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The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.

(1) Herpes simplex virus (HSV) reactivation in critically ill patients can cause infection in the lower respiratory tract, prolonging mechanical ventilation. However, the association of HSV reactivation with cardiogenic shock (CS) is unclear. As CS is often accompanied by pulmonary congestion and reduced immune system activity, the aim of our study was to determine the incidence and outcome of HSV reactivation in these patients. (2) In this retrospective, single-center study, bronchial lavage (BL) was performed on 181 out of 837 CS patients with mechanical ventilation. (3) In 44 of those patients, HSV was detected with a median time interval of 11 days since intubation. The occurrence of HSV was associated with an increase in C-reactive protein and the fraction of inspired oxygen at the time of HSV detection. Arterial hypertension, bilirubin on ICU admission, the duration of mechanical ventilation and out-of-hospital cardiac arrest were associated with HSV reactivation. (4) HSV reactivation could be detected in 24.3% of patients with CS on whom BL was performed, and its occurrence should be considered in patients with prolonged mechanical ventilation. Due to the limited current evidence, the initiation of treatment for these patients remains an individual choice. Dedicated randomized studies are necessary to investigate the efficacy of antiviral therapy.

BACKGROUND. Dose reduction strategies for coronary CTA (CCTA) have been underused in clinical practice given concern that the strategies may lower image quality. OBJECTIVE. The purpose of this study was to explore associations between dose reduction strategies and CCTA image quality in real-world clinical practice. METHODS. This subanalysis of the international Prospective Multicenter Registry on Radiation Dose Estimates of Cardiac CT Angiography in Daily Practice in 2017 (PROTECTION VI) study included 3725 patients (2109 men, 1616 women; median age, 59 years) who underwent CCTA for coronary artery evaluation performed at 55 sites in 32 countries. CCTA image sets were reviewed at a core laboratory. A range of patient and scan characteristics, including use of three dose reduction strategies (prospective ECG triggering, low tube potential, and iterative image reconstruction) and image dose, were recorded. A single core laboratory member reviewed all examinations for quantitative image quality measures, including signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), and reviewed 50% of examinations to assign a qualitative CCTA image quality score and a semiquantitative coronary calcification measure. Multivariable logistic regression models were used to identify predictors of image quality. A second core laboratory member repeated quantitative measures for 100 examinations and the qualitative measure for 383 (approximately 20%) examinations to assess interreader agreement. RESULTS. Independent predictors ( p < .05) of SNR were female sex (effect size, 2.70), lower body mass index (0.38 per 1-unit decrease), stable sinus rhythm (1.71), and scanner manufacturer (variable effect across manufacturers). These factors were also the only independent predictors of CNR. Independent predictors ( p < .05) of CCTA image quality were heart rate (0.17 per 10 beats/min reduction) and coronary calcification (0.15 per coronary calcification grade). None of the three dose-saving strategies or dose-length product was an independent predictor of any image quality measure. Interreader agreement analysis showed intraclass correlation coefficients of 0.874 for SNR and 0.891 for CNR and a kappa value of 0.812 for the qualitative score. CONCLUSION. This large international multicenter study shows that three dose reduction strategies were not associated with decreased CCTA image quality. CLINICAL IMPACT. The dose reduction strategies should be routinely implemented in clinical CCTA.

Aims Automated coronary total plaque volume (TPV) quantification derived from coronary computed tomographic angiography (CTA) datasets provide exact and reliable assessment of calcified and non-calcified coronary atherosclerosis burden. The aim of this analysis was to investigate the long-term predictive value of TPV. Methods and results TPV was quantified in 1577 patients undergoing coronary CTA and cardiovascular events were collected during 10.5 years (interquartile range 6.0–11.4) of follow-up. The study endpoint comprised cardiac death and acute coronary syndrome and occurred in 59 (3.7%) patients. Coronary TPV provided additive prognostic value over clinical risk assessed with the Morise Score and coronary artery disease severity (rise in C-index from 0.744 to 0.769, P = 0.03). A category-based reclassification approach combining the Morise Score and TPV revealed superior risk stratification (categorical net reclassification improvement: 0.48 with 95% CI 0.13–0.68, P Conclusion Quantification of TPV from coronary CTA permits an improved 10-year cardiovascular risk stratification.

Highlights • Acute cardiac tamponade is a highly relevant complication in modern cardiology. • Continuous pericardial drainage is safe and does not increase total drainage volume. • Continuous drainage associates with lower rates of open-heart surgical interventions. • Continuous drainage associates with reduced re-tamponades and mortality on day 5., Background Acute cardiac tamponade is a life-threatening pathology in modern cardiology as catheter-based interventions become increasingly relevant. Pericardiocentesis is usually the primary treatment of choice. However, protocols for handling of draining pigtail catheters are very variable due to limit data and require further investigation. Methods We retrospectively analyzed 52 patients with acute cardiac tamponade requiring immediate pericardiocentesis from January 2017 to August 2020. Patients were treated with a classical approach of intermittent manual aspiration or continuous pericardial drainage using a redon drainage system. Results Mean age of patients was 74 years in both groups. Most common causes for cardiac tamponade were percutaneous coronary interventions in about 50% and transaortic valve implantations in 25% of all cases. 28 patients were treated with classic intermittent drainage from 2017 to 2020. 24 patients were treated with continuous drainage from December 2018–2020. Compared to classical intermittent drainage treatment, continuous drainage was associated with a lower rate of a surgical intervention or cardiac re-tamponade and a lower mortality at 5 days (HR 0.2, 95% CI 0.1–0.9, log-rank p = 0.03). Despite a longer total drainage time under continuous suction, drainage volumes were comparable in both groups. Conclusion Acute cardiac tamponade can be efficiently treated by pericardiocentesis with subsequent continuous negative pressure drainage via a pigtail catheter. Our retrospective analysis shows a significantly lower mortality, a decreased rate of interventions and lower rates of cardiac re-tamponade without any relevant side effects when compared to classical intermittent manual drainage. These findings require further investigations in larger, randomized trials.

Objective: Percutaneous dilatational tracheotomy has become a routine procedure in ICUs. However, given the high and steadily growing number of patients receiving anticoagulation, dual antiplatelet therapy, or even a combination of both (also known as “triple therapy”), there are concerns about the safety of the procedure, in particular for critically ill patients with a high risk of bleeding. In this retrospective study, we investigated whether percutaneous dilatational tracheotomy in this high-risk population was associated with elevated procedural complications. Design: Retrospective single-center study with analysis of all percutaneous dilatational tracheotomies performed in our cardiac ICU from January 2018 to May 2019. Setting: Munich university hospital’s cardiac ICU. Patients and Interventions: A total of 34 patients who underwent percutaneous dilatational tracheotomy according to Ciaglia technique with accompanying bronchoscopy in our cardiac ICU from January 2018 to May 2019 were included. Patients were stratified into clinically relevant risk groups based on anticoagulation and antiplatelet therapy considering standard laboratory coagulation parameters, that is, activated partial thromboplastin time, international normalized ratio, and platelet count with differentiated analysis of procedure-related complications in each risk group until hospital discharge. Measurements and Main Results: A total of 34 patients who underwent percutaneous dilatational tracheotomy were included and assigned to five clinically relevant treatment groups: IV unfractionated heparin (prophylactic dosage) (n = 4), IV unfractionated heparin (therapeutic dosage) (n = 4), aspirin and IV unfractionated heparin (therapeutic dosage) (n = 7), dual antiplatelet therapy with IV unfractionated heparin (prophylactic dosage) (n = 5), and dual antiplatelet therapy with IV unfractionated heparin (therapeutic dosage) (n = 14). Three bleedings without surgical intervention or blood transfusion were documented in the whole cohort, but no single bleeding did occur in the triple therapy group. These were exclusively caused by skin bleedings at the immediate puncture site—each of which could be easily treated with one or two single stitches. There were no severe bleeding complications or potentially life-threatening procedure-related complications. Additionally, the rate of complications in patients with elevated body mass index was not increased. Conclusions: Bronchoscopy-guided percutaneous dilatational tracheotomy according to Ciaglia technique with careful consideration of all potential indications and contraindications may be a safe and low-complication procedure for airway management, even in patients receiving dual antiplatelet therapy and therapeutic anticoagulation simultaneously in our cohort with a high risk of bleeding.

Background: To investigate the impact of diabetes on coronary artery total plaque volume (TPV) and adverse events in long-term follow-up.Methods: One-hundred-and-eight diabetic patients were matched to 324 non-diabetic patients, with respect to age, sex, body-mass index, hypertension, smoking habits, LDL and HDL cholesterol, family history for CAD as well as aspirin and statin medication. In all patients, TPV was quantified from coronary CT angiographies (CTA) using dedicated software. All-cause mortality, acute coronary syndrome and late revascularisation ( > 90 days) served as combined endpoint.Results: Patients were followed for 5.6 years. The endpoint occurred in 18 (16.7%) diabetic and 26 (8.0%) nondiabetic patients (odds ratio 2.3, p = 0.03). Diabetic patients had significantly higher TPV than non-diabetic patients (55.1 mm 3 [IQR: 6.2 and 220.4 mm(3)] vs. 24.9 mm 3 [IQR: 0 and 166.7 mm(3)], p = 0.02). A TPV threshold of 110.5 mm(3) provided good separation of diabetic and non-diabetic patients at higher and lower risk for adverse events. Noteworthy, diabetic and non-diabetic patients with a TPV < 110.5 mm(3) had comparable outcome (hazard ratio: 1.3, p = 0.59), while diabetic patients with TPV > 110.5 mm(3) had significantly higher incidence of adverse events (hazard ratio 2.3, p = 0.03) compared to non-diabetic patients with TPV > 110.5 mm(3). There was incremental prognostic value in diabetic and non-diabetic patients over the Framingham Risk Score (Integrated Discrimination Improvement: 0.052 and 0.012, p for both < 0.05).Conclusion: Diabetes is associated with significantly higher TPV, which is independent of other CAD risk factors. Quantification of TPV improves the identification of diabetic patients at higher risk for future adverse events.

Aims: Advances of cardiac computed tomography angiography (CTA) have been developed for dose reduction, but their efficacy in clinical practice is largely unknown. This study was designed to evaluate radiation dose exposure and utilization of dose-saving strategies for contrast-enhanced cardiac CTA in daily practice.Methods and results: Sixty one hospitals from 32 countries prospectively enrolled 4502 patients undergoing cardiac CTA during one calendar month in 2017. Computed tomography angiography scan data and images were analysed in a central core lab and compared with a similar dose survey performed in 2007. Linear regression analysis was performed to identify independent predictors associated with dose. The most frequent indication for cardiac CTA was the evaluation of coronary artery disease in 89% of patients. The median dose-length product (DLP) of coronary CTA was 195 mGy*cm (interquartile range 110-338 mGy*cm). When compared with 2007, the DLP was reduced by 78% (P Conclusion: This large international radiation dose survey demonstrates considerable reduction of radiation exposure in coronary CTA during the last decade. However, the large inter-site variability in radiation exposure underlines the need for further site-specific training and adaptation of contemporary cardiac scan protocols.

Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet–neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet–neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation., Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.

Background. Wearable cardioverter defibrillator (WCD) therapy is feasible and safe in patients as a transient protection against sudden cardiac death (SCD). However, the impact of WCD therapy on quality of life (QoL) has not been studied. Methods. In our single-centre study, 109 consecutive patients with a prescription of WCD were retrospectively analysed. Quality of life has been assessed by a standardized questionnaire (EQ-5D-3L, modified). Additionally, clinical baseline and follow-up data and recorded arrhythmic episodes were evaluated. Results. Mean WCD therapy time was 56.2 (± 42.4) days, with a daily wear time of 19.7 (± 5) hours. A total of 3441 arrhythmia episodes were detected. Of these, 27 (1%) were adequate but did not require shock therapy. Likewise, no inadequate shock therapy occurred. WCD therapy negatively affected quality of life: 43% of patients reported mental health issues. 37% reported pain or discomfort. Self-care, usual activities, and mobility were restricted in 17%, 48%, and 36%, respectively. 29% were afraid of receiving shock therapy, and 48% suffered from sleep disturbance. However, 64% indicated having felt safe during WCD therapy. Accordingly, average quality of life was rated 70/100 points. Conclusion. In our cohort, no SCD was prevented by WCD therapy. In contrast, in this preliminary study quality of life was reduced. Thus, careful recommendation of WCD therapy for high risk patients should be considered.

BACKGROUND: Cardiac computed tomography angiography (cardiac CTA) is an increasingly used versatile imaging method to evaluate coronary and cardiac morphology. Owing to improvements in technology, image quality has continuously improved over the last 10-20 years. At the same time, numerous non-randomized and randomized studies have been performed to reduce the associated radiation exposure. Currently, it is unclear if the advances in technology and knowledge about radiation reduction translated into reduced levels of cardiac CTA radiation dose in daily clinical practice as well as a wide utilization of dose-saving strategies.METHODS: The PROTECTION VI study is a multicenter, prospective, worldwide registry designed to evaluate radiation dose exposure, utilization of dose-saving strategies and diagnostic image quality during cardiac CTA in current daily practice. Assessment of image quality will be addressed by the evaluation of diagnostic image quality at the local study site and the calculation of quantitative image quality parameters in an imaging core laboratory. Above 4000 patients will be enrolled from approximately 70 sites in Europe, North America, South America, Asia and Australia. The study will analyze median radiation dose levels, image quality, frequency of use and efficacy of algorithms for dose reduction, and patient and study-related predictors associated with radiation dose.CONCLUSIONS: The PROTECTION VI study is designed to provide a reliable estimate of current radiation dose for cardiac CTA and to assess the potential for additional dose reductions.