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Background: The goal of our study is to evaluate a method to quantify aortic valve calcification (AVC) in contrast-enhanced computed tomography for patients with suspected severe aortic stenosis pre-interventionally. Methods: A total of sixty-five patients with aortic stenosis underwent both a native and a contrast-enhanced computed tomography (CECT) scan of the aortic valve (45 in the training cohort and 20 in the validation cohort) using a standardized protocol. Aortic valve calcification was semi-automatically quantified via the Agatston score method for the native scans and was used as a reference. For contrast-enhanced computed tomography, a calcium threshold of the Hounsfield units of the aorta plus four times the standard deviation was used. Results: For the quantification of aortic valve calcification in contrast-enhanced computed tomography, a conversion formula (691 + 1.83 x AVCCECT) was derived via a linear regression model in the training cohort. The validation in the second cohort showed high agreement for this conversion formula with no significant proportional bias (Bland–Altman, p = 0.055) and with an intraclass correlation coefficient in the validation cohort of 0.915 (confidence interval 95% 0.786–0.966) p < 0.001. Conclusions: Calcium scoring in patients with aortic valve stenosis can be performed using contrast-enhanced computed tomography with high validity. Using a conversion factor led to an excellent agreement, thereby obviating an additional native computed tomography scan. This might contribute to a decrease in radiation exposure. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential differences in characteristics of femoropopliteal in-stent restenosis (ISR) stratified by stent design with a focus on the swirling flow-inducing BioMimics 3D helical centerline stent. Methods: Patients with ISR of the superficial femoral and popliteal arteries undergoing reintervention were included in this study. The primary endpoint was the angiographic localization and extent of restenosis or reocclusion with the following five different stent systems: SMART Control stent, Supera peripheral stent, GORE® VIABAHN® endoprosthesis, BioMimics 3D stent, and Zilver® PTX® stent. Results: 414 ISR lesions were analyzed, affecting 236 Supera stents, 67 BioMimics 3D stents, 48 Zilver® PTX® stents, 38 SMART Control stents, and 25 VIABAHN® endoprostheses. The mean stent diameter and length were 5.7 ± 0.77 mm and 121.4 ± 94.8 mm, respectively. ISR included 310 (74.9%) lesions with 1 stent, 89 (21.5%) lesions with 2 stents, 14 (3.4%) lesions with 3 stents, and 1 lesion (0.2%) with 4 stents. Most lesions presented as reocclusions (67.4%) rather than focal (13.3%) or diffuse restenoses (19.3%). No significant differences in ISR lesion morphology were found. By trend, BioMimics 3D stent lesion extension was more focal (16.4% versus 12.7%, p = 0.258), with the highest proportion of lesions in which only the proximal stent third was affected (9.0% versus 5.8%, p = 0.230), as compared to the average of the other four devices. The occlusion rate was the second lowest for the BioMimics 3D stent (64.2 vs. 68.0%, p = 0.316). Risk factors for restenosis or occlusion were active smoking, pre-interventional occlusion, and popliteal intervention. Conclusion: Our results suggest that the helical centerline stent design of the BioMimics 3D stent, which results in a swirling flow with increased wall shear stress, may offer protective properties over straight stent designs, including DES and endoprosthesis, regarding localization and extension of restenosis. Prospective, randomized studies are warranted. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the feasibility of a non-contrast time-of-flight magnetic resonance angiography (TOF-MRA) protocol for the pre-procedural access route assessment of transcatheter aortic valve implantation (TAVI) in comparison with contrast-enhanced cardiac dual-source computed tomography angiography (CTA). Methods and Results: In total, 51 consecutive patients (mean age: 82.69 ± 5.69 years) who had undergone a pre-TAVI cardiac CTA received TOF-MRA for a pre-procedural access route assessment. The MRA image quality was rated as very good (median of 5 [IQR 4–5] on a five-point Likert scale), with only four examinations rated as non-diagnostic. The TOF-MRA systematically underestimated the minimal effective vessel diameter in comparison with CTA (for the effective vessel diameter in mm, the right common iliac artery (CIA)/external iliac artery (EIA)/common femoral artery (CFA) MRA vs. CTA was 8.04 ± 1.46 vs. 8.37 ± 1.54 (p < 0.0001) and the left CIA/EIA/CFA MRA vs. CTA was 8.07 ± 1.32 vs. 8.28 ± 1.34 (p < 0.0001)). The absolute difference between the MRA and CTA was small (for the Bland–Altman analyses in mm, the right CIA/EIA/CFA was −0.36 ± 0.77 and the left CIA/EIA/CFA was −0.25 ± 0.61). The overall correlation between the MRA and CTA measurements was very good (with a Pearson correlation coefficient of 0.87 (p < 0.0001) for the right CIA/EIA/CFA and a Pearson correlation coefficient of 0.9 (p < 0.0001) for the left CIA/EIA/CFA). The feasibility agreement between the MRA and CTA for transfemoral access was good (the right CIA/EIA/CFA agreement was 97.9% and the left CIA/EIA/CFA agreement was 95.7%, Kohen's kappa: 0.477 (p = 0.001)). Conclusions: The TOF-MRA protocol was feasible for the assessment of the access route in an all-comer pre-TAVI population. This protocol might be a reliable technique for patients at an increased risk of contrast-induced nephropathy. [ABSTRACT FROM AUTHOR]

We aimed to investigate the safety, feasibility, and long-term results of drug-eluting stent implantation before covered stents for treating coronary artery perforation (CAP). Between 2015 and 2020, 12,733 patients undergoing percutaneous coronary intervention (PCI) were retrospectively analyzed. The primary endpoint was 1-year target lesion revascularization (TLR), whereas secondary endpoints included the rate of major adverse cardiac and cerebrovascular events (MACCE) and all-cause death at 1 year. A total of 159 patients with CAP were identified during the study period, of whom 47.2% (n = 75) were treated with a covered stent (CS group) because of complex and/or severe CAP and 84 (52.8%) without (non-CS group). In the majority of patients, emergency drug-eluting stent placement before covered stent implantation was feasible (n = 69, 82%). There were no significant differences among patients treated with or without a covered stent in terms of primary or secondary clinical endpoints: a similar rate of TLR (18.67% vs. 21.43%, p = 0.6646), MACCE (25.33% vs. 22.62%, p = 0.6887), and 1-year mortality (12.00% vs. 11.90%, p = 0.9853) were identified comparing cases with covered stent implantation and without. In conclusion, our study implicates that the use of covered stents for sealing coronary perforation might not impact the 1-year clinical outcome if used properly. Moreover, the emergent use of drug-eluting stents before covered stent implantation in CAP is a safe and effective method to avoid target lesion revascularization in patients treated with covered stents. [ABSTRACT FROM AUTHOR]

Clinical outcomes in patients with reduced left ventricular systolic function undergoing rotational atherectomy (RA) for percutaneous coronary intervention (PCI) remain understudied. Our study sought to evaluate the impact of RA-PCI in patients with LV systolic dysfunction on long-term outcomes. Between 2015 and 2019, 4941 patients with reduced LV function (rEF) undergoing PCI (with or without RA) were included in the hospital database. The primary endpoint was in-hospital major adverse cardiovascular and cerebral events (MACCE). The secondary endpoint was 3-year MACCE. In-hospital MACCE rates were significantly higher in RA-PCI compared to standard PCI without RA (PCI) (7.6% vs. 3.9%, p = 0.0009). However, 3-years MACCE rates were similar in RA-PCI and PCI (26.40% vs. 26.6%, p = 0.948). In conclusion, RA-PCI in patients with rEF is feasible, safe, and shows similar long-term results to PCI. [ABSTRACT FROM AUTHOR]

Background: In addition to manual compression, various vascular closure devices (VCD) are available to seal the puncture site following arterial vascular procedures. Purpose: To evaluate the efficacy and safety of the extravascular MYNX CONTROL closure system for achieving primary hemostasis after femoral arterial access following peripheral arterial procedures, compared to the intravascular FemoSeal Aclosure system. Patients and Methods: A retrospective analysis of consecutive patients who underwent endovascular intervention between April and November 2022 was performed. The primary endpoint was the incidence of significant puncture site complication defined as a complication resulting in medical treatment. Secondary endpoints included peri-interventional incidence of hematoma, peri-interventional changes in hemoglobin, incidence of emergency diagnostics and predictors for closure system failure. Results: Five hundred and forty-eight patients were included in this analysis. False aneurysm occurred in 18/273 cases (6.6%) following the use of the MYNX closure system, compared to 6/275 cases after using the FemoSeal closure system (2.2%, p = 0.006). The incidence of post-interventional hematoma was not significantly different (28 (10.3%) in the MYNX group versus 32 (11.6%) in the FemoSeal group, p = 0.358). Peri-interventional hemoglobin drop did not differ between groups (p = 0.449). Emergency diagnostics were not significantly performed more often in the MYNX group (14 (5.1%) versus 8 (2.9%), p = 0.134). A post-interventional duplex sonography showed stenosis at the puncture site in one patient after use of the MYNX system. For the entire cohort, oral anticoagulation was the only predictor for the failure of the closure device (p = 0.036). Conclusions: Device failure was more common after using the extravascular MYNX CONTROL system than after using the intravascular FemoSeal system. However, the need for surgical or interventional therapy due to device failure was low. [ABSTRACT FROM AUTHOR]

Present research on the influence of gender on the treatment of coronary artery disease (CAD) and the outcome after percutaneous coronary intervention (PCI) is inconsistent. Sex differences in the presentation of CAD and the success after treatment have been described. We intend to compare the male and female sex in the procedure and the long-term outcome of Rotational Atherectomy (RA). A total of 597 consecutive patients (20.3% female and 79.7% male, mean age 75.3 ± 8.9 years vs. 72.7 ± 9 years, p < 0.001) undergoing Rotational Atherectomy between 2015 and 2020 were enrolled in the analysis. Demographic and clinical data were registered. In-hospital, 1-year, and 3-year MACCEs (major adverse cardiac and cerebrovascular events) were calculated. Women presented more often with myocardial infarction (23.9% vs. 14.9%, p = 0.017). The intervention was mainly performed via femoral access compared to radial access (65.4% vs. 33.6%, p = 0.002). Women had a smaller diameter of the balloon predilatation compared to men (2.8 ± 0.5 mm vs. 3.15 ± 2.4 mm, p < 0.05) and a smaller maximum diameter of the implanted stent (3.5 ± 1.2 mm vs. 4.10 ± 6.5 mm, p = 0.01). In-hospital, 1-year-, and 3-year MACCEs did not differ between the sexes. After a multivariate analysis, no difference between men and women could be detected. In conclusion, this analysis shows differences between women and men in periprocedural characteristics but does not show any differences after RA regarding in-hospital, 1-year-, and 3-year MACCEs. [ABSTRACT FROM AUTHOR]

(1) Background: Inflammatory bowel diseases are complex and multifactorial disorders of unknown etiology. The extravasation of activated leukocytes is a critical step in the pathogenesis of these diseases. Leukocyte integrin Mac-1 (αMβ2; CD11b/CD18) is crucial for the extravasation of myeloid cells, and a novel activation-specific anti-Mac-1 Designed Ankyrin Repeat protein (DARPin F7) is a promising therapeutic agent for inflammatory diseases. In its activated conformation, Mac-1 expresses the high-affinity binding site I-domain, which the DARPin F7 selectively targets. In our study, we aimed to explore the therapeutic potential of anti-Mac-1 DARPin F7 in murine dextrane sodium sulfate (DSS)-induced colitis. (2) Methods: C57BL/6J mice received 3% DSS drinking water for five days, followed by normal drinking water for one week. The mice were treated with DARPin F7 or a control substance daily via intraperitoneal injections. Disease activity index (DAI), colon length, myeloperoxidase (MPO) activity measurements, H&E staining, and qRT-PCR were conducted after euthanizing the mice on day 12. (3) Results: Treatment with DARPin F7 resulted in less pronounced colon shortening and significantly lower histological scores. The DARPin F7-treated animals experienced substantially less disease and myeloperoxidase (MPO) activity. Animals that received DARPin F7 treatment suffered less weight loss and recovered from the weight loss more efficiently. Treatment with DARPin F7 also led to significantly reduced mRNA expression of inflammatory cytokines. (4) Conclusion: Anti-Mac-1 treatment markedly reduced disease activity and inflammatory reaction accompanying DSS-induced colitis in mice. [ABSTRACT FROM AUTHOR]

This paper presents a hierarchical Digital Twin architecture and implementation that uses real-time simulation to emulate the physical grid and support grid planning and operation. With the demand for detailed grid information for automated grid operations and the ongoing transformation of energy systems, the Digital Twin can extend data acquisition by establishing a reliable real-time simulation. The system uses observer algorithms to process model information about the voltage dependencies of grid nodes, providing information about the dynamic behavior of the grid. The architecture implements multiple layers of data monitoring, processing, and simulation to create node-specific Digital Twins that are integrated into a real-time Hardware-in-the-Loop setup. The paper includes a simulation study that validates the accuracy of the Digital Twin, in terms of steady-state conditions, dynamic behavior, and required processing time. The results show that the proposed architecture can replicate the physical grid with high accuracy and corresponding dynamic behavior. [ABSTRACT FROM AUTHOR]

Recent data suggest that uric acid (UA) might be an independent predictor of clinical outcomes following percutaneous coronary intervention (PCI). The predictive value of uric acid in patients undergoing PCI for chronic total occlusions (CTO) is unknown. We included patients with CTO who underwent PCI at our center in 2005 and 2012, with available uric acid levels before angiography. Subjects were divided into groups according to uric acid tertiles (<5.5 mg/dL, 5.6–6.9 mg/dL, and >7.0 mg/dL), and outcomes were compared among the groups. Out of the 1963 patients (mean age 65.2 ± 11 years), 34.7% (n = 682) had uric acid concentrations in the first tertile, 34.3% (n = 673) in the second tertile, and 31% (n = 608) in the third tertile. Median follow-up was 3.0 years. Uric acid levels in the first tertile were associated with significantly lower all-cause mortality, as compared to the third tertile, with an adjusted hazard ratio (HR) of 0.67 (95% confidence interval (CI): 0.49 to 0.92; p = 0.012). No significant differences regarding all-cause mortality were found between patients in the first and second tertiles (HR: 0.96 [95% CI: 0.71 to 1.3; p = 0.78]). High levels of uric acid emerged as an independent predictor of all-cause mortality in patients with chronic total occlusion treated with PCI. Hence, uric acid levels should be incorporated into the risk assessment of patients with CTO. [ABSTRACT FROM AUTHOR]

The study sought to assess the procedural success of rotational atherectomy (RA) in coronary chronic total occlusion (CTO) and to investigate the in-hospital and one-year outcomes following RA. From 2015 to 2019, patients undergoing percutaneous coronary intervention for CTO (CTO PCI) were retrospectively included into the hospital database. The primary endpoint was procedural success. Secondary endpoints were in-hospital and one-year major adverse cardiovascular and cerebral event (MACCE) rates. During the study period of 5 years, 2.789 patients underwent CTO PCI. Patients treated with RA (n = 193, 6.92%) had a significantly higher procedural success (93.26% vs. 85.10%, p = 0.0002) compared to those treated without RA (n = 2.596, 93.08%). Despite a significantly higher rate of pericardiocentesis (3.11% vs. 0.50%, p = 0.0013) in the RA group, the in-hospital and one-year MACCE rate was similar in both groups (4.15% vs. 2.77%, p = 0.2612; 18.65% vs. 16.72%, p = 0.485). In conclusion, RA is associated with higher procedural success for CTO PCI, but has higher risks for pericardial tamponade than CTO PCI without the need for RA. Nevertheless, in-hospital and one-year MACCE rates did not differ in-between both groups. [ABSTRACT FROM AUTHOR]

Background: In light of overlapping symptoms, discrimination between non-ST-elevation (NSTE) acute coronary syndrome (ACS) and acute heart failure (HF) is challenging, particularly in patients with equivocal clinical presentation for suspected ACS. We sought to evaluate the diagnostic and prognostic properties of copeptin in this scenario. Methods: Data from 1088 patients from a single-center observational registry were used to test the ability of serial high sensitivity cardiac troponin T (hs-cTnT)—compared to copeptin, or a combination of copeptin with hs-cTnT—to discriminate acute HF from uncomplicated non-ST-elevation myocardial infarction (NSTEMI) and to evaluate all-cause mortality after 365 days. Patients with STEMI, those with unstable angina and either normal or undetectable hs-cTnT concentrations were excluded. The findings were validated in an independent external NSTE-ACS cohort. Results: A total of 219 patients were included in the analysis. The final diagnosis was acute HF in 56 and NSTE-ACS in 163, with NSTEMI in 78 and unstable angina having stable elevation of hs-cTnT >ULN in 85. The rate of all-cause death at 1 year was 9.6% and occurred significantly more often in acute HF than in NSTE-ACS (15 vs. 6%, p < 0.001). In the test cohort, the area under the receiver operator curve (AUC) for the discrimination of acute HF vs. NSTE-ACS without HF was 0.725 (95% confidence interval [CI] 0.625–0.798) for copeptin and significantly higher than for hs-cTnT at 0 h (AUC = 0.460, 0.370–0.550) or at 3 h (AUC = 0.441, 0.343–0.538). Copeptin and hs-cTnT used either as continuous values or at cutoffs optimized to yield 90% specificity for acute HF were associated with significantly higher age- and sex-adjusted risk for all-cause mortality at 365 days. The findings from the test cohort were consistently replicated in the independent external NSTE-ACS validation cohort. Conclusions: High concentrations of copeptin in patients with suspected NSTE-ACS and equivocal clinical presentation suggest the presence of acute HF compared to uncomplicated NSTE-ACS and are associated with higher rates of all-cause death at 365 days. [ABSTRACT FROM AUTHOR]

Highlights: What are the main findings? This study not only focuses on the first wave of the pandemic, but also on its subsequent progression. What is the implication of the main finding? This study shows an increase in peripheral interventions of patients referred with wounds requiring more complex interventions. However, as a potential benefit of the endovascular treatment in a high volume center with mainly experienced operators, no increase in overall acute amputations was found. Objective: To better manage the burden of the COVID-19 pandemic on hospitals, numerous scheduled procedures have been postponed nationwide. Design and Methods: Retrospective analysis of patient characteristics and outcomes of patients hospitalized with peripheral arterial disease (PAD) in the period prior to the COVID-19 pandemic (2018 and 2019) and during the pandemic (2020 and 2021). This study assesses the in-hospital outcomes. Main endpoints are Rutherford stages at admission for intervention, incidence of amputation, of total occlusion, and duration of intervention. The data were analyzed descriptively. Results: The total number of interventions due to PAD had decreased in 2020, but not significantly during the pandemic period (n = 5351) compared to the period prior to COVID-19 pandemic (n = 5351) (p = 0.589). The proportion of interventions treated for critical limb-threatening ischaemia (CLTI) increased from 2018/2019 (n = 2112) to 2020/2021 (n = 2426) (p < 0.001). However, the proportion of patients with wounds requiring amputation was not higher during the pandemic (n = 191) than before (n = 176) (minor amputations p = 0.2302, major amputations p = 0.9803). The proportion of total occlusions did not differ significantly between the pre-COVID-19 (n = 3082) and the COVID-19 pandemic periods (n = 2996) (p = 0.8207). Multilevel interventions did not increase significantly from 2018/2019 (n = 1930) to 2020/2021 (n = 2071). Between 2018/2019 and 2020/2021, the procedure duration and fluoroscopy duration increased significantly. However, parameters such as contrast agent volume and radiation dose did not differ significantly. The average length of stay was 4.6 days. Conclusion: The COVID-19 pandemic had an impact on the in-patient care of PAD patients in terms of disease stage severity and complexity. However, the amputation rate was not affected. [ABSTRACT FROM AUTHOR]

Background: Permanent pacemaker implantation (PPI) after transcatheter valve implantation (TAVI) is a common complication. Pre-existing right bundle branch block (RBBB) is a strong risk factor for PPI after TAVI. However, a patient-specific approach for risk stratification in this subgroup has not yet been established. Methods: We investigated TAVI patients with pre-existing RBBB to stratify risk factors for PPI and 1-year-mortality by detailed analysis of ECG data, RBBB morphology and degree of calcification in the implantation area assessed by computed tomography angiography. Results: Between 2010 and 2018, 2129 patients underwent TAVI at our institution. Among these, 98 pacemaker-naïve patients with pre-existing RBBB underwent a TAVI procedure. PPI, because of relevant conduction disturbances (CD), was necessary in 43 (43.9%) patients. PPI was more frequently indicated in women vs. men (62.1% vs. 32.8%, p = 0.004) and in men treated with a self-expandable vs. a balloon-expandable valve (58.3% vs. 26.5%, p = 0.035). ECG data (heart rhythm, PQ, QRS, QT) and RBBB morphology had no influence on PPI rate, whereas risk for PPI increased with the degree of calcification in the left septal His-/left bundle branch-area to a 9.375-fold odds for the 3rd tertile of calcification (1.639–53.621; p = 0.012). Overall, 1-year-mortality was comparable among patients with or without PPI (14.0% vs. 16.4%; p = 0.697). Conclusions: Patients with RBBB undergoing TAVI have a high risk of PPI. Among this subgroup, female patients, male patients treated with self-expandable valve types, patients with high load/degree of non-coronary LVOT calcification and patients with atrial fibrillation need enhanced surveillance for CD after procedure. [ABSTRACT FROM AUTHOR]

Featured Application: Synchrophasor based data compression and post-mortem analysis as well as online detection and classification of grid disturbances. Synchrophasor based applications become more and more popular in today's control centers to monitor and control transient system events. This can ensure secure system operation when dealing with bidirectional power flows, diminishing reserves and an increased number of active grid components. Today's synchrophasor applications provide a lot of additional information about the dynamic system behavior but without significant improvement of the system operation due to the lack of interpretable and condensed results as well as missing integration into existing decision-making processes. This study presents a holistic framework for novel machine learning based applications analyzing both historical as well as online synchrophasor data streams. Different methods from dimension reduction, anomaly detection as well as time series classification are used to automatically detect disturbances combined with a web-based online visualization tool. This enables automated decision-making processes in control centers to mitigate critical system states and to ensure secure system operations (e.g., by activating curate actions). Measurement and simulation-based results are presented to evaluate the proposed synchrophasor application modules for different use cases at the transmission and distribution level. [ABSTRACT FROM AUTHOR]

Parvovirus B19 (B19V) is the predominant cardiotropic virus currently found in endomyocardial biopsies (EMBs). However, direct evidence showing a causal relationship between B19V and progression of inflammatory cardiomyopathy are still missing. The aim of this study was to analyze the impact of transcriptionally active cardiotropic B19V infection determined by viral RNA expression upon long-term outcomes in a large cohort of adult patients with non-ischemic cardiomyopathy in a retrospective analysis from a prospective observational cohort. In total, the analyzed study group comprised 871 consecutive B19V-positive patients (mean age 50.0 ± 15.0 years) with non-ischemic cardiomyopathy who underwent EMB. B19V-positivity was ascertained by routine diagnosis of viral genomes in EMBs. Molecular analysis of EMB revealed positive B19V transcriptional activity in n = 165 patients (18.9%). Primary endpoint was all-cause mortality in the overall cohort. The patients were followed up to 60 months. On the Cox regression analysis, B19V transcriptional activity was predictive of a worse prognosis compared to those without actively replicating B19V (p = 0.01). Moreover, multivariable analysis revealed transcriptional active B19V combined with inflammation [hazard ratio 4.013, 95% confidence interval 1.515–10.629 (p = 0.005)] as the strongest predictor of impaired survival even after adjustment for age and baseline LVEF (p = 0.005) and independently of viral load. The study demonstrates for the first time the pathogenic clinical importance of B19V with transcriptional activity in a large cohort of patients. Transcriptionally active B19V infection is an unfavourable prognostic trigger of adverse outcome. Our findings are of high clinical relevance, indicating that advanced diagnostic differentiation of B19V positive patients is of high prognostic importance. [ABSTRACT FROM AUTHOR]

Fibroblasts contribute to approximately 20% of the non-cardiomyocytic cells in the heart. They play important roles in the myocardial adaption to stretch, inflammation, and other pathophysiological conditions. Fibroblasts are a major source of extracellular matrix (ECM) proteins whose production is regulated by cytokines, such as TNF-α or TGF-β. The resulting myocardial fibrosis is a hallmark of pathological remodeling in dilated cardiomyopathy (DCM). Therefore, in the present study, the secretome and corresponding transcriptome of human cardiac fibroblasts from patients with DCM was investigated under normal conditions and after TNF-α or TGF-β stimulation. Secreted proteins were quantified via mass spectrometry and expression of genes coding for secreted proteins was analyzed via Affymetrix Transcriptome Profiling. Thus, we provide comprehensive proteome and transcriptome data on the human cardiac fibroblast's secretome. In the secretome of quiescent fibroblasts, 58% of the protein amount belonged to the ECM fraction. Interestingly, cytokines were responsible for 5% of the total protein amount in the secretome and up to 10% in the corresponding transcriptome. Furthermore, cytokine gene expression and secretion were upregulated upon TNF-α stimulation, while collagen secretion levels were elevated after TGF-β treatment. These results suggest that myocardial fibroblasts contribute to pro-fibrotic and to inflammatory processes in response to extracellular stimuli. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) led to an ongoing pandemic with a surge of critically ill patients. Very little is known about the occurrence and characteristic of cardiac arrest in critically ill patients with COVID-19 treated at the intensive care unit (ICU). The aim was to investigate the incidence and outcome of intensive care unit cardiac arrest (ICU-CA) in critically ill patients with COVID-19. This was a retrospective analysis of prospectively recorded data of all consecutive adult patients with COVID-19 admitted (27 February 2020–14 January 2021) at the University Medical Centre Hamburg-Eppendorf (Germany). Of 183 critically ill patients with COVID-19, 18% (n = 33) had ICU-CA. The median age of the study population was 63 (55–73) years and 66% (n = 120) were male. Demographic characteristics and comorbidities did not differ significantly between patients with and without ICU-CA. Simplified Acute Physiological Score II (SAPS II) (ICU-CA: median 44 points vs. no ICU-CA: 39 points) and Sequential Organ Failure Assessment (SOFA) score (median 12 points vs. 7 points) on admission were significantly higher in patients with ICU-CA. Acute respiratory distress syndrome (ARDS) was present in 91% (n = 30) with and in 63% (n = 94) without ICU-CA (p = 0.002). Mechanical ventilation was more common in patients with ICU-CA (97% vs. 67%). The median stay in ICU before CA was 6 (1–17) days. A total of 33% (n = 11) of ICU-CAs occurred during the first 24 h of ICU stay. The initial rhythm was non-shockable (pulseless electrical activity (PEA)/asystole) in 91% (n = 30); 94% (n = 31) had sustained return of spontaneous circulation (ROSC). The median time to ROSC was 3 (1–5) minutes. Patients with ICU-CA had significantly higher ICU mortality (61% vs. 37%). Multivariable logistic regression showed that the presence of ARDS (odds ratio (OR) 4.268, 95% confidence interval (CI) 1.211–15.036; p = 0.024) and high SAPS II (OR 1.031, 95% CI 0.997–1.065; p = 0.077) were independently associated with the occurrence of ICU-CA. A total of 18% of critically ill patients with COVID-19 suffered from a cardiac arrest within the intensive care unit. The occurrence of ICU-CA was associated with presence of ARDS and severity of illness. [ABSTRACT FROM AUTHOR]

Aims: The diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim of this study was to demonstrate the feasibility of gene profiling as a new diagnostic method in clinical practice, namely in a large cohort of patients suffering from acute cardiac decompensation. Methods and Results: In this retrospective multicenter study, EMBs taken from n = 427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age: 47.03 ± 15.69 years). In each patient, the EMBs were analyzed on the basis of histology, immunohistology, molecular virology, and gene-expression profiling. Out of the total of n = 427 patient samples examined, GCs could be detected in 26 cases (6.1%) by histology. An established myocardial gene profile consisting of 27 genes was revealed; this was narrowed down to a specified profile of five genes (CPT1, CCL20, CCR5, CCR6, TLR8) which serve to identify histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Once this newly established profiling approach was applied to the remaining patient samples, an additional n = 31 patients (7.3%) could be identified as having IGCM without any histologic proof of myocardial GCs. In a subgroup analysis, patients diagnosed with IGCM using this gene profiling respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone. Conclusions: Myocardial gene-expression profiling is a promising new method in clinical practice, one which can predict IGCM even in the absence of any direct histologic proof of GCs in EMB sections. Gene profiling is of great clinical relevance in terms of (a) overcoming the sampling error associated with purely histologic examinations and (b) monitoring the effectiveness of therapy. [ABSTRACT FROM AUTHOR]

The electrocardiogram (ECG) is an important diagnostic tool for patients with suspected acute myocardial infarction (AMI). Current guidelines recommend serial ECGs in case of persisting symptoms. We aimed to analyze the predictive value of ischemic ECG-signs in patients with suspected AMI. Patients presenting to the emergency department with suspected AMI were included. All patients with ST-elevation AMI were excluded from analyses. Patients received 12-lead-ECG and high-sensitive Troponin T (hs-TnT)-measurement at admission and after 3 h. Four groups were defined: no ischemic signs in either ECG; new ischemic signs in the second ECG; resolved ischemic signs in the second ECG; and persistent ischemic signs in both ECGs. Patients were followed for 2 years to assess the composite endpoint of all-cause-mortality, AMI, and coronary revascularization. Using a 30-day landmark analysis, a Cox regression with ischemic signs as the variable of interest, adjusted by cardiovascular risk factors, was calculated. Of 1675 patients, 1321 showed no ischemic signs, in 25 new-, in 92 resolved- and in 237 patients, persistent ischemic signs were documented. Patients with persistent ischemic signs had significantly worse outcomes, compared to those without. Compared to no ischemic signs, adjusted hazard ratios for the combined endpoint were 0.81 (95% CI 0.20, 3.31; p-value = 0.77) for new-, 0.59 (95% CI 0.26, 1.34; p-value = 0.21) for resolved-, and 1.47 (95% CI 1.102, 2.13; p-value = 0.041) for persistent ischemic signs. In patients with suspected AMI, persistent ischemic ECG-signs are predictive of a higher rate of all-cause-mortality, AMI, and revascularization. [ABSTRACT FROM AUTHOR]

Sex differences in patients with acute coronary syndrome (ACS) are a matter of debate. We investigated sex-specific differences in the incidence, outcomes, and related interventions in patients diagnosed with ACS in Germany over the past decade. All ACS cases from 2005 to 2015 were collected. Procedures and inhospital mortality were assessed by sex. Age-adjusted incidence rates were calculated. In total, 1,366,045 females and 2,431,501 males presenting with ACS were recorded. Females were older than males (73.1 vs. 66.4 years of age), had a longer mean hospital stay (7.7 vs. 6.9 days), and less frequently underwent coronary angiographies (55% vs. 66%) and coronary interventions (35% vs. 47%). The age-adjusted incidence rate of ACS was lower in females than in males, and decreased in both sexes from 2005 to 2015. The age-adjusted inhospital mortality rate was substantially higher in females than in males, but decreased in both sexes over time (in females, from 87 to 71 cases per 1000 person years; in males, from 57 to 51 cases per 1000 person years). In conclusion, we reported sex differences in the incidence, treatment, and outcomes of ACS patients in Germany within the past decade. Women had a substantially higher mortality rate and lower rate of coronary interventions. [ABSTRACT FROM AUTHOR]

Aim: Evidence on non-ischemic cardiogenic shock (CS) is scarce. The aim of this study was to investigate differences in patient characteristics, use of treatments and outcomes in patients with non-ischemic vs. ischemic CS. Methods: Patients with CS admitted between October 2009 and October 2017 were identified and stratified as non-ischemic/ischemic CS based on the absence/presence of acute myocardial infarction. Logistic/Cox regression models were fitted to investigate the association between non-ischemic CS and patient characteristics, use of treatments and 30-day in-hospital mortality. Results: A total of 978 patients were enrolled in this study; median age was 70 (interquartile range 58, 79) years and 70% were male. Of these, 505 patients (52%) had non-ischemic CS. Patients with non-ischemic CS were more likely to be younger and female; were less likely to be active smokers, to have diabetes or decreased renal function, but more likely to have a history of myocardial infarction; and they were more likely to present with unfavorable hemodynamics and with mechanical ventilation. Regarding treatments, patients with non-ischemic CS were more likely to be treated with catecholamines, but less likely to be treated with extracorporeal membrane oxygenation or percutaneous left-ventricular assist devices. After adjustment for multiple relevant confounders, non-ischemic CS was associated with a significant increase in the risk of 30-day in-hospital mortality (hazard ratio 1.14, 95% confidence interval 1.04–1.24, p < 0.01). Conclusion: In this large study, non-ischemic CS accounted for more than 50% of all CS cases. Non-ischemic CS was not only associated with relevant differences in patient characteristics and use of treatments, but also with a worse prognosis. These findings highlight the need for effective treatment strategies for patients with non-ischemic CS. [ABSTRACT FROM AUTHOR]

High-sensitivity troponin has proven to be a promising biomarker for the prediction of future adverse cardiovascular events. We aimed to assess the prognostic value of high-sensitivity troponin I (hs-TnI) on admission in patients with suspected acute myocardial infarction (AMI) analyzed by a novel (Singulex Clarity cTnI) and established hs-TnI assay (ARCHITECT STAT hs-TnI, Abbott). Hs-TnI was measured in a total of 2332 patients from two prospective cohort studies presenting to the emergency department with suspected AMI. The prognostic impact for overall and cardiovascular mortality of both hs-TnI assays was assessed in the total patient cohort as well as in the subgroups of patients with AMI (n = 518) and without AMI (non-AMI) (n = 1814). Patients presenting with highest hs-TnI levels showed higher overall and cardiovascular mortality rates compared to those with lower troponin levels, irrespective of the assay used. Both hs-TnI assays indicated association with overall mortality according to adjusted hazard ratio (HR) among the entire study population (HR for Singulex assay: 1.16 (95% CI 1.08–1.24) and HR for Abbott assay: 1.17 (95% CI 1.09–1.25)). This finding was particularly pronounced in non-AMI patients, whereas no association between hs-TnI and overall mortality was found in AMI patients for either assay. In non-AMI patients, both assays equally improved risk prediction for cardiovascular mortality beyond conventional cardiovascular risk factors. Hs-TnI is independently predictive for adverse outcomes in patients with suspected AMI, especially in the subset of patients without confirmed AMI. There was no difference between the established and the novel assay in the prediction of mortality. [ABSTRACT FROM AUTHOR]

(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status as well as systolic and diastolic blood pressure, body mass index (BMI), LDL cholesterol, HDL cholesterol, and triglycerides. (3) Results: A significant correlation was shown for RTL, with age as a quality control in our study (effect = −0.004, p = 3.2 × 10−47). Analysis of the relation between RTL and cardiovascular risk factors showed a significant association of RTL in patients who were current smokers (effect = −0.016, p = 0.048). No significant associations with RTL were seen for cardiovascular risk factors of LDL cholesterol (p = 0.127), HDL cholesterol (p = 0.713), triglycerides (p = 0.359), smoking (p = 0.328), diastolic blood pressure (p = 0.615), systolic blood pressure (p = 0.949), or BMI (p = 0.903). In a subsequent analysis, we calculated the tertiles of RTL. No significant difference across RTL tertiles was detectable for BMI, blood pressure, lipid levels, or smoking status. Finally, we studied the association of RTL and cardiovascular risk factors stratified by tertiles of age. We found a significant association of RTL and LDL cholesterol in the oldest tertile of age (effect = 0.0004, p = 0.006). (4) Conclusions: We determined the association of relative telomere length and cardiovascular risk factors in a population setting. An association of telomere length with age, current smoking status, as well as with LDL cholesterol in the oldest tertile of age was found, whereas no associations were observed between telomere length and triglycerides, HDL cholesterol, blood pressure, or BMI. [ABSTRACT FROM AUTHOR]

The soluble urokinase-type plasminogen activator receptor (suPAR) is a new marker for immune activation and inflammation and may provide diagnostic value on top of established biomarkers in patients with suspected acute myocardial infarction (AMI). Here, we evaluate the diagnostic potential of suPAR levels on top of high-sensitivity troponin I (hs-TnI) in a cohort of patients with suspected AMI. A total of 1220 patients presenting to the emergency department with suspected AMI were included, of whom 245 were diagnosed with AMI. Median suPAR levels at admission were elevated in subjects with AMI compared to non-AMI (3.8 ng/mL vs. 3.3 ng/mL, p = 0.001). In C-statistics, the area under the curve (AUC) regarding the diagnosis of AMI was low (0.57 at an optimized cut-off of 3.7 ng/mL). Moreover, baseline suPAR levels on top of troponin values at admission and hour 1 reduced the number of patients who were correctly ruled-out as non-AMI, and who were correctly ruled-in as AMI. Our study shows that circulating levels of suPAR on top of high-sensitivity troponin I do not improve the early diagnosis of AMI. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine known to play a major role in inflammatory diseases such as myocardial infarction (MI), where its expression increases. Cardio-protective functions of MIF during ischemia have been reported. Recently, the structurally related MIF-2 was identified and similar effects are assumed. We wanted to further investigate the role of MIF and MIF-2 on inflammatory processes during MI. Therefore, we subjected mice to experimentally induced MI by coronary occlusion for one and five days. During the acute phase of MI, the gene expression of Mif was upregulated in the infarct zone, whereas Mif-2 was downregulated, suggesting a minor role of MIF-2. Simulating ischemic conditions or mechanical stress in vitro, we demonstrated that Mif expression was induced in resident cardiac cells. To investigate possible auto-/paracrine effects, cardiomyocytes and cardiac fibroblasts were individually treated with recombinant murine MIF, which in turn induced Mif expression and the expression of pro-inflammatory genes in cardiac fibroblasts. Cardiomyocytes did not respond to recombinant MIF with pro-inflammatory gene expression. While MIF stimulation alone did not change the expression of pro-fibrotic genes in cardiac fibroblasts, ischemia reduced their expression. Mimicking the increased MIF levels during MI, we exposed cardiac fibroblasts to simulated ischemia in the presence of MIF, which led to further reduced expression of pro-fibrotic genes. The presented data show that MIF was expressed by resident cardiac cells during MI. In vitro, Mif expression was induced by different external stimuli in cardiomyocytes and cardiac fibroblasts. Addition of recombinant MIF protein increased the expression of pro-inflammatory genes in cardiac fibroblasts including Mif expression itself. Thereby, cardiac fibroblasts may amplify Mif expression during ischemia promoting cardiomyocyte survival. [ABSTRACT FROM AUTHOR]

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 1.07–2.81; 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 1.02–2.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome. [ABSTRACT FROM AUTHOR]