Schwerpunkt Muskeldystrophien - Fokus Fazioskapulohumerale Muskeldystrophie Typ 1

Cardiac involvement in muscle diseases is of growing importance in cardiology, especially as also young people, suffering from different muscle dystrophies, develop clinically relevant cardiac arrhythmias and/or heart failure. Facioscapulohumeral Muscular Dystrophy Type1(FSHD1) is an autosomal dominant disorder with an incidence of 1:8000-1:20.000, which typically affects the facial and shoulder girdle muscles. Cardiac involvement in some muscular dystrophies (MD) such as Duchenne and Becker MD is common and has often been reported. In FSHD1 there are conflicting reports. Single case reports have described sudden cardiac death and the development of cardiac insufficiency. However, FSHD1 is usually patients with molecular-genetically confirmed FSHD1 were examined including echocardiography, ECG and Holter. In 52 patients with preserved LVEF, a CMR was performed, which included both contrast-free and enhanced techniques. Contrast-free techniques were used not only to quantify morphology and function, but also to evaluate fatty infiltrations, diffuse fibrosis and inflammation. Contrast enhanced techniques were used to detect the focal and diffuse fibrosis, including 24h-Holter were performed to detect MD-specific Groh criteria and other arrhythmias. According to the inclusion criteria, LVEF was normal in all patients. Focal myocardial fibrosis was reported in 26% of the patients (13patients,10 men). In some patients, diffuse fibrosis could be identified. Focal fat infiltrations were detectable in 13% of the patients (7 patients, 5 men). These myocardial changes were undetectable in healthy individuals. In the Holter, arrhythmic events were CMR offers the chance of detecting subclinical changes in the meaning of a "virtual biopsy". It was shown for the first time that in patients with FSHD1 both focal and diffuse myocardial changes can be detected even while LVEF is still preserved. These results support the hypothesis that cardiac involvement in FSHD1 is underestimated. However, clinical relevance must be demonstrated in follow-up studies.Die kardiale Beteiligung bei Muskelerkrankungen gewinnt zunehmende Bedeutung in der Kardiologie, da insbesondere auch junge Menschen bei vielen Muskeldystrophien klinisch relevante Herzrhythmusstörungen oder/und eine Herzschwäche entwickeln. Die Fazioskapulohumerale Muskeldystrophie Typ 1 (FSHD1) ist eine autosomal dominant vererbte Erkrankung mit einer Inzidenz von 1:8.000–1:20.000, die typischerweise die Gesichts- und Schultergürtelmuskulatur betrifft. Eine kardiale Mitbeteiligung des Herzens wurde bisher bei einigen Muskeldystrophien (MD) wie Duchenne MD und Becker MD häufig beschrieben. Bei FSHD1 gibt es in Literatur widersprüchliche Berichte. Es wurden in Einzelfallberichten sowohl plötzlicher Herztod als auch die Entwicklung einer Herzschwäche beschrieben. Meist wird aber FSHD1 als MD mit geringfügiger Herzerkrankung gesehen. Ziel dieser Arbeit ist es, potenzielle Herzmuskelschäden bereits bei FSHD1-Patienten mit erhaltener linksventrikulärer Funktion (LVEF) mittels kardiovaskulärer Magnetresonanztomographie (CMR) zu identifizieren. Patienten mit molekulargenetisch bestätigter Diagnose FSHD1 wurden kardiologisch mittels Echokardiographie, Ruhe-EKG und Langzeit-EKG untersucht. Bei 52 Patienten mit erhaltener linksventrikulärer Funktion wurde ein CMR durchgeführt, das sowohl kontrastmittelfreie als auch –verstärkte Techniken beinhaltete. Mittels kontrastmittelfreier Techniken können neben der Quantifizierung von Morphologie und Funktion auch Fettinfiltrationen, diffuse Fibrose und Entzündungsreaktionen evaluiert werden. Die kontrastmittelverstärkten Techniken zeigen den Nachweis sowohl fokaler als auch diffuser Fibrose einschließlich des extrazellulären Volumens (ECV). Die Anwendung quantitativer Parameter (parametrisches Mapping) sind nicht in der Routine etabliert, sondern innovative Messgrößen, um auch kleine Veränderungen zu erfassen. Aus diesem Grunde wurden 29 alters- und geschlechtsgematchte gesunde Kontrollen untersucht und mit FSHD1 Patienten verglichen. Die Untersuchungen wurden an einem 1,5 Tesla MRT-Scanner durchgeführt. Ein 12-Kanal-Elektrokardiogramm und ein 24-Stunden-Holter wurden durchgeführt, um MD-spezifische Groh-Kriterien und Arrhythmien zu bestimmen. Entsprechend der Einschlusskriterien war bei allen Patienten die LVEF erhalten. Es wurde bei 26% der Patienten fokale myokardiale Fibrose gezeigt (13 Patienten, 10 Männer). Bei einigen Patienten war diffuse Fibrose quantifizierbar. In 13% der Patienten waren fokale Fettinfiltrationen nachweisbar (7 Patienten, 5 Männer). Diese Myokardveränderungen waren bei den Gesunden nicht nachweisbar. Im 24-Stunden-Holter wurden bei 23% der Patienten arrhythmische Ereignisse registriert. Die Groh-Kriterien waren jedoch nur bei einem Patienten positiv. Die Kardiovaskuläre MRT bietet im Sinne einer „virtual biopsy“ die Chance subklinische Veränderungen zu erfassen. Es konnte erstmals gezeigt werden, dass bei Patienten mit FSHD1 sowohl fokale als auch diffuse myokardiale Veränderungen bereits bei erhaltener LVEF nachgewiesen werden können. Diese Ergebnisse unterstützen die These, dass die kardiale Beteiligung bei FSHD1 unterschätzt wird. Die klinische Relevanz muss jedoch in Follow-up-Studien nachgewiesen werden

Ghrelin and obestatin in thyroid gland — immunohistochemical expression in nodular goiter, papillary and medullary cancer

Introduction. Previous studies analyzing ghrelin and obestatin expression in thyroid gland tissue are not unanimous and are mostly related to ghrelin. The role of ghrelin and obestatin in the thyroid gland appears very interesting due to their probable involvement in cell proliferation. Furthermore, since the thyroid gland is associated with the maintenance of energy balance, the relationship between ghrelin, obestatin and thyroid function is worthy of consideration. The aim of the study was to assess ghrelin and obestatin immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and medullary cancer (MTC). Material and methods. Analyzed samples included 9 cases of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin expression was performed by use of the immunohistochemical (IHC) EnVision system and evaluated with filter HSV software (quantitative morphometric analysis). Results. Quantitative ghrelin expression in MTC cells was higher than in NG (p = 0.013) and correlated negatively with the size of the tumor (r= –0.829, p < 0.05). We did not observe any differences in ghrelin expression neither between MTC and PTC nor between NG and PTC. Obestatin immunoexpression pattern in all analyzed specimens was irregular and poorly accented. The strongest immunoreactivity for obestatin was demonstrated in NG. In MTC obestatin expression was significantly weaker than in NG and PTC (p < 0.05 in both cases). In NG the intensity of obestatin immunostaining was significantly higher than that of ghrelin (p = 0.03). Conversely, ghrelin expression in MTC was definitely more evident than obestatin immunoreactivity (p < 0.01). There was no statistically significant difference between ghrelin and obestatin expression in PTC. No correlations were detected between reciprocal tissue expressions of ghrelin and obestatin in the analyzed specimens of NG, PTC or MTC. Conclusions. The differences between ghrelin expression in NG and MTC suggest that ghrelin may be involved in thyroid cell proliferation. The differences between ghrelin and obestatin immunoreactivity in benign and malignant thyroid tumors could support the theory of alternative transcription of the preproghrelin gene and independent production of ghrelin and obestatin

Characterization of critically ill patients with septic shock and sepsis‐associated cardiomyopathy using cardiovascular MRI

Abstract Aims Sepsis‐induced cardiomyopathy is a major complication of septic shock and contributes to its high mortality. This pilot study investigated myocardial tissue differentiation in critically ill, sedated, and ventilated patients with septic shock using cardiovascular magnetic resonance (MR). Methods and results Fifteen patients with septic shock were prospectively recruited from the intensive care unit. Individuals received a cardiac MR scan (1.5 T) within 48 h after initial catecholamine peak and a transthoracic echocardiography at 48 and 96 h after cardiac MR. Left ventricular ejection fraction was assessed using both imaging modalities. During cardiac MR imaging, balanced steady‐state free precession imaging was performed for evaluation of cardiac anatomy and function in long‐axis and short‐axis views. Native T1 maps (modified Look–Locker inversion recovery 5 s(3 s)3 s), T2 maps, and extracellular volume maps were acquired in mid‐ventricular short axis and assessed for average plane values. Patients were given 0.2 mmol/kg of gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Critical care physicians monitored sedated and ventilated patients during the scan with continuous invasive monitoring and realized breathholds through manual ventilation breaks. Laboratory analysis included high‐sensitive troponine T and N terminal pro brain natriuretic peptide levels. Twelve individuals with complete datasets were available for analysis (age 59.5 ± 16.9 years; 6 female). Nine patients had impaired systolic function with left ventricular ejection fraction (LVEF) < 50% (39.8 ± 5.7%), and three individuals had preserved LVEF (66.9 ± 6.7%). Global longitudinal strain was impaired in both subgroups (LVEF impaired: 11.0 ± 1.8%; LVEF preserved: 16.0 ± 5.8%; P = 0.1). All patients with initially preserved LVEF died during hospital stay; in‐hospital mortality with initially impaired LVEF was 11%. Upon echocardiographic follow‐up, LVEF improved in all previously impaired patients at 48 (52.3 ± 9.0%, P = 0.06) and 96 h (54.9 ± 7.0%, P = 0.02). Patients with impaired systolic function had increased T2 times as compared with patients with preserved LVEF (60.8 ± 5.6 ms vs. 52.2 ± 2.8 ms; P = 0.02). Left ventricular GLS was decreased in all study individuals with impaired LVEF (11.0 ± 1.8%) and less impaired with preserved LVEF (16.0 ± 5.8%; P = 0.01). T1 mapping showed increased T1 times in patients with LVEF impairment as compared with patients with preserved LVEF (1093.9 ± 86.6 ms vs. 987.7 ± 69.3 ms; P = 0.03). Extracellular volume values were elevated in patients with LVEF impairment (27.9 ± 2.1%) as compared with patients with preserved LVEF (22.7 ± 1.9%; P < 0.01). Conclusions Septic cardiomyopathy with impaired LVEF reflects inflammatory cardiomyopathy. Takotsubo‐like contractility patterns occur in some cases. Cardiac MR is safely feasible in critically ill, sedated, and ventilated patients using extensive monitoring and experienced staff. Trial Registration: retrospectively registered (ISRCTN85297773

Quantification in cardiovascular magnetic resonance: agreement of software from three different vendors on assessment of left ventricular function, 2D flow and parametric mapping

Abstract Background Quantitative results of cardiovascular magnetic resonance (CMR) image analysis influence clinical decision making. Image analysis is performed based on dedicated software. The manufacturers provide different analysis tools whose algorithms are often unknown. The aim of this study was to evaluate the impact of software on quantification of left ventricular (LV) assessment, 2D flow measurement and T1- and T2-parametric mapping. Methods Thirty-one data sets of patients who underwent a CMR Scan on 1.5 T were analyzed using three different software (Circle CVI: cvi42, Siemens Healthineers: Argus, Medis: Qmass/Qflow) by one reader blinded to former results. Cine steady state free precession short axis images were analyzed regarding LV ejection fraction (EF), end-systolic and end-diastolic volume (ESV, EDV) and LV mass. Phase-contrast magnetic resonance images were evaluated for forward stroke volume (SV) and peak velocity (Vmax). Pixel-wise generated native T1- and T2-maps were used to assess T1- and T2-time. Forty-five data sets were evaluated twice (15 per software) for intraobserver analysis. Equivalence was considered if the confidence interval of a paired assessment of two sofware was within a tolerance interval defined by ±1.96 highest standard deviation obtained by intraobserver analysis. Results For each parameter, thirty data sets could be analyzed with all three software. All three software (A/B, A/C, B/C) were considered equivalent for LV EF, EDV, ESV, mass, 2D flow SV and T2-time. Differences between software were detected in flow measurement for Vmax and in parametric mapping for T1-time. For Vmax, equivalence was given between software A and C and for T1-time equivalence was given between software B and C. Conclusion Software had no impact on quantitative results of LV assessment, T2-time and SV based on 2D flow. In contrast to that, Vmax and T1-time may be influenced by software. CMR reports should contain the name and version of the software applied for image analysis to avoid misinterpretation upon follow-up and research examinations. Trial registration ISRCTN12210850. Registered 14 July 2017, retrospectively registered

Assessment of diastolic dysfunction: comparison of different cardiovascular magnetic resonance techniques.

AIMS Heart failure with preserved ejection fraction is still a diagnostic and therapeutic challenge, and accurate non-invasive diagnosis of left ventricular (LV) diastolic dysfunction (DD) remains difficult. The current study aimed at identifying the most informative cardiovascular magnetic resonance (CMR) parameters for the assessment of LVDD. METHODS AND RESULTS We prospectively included 50 patients and classified them into three groups: with DD (DD+, n = 15), without (DD-, n = 26), and uncertain (DD±, n = 9). Diagnosis of DD was based on echocardiographic E/E', invasive LV end-diastolic pressure, and N-terminal pro-brain natriuretic peptide. CMR was performed at 1.5 T to assess LV and left atrial (LA) morphology, LV diastolic strain rate (SR) by tissue tracking and tagging, myocardial peak velocities by tissue phase mapping, and transmitral inflow profile using phase contrast techniques. Statistics were performed only on definitive DD+ and DD- (total number 41). DD+ showed enlarged LA with LA end-diastolic volume/height performing best to identify DD+ with a cut-off value of ≥0.52 mL/cm (sensitivity = 0.71, specificity = 0.84, and area under the receiver operating characteristic curve = 0.75). DD+ showed significantly reduced radial (inferolateral E peak: DD-: -14.5 ± 6.5%/s vs. DD+: -10.9 ± 5.9%/s, P = 0.04; anterolateral A peak: DD-: -4.2 ± 1.6%/s vs. DD+: -3.1 ± 1.4%/s, P = 0.04) and circumferential (inferolateral A peak: DD-: 3.8 ± 1.2%/s vs. DD+: 2.8 ± 0.8%/s, P = 0.007; anterolateral A peak: DD-: 3.5 ± 1.2%/s vs. DD+: 2.5 ± 0.8%/s, P = 0.048) SR in the basal lateral wall assessed by tissue tracking. In the same segments, DD+ showed lower peak myocardial velocity by tissue phase mapping (inferolateral radial peak: DD-: -3.6 ± 0.7 ms vs. DD+: -2.8 ± 1.0 ms, P = 0.017; anterolateral longitudinal peak: DD-: -5.0 ± 1.8 ms vs. DD+: -3.4 ± 1.4 ms, P = 0.006). Tagging revealed reduced global longitudinal SR in DD+ (DD-: 45.8 ± 12.0%/s vs. DD+: 34.8 ± 9.2%/s, P = 0.022). Global circumferential and radial SR by tissue tracking and tagging, LV morphology, and transmitral flow did not differ between DD+ and DD-. CONCLUSIONS Left atrial size and regional quantitative myocardial deformation applying CMR identified best patients with DD

Multi-site comparison of parametric T1 and T2 mapping: healthy travelling volunteers in the Berlin research network for cardiovascular magnetic resonance (BER-CMR)

Abstract Background Parametric mapping sequences in cardiovascular magnetic resonance (CMR) allow for non-invasive myocardial tissue characterization. However quantitative myocardial mapping is still limited by the need for local reference values. Confounders, such as field strength, vendors and sequences, make intersite comparisons challenging. This exploratory study aims to assess whether multi-site studies that control confounding factors provide first insights whether parametric mapping values are within pre-defined tolerance ranges across scanners and sites. Methods A cohort of 20 healthy travelling volunteers was prospectively scanned at three sites with a 3 T scanner from the same vendor using the same scanning protocol and acquisition scheme. A Modified Look-Locker inversion recovery sequence (MOLLI) for T1 and a fast low-angle shot sequence (FLASH) for T2 were used. At one site a scan-rescan was performed to assess the intra-scanner reproducibility. All acquired T1- and T2-mappings were analyzed in a core laboratory using the same post-processing approach and software. Results After exclusion of one volunteer due to an accidentally diagnosed cardiac disease, T1- and T2-maps of 19 volunteers showed no significant differences between the 3 T sites (mean ± SD [95% confidence interval] for global T1 in ms: site I: 1207 ± 32 [1192–1222]; site II: 1207 ± 40 [1184–1225]; site III: 1219 ± 26 [1207–1232]; p = 0.067; for global T2 in ms: site I: 40 ± 2 [39–41]; site II: 40 ± 1 [39–41]; site III 39 ± 2 [39–41]; p = 0.543). Conclusion Parametric mapping results displayed initial hints at a sufficient similarity between sites when confounders, such as field strength, vendor diversity, acquisition schemes and post-processing analysis are harmonized. This finding needs to be confirmed in a powered clinical trial. Trial registration ISRCTN14627679 (retrospectively registered