Kardiovaskuläre Magnetresonanztomographie in der klinischen Routine - Etablierung zeiteffizienter Ansätze

Die zunehmende Bedeutung der kardiovaskulären Magnetresonanztomographie zur Diagnostik und Therapiesteuerung findet sich auch in den aktuellen Leitlinien der Kardiologie wieder. Dennoch ist ihre Anwendung noch nicht so routinemäßig verfügbar, wie es sich anbieten würde. Als ein limitierender Faktor gilt hierbei die Untersuchungsdauer. Für eine zeiteffizientere Untersuchung ist eine Nutzung bereits vorhandener Routineaufnahmen für weitere Fragestellungen sinnvoll. Gleichzeitig müssen neu entwickelte, schnellere Techniken validiert werden. Nur so können die Möglichkeiten der kardialen Magnetresonanztomographie, insbesondere die einzigartige Möglichkeit zur nicht-invasiven Gewebedifferenzierung, künftig eine breitere Anwendung finden. Ziel dieser Arbeit ist es, Möglichkeiten zur effizienteren und schnelleren Untersuchung aufzuzeigen, um die Möglichkeiten der kardialen Magnetresonanztomographie innovativ und in breiterer Anwendung nutzbar zu machen. Bei 203 gesunden Probanden wurde der linke Vorhof analysiert, um Normwerte basierend auf einem zeitsparenden klinischen Routineprotokoll zu erstellen. Abhängigkeiten von Alter, Geschlecht und Feldstärke wurden aufgezeigt.[1] Des weiteren wurden zwei neue, schnellere Aufnahmetechniken zur Narbendarstellung bei 312 Patienten mit verschiedenen Pathologien anhand des Vergleichs zur Referenzstandardsequenz evaluiert.[2] Außerdem wurden 23 Sarkompatienten vor und im Laufe ihrer Anthrazyklin-Therapie wiederholt untersucht, um einen potentiellen Markers einer anthrazyklin-induzierten Kardiomyopathie zu ermitteln.[3] Die Evaluierung der Normwerte des linken Vorhofs ergab einen Unterschied zwischen den Geschlechtern bezüglich der absoluten Volumina des linken Vorhofs. Dieser Unterschied war nicht mehr erkennbar nach Normierung der Werte auf Body-Surface-Area oder Körpergröße. Die Feldstärke hatte keinen Einfluss. Das enddiastolische Volumen des linken Vorhofs nahm mit zunehmendem Alter ab.[1] Die neuen Aufnahmetechniken hatten eine signifikant kürzere Aufnahmezeit und erlaubten darüber hinaus auch eine Auswertung bei Patienten mit arrhythmischem Herzschlag. Alle 201 in der Referenzstandardsequenz positiven Befunde wurden ebenfalls mit einer der neuen Aufnahmetechniken erkannt. In der anderen neuen Aufnahmetechnik wurden zwei kleine Narben (<1g) übersehen.[2] Sarkompatienten, die nach Beendigung der Anthrazyklintherapie eine anthrazyklin-induzierte Kardiomyopathie entwickelten, zeigten bereits 48h nach Therapiebeginn myokardiale Gewebeveränderungen, welche sich bis zum Ende der Therapie wieder erholten.[3] Zusammenfassend konnten durch die Etablierung von Normwerten des linken Vorhofs anhand eines zeitsparenden Routineprotokolls sowie der Validierung zeitsparender Aufnahmen zur Narbendarstellung Ansätze zur zeiteffizienteren und schnelleren Durchführung einer kardialen Magnetresonanztomographieuntersuchung gezeigt werden, durch die perspektivisch zeiteffizientere Untersuchungen möglich sind und somit eine breitere Anwendung auch innovativ zur Prädiktion von Kardiomyopathien möglich macht. 1. Funk S, Kermer J, Doganguezel S, Schwenke C, von Knobelsdorff-Brenkenhoff F, Schulz-Menger J. Quantification of the left atrium applying cardiovascular magnetic resonance in clinical routine. Scand Cardiovasc J. 2018;52(2):85-92. 2. Muehlberg F, Arnhold K, Fritschi S, Funk S, Prothmann M, Kermer J, Zange L, von Knobelsdorff-Brenkenhoff F, Schulz-Menger J. Comparison of fast multi-slice and standard segmented techniques for detection of late gadolinium enhancement in ischemic and non-ischemic cardiomyopathy - a prospective clinical cardiovascular magnetic resonance trial. J Cardiovasc Magn Reson. 2018;20(1):13. 3. Muehlberg F, Funk S, Zange L, von Knobelsdorff-Brenkenhoff F, Blaszczyk E, Schulz A, Ghani S, Reichardt A, Reichardt P, Schulz-Menger J. Native myocardial T1 time can predict development of subsequent anthracycline-induced cardiomyopathy. ESC Heart Fail. 2018.The increasing importance of cardiovascular magnetic resonance for diagnostics and therapy guiding is reflected in current guidelines of cardiology. The clinical application, however, is not as widely spread as could be expected from that. The length of the examination is often seen as one limitation. For a more time-efficient examination the use of already acquired images for additional information is sensible. Also, newly developed, faster sequences have to be validated for future routine use. Thereby the potential of cardiovascular magnetic resonance, especially the unique possibility of non-invasive myocardial tissue differentiation, can be spread more broadly. Aim of this work is to show possibilities for a more efficient and faster examination to use the full potential of cardiovascular magnetic resonance also innovatively and for a broader spectrum. Left atria of 203 healthy volunteers were analyzed to establish normal values based on a time-efficient clinical routine protocol. Influence of age, sex and field strengths was evaluated.[1] Additionally, two new, faster acquisition techniques for scar imaging were compared to a reference standard sequence in 312 patients with different pathologies.[2] Furthermore 23 patients with sarcoma were examined before, during and after their anthracyclin-therapy to find a potential marker of anthracyclin-induced cardiomyopathy.[3] Evaluation the newly established normal values of the left atria showed a significant difference of the absolute volumes between both sexes, which could not be observed anymore after adjusting to body-surface-area or height. Field strength did not influence the results. The enddiastolic volume of the left atria decreased with age.[1] The new acquisition techniques had a significantly shorter acquisition time and additionally allowed for evaluation in patients with arrhythmia. All 201 positive results as depicted by the standard reference sequence were also detectable by one technique. With the other technique two small scars (<1g) were missed.[2] Patients with sarcoma, who developed an anthracyclin-induced cardiomyopathy after the anthracyclin-therapy, already showed 48 hours after beginning of treatment changes in myocardial tissue differentiation, which recovered until the end of the therapy.[3] In summary by establishing normal values for the left atria in a fast routine protocol and by validating newer, faster techniques for scar detection approaches for a more time-efficient and faster application of cardiovascular magnetic resonance could be shown, which will help expanding the application also to innovatively predict cardiomyopathies. 1. Funk S, Kermer J, Doganguezel S, Schwenke C, von Knobelsdorff-Brenkenhoff F, Schulz-Menger J. Quantification of the left atrium applying cardiovascular magnetic resonance in clinical routine. Scand Cardiovasc J. 2018;52(2):85-92. 2. Muehlberg F, Arnhold K, Fritschi S, Funk S, Prothmann M, Kermer J, Zange L, von Knobelsdorff-Brenkenhoff F, Schulz-Menger J. Comparison of fast multi-slice and standard segmented techniques for detection of late gadolinium enhancement in ischemic and non-ischemic cardiomyopathy - a prospective clinical cardiovascular magnetic resonance trial. J Cardiovasc Magn Reson. 2018;20(1):13. 3. Muehlberg F, Funk S, Zange L, von Knobelsdorff-Brenkenhoff F, Blaszczyk E, Schulz A, Ghani S, Reichardt A, Reichardt P, Schulz-Menger J. Native myocardial T1 time can predict development of subsequent anthracycline-induced cardiomyopathy. ESC Heart Fail. 2018

Should Postponing Motherhood via “Social Freezing” Be Legally Banned? An Ethical Analysis

In industrial societies, women increasingly postpone motherhood. While men do not fear a loss of fertility with age, women face the biological boundary of menopause. The freezing of unfertilized eggs can overcome this biological barrier. Due to technical improvements in vitrification, so-called “social freezing” (SF) for healthy women is likely to develop into clinical routine. Controversial ethical debates focus on the risks of the technique for mother and child, the scope of reproductive autonomy, and the medicalization of reproduction. Some criticize the use of the technique in healthy women in general, while others support a legally defined maximum age for women at the time of an embryo transfer after oocyte cryopreservation. Since this represents a serious encroachment on the reproductive autonomy of the affected women, the reasons for and against must be carefully examined. We analyze arguments for and against SF from a gendered ethical perspective. We show that the risk of the cryopreservation of oocytes for mother and future child is minimal and that the autonomy of the women involved is not compromised. The negative ethical evaluation of postponed motherhood is partly due to a biased approach highlighting only the medical risks for the female body without recognizing the potential positive effects for the women involved. In critical accounts, age is associated in an undifferentiated way with morbidity and psychological instability and is thus used in a discriminatory way. We come to the conclusion that age as a predictor of risk in the debate about SF is, from an ethical point of view, an empty concept based on gender stereotypes and discriminatory connotations of aging. A ban on postponing motherhood via SF is not justified

Traveling Volunteers: A Multi‐Vendor, Multi‐Center Study on Reproducibility and Comparability of 4D Flow Derived Aortic Hemodynamics in Cardiovascular Magnetic Resonance

Background: Implementation of four-dimensional flow magnetic resonance (4D Flow MR) in clinical routine requires awareness of confounders. Purpose: To investigate inter-vendor comparability of 4D Flow MR derived aortic hemodynamic parameters, assess scan-rescan repeatability, and intra- and interobserver reproducibility. Study type: Prospective multicenter study. Population: Fifteen healthy volunteers (age 24.5 ± 5.3 years, 8 females). Field strength/sequence: 3 T, vendor-provided and clinically used 4D Flow MR sequences of each site. Assessment: Forward flow volume, peak velocity, average, and maximum wall shear stress (WSS) were assessed via nine planes (P1-P9) throughout the thoracic aorta by a single observer (AD, 2 years of experience). Inter-vendor comparability as well as scan-rescan, intra- and interobserver reproducibility were examined. Statistical tests: Equivalence was tested setting the 95% confidence interval of intraobserver and scan-rescan difference as the limit of clinical acceptable disagreement. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used for scan-rescan reproducibility and intra- and interobserver agreement. A P-value 0.9: excellent, 0.75-0.9: good). Results: Ten volunteers finished the complete study successfully. 4D flow derived hemodynamic parameters between scanners of three different vendors are not equivalent exceeding the equivalence range. P3-P9 differed significantly between all three scanners for forward flow (59.1 ± 13.1 mL vs. 68.1 ± 12.0 mL vs. 55.4 ± 13.1 mL), maximum WSS (1842.0 ± 190.5 mPa vs. 1969.5 ± 398.7 mPa vs. 1500.6 ± 247.2 mPa), average WSS (1400.0 ± 149.3 mPa vs. 1322.6 ± 211.8 mPa vs. 1142.0 ± 198.5 mPa), and peak velocity between scanners I vs. III (114.7 ± 12.6 cm/s vs. 101.3 ± 15.6 cm/s). Overall, the plane location at the sinotubular junction (P1) presented most inter-vendor stability (forward: 78.5 ± 15.1 mL vs. 80.3 ± 15.4 mL vs. 79.5 ± 19.9 mL [P = 0.368]; peak: 126.4 ± 16.7 cm/s vs. 119.7 ± 13.6 cm/s vs. 111.2 ± 22.6 cm/s [P = 0.097]). Scan-rescan reproducibility and intra- and interobserver variability were good to excellent (ICC ≥ 0.8) with best agreement for forward flow (ICC ≥ 0.98). Data conclusion: The clinical protocol used at three different sites led to differences in hemodynamic parameters assessed by 4D flow. Level of evidence: 2 TECHNICAL EFFICACY STAGE: 2

Extracellular Myocardial Volume in Patients With Aortic Stenosis

BACKGROUND: Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. OBJECTIVES: This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. METHODS: Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery-based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. RESULTS: Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013). CONCLUSIONS: In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality

Should Postponing Motherhood via “Social Freezing” Be Legally Banned? An Ethical Analysis

In industrial societies, women increasingly postpone motherhood. While men do not fear a loss of fertility with age, women face the biological boundary of menopause. The freezing of unfertilized eggs can overcome this biological barrier. Due to technical improvements in vitrification, so-called “social freezing” (SF) for healthy women is likely to develop into clinical routine. Controversial ethical debates focus on the risks of the technique for mother and child, the scope of reproductive autonomy, and the medicalization of reproduction. Some criticize the use of the technique in healthy women in general, while others support a legally defined maximum age for women at the time of an embryo transfer after oocyte cryopreservation. Since this represents a serious encroachment on the reproductive autonomy of the affected women, the reasons for and against must be carefully examined. We analyze arguments for and against SF from a gendered ethical perspective. We show that the risk of the cryopreservation of oocytes for mother and future child is minimal and that the autonomy of the women involved is not compromised. The negative ethical evaluation of postponed motherhood is partly due to a biased approach highlighting only the medical risks for the female body without recognizing the potential positive effects for the women involved. In critical accounts, age is associated in an undifferentiated way with morbidity and psychological instability and is thus used in a discriminatory way. We come to the conclusion that age as a predictor of risk in the debate about SF is, from an ethical point of view, an empty concept based on gender stereotypes and discriminatory connotations of aging. A ban on postponing motherhood via SF is not justified

Early Genital Surgery in Disorders/Differences of Sex Development: Patients’ Perspectives

Controversy continues over a proposed moratorium on elective genital surgery in childhood for disorders/differences of sex development (DSD). Empirical evidence on patient preference is needed to inform decision-making. We conducted a multicentre survey by cross-sectional questionnaire in 14 specialized clinics in six European countries. The sample comprised 459 individuals (≥ 16 years) with a DSD diagnosis, including individuals with congenital adrenal hyperplasia (CAH) (n = 192), XY DSD with prenatal androgen effect (A) (n = 150), and without (nA) (n = 117). Main outcome measures were level of agreement with given statements regarding genital surgery, including clitoris reduction, vaginoplasty, and hypospadias repair. A total of 66% of individuals with CAH and 60% of those with XY DSD-A thought that infancy or childhood were the appropriate age for genital surgery. Females with XY DSD were divided on this issue and tended to prefer vaginoplasty at a later age (XY DSD-A 39%, XY DSD-nA 32%). A total of 47% of males preferred early hypospadias surgery. Only 12% (CAH), 11% (XY DSD-A), and 21% (XY DSD-nA) thought they would have been better off without any surgery in childhood or adolescence. Individuals who had early genital surgery were more likely to approve of it. Outcome data failed to support a general moratorium on early elective genital surgery. Participant perspectives varied considerably by diagnostic category, gender, history of surgery, and contact with support groups. Case-by-case decision-making is better suited to grasping the ethical complexity of the issues at stake.Trial registration: German Clinical Trials Register DRKS00006072

Impact of sequence type and field strength (1.5, 3, and 7T) on 4D flow MRI hemodynamic aortic parameters in healthy volunteers

International audiencePurpose: 4D flow magnetic resonance imaging (4D-MRI) allows time-resolved visualization of blood flow patterns, quantification of volumes, velocities, and advanced parameters, such as wall shear stress (WSS). As 4D-MRI enters the clinical arena, standardization and awareness of confounders are important. Our aim was to evaluate the equivalence of 4D flow-derived aortic hemodynamics in healthy volunteers using different sequences and field strengths.Methods: 4D-MRI was acquired in 10 healthy volunteers at 1.5T using three different prototype sequences, at 3T and at 7T (Siemens Healthineers). After evaluation of diagnostic quality in three segments (ascending-, descending aorta, aortic arch), peak velocity, flow volumes, and WSS were investigated. Equivalence limits for comparison of field strengths/sequences were based on the limits of Bland-Altman analyses of the intraobserver variability.Results: Non-diagnostic quality was found in 10/144 segments, 9/10 were obtained at 7T. Apart for the comparison of forward flow between sequence 1 and 3, the differences in measurements between field strengths/sequences exceeded the range of agreement. Significant differences were found between field strengths/sequences for forward flow (1.5T vs. 3T, 3T vs. 7T, sequence 1 vs. 3, 2 vs. 3 [P .001]). All parameters at all field strengths/with all sequences correlated moderately to strongly (r ≥ 0.5).Conclusion: Data from all sequences could be acquired and resulting images showed sufficient quality for further analysis. However, the variability of the measurements of peak velocity, flow volumes, and WSS was higher when comparing field strengths/sequences as the equivalence limits defined by the intraobserver assessments

US Nurses’ Challenges with Personal Protective Equipment during COVID-19: Interview Findings from the Frontline Workforce

This study aimed to describe nurses’ experiences with personal protective equipment while providing patient care during the first wave of the COVID-19 pandemic in the US. From May 2020 to September 2020, 100 individual interviews were conducted with nurses from diverse backgrounds and practice settings. Interviews were audio-recorded, transcribed, and verified for thematic analysis. Three key themes emerged related to personal protective equipment during COVID-19: (1) concerns with safety, (2) concerns with personal protective equipment supply, and (3) concerns with health care systems changing personal protective equipment policies. These findings support the importance of transparent and equitable institution-wide PPE standards in creating safe working environments. Clear communication around personal protective equipment policies and procedures, personal protective equipment education, and assurance of equitable access to equipment that can mitigate risk and disability while also reducing fear, confusion, and frustration among nurses. Maintaining clear and consistent personal protective equipment guidelines and communication regarding supplies and procedures enhances transparency during both routine and critical times de-escalating the inevitable strain concomitant with providing patient care during a global pandemic