Non-invasive assessment of left ventricular contractility by myocardial work index in veno-arterial membrane oxygenation patients: rationale and design of the MIX-ECMO multicentre observational study.

Introduction and aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients. Methods: The MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48-72 h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score. Conclusions: The MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.

Prognostic value of extended cardiac risk assessment before elective open abdominal aortic surgery.

BACKGROUND: Major vascular surgery is associated with a high perioperative risk and significant mortality. Despite advances in risk stratification, monitoring, and management of perioperative complications, cardiac complications are still common. Stress echocardiography is well established in coronary artery disease diagnostics; however, its prognostic value before high-risk aortic surgery is unknown. This prospective, single-center study compared the outcome of patients undergoing extended cardiac risk assessment before open abdominal aortic surgery with the outcome of patients who had received standard preoperative assessment. METHODS: The study included patients undergoing elective open abdominal aortic surgery. Patients who underwent standard preoperative assessment before the start of a dedicated protocol were compared with patients who had extended cardiac risk assessment, including dobutamine stress echocardiography, as part of a stepwise interdisciplinary cardiovascular team approach. The combined primary endpoint was cardiovascular death, myocardial infarction, emergency coronary revascularization, and life-threatening arrhythmia within 30 days. The secondary endpoint was acute renal failure and severe bleeding. RESULTS: In total, 77 patients (mean age 68.1 ± 8.1 years, 70% male) were included: 39 underwent standard and 38 underwent cardiac risk assessment. The combined primary endpoint was reached significantly more often in patients before than after implementation of the extended cardiac stratification procedure (15% vs. 0%, p = 0.025). The combined secondary endpoint did not differ between the groups. CONCLUSIONS: Patients with extended cardiac risk assessment undergoing elective open abdominal aortic surgery had better 30-day outcomes than did those who had standard preoperative assessment.

First experiences of ultrasound vector flow imaging at the femoropopliteal artery in peripheral arterial disease.

Background: The femoropopliteal artery (FPA) plays a central role in diagnosing and treating peripheral arterial disease (PAD). FPA lesions are the most frequent cause of intermittent claudication, and no other artery of the lower extremities is recanalised more frequently. Generally, ultrasound is the primary imaging tool in PAD, particularly FPA. With the development of high-frame-rate ultrasound technology in addition to traditional ultrasound modes, vector flow imaging (VFI) has provided deeper haemodynamic insights when used in the carotid artery. Here, we report the use of VFI at the FPA level in routine PAD examinations. Patients and methods: In this single-centre prospective study, we evaluated consecutive patients with PAD using B-mode imaging, colour Doppler, pulsed wave Doppler (PW) and vector flow. Hemodynamic parameters at predefined locations at the carotid artery and FPA were compared. Results: Qualitatively adequate VFI at all sites was possible in 76% of the patients with PAD. With decreasing volume flow from the common carotid artery to the internal carotid artery and from the common femoral artery via the superficial femoral artery to the popliteal artery, the correlation between VFI- and PW-derived-volume flow was high at every site. Based on different techniques, the VFI-derived values were significantly lower than the PW-derived values. The mean wall shear stress was significantly lower at all femoropopliteal sites than at the carotid sites, whereas the oscillatory shear index at the femoral site was higher than that at the carotid sites rather than at the popliteal location. Conclusions: Our findings suggest that vector flow data acquisition in the FPA is feasible in most patients with PAD. Therefore, with knowledge of the method and its limitations, VFI provides haemodynamic information beyond traditional ultrasound techniques and is a promising new tool for flow analysis in PAD.

Novel Aspects Targeting Platelets in Atherosclerotic Cardiovascular Disease-A Translational Perspective.

Platelets are important cellular targets in cardiovascular disease. Based on insights from basic science, translational approaches and clinical studies, a distinguished anti-platelet drug treatment regimen for cardiovascular patients could be established. Furthermore, platelets are increasingly considered as cells mediating effects "beyond thrombosis", including vascular inflammation, tissue remodeling and healing of vascular and tissue lesions. This review has its focus on the functions and interactions of platelets with potential translational and clinical relevance. The role of platelets for the development of atherosclerosis and therapeutic modalities for primary and secondary prevention of atherosclerotic disease are addressed. Furthermore, novel therapeutic options for inhibiting platelet function and the use of platelets in regenerative medicine are considered.

Improved mid-term stability of MR reduction with an increased number of clips after percutaneous mitral valve repair in functional MR.

Background: Percutaneous mitral valve repair (PMVR) has evolved to be a standard procedure in suitable patients with mitral regurgitation (MR) not accessible for open surgery. Here, we analyzed the influence of the number and positioning of the clips implanted during the procedure on MR reduction analyzing also sub-collectives of functional and degenerative MR (DMR). Results: We included 410 patients with severe MR undergoing PMVR using the MitraClip® System. MR and reduction of MR were analyzed by TEE at the beginning and at the end of the PMVR procedure. To specify the clip localization, we sub-divided segment 2 into 3 sub-segments using the segmental classification of the mitral valve. Results: We found an enhanced reduction of MR predominantly in DMR patients who received more than one clip. Implantation of only one clip led to a higher MR reduction in patients with functional MR (FMR) in comparison to patients with DMR. No significant differences concerning pressure gradients could be observed in degenerative MR patients regardless of the number of clips implanted. A deterioration of half a grade of the achieved MR reduction was observed 6 months post-PMVR independent of the number of implanted clips with a better stability in FMR patients, who got 3 clips compared to patients with only one clip. Conclusions: In patients with FMR, after 6 months the reduction of MR was more stable with an increased number of implanted clips, which suggests that this specific patient collective may benefit from a higher number of clips.

[What is confirmed in the treatment of atrial fibrillation?] / Was ist gesichert in der Therapie von Vorhofflimmern?

Atrial fibrillation is the most common clinically relevant cardiac arrhythmia. Important goals in the treatment of atrial fibrillation are improvement of the quality of life, relief of symptoms and the prevention of stroke. New in the current European guidelines on atrial fibrillation from 2020 is a structured approach with the introduction of the 4S-AF scheme (4S estimation of the risk of stroke, severity of symptoms, degree of severity of atrial fibrillation load and substrate, AF atrial fibrillation) for better characterization of atrial fibrillation and the ABC pathway in the treatment. The decision on the use of anticoagulation should be made after appropriate risk stratification. Depending on the characterization and symptoms of atrial fibrillation, the planning of further treatment should be made with respect to symptom control. Based on recent studies, rhythm-maintaining treatment by means of drugs or catheter ablation is gaining in importance over a strategy purely aimed at controlling the frequency. Integral components of treatment are also the identification and treatment of comorbidities and cardiovascular risk factors as well as the modification of an unhealthy lifestyle.

Severe Acute Respiratory Distress Syndrome (ARDS) or Severely Increased Chest Wall Elastance?

Esophageal manometry can be used to calculate transpulmonary pressures and optimize ventilator settings accordingly. We present the case of a 31-year-old male patient with ataxia-telangiectasia (Louis-Bar syndrome) and a BMI of 20 kg/m2, admitted to our intensive care unit for coronavirus disease 2019 (COVID-19) pneumonia. The patient soon required mechanical ventilation; however, there was very poor respiratory system compliance. Cholecystitis complicated the clinical course, and veno-venous extracorporeal membrane oxygenation (ECMO) was initiated as gas exchange deteriorated. Esophageal manometry was introduced and revealed severely increased intrathoracic pressure and chest wall elastance.

[Subjective well-being and ability to work of hospital staff after SARS-CoV2 immunization with the mRNA vaccine BNT162b2]. / Subjektives Wohlbefinden und Arbeitsfähigkeit von Krankenhauspersonal nach SARS-CoV-2-Immunisierung mit dem mRNS-Impfstoff BNT162b2 ­ Ergebnisse einer anonymen Umfrage.

BACKGROUND: Since December 27, 2020, employees of the health system in Germany have been vaccinated against the SARS coronavirus-2 with the vaccine BNT162B2. Initial observations show that especially among younger vaccinated people side effects are common. In this study, using the example of clinic employees, the self-perceived well-being after the first and second dose of the vaccine was examined. METHODS: Anonymized online questionnaire to be filled out once by all employees after the second dose of BNT162B2 was offered. The severity of side effects was queried using an ordinal numerical rating scale with values between 0 and 10. Other key data points were age, gender, and occupational group. The ability to work in the days following the injections was recorded by self-reporting. RESULTS: Data from 555 respondents were evaluated. The mean age was 40.25 years (standard deviation 12.35). 56 % of the respondents were female, 44.3 % belonged to the medical service, 42.9 % to the nursing service and 12.8 % were assigned to other professional groups with COVID-19 patient contact. Around 2 % of all employees did not experience any side effects at all. The most common side effect was pain at the injection site. Fatigue, headaches and myalgia followed with decreasing frequency. After the first dose, ¾ of the respondents said they had tolerated the vaccination well overall, after the second dose it was only half. After the first dose, over 90 % of the respondents felt that they were able to work again on the following day, after the second dose one third stated that they were only able to work again on the second day. 2.2 % of all employees had to report that they were unable to work for at least one day after the first dose and 19.5 % after the second dose. CONCLUSIONS: Vaccination with BNT162B2 frequently leads to side effects, especially after the second dose. Perception of side effects resulted in 19 % of those questioned being sick after the second dose. Nevertheless, 95 % of all respondents would choose a coronavirus vaccination again.

[Interdisciplinary aspects of oral anticoagulation with NOACs in atrial fibrillation]. / Interdisziplinäre Aspekte der oralen Antikoagulation mit NOAKs bei Vorhofflimmern.

Stroke prophylaxis with non-vitamin K-dependent oral anticoagulants (NOAKs) in patients with non-valvular atrial fibrillation (nvVHF) is now firmly established in routine clinical practice. The definition of nvVHF includes the absence of a mechanical heart valve and AF not associated with moderate- or high-grade mitral valve stenosis. The management of oral anticoagulation (OAC) requires a high degree of interdisciplinarity. Not least for this reason, uncertainties are repeatedly observed in practice, which can have far-reaching consequences for the individual patient. For this reason, a committee consisting of representatives from general medicine, geriatrics, cardiology, nephrology and neurology has gathered to identify aspects of practical relevance from the various disciplines and to jointly develop practical guidelines to improve therapy safety for patients in everyday life.

Use and Outcomes of Acute Treatment Strategies in Patients with Severe Aortic Valve Stenosis.

Background: This study aimed to evaluate the acute treatment of patients with severe aortic valve stenosis in Germany. Methods and Results: Three treatment strategies in 11,027 patients acutely admitted due to aortic valve stenosis were compared from 2014 until 2018 using German nationwide records: The annual number of transcatheter aortic valve replacement (TAVR) procedures (1,294 to 1,827) and balloon valvuloplasty (BV only) procedures (170 to 233) in patients acutely admitted increased, but surgical aortic valve replacement (SAVR) procedures decreased (426 to 316). In comparison to BV only patients (mean age 81.3; EuroSCORE 23.2) SAVR patients were younger and at lower logistic EuroSCORE (mean age 66.9; EuroSCORE 9.4). Patients treated with TAVR were at comparable age and operative risk (mean age 81.3; EuroSCORE 24.4) as those patients treated with BV only. Primary outcome was in-hospital mortality. Reimbursement was considered secondary outcome. After risk adjustment using multivariable logistic and linear regression analyses, SAVR (OR 0.26 [96%CI 0.16;0.45], p < 0.001) and TAVR (OR 0.38 [0.29;0.49], p < 0.001) were associated with lower risk for mortality compared to BV only. Compared to BV only, hospitalization costs of patients undergoing SAVR were reduced by €5,578 ([95%CI €8,023; €3,133], p < 0.001). TAVR procedures were associated with higher hospitalization costs than BV only (risk-adjusted difference €4,143 [€2,330; €5,926], p < 0.001). Conclusions: BV only was associated with a substantially increased risk of in-hospital mortality in acute patients. We conclude that a definitive aortic valve replacement should be preferred as primary treatment in patients with severe aortic valve stenosis causing an acute admission.

Spatial distribution patterns of interphase centromeres during retinoic acid-induced differentiation of promyelocytic leukemia cells.

BACKGROUND: The pericentromeric heterochromatin is an important element for the regulation of gene silencing. Its spatial distribution during interphase appears to be cell-type specific. This study analyzes three-dimensional (3D) centromere distribution patterns during cellular differentiation along the neutrophil pathway. METHODS: Differentiation of the promyelocytic leukemia cell line NB4 was induced by retinoic acid. Centromeres in interphase nuclei were visualized by immunofluorescence staining of centromere-associated proteins with CREST serum. 3D images of nuclei were obtained by confocal microscopy. Automated methods for the segmentation of point-like objects in 3D images were implemented to detect the position of centromeres. Features of centromere localization patterns were determined by constructing the minimal spanning tree of the centromere distribution. RESULTS: In differentiated NB4 cells, the number of centromere conglomerates (chromocenters) was decreased and the distance between chromocenters was increased as compared with untreated controls. The nuclear volume did not differ between the two groups. CONCLUSIONS: The measured rearrangement of centromeres indicates a progressive clustering of heterochromatin and a global remodeling of interphase chromosome territories during differentiation of NB4 cells. The developed methods for the analysis of 3D centromere distribution patterns provide the opportunity for a fast and objective analysis of heterochromatin remodeling.