Publications by authors named "Edyta Blaszczyk"

16 Publications

  • Page 1 of 1

Role of CMR Imaging in Diagnostics and Evaluation of Cardiac Involvement in Muscle Dystrophies.

Curr Heart Fail Rep 2021 Aug 28;18(4):211-224. Epub 2021 Jul 28.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center a joint cooperation between the Charité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Berlin, Germany.

Purpose Of Review: This review aims to outline the utility of cardiac magnetic resonance (CMR) in patients with different types of muscular dystrophies for the assessment of myocardial involvement, risk stratification and in guiding therapeutic decisions.

Recent Findings: In patients suffering from muscular dystrophies (MD), even mild initial dysfunction may lead to severe heart failure over a time course of years. CMR plays an increasing role in the diagnosis and clinical care of these patients, mostly due to its unique capability to precisely characterize subclinical and progressive changes in cardiac geometry, function in order to differentiate myocardial injury it allows the identification of inflammation, focal and diffuse fibrosis as well as fatty infiltration. CMR may provide additional information in addition to the physical examination, laboratory tests, ECG, and echocardiography. Further trials are needed to investigate the potential impact of CMR on the therapeutic decision-making as well as the assessment of long-term prognosis in different forms of muscular dystrophies. In addition to the basic cardiovascular evaluation, CMR can provide a robust, non-invasive technique for the evaluation of subclinical myocardial tissue injury like fat infiltration and focal and diffuse fibrosis. Furthermore, CMR has a unique capability to detect the progression of myocardial tissue damage in patients with a preserved systolic function.
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http://dx.doi.org/10.1007/s11897-021-00521-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342365PMC
August 2021

Cardiomyocyte Injury Following Acute Ischemic Stroke: Protocol for a Prospective Observational Cohort Study.

JMIR Res Protoc 2021 Feb 5;10(2):e24186. Epub 2021 Feb 5.

Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: Elevated cardiac troponin, which indicates cardiomyocyte injury, is common after acute ischemic stroke and is associated with poor functional outcome. Myocardial injury is part of a broad spectrum of cardiac complications that may occur after acute ischemic stroke. Previous studies have shown that in most patients, the underlying mechanism of stroke-associated myocardial injury may not be a concomitant acute coronary syndrome. Evidence from animal research and clinical and neuroimaging studies suggest that functional and structural alterations in the central autonomic network leading to stress-mediated neurocardiogenic injury may be a key underlying mechanism (ie, stroke-heart syndrome). However, the exact pathophysiological cascade remains unclear, and the diagnostic and therapeutic implications are unknown.

Objective: The aim of this CORONA-IS (Cardiomyocyte injury following Acute Ischemic Stroke) study is to quantify autonomic dysfunction and to decipher downstream cardiac mechanisms leading to myocardial injury after acute ischemic stroke.

Methods: In this prospective, observational, single-center cohort study, 300 patients with acute ischemic stroke, confirmed via cerebral magnetic resonance imaging (MRI) and presenting within 48 hours of symptom onset, will be recruited during in-hospital stay. On the basis of high-sensitivity cardiac troponin levels and corresponding to the fourth universal definition of myocardial infarction, 3 groups are defined (ie, no myocardial injury [no cardiac troponin elevation], chronic myocardial injury [stable elevation], and acute myocardial injury [dynamic rise/fall pattern]). Each group will include approximately 100 patients. Study patients will receive routine diagnostic care. In addition, they will receive 3 Tesla cardiovascular MRI and transthoracic echocardiography within 5 days of symptom onset to provide myocardial tissue characterization and assess cardiac function, 20-min high-resolution electrocardiogram for analysis of cardiac autonomic function, and extensive biobanking. A follow-up for cardiovascular events will be conducted 3 and 12 months after inclusion.

Results: After a 4-month pilot phase, recruitment began in April 2019. We estimate a recruitment period of approximately 3 years to include 300 patients with a complete cardiovascular MRI protocol.

Conclusions: Stroke-associated myocardial injury is a common and relevant complication. Our study has the potential to provide a better mechanistic understanding of heart and brain interactions in the setting of acute stroke. Thus, it is essential to develop algorithms for recognizing patients at risk and to refine diagnostic and therapeutic procedures.

Trial Registration: Clinicaltrials.gov NCT03892226; https://www.clinicaltrials.gov/ct2/show/NCT03892226.

International Registered Report Identifier (irrid): DERR1-10.2196/24186.
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http://dx.doi.org/10.2196/24186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895641PMC
February 2021

Quantification of myocardial strain assessed by cardiovascular magnetic resonance feature tracking in healthy subjects-influence of segmentation and analysis software.

Eur Radiol 2021 Jun 4;31(6):3962-3972. Epub 2020 Dec 4.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a Joint Cooperation Between the Charité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Berlin, Germany.

Objectives: Quantification of myocardial deformation by feature tracking is of growing interest in cardiovascular magnetic resonance. It allows the assessment of regional myocardial function based on cine images. However, image acquisition, post-processing, and interpretation are not standardized. We aimed to assess the influence of segmentation procedure such as slice selection and different types of analysis software on values and quantification of myocardial strain in healthy adults.

Methods: Healthy volunteers were retrospectively analyzed. Post-processing was performed using CVI and TomTec. Longitudinal and radial strain were quantified using 4-chamber-view, 3-chamber-view, and 2-chamber-view. Circumferential and radial strain were assessed in basal, midventricular, and apical short-axis views and using full coverage. Global and segmental strain values were compared to each other regarding their post-processing approach and analysis software package.

Results: We screened healthy volunteers studied at 1.5 or 3.0 T and included 67 (age 44.3 ± 16.3 years, 31 females). Circumferential and radial strain values were different between a full coverage approach vs. three short slices (- 17.6 ± 1.8% vs. - 19.2 ± 2.3% and 29.1 ± 4.8% vs. 34.6 ± 7.1%). Different analysis software calculated significantly different strain values. Within the same vendor, different field strengths (- 17.0 ± 2.1% at 1.5 T vs. - 17.0 ± 1.7% at 3 T, p = 0.845) did not influence the calculated global longitudinal strain (GLS), and were similar in gender (- 17.4 ± 2.0% in females vs. - 16.6 ± 1.8% in males, p = 0.098). Circumferential and radial strain were different in females and males (circumferential strain - 18.2 ± 1.7% vs. - 17.1 ± 1.8%, p = 0.029 and radial strain 30.7 ± 4.7% vs. 27.8 ± 4.6%, p = 0.047).

Conclusions: Myocardial deformation assessed by feature tracking depends on segmentation procedure and type of analysis software. Circumferential and radial depend on the number of slices used for feature tracking analysis. As known from other imaging modalities, GLS seems to be the most stable parameter. During follow-up studies, standardized conditions should be warranted. Trial registration Retrospectively registered KEY POINTS: • Myocardial deformation assessed by feature tracking depends on the segmentation procedure. • Global myocardial strain values differ significantly among vendors. • Standardization in post-processing using CMR feature tracking is essential.
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http://dx.doi.org/10.1007/s00330-020-07539-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128822PMC
June 2021

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

ESC Heart Fail 2020 10 20;7(5):2637-2649. Epub 2020 Jul 20.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrueck Center for Molecular Medicine, Lindenberger Weg 80, Berlin, 13125, Germany.

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.
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http://dx.doi.org/10.1002/ehf2.12846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524101PMC
October 2020

Fast myocardial T mapping using cardiac motion correction.

Magn Reson Med 2020 02 16;83(2):438-451. Epub 2019 Aug 16.

Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany.

Purpose: To improve the efficiency of native and postcontrast high-resolution cardiac T mapping by utilizing cardiac motion correction.

Methods: Common cardiac T mapping techniques only acquire data in a small part of the cardiac cycle, leading to inefficient data sampling. Here, we present an approach in which 80% of each cardiac cycle is used for T mapping by integration of cardiac motion correction. Golden angle radial data was acquired continuously for 8 s with in-plane resolution of 1.3 × 1.3 mm . Cine images were reconstructed for nonrigid cardiac motion estimation. Images at different TIs were reconstructed from the same data, and motion correction was performed prior to T mapping. Native T mapping was evaluated in healthy subjects. Furthermore, the technique was applied for postcontrast T mapping in 5 patients with suspected fibrosis.

Results: Cine images with high contrast were obtained, leading to robust cardiac motion estimation. Motion-corrected T maps showed myocardial T times similar to cardiac-triggered T maps obtained from the same data (1288 ± 49 ms and 1259 ± 55 ms, respectively) but with a 34% improved precision (spatial variation: 57.0 ± 12.5 ms and 94.8 ± 15.4 ms, respectively, P < 0.0001) due to the increased amount of data. In postcontrast T maps, focal fibrosis could be confirmed with late contrast-enhancement images.

Conclusion: The proposed approach provides high-resolution T maps within 8 s. Data acquisition efficiency for T mapping was improved by a factor of 5 by integration of cardiac motion correction, resulting in precise T maps.
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http://dx.doi.org/10.1002/mrm.27935DOI Listing
February 2020

Correction to: Subclinical myocardial injury in patients with Facioscapulohumeral muscular dystrophy 1 and preserved ejection fraction - assessment by cardiovascular magnetic resonance.

J Cardiovasc Magn Reson 2019 Jun 3;21(1):32. Epub 2019 Jun 3.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center a joint cooperation between the Charité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch,Department of Cardiology and Nephrology, Berlin, Germany.

In the original version of this article [1], published on 29 April 2019, there is 1 error in the 'Method' section of the article.
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http://dx.doi.org/10.1186/s12968-019-0541-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545672PMC
June 2019

Subclinical myocardial injury in patients with Facioscapulohumeral muscular dystrophy 1 and preserved ejection fraction - assessment by cardiovascular magnetic resonance.

J Cardiovasc Magn Reson 2019 04 29;21(1):25. Epub 2019 Apr 29.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center a joint cooperation between the Charité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch,Department of Cardiology and Nephrology, Berlin, Germany.

Background: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is an autosomal dominant and the third most common inherited muscle disease. Cardiac involvement is currently described in several muscular dystrophies (MD), but there are conflicting reports in FSHD1. Mostly, FSHD1 is recognized as MD with infrequent cardiac involvement, but sudden cardiac deaths are reported in single cases. The aim of this study is to investigate whether subclinical cardiac involvement in FSHD1 patients is detectable in preserved left ventricular systolic function applying cardiovascular magnetic resonance (CMR).

Methods: We prospectively included patients with genetically confirmed FSHD1 (n = 52, 48 ± 15 years) and compared them with 29 healthy age-matched controls using a 1.5 T CMR scanner. Myocardial tissue differentiation was performed qualitatively using focal fibrosis imaging (late gadolinium enhancement (LGE)), fat imaging (multi-echo sequence for fat/water-separation) and parametric T2- and T1-mapping for quantifying inflammation and diffuse fibrosis. Extracellular volume fraction was calculated. A 12-lead electrocardiogram and 24-h Holter were performed for the assessment of MD-specific Groh-criteria and arrhythmia.

Results: Focal fibrosis by LGE was present in 13 patients (25%,10 men), fat infiltration in 7 patients (13%,5 men). T2 values did not differ between FSHD1 and healthy controls. Native T1 mapping revealed significantly higher values in patients (global native myocardial T1 values basal: FSHD1: 1012 ± 26 ms vs. controls: 985 ± 28 ms, p < 0.01, medial FSHD1: 994 ± 37 ms vs. controls: 982 ± 28 ms, p = 0.028). This was also evident in regions adjacent to focal fibrosis, indicating diffuse fibrosis. Groh-criteria were positive in 1 patient. In Holter, arrhythmic events were recorded in 10/43 subjects (23%).

Conclusions: Patients with FSHD1 and preserved left ventricular ejection fraction present focal and diffuse myocardial injury. Longitudinal multi-center trials are needed to define the impact of myocardial changes as well as a relation between myocardial injury and arrhythmias on long-term prognosis and therapeutic decision-making.

Trial Registration: ISRCTN registry with study ID ISRCTN13744381 .
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http://dx.doi.org/10.1186/s12968-019-0537-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487526PMC
April 2019

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

J Cardiovasc Magn Reson 2019 02 21;21(1):12. Epub 2019 Feb 21.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine and HELIOS Hospital Berlin-Buch, Department of Cardiology and Nephrology, Medical University Berlin, Charité Campus Buch, Lindenberger Weg 80, 13125, Berlin, Germany.

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: cvi, 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.
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http://dx.doi.org/10.1186/s12968-019-0522-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383230PMC
February 2019

Native myocardial T1 time can predict development of subsequent anthracycline-induced cardiomyopathy.

ESC Heart Fail 2018 08 19;5(4):620-629. Epub 2018 Apr 19.

Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center - a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany.

Aims: This study aims to assess subclinical changes in functional and morphological myocardial magnetic resonance parameters very early into an anthracycline treatment, which may predict subsequent development of anthracycline-induced cardiomyopathy (aCMP).

Methods And Results: Thirty sarcoma patients with planned anthracycline-based chemotherapy (360-400 mg/m doxorubicin-equivalent) were recruited. Median treatment time was 19.1 ± 2.1 weeks. Enrolled individuals received three cardiovascular magnetic resonance studies (before treatment, 48 h after first anthracycline treatment, and upon completion of treatment). Native T1 mapping (modified Look-Locker inversion recovery 5s(3s)3s), T2 mapping, and extracellular volume maps were acquired in addition to a conventional cardiovascular magnetic resonance with steady-state free precession cine imaging at 1.5 T. Patients were given 0.2 mmol/kg gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Development of relevant aCMP was defined as drop of left ventricular ejection fraction (LVEF) by >10%. For analysis, 23 complete data sets were available. Nine patients developed aCMP with LVEF reduction >10% until end of chemotherapy. Baseline LVEF was not different between patients with and without subsequent aCMP. When assessed 48 h after first dose of antracyclines, patients with subsequent aCMP had significantly lower native myocardial T1 times compared with before therapy (1002.0 ± 37.9 vs. 956.5 ± 29.2 ms, P < 0.01) than patients who did not develop aCMP (990.9 ± 56.4 vs. 978.4 ± 57.4 ms, P > 0.05). Patients with aCMP had decreased left ventricular mass upon completion of therapy (86.9 ± 24.5 vs. 81.1 ± 22.3 g; P = 0.02), while patients without aCMP did not show a change in left ventricular mass (81.8 ± 21.0 vs. 79.2 ± 18.1 g; P > 0.05). No patient developed new myocardial scars or compact myocardial fibrosis under chemotherapy.

Conclusions: Early decrease of T1 times 48 h after first treatment with anthracyclines can predict the development of subsequent aCMP after completion of chemotherapy.
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http://dx.doi.org/10.1002/ehf2.12277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073029PMC
August 2018

Influence of spatial resolution and contrast agent dosage on myocardial T1 relaxation times.

MAGMA 2017 Feb 20;30(1):85-91. Epub 2016 Aug 20.

Working Group Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, A Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.

Objective: Our aim was to study the influence of small variations in spatial resolution and contrast agent dosage on myocardial T1 relaxation time.

Materials And Methods: Twenty-nine healthy volunteers underwent cardiovascular magnetic resonance at 3T twice, including a modified look-locker inversion recovery (MOLLI) technique-3(3)3(3)5-for T1 mapping. Native T1 was assessed in three spatial resolutions (voxel size 1.4 × 1.4 × 6, 1.6 × 1.6 × 6, 1.7 × 1.7 × 6 mm), and postcontrast T1 after 0.1 and 0.2 mmol/kg gadobutrol. Partition coefficient was calculated based on myocardial and blood T1. T1 analysis was done per segment, per slice, and for the whole heart.

Results: Native T1 values did not differ with varying spatial resolution per segment (p = 0.116-0.980), per slice (basal: p = 0.772; middle: p = 0.639; apex: p = 0.276), and globally (p = 0.191). Postcontrast T1 values were significantly lower with higher contrast agent dosage (p < 0.001). The global partition coefficient was 0.43 ± 0.3 for 0.2 and 0.1 mmol gadobutrol (p = 0.079).

Conclusion: Related to the tested MOLLI technique at 3T, very small variations in spatial resolution (voxel sizes between 1.4 × 1.4 × 6 and 1.7 × 1.7 × 6 mm) remained without effect on the native T1 relaxation times. Postcontrast T1 values were naturally shorter with higher contrast agent dosage while the partition coefficient remained constant. Further studies are necessary to test whether these conclusions hold true for larger matrix sizes and in larger cohorts.
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http://dx.doi.org/10.1007/s10334-016-0581-0DOI Listing
February 2017

Cardiac Involvement in Myotonic Dystrophy Type 2 Patients With Preserved Ejection Fraction: Detection by Cardiovascular Magnetic Resonance.

Circ Cardiovasc Imaging 2016 07;9(7)

From the Working Group on Cardiovascular Magnetic Resonance, Experimental, and Clinical Research Center, a joint cooperation between the Charité University Medicine Berlin and the Max-Delbrueck Center for Molecular Medicine, and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Germany (L.S., J.T., W.U., M.A.D., E.B., F.v.K.-B., J.S.-M.); DZHK (German Center for Cardiovascular Research), partner site Berlin, Germany (L.S., F.v.K.-B, J.S.-M.); Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (U.G., S.S.); and Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (P.K.).

Background: Myotonic dystrophy type 2 (DM2) is a genetic disorder characterized by skeletal muscle symptoms, metabolic changes, and cardiac involvement. Histopathologic alterations of the skeletal muscle include fibrosis and fatty infiltration. The aim of this study was to investigate whether subclinical cardiac involvement in DM2 is already detectable in preserved left ventricular function by cardiovascular magnetic resonance.

Methods And Results: Twenty-seven patients (mean age, 54±10 years; 20 females) with a genetically confirmed diagnosis of DM2 were compared with 17 healthy age- and sex-matched controls using a 1.5 T magnetic resonance imaging. For myocardial tissue differentiation, T1 and T2 mapping, fat/water-separated imaging, focal fibrosis imaging (late gadolinium enhancement [LGE]), and (1)H magnetic resonance spectroscopy were performed. Extracellular volume fraction was calculated. Conduction abnormalities were diagnosed based on Groh criteria. LGE located subepicardial basal inferolateral was detectable in 22% of the patients. Extracellular volume was increased in this region and in the adjacent medial inferolateral segment (P=0.03 compared with healthy controls). In 21% of patients with DM2, fat deposits were detectable (all women). The control group showed no abnormalities. Myocardial triglycerides were not different in LGE-positive and LGE-negative subjects (P=0.47). Six patients had indicators for conduction disease (60% of LGE-positive patients and 12.5% of LGE-negative patients).

Conclusions: In DM2, subclinical myocardial injury was already detectable in preserved left ventricular ejection fraction. Extracellular volume was also increased in regions with no focal fibrosis. Myocardial fibrosis was related to conduction abnormalities.
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http://dx.doi.org/10.1161/CIRCIMAGING.115.004615DOI Listing
July 2016

Evaluation of Aortic Blood Flow and Wall Shear Stress in Aortic Stenosis and Its Association With Left Ventricular Remodeling.

Circ Cardiovasc Imaging 2016 Mar;9(3):e004038

From the Working Group Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, a Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine and HELIOS Klinikum Berlin Buch, Department of Cardiology and Nephrology, Berlin, Germany (F.v.K.-B., A.K., R.F.T., E.B., J.S.-M.); Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, IL (A.J.B., M.M.); and Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.M.).

Background: Aortic stenosis (AS) leads to variable stress for the left ventricle (LV) and consequently a broad range of LV remodeling. The aim of this study was to describe blood flow patterns in the ascending aorta of patients with AS and determine their association with remodeling.

Methods And Results: Thirty-seven patients with AS (14 mild, 8 moderate, 15 severe; age, 63±13 years) and 37 healthy controls (age, 60±10 years) underwent 4-dimensional-flow magnetic resonance imaging. Helical and vortical flow formations and flow eccentricity were assessed in the ascending aorta. Normalized flow displacement from the vessel center and peak systolic wall shear stress in the ascending aorta were quantified. LV remodeling was assessed based on LV mass index and the ratio of LV mass:end-diastolic volume (relative wall mass). Marked helical and vortical flow formation and eccentricity were more prevalent in patients with AS than in healthy subjects, and patients with AS exhibited an asymmetrical and elevated distribution of peak systolic wall shear stress. In AS, aortic orifice area was strongly negatively associated with vortical flow formation (P=0.0274), eccentricity (P=0.0070), and flow displacement (P=0.0021). Bicuspid aortic valve was associated with more intense helical (P=0.0098) and vortical flow formation (P=0.0536), higher flow displacement (P=0.11), and higher peak systolic wall shear stress (P=0.0926). LV mass index and relative wall mass were significantly associated with aortic orifice area (P=0.0611, P=0.0058) and flow displacement (P=0.0058, P=0.0283).

Conclusions: In this pilot study, AS leads to abnormal blood flow pattern and peak systolic wall shear stress in the ascending aorta. In addition to aortic orifice area, normalized flow displacement was significantly associated with LV remodeling.
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http://dx.doi.org/10.1161/CIRCIMAGING.115.004038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772425PMC
March 2016

[Multiple right ventricular thrombi in arrhythmogenic right ventricular cardiomyopathy - a case report].

Pol Merkur Lekarski 2015 May;38(227):273-7

Józef Struś Hospital, Poznań, Poland: Department of Cardiology.

Typical complications of arrhythmogenic right ventricular cardiomyopathy (ARVC) are heart failure and ventricular arrhythmias which may lead to sudden cardiac death. Intracardiac thrombosis is diagnosed only in 2-4% of patients. The authors present a case of a 50-year-old male admitted to hospital due to symptomatic ventricular tachycardia. Echocardiography and cardiac magnetic resonance showed advanced ARVC with multiple right ventricular thrombi. The biggest one was localized in the inflow tract below the tricuspid valve, whereas the smallest one beneath it, on the inferior wall; the remaining two - in the apex. Chest computed tomography did not confirm pulmonary embolism. Disappearance of thrombi was observed after 4 weeks of anticoagulation. Detection and appropriate treatment of intracardiac thrombi in ARVC may have relevance in prevention of sudden death, not related to arrhythmia, and is of special importance before cardioverterdefibrillator implantation.
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May 2015

Novel synthesis, cytotoxic evaluation, and structure-activity relationship studies of a series of alpha-alkylidene-gamma-lactones and lactams.

J Med Chem 2005 May;48(10):3516-21

Institute of Organic Chemistry, Technical University of Łódź, Zeromskiego 116, 90-924 Łódź, Poland.

5-Alkyl- and 5-arylalkyl-3-methylenedihydrofuran-2-ones 13a-e, 3-alkylidenedihydrofuran-2-ones 18a-c, and 3-methylenepyrrolidin-2-ones 16a-e were synthesized utilizing ethyl 2-diethoxyphosphoryl-4-nitroalkanoates 9a-e as common intermediates. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemia cells. The highest cytotoxic activity was observed for 3-methylenefuranones 13d,e bearing benzyl or 3,4-dimethoxyphenylmethyl substituents at position 5, with IC(50) values of 5.4 and 6.0 microM, respectively. Contrary to the literature reports, no enhancement in activity due to the presence of a hydroxy group was found when the cytotoxicity of furanones 13a,b,d and 5-(1'-hydroxyalkyl)-3-methylenedihydrofuran-2-ones 6a,b,d was compared. The anticancer activity of pyrrolidinones 16a-e and 3-alkylidenefuranones 18a-c was much weaker than that of furanones 13a-e.
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http://dx.doi.org/10.1021/jm048970aDOI Listing
May 2005

New stereocontrolled synthesis and biological evaluation of 5-(1'-hydroxyalkyl)-3-methylidenetetrahydro-2-furanones as potential cytotoxic agents.

J Med Chem 2002 Feb;45(5):1142-5

Institute of Organic Chemistry, Technical University, Zeromskiego 116, 90-924 Łódź, Poland.

A series of 3-methylidenetetrahydro-2-furanones 7 bearing various hydroxyalkyl substituents in position 5 were synthesized using novel diastereo- and enantioselective methodology. In vitro cytotoxicity data demonstrated that all prepared compounds were active against L-1210 and HL-60 tissue culture cells with 7e being the most potent (IC(50) = 6.9 microM). Also an increase in activity with an increase in lipophilicity of the substituents in the order H < alkyl < phenyl was observed.
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http://dx.doi.org/10.1021/jm011019vDOI Listing
February 2002
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