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

Loxapine in patient with clozapine-resistant psychosis

Clozapine is recognized as the drug of choice for treatment-refractory schizophrenia, but use may be limited because of strict monitoring requirements and adverse effects including severe neutropenia, seizures, and myocarditis. Loxapine is a first-generation antipsychotic with similarities to clozapine in both structure and receptor binding. This case describes a 57-year-old male with a history of severe paranoid schizophrenia despite treatment with clozapine and other psychotropic agents, who experienced clinical improvement after a cross titration from clozapine to loxapine. Loxapine may be a reasonable alternative in patients with treatment-refractory schizophrenia who do not tolerate or respond to clozapine

Assessment of Global Longitudinal and Circumferential Strain Using Computed Tomography Feature Tracking: Intra-Individual Comparison with CMR Feature Tracking and Myocardial Tagging in Patients with Severe Aortic Stenosis

In this study, we used a single commercially available software solution to assess global longitudinal (GLS) and global circumferential strain (GCS) using cardiac computed tomography (CT) and cardiac magnetic resonance (CMR) feature tracking (FT). We compared agreement and reproducibility between these two methods and the reference standard, CMR tagging (TAG). Twenty-seven patients with severe aortic stenosis underwent CMR and cardiac CT examinations. FT analysis was performed using Medis suite version 3.0 (Leiden, The Netherlands) software. Segment (Medviso) software was used for GCS assessment from tagged images. There was a trend towards the underestimation of GLS by CT-FT when compared to CMR-FT (19.4 +/- 5.04 vs. 22.40 +/- 5.69, respectively; p = 0.065). GCS values between TAG, CT-FT, and CMR-FT were similar (p = 0.233). CMR-FT and CT-FT correlated closely for GLS (r = 0.686, p < 0.001) and GCS (r = 0.707, p < 0.001), while both of these methods correlated moderately with TAG for GCS (r = 0.479, p < 0.001 for CMR-FT vs. TAG; r = 0.548 for CT-FT vs. TAG). Intraobserver and interobserver agreement was excellent in all techniques. Our findings show that, in elderly patients with severe aortic stenosis (AS), the FT algorithm performs equally well in CMR and cardiac CT datasets for the assessment of GLS and GCS, both in terms of reproducibility and agreement with the gold standard, TAG

Strain des Herzmuskels: Über Vergleichbarkeit und Reproduzierbarkeit eines neuen Parameters zur Bestimmung der ventrikulären Funktion

Background. Strain is a novel quantitative parameter to determine heart function and heart failure by measuring the shortening of the heart muscle from diastole to systole. Using cardiovascular magnetic resonance imaging (CMR), various techniques are available to quantify strain: tagging (TAG), feature tracking (FT) and strain-encoding (SENC)/ fast strain-encoding (fSENC). In echocardiography, strain can be calculated using speckle-tracking (STE). Whereas the problem of inter-vendor variability of different ultrasound systems is well analyzed for STE, it is unknown if the choice of the magnetic resonance imaging scanner influences CMR-strain measurements. Moreover, important aspects of reproducibility have not been thoroughly explored for many modalities and techniques, such as fSENC, limiting the use of strain measurements in clinical routine. This dissertation focuses on a study published by our working group to address these obstacles regarding the fSENC-technique. Furthermore, it integrates the results into a clinical context and compares the analysis to research on other modalities and techniques. Methods. Fifteen healthy volunteers were scanned at three centers with different 3T magnetic resonance scanners from leading vendors: the German Heart Institute Berlin, the Charité University Medicine Berlin-Campus Buch and the Theresien-Hospital Mannheim. Every volunteer received four fSENC-scans with a uniform imaging protocol, interrupted by a fifteen-minute break between scan number two and three. Left ventricular (LV) global longitudinal strain (GLS) and circumferential strain (GCS) were analyzed (Myostrain 5.0, Myocardial Solutions). Inter-vendor agreement was determined using Bland-Altman analysis. Test-retest reproducibility and inter- and intra-observer reproducibility were calculated using intraclass correlation (ICC) and coefficients of variation (CoV). The results are demonstrated and compared to studies on different modalities and techniques for strain analysis. Results. fSENC showed good to moderate inter-vendor agreement between different sites (bias of 0.01-1.88%) and excellent test-retest reproducibility, regardless of the vendor. Inter- and intra-observer agreement of all global strain analyses were excellent. Conclusion. Our findings show that a bias should be expected when using fSENC in volunteers. Although this bias needs to be validated in a larger cohort and in patients, it should be considered when planning multi-center studies and when comparing fSENC scans that were acquired at different sites. The excellent test-retest reproducibility and intra- and inter-observer reproducibility reflect the reliability of fSENC, which is in accordance with other modalities and techniques to determine strain.Hintergrund. „Strain“ (Verformung) ist ein neuer quantitativer Parameter zur Bestimmung von Herzfunktion und Herzinsuffizienz anhand der Messung der Verkürzung des Herzmuskels von Diastole zu Systole. In der kardiovaskulären Magnetresonanztomographie (MRT) sind verschiedene Techniken zur Quantifizierung von „Strain“ verfügbar: „Tagging“ (TAG), „Feature Tracking“ (FT) und „Strain-encoding“ (SENC)/ „fast Strain-encoding“ (fSENC). In der Echokardiographie kann „Strain“ mittels „Speckle-tracking“ (STE) berechnet werden. Während das Problem der Variabilität zwischen verschiedenen Ultraschallsystemen für „STE“ bereits gut untersucht ist, ist es ungewiss ob die Wahl des Scanners einen Einfluss auf die MRT „Strain“-Messwerte hat. Außerdem wurden wichtige Aspekte der Reproduzierbarkeit für viele Modalitäten und Techniken, wie zum Beispiel „fSENC“, noch nicht vollständig erforscht, was den Nutzen von „Strain“-Messungen in der klinischen Routine einschränkt. Diese Dissertation fokussiert sich auf eine Studie, die unsere Arbeitsgruppe publizierte, um diese Hindernisse in Bezug auf die „fSENC“ Technik zu adressieren. Darüber hinaus integriert sie die Ergebnisse in einen klinischen Kontext und vergleicht diese Analyse mit der Forschung zu anderen Modalitäten und Techniken. Methoden. Fünfzehn gesunde Probanden wurden an drei Zentren mit verschiedenen 3T MRT-Geräten der führenden Hersteller untersucht: am Deutschen Herzzentrum Berlin; der Charité Universitätsmedizin Berlin- Campus Buch und dem Theresien-Krankenhaus Mannheim. Jeder Proband erhielt vier „fSENC“-Untersuchungen mit einem einheitlichen Bildgebungsprotokoll, unterbrochen von einer fünfzehn-minütigen Pause zwischen den Untersuchungen Nummer zwei und drei. Der linksventrikuläre (LV) globale longitudinale „Strain“ (GLS) und der LV zirkumferentielle „Strain“ (GCS) wurden analysiert (Myostrain 5.0, Myocardial Solutions). Die Übereinstimmung zwischen den Herstellern wurde mittels Bland-Altman Analyse bestimmt. Die Reproduzierbarkeit wiederholter Messungen sowie die Inter- und Intraobserver-Vergleichbarkeit wurden mit der Intraklassen-Korrelation (ICC) und dem Variationskoeffizienten (CoV) berechnet. Die dargestellten Ergebnisse werden demonstriert und mit Studien zu anderen Modalitäten und Techniken zur Messung von „Strain“ verglichen. Ergebnisse. „fSENC“ zeigte eine gute bis moderate Übereinstimmung zwischen verschiedenen Standorten (Bias von 0.01-1.88%) und eine exzellente Reproduzierbarkeit aufeinanderfolgender Tests, ungeachtet des Herstellers. Die Interobserver und Intraobserver-Vergleichbarkeiten aller globalen „Strain“-Analysen waren exzellent. Schlussfolgerung. Unsere Ergebnisse zeigten, dass ein Bias bei der Nutzung von „fSENC“ bei Probanden erwartet werden muss. Obwohl dieser Bias in einer größeren Kohorte und in Patienten validiert werden muss, sollte er bei der Planung von multizentrischen Studien und beim Vergleich von „fSENC“ Messungen an verschiedenen Standorten berücksichtigt werden. Die exzellente Reproduzierbarkeit wiederholter Messungen sowie die Interobserver- und Intraobserver-Vergleichbarkeiten reflektieren die Verlässlichkeit von „fSENC“. Dies ist in Übereinstimmung mit anderen Modalitäten und Techniken zur Bestimmung von „Strain“

Multi-parametric assessment of left ventricular hypertrophy using late gadolinium enhancement, T1 mapping and strain-encoded cardiovascular magnetic resonance

Aim!#!To evaluate the ability of single heartbeat fast-strain encoded (SENC) cardiovascular magnetic resonance (CMR) derived myocardial strain to discriminate between different forms of left ventricular (LV) hypertrophy (LVH).!##!Methods!#!314 patients (228 with hypertensive heart disease (HHD), 45 with hypertrophic cardiomyopathy (HCM), 41 with amyloidosis, 22 competitive athletes, and 33 healthy controls) were systematically analysed. LV ejection fraction (LVEF), LV mass index and interventricular septal (IVS) thickness, T1 mapping and atypical late gadolinium enhancement (LGE) were assessed. In addition, the percentage of LV myocardial segments with strain ≤ - 17% (%normal myocardium) was determined.!##!Results!#!Patients with amyloidosis and HCM exhibited the highest IVS thickness (17.4 ± 3.3 mm and 17.4 ± 6 mm, respectively, p &amp;lt; 0.05 vs. all other groups), whereas patients with amyloidosis showed the highest LV mass index (95.1 ± 20.1 g/m!##!Conclusion!#!Fast-SENC derived myocardial strain is a valuable tool for differentiating between athletes vs. HCM and athletes vs. HHD. Combining strain and LGE data is useful for differentiating between HHD vs. HCM and HCM vs. cardiac amyloidosis

Left and right ventricular strain using fast strain-encoded cardiovascular magnetic resonance for the diagnostic classification of patients with chronic non-ischemic heart failure due to dilated, hypertrophic cardiomyopathy or cardiac amyloidosis

Aims!#!To compare the ability of left ventricular (LV) and right ventricular (RV) strain measured by fast-strain encoded cardiovascular magnetic resonance (CMR) (fast-SENC) with LV- and RV-ejection fraction for the diagnostic classification of patients with different stages of chronic heart failure (stages A-D based on American College of Cardiology/American Heart Association guidelines) due to non-ischemic cardiomyopathies.!##!Methods!#!Our study population consisted of 276 consecutive patients who underwent CMR for clinical reasons, and 19 healthy subjects. Wall motion score index and non-infarct related late gadolinium enhancement (LGE), LV ejection fraction (LVEF) and RV ejection fraction (RVEF) and global LV- and RV-longitudinal (GLS) and circumferential strain (GCS) based on fast-SENC acquisitions, were calculated in all subjects. The percentage of LV and RV myocardial segments with strain ≤ - 17% (%normal LV and RV myocardium) was determined in all subjects.!##!Results!#!LVEF and RVEF, LV-GLS, LV-GCS, RV-GLS, RV-GCS and %normal LV- and RV myocardium depressed with increasing heart failure stage (p &amp;lt; 0.001 for all by ANOVA). By multivariable analysis, %normal LV and RV myocardium exhibited closer associations to heart failure stages than LVEF and RVEF (r!##!Conclusions!#!In patients with non-ischemic cardiomyopathy, %normal LV and RV myocardium, by fast-SENC, enables improved identification of asymptomatic patients with subclinical LV-dysfunction. This technique may be useful for the early identification of such presumably healthy subjects at risk for heart failure and for monitoring LV and RV deformation during pharmacologic interventions in future studies

Comparison of feature tracking, fast-SENC, and myocardial tagging for global and segmental left ventricular strain

AIMS: A multitude of cardiac magnetic resonance (CMR) techniques are used for myocardial strain assessment; however, studies comparing them are limited. We sought to compare global longitudinal (GLS), circumferential (GCS), segmental longitudinal (SLS), and segmental circumferential (SCS) strain values, as well as reproducibility between CMR feature tracking (FT), tagging (TAG), and fast-strain-encoded (fast-SENC) CMR techniques. METHODS AND RESULTS: Eighteen subjects (11 healthy volunteers and seven patients with heart failure) underwent two CMR scans (1.5T, Philips) with identical parameters. Global and segmental strain values were measured using FT (Medis), TAG (Medviso), and fast-SENC (Myocardial Solutions). Friedman's test, linear regression, Pearson's correlation coefficient, and Bland-Altman analyses were used to assess differences and correlation in measured GLS and GCS between the techniques. Two-way mixed intra-class correlation coefficient (ICC), coefficient of variance (COV), and Bland-Altman analysis were used for reproducibility assessment. All techniques correlated closely for GLS (Pearson's r: 0.86-0.92) and GCS (Pearson's r: 0.85-0.94). Intra-observer and inter-observer reproducibility was excellent in all techniques for both GLS (ICC 0.92-0.99, CoV 2.6-10.1%) and GCS (ICC 0.89-0.99, CoV 4.3-10.1%). Inter-study reproducibility was similar for all techniques for GLS (ICC 0.91-0.96, CoV 9.1-10.8%) and GCS (ICC 0.95-0.97, CoV 7.6-10.4%). Combined segmental intra-observer reproducibility was good in all techniques for SLS (ICC 0.914-0.953, CoV 12.35-24.73%) and SCS (ICC 0.885-0.978, CoV 10.76-19.66%). Combined inter-study SLS reproducibility was the worst in FT (ICC 0.329, CoV 42.99%), while fast-SENC performed the best (ICC 0.844, CoV 21.92%). TAG had the best reproducibility for combined inter-study SCS (ICC 0.902, CoV 19.08%), while FT performed the worst (ICC 0.766, CoV 32.35%). Bland-Altman analysis revealed considerable inter-technique bia

Effect of comprehensive initial training on the variability of left ventricular measures using fast-SENC cardiac magnetic resonance imaging

Cardiac magnetic resonance (CMR) is becoming the imaging modality of choice in multicenter studies where highly reproducible measurements are necessary. The purpose of this study was to assess the effect of comprehensive initial training on reproducibility of quantitative left ventricular (LV) parameters estimated using strain-encoded (SENC) imaging. Thirty participants (10 patients with heart failure (HF) and preserved LV ejection fraction (HFpEF), 10 patients with HF and reduced LV ejection fraction (HFrEF) and 10 healthy volunteers) were examined using fast-SENC imaging. Four observers with different experience in non-invasive cardiac imaging completed comprehensive initial training course and were invited to perform CMR data analysis. To assess agreement between observers, LV volumes, mass, ejection fraction (LVEF), global longitudinal strain (GLS) and global circumferential strain (GCS) were estimated using dedicated software (MyoStrain, USA). To test intraobserver agreement data analysis was repeated after 4 weeks. SENC imaging and analysis were fast and were completed in less than 5 minutes. LV end-diastolic volume index (LVEDVi), LVEF and strain were significantly lower in HFpEF patients than in healthy volunteers (p = 0.019 for LVEDVi; p = 0.023 for LVEF; p = 0.004 for GLS and p < 0.001 for GCS). All LV functional parameters were further reduced in HFrEF. Excellent interobserver agreement was found for all LV parameters independently of the level of experience. The reproducibility of LV mass was lower, especially at the intraobserver level (ICC 0.91; 95% CI 0.74-0.96). LV volumetric and functional parameters derived using fast-SENC imaging, are highly reproducible. The appropriate initial training is relevant and allows to achieve highest concordance in fast-SENC measurements

Cardiac magnetic resonance feature tracking global and segmental strain in acute and chronic ST-elevation myocardial infarction

Abstract Strain is an important imaging parameter to determine myocardial deformation. This study sought to 1) assess changes in left ventricular strain and ejection fraction (LVEF) from acute to chronic ST-elevation myocardial infarction (STEMI) and 2) analyze strain as a predictor of late gadolinium enhancement (LGE). 32 patients with STEMI and 18 controls prospectively underwent cardiac magnetic resonance imaging. Patients were scanned 8 $$\pm$$ ± 5 days and six months after infarction (± 1.4 months). Feature tracking was performed and LVEF was calculated. LGE was determined visually and quantitatively on short-axis images and myocardial segments were grouped according to the LGE pattern (negative, non-transmural and transmural). Global strain was impaired in patients compared to controls, but improved within six months after STEMI (longitudinal strain from −14 ± 4 to −16 ± 4%, p < 0.001; radial strain from 38 ± 11 to 42 ± 13%, p = 0.006; circumferential strain from −15 ± 4 to −16 ± 4%, p = 0.023). Patients with microvascular obstruction showed especially attenuated strain results. Regional strain persisted impaired in LGE-positive segments. Circumferential strain could best distinguish between LGE-negative and -positive segments (AUC 0.73- 0.77). Strain improves within six months after STEMI, but remains impaired in LGE-positive segments. Strain may serve as an imaging biomarker to analyze myocardial viability. Especially circumferential strain could predict LGE

Noninvasive evaluation of pulmonary artery stiffness in heart failure patients via cardiovascular magnetic resonance

Abstract Heart failure (HF) presents manifestations in both cardiac and vascular abnormalities. Pulmonary hypertension (PH) is prevalent in up 50% of HF patients. While pulmonary arterial hypertension (PAH) is closely associated with pulmonary artery (PA) stiffness, the association of HF caused, post-capillary PH and PA stiffness is unknown. We aimed to assess and compare PA stiffness and blood flow hemodynamics noninvasively across HF entities and control subjects without HF using CMR. We analyzed data of a prospectively conducted study with 74 adults, including 55 patients with HF across the spectrum (20 HF with preserved ejection fraction [HFpEF], 18 HF with mildly-reduced ejection fraction [HFmrEF] and 17 HF with reduced ejection fraction [HFrEF]) as well as 19 control subjects without HF. PA stiffness was defined as reduced vascular compliance, indicated primarily by the relative area change (RAC), altered flow hemodynamics were detected by increased flow velocities, mainly by pulse wave velocity (PWV). Correlations between the variables were explored using correlation and linear regression analysis. PA stiffness was significantly increased in HF patients compared to controls (RAC 30.92 ± 8.47 vs. 50.08 ± 9.08%, p < 0.001). PA blood flow parameters were significantly altered in HF patients (PWV 3.03 ± 0.53 vs. 2.11 ± 0.48, p < 0.001). These results were consistent in all three HF groups (HFrEF, HFmrEF and HFpEF) compared to the control group. Furthermore, PA stiffness was associated with higher NT-proBNP levels and a reduced functional status. PA stiffness can be assessed non-invasively by CMR. PA stiffness is increased in HFrEF, HFmrEF and HFpEF patients when compared to control subjects. Trial registration The study was registered at the German Clinical Trials Register (DRKS, registration number: DRKS00015615)