/NT-pro BNP with mortality patients with coronary artery disease but without known chronic heart failure. Methods The present analysis is based on the ECAD registry of patients undergoing conventional coronary angiography at the Department of Cardiology and Vascular Medicine between 2004 and 2019. For this analysis, we excluded all patients with a diagnosis of heart failure or with elevated BNP/NT-proBNP values at baseline (>100pg/nl for BNP, >400pg/nl for NTproBNP). Moreover, patients with missing follow-up information or without BNP/NT-proBNP levels at admission were excluded. As either BNP or NT-proBNP was available for singular patients, we standardized BNP and NT pro BNP levels based on percentile rank in levels from 0 to 99. Cox regression analysis was used to determine the association of BNP/NT-proBNP with morality in unadjusted and risk factor adjusted models with effect sizes depicted per one standard deviation change in BNP/NT-proBNP rank. Results Overall, 3738 patients (mean age: 62.8±12.6 years, 71% male) were included in our analysis. During a mean follow-up of 2.6±3.5 years, 172 deaths of any cause occurred. Patients without fatal events had significantly lower BNP/NT-prBNP values compared to patients who died (48.4±28.8 vs. 58.4±27.5, p Conclusion In patients without heart failure undergoing coronary angiography, BNP/NT-proBNP levels stratify mortality risk independently of traditional cardiovascular risk factors. Our results support the routine assessment of natriuretic peptides also in patients without heart failure to identify patients at increased risk. Funding Acknowledgement Type of funding source: None

Background Anemia is a frequent comorbidity in patients with coronary artery disease (CAD). Besides a complemental effect on myocardial oxygen undersupply of CAD and anemia, available data suggests that it may independently impact the prognosis in CAD patients. We aimed to determine the association of anemia with long-term survival in a longitudinal registry of patients undergoing conventional coronary angiography. Methods The present analysis is based on the ECAD registry of patients undergoing conventional coronary angiography at the Department of Cardiology and Vascular Medicine at the University Clinic Essen between 2004 and 2019. For this analysis, we excluded all patients with missing hemoglobin levels at baseline admission or missing follow-up information. Anemia was defined as a hemoglobin level of Results Overall, data from 28,917 patient admissions (mean age: 65.3±13.2 years, 69% male) were included in our analysis (22,570 patients without and 6,347 patients with anemia). Prevalence of anemia increased by age group (age Conclusion In this large registry of patients undergoing conventional coronary angiography, anemia was a frequent comorbidity. Anemia relevantly influences log-term survival, especially in patients receiving percutaneous coronary interventions. Our results confirm the important role of anemia for prognosis in patients with coronary artery disease, demonstrating the need for specific treatment options. Figure 1. Kaplan Meier analysis Funding Acknowledgement Type of funding source: None

Background: An increasing number of high-risk percutaneous coronary interventions (PCI) are performed with mechanical circulatory support (MCS) to minimize the risk of periprocedural hemodynamic compromise. Prior studies have demonstrated that an elevated left-ventricular end-diastolic pressure (LVEDP) is associated with worse outcome after acute myocardial infarction or cardiac surgery. Although LVEDP is frequently measured, little is known about the usefulness for predicting periprocedural hemodynamic deterioration in high-risk PCI. The objective of this study is to assess the impact of preprocedural measured LVEDP in non-shock patients undergoing high-risk PCI with MCS on periprocedural hemodynamic deterioration. Methods and Results: We reviewed the PCI protocol and the Automated Impella Controller in a consecutive series of 64 patients (mean age 73 years, 80% male), who underwent high-risk PCI with Impella MCS (period 01/2017–12/2018). LVEDP (17 ± 8 mm Hg) was measured in all cases before Impella insertion and start of PCI. Periprocedural hemodynamic deterioration was defined as: systolic blood pressure (SBP) drop (decrease ≥20 mm Hg or ≤90 mm Hg), or transient loss of arterial pressure pulsatility. Hemodynamic deterioration occurred in 33% (n = 21) of all patients but did not lead to a hemodynamic compromise due to the Impella support. Regression analysis of LVEDP for periprocedural hemodynamic deterioration or in-hospital major adverse cardiac and cerebrovascular events (MACCE) showed no significant results. Conclusion: LVEDP was not associated with periprocedural hemodynamic deterioration or a higher rate of in-hospital MACCE. Our data propose that LVEDP may not be used as a risk stratification variable for MCS usage in non-shock patients undergoing high-risk PCI. Keywords: Coronary artery disease, Impella, High-risk PCI, Mechanical circulatory support, Percutaneous coronary intervention

In den letzten Jahrzehnten konnten wesentliche Fortschritte in der Therapie maligner Erkrankungen das langfristige Uberleben deutlich verbessern. Hierdurch wird allerdings das Nebenwirkungsspektrum der therapeutischen Verfahren insbesondere fur das Herz-Kreislauf-System relevant. Kardiotoxizitat kann sich akut und chronisch u. a. durch Bluthochdruck, Herzinsuffizienz, Arrhythmien, Herzinfarkte, venose Thrombembolien, Schlaganfalle und Herzklappenerkrankungen bemerkbar machen. Wahrend das Auftreten von Kardiotoxizitat fur viele altere Tumortherapeutika bekannt ist, muss dies fur neuere Therapieformen noch weitgehend evaluiert werden. Die Diagnose moglicher kardiotoxischer Nebenwirkungen ist fur eine optimale Behandlung unerlasslich, bleibt jedoch eine Herausforderung. Troponin und natriuretische Peptide als kardiale Biomarker spielen eine wichtige Rolle in der Diagnostik primarer Herzerkrankungen. Sie scheinen aber auch bei der Erkennung von Kardiotoxizitat und im Rahmen der Therapie onkokardiologischer Patienten einen wesentlichen Stellenwert zu besitzen. Erhohte Spiegel von Troponin oder natriuretischem Peptid vom B‑Typ (BNP) bzw. N‑terminalem pro-natriuretischem Peptid vom B‑Typ (NT-proBNP) sind hierbei mit einer erhohten Gesamtmortalitat verbunden und waren in ausgewahlten Kollektiven mit der Entwicklung einer Herzinsuffizienz assoziiert. Daruber hinaus kann Troponin zur Identifizierung einer Myokarditis im Rahmen einer Immuncheckpointinhibitortherapie verwendet werden. Diese Ubersichtsarbeit soll das aktuelle Wissen uber Biomarker bei tumortherapiebedingter Kardiotoxizitat zusammenfassen. Wir beschreiben hierbei auch mogliche klinische Empfehlungen fur den Nachweis und die Behandlung kardiotoxischer Wirkungen unter Verwendung von Biomarkern.

OBJECTIVES To evaluate the impact of baseline left ventricular ejection fraction (LVEF) and its interaction with low-gradient aortic stenosis (LGAS) on all-cause mortality after transfemoral aortic valve implantation (TF-TAVI). METHODS We reviewed mortality data of 624 consecutive single center TF-TAVI patients and categorized LVEF according to current ASE/EACVI recommendations (normal, mildly-, moderately-, and severely abnormal). RESULTS Baseline LVEF was normal in 336 (53.8%), mildly abnormal in 160 (25.6%), moderately abnormal in 91 (14.6%), and severely abnormal in 37 (5.9%) patients, and 1-year mortality was 19%, 17%, 23%, and 43% (P = 0.002), respectively. Patients with LGAS had a similar 1-year mortality compared to those without LGAS in groups with normal (19% vs 19%, P = 0.899) and mildly abnormal LVEF (16% vs 17%, P = 0.898). One-year mortality of patients with LGAS was significantly greater than in those without LGAS in presence of moderately abnormal LVEF (31% vs 11%, P = 0.022), and it was numerically greater than in those without LGAS in presence of severely abnormal LVEF (48% vs 25%, P = 0.219). In multivariate analysis, only the combination of moderately/severely abnormal LVEF and LGAS predicted increased 1-year mortality (HR: 2.12, 95% CI: 1.4-3.2, P

The improvement of anticancer-therapies results in a greater amount of long-term survivors after radiotherapy. Therefore, the understanding of cardiotoxicity after irradiation is of increasing importance. Cardiovascular adverse events after chest irradiation have been acknowledged for a long time but remain difficult to diagnose. Long-term cardiovascular adverse events may become evident years or decades after radiotherapy and the spectrum of potential cardiovascular side effects is large. Recent experimental and clinical data indicate that cardiovascular symptoms may be caused especially by heart failure with preserved ejection fraction, which remains incompletely understood in patients after radiation therapy. Heart radiation dose and co-existing cardiovascular risk factors represent some of the most important contributors for incidence and severity of radiation-induced cardiovascular side effects. In this review, we aim to elucidate the underlying patho-mechanisms and to characterize the development of radiation-induced cardiovascular damage. Additionally, approaches for clinical management and treatment options are presented.

The outcome of transfemoral transcatheter aortic valve implantation (TF-TAVI) with a self-expanding (SEP) versus a balloon-expandable prosthesis (BEP) in patients with a reduced ejection fraction (rEF, ≤40%) has not been previously investigated. Patients with rEF have an increased risk of death after TF-TAVI compared to patients with a preserved ejection fraction (pEF), and prosthesis choice might influence the outcome of these patients. We, therefore, sought to compare all-cause mortality of patients with rEF using a SEP versus a BEP. We retrospectively analyzed data of 679 single-center TF-TAVI patients. Patients were censored at death or completion of 1-year follow-up, whichever occurred first. Patients with rEF (n = 141, 21%) had an increased 1-year mortality compared to patients with pEF (28% vs 19%, p = 0.007). SEP were implanted in 149 patients (49 with rEF, 33%), while BEP were implanted in 530 patients (92 with rEF, 17%). In patients with pEF, 1-year mortality was similar after SEP- and BEP-implantation (16% vs 19%, p = 0.516). In patients with rEF, however, 1-year mortality was higher after SEP- than after BEP-implantation (43% vs 21%, p = 0.004). These patients had a higher incidence of new permanent pacemaker implantation (26.5% vs 13%, p = 0.046) and paravalvular leak ≥II° (21% vs 10%, p = 0.07), but both factors could not explain the excess mortality after SEP-implantation in the multivariate analysis. In patients with rEF, the use of a SEP was an independent predictor of 1-year mortality (HR 2.44, 95% CI 1.27 to 4.27, p = 0.007). In conclusion, patients with rEF had a higher 1-year mortality after TF-TAVI when a SEP instead of a BEP was used.