Publications by authors named "Jeanette Schulz-Menger"

189 Publications

Low-fat hypocaloric diet reduces neprilysin in overweight and obese human subjects.

ESC Heart Fail 2021 Feb 27. Epub 2021 Feb 27.

Section of Metabolic and Vascular Medicine, Medical Clinic III, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.

Aims: Neprilysin (NEP), a zinc metallopeptidase, degrades a variety of bioactive peptides including natriuretic peptides terminating their biological action on arterial blood pressure and natriuresis. Pharmacological inhibition of NEP reduces mortality in patients with heart failure with reduced ejection fraction. Physiological interventions reducing NEP levels are unknown in humans. Because obesity leads to increased NEP levels and increases the risk for heart failure, we hypothesized that weight loss reduces NEP concentrations in plasma and tissue.

Methods And Results: We randomized overweight to obese human subjects to a low-fat or low-carbohydrate hypocaloric 6 month weight loss intervention. Soluble NEP was determined in plasma, and NEP mRNA was analysed from subcutaneous adipose tissue before and after diet. Low-fat diet-induced weight loss reduced soluble NEP levels from 0.83 ± 0.18 to 0.72 ± 0.18 μg/L (P = 0.038), while subcutaneous adipose tissue NEP mRNA expression was reduced by both dietary interventions [21% (P = 0.0057) by low-fat diet and 16% (P = 0.048) by low-carbohydrate diet]. We also analysed the polymorphisms of the gene coding for NEP, rs9827586 and rs701109, known to be associated with plasma NEP levels. For both single-nucleotide polymorphisms, minor allele carriers (A/A) had higher baseline plasma NEP levels (rs9827586: β = 0.53 ± 0.23, P < 0.0001; rs701109: β = 0.43 ± 0.22, P = 0.0016), and minor allele carriers of rs9827586 responded to weight loss with a larger NEP reduction (rs9827586: P = 0.0048).

Conclusions: Our study identifies weight loss via a hypocaloric low-fat diet as the first physiological intervention in humans to reduce NEP in plasma and adipose tissue. Specific single-nucleotide polymorphisms further contribute to the decrease. Our findings may help to explain the beneficial effect of weight loss on cardiac function in patients with heart failure.
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http://dx.doi.org/10.1002/ehf2.13220DOI Listing
February 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

Quality assurance of quantitative cardiac T1-mapping in multicenter clinical trials - A T1 phantom program from the hypertrophic cardiomyopathy registry (HCMR) study.

Int J Cardiol 2021 Jan 31. Epub 2021 Jan 31.

Oxford Centre for Clinical Magnetic Resonance Research, Oxford BRC NIHR, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK.

Background: Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials.

Purpose: To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use.

Methods: MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites.

Results: T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions.

Conclusions: The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.026DOI Listing
January 2021

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

Eur Radiol 2020 Dec 4. 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
December 2020

Stress CMR in patients with obesity: insights from the Stress CMR Perfusion Imaging in the United States (SPINS) registry.

Eur Heart J Cardiovasc Imaging 2020 Nov 9. Epub 2020 Nov 9.

Noninvasive Cardiovascular Imaging Section, Cardiovascular Division of Department of Medicine and Department of Radiology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Aims: Non-invasive assessment and risk stratification of coronary artery disease in patients with large body habitus is challenging. We aim to examine whether body mass index (BMI) modifies the prognostic value and diagnostic utility of stress cardiac magnetic resonance imaging (CMR) in a multicentre registry.

Methods And Results: The SPINS Registry enrolled consecutive intermediate-risk patients who presented with a clinical indication for stress CMR in the USA between 2008 and 2013. Baseline demographic data including BMI, CMR indices, and ratings of study quality were collected. Primary outcome was defined by a composite of cardiovascular death and non-fatal myocardial infarction. Of the 2345 patients with available BMI included in the SPINS cohort, 1177 (50%) met criteria for obesity (BMI ≥ 30) with 531 (23%) at or above Class 2 obesity (BMI ≥ 35). In all BMI categories, >95% of studies were of diagnostic quality for cine, perfusion, and late gadolinium enhancement (LGE) sequences. At a median follow-up of 5.4 years, those without ischaemia and LGE experienced a low annual rate of hard events (<1%), across all BMI strata. In patients with obesity, both ischaemia [hazard ratio (HR): 2.14; 95% confidence interval (CI): 1.30-3.50; P = 0.003] and LGE (HR: 3.09; 95% CI: 1.83-5.22; P < 0.001) maintained strong adjusted association with the primary outcome in a multivariable Cox regression model. Downstream referral rates to coronary angiography, revascularization, and cost of care spent on ischaemia testing did not significantly differ within the BMI categories.

Conclusion: In this large multicentre registry, elevated BMI did not negatively impact the diagnostic quality and the effectiveness of risk stratification of patients referred for stress CMR.
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http://dx.doi.org/10.1093/ehjci/jeaa281DOI Listing
November 2020

Cardiovascular disease in women: insights from magnetic resonance imaging.

J Cardiovasc Magn Reson 2020 09 28;22(1):71. Epub 2020 Sep 28.

University of California San Francisco, San Francisco, CA, USA.

The presentation and identification of cardiovascular disease in women pose unique diagnostic challenges compared to men, and underrecognized conditions in this patient population may lead to clinical mismanagement.This article reviews the sex differences in cardiovascular disease, explores the diagnostic and prognostic role of cardiovascular magnetic resonance (CMR) in the spectrum of cardiovascular disorders in women, and proposes the added value of CMR compared to other imaging modalities. In addition, this article specifically reviews the role of CMR in cardiovascular diseases occurring more frequently or exclusively in female patients, including Takotsubo cardiomyopathy, connective tissue disorders, primary pulmonary arterial hypertension and peripartum cardiomyopathy. Gaps in knowledge and opportunities for further investigation of sex-specific cardiovascular differences by CMR are also highlighted.
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http://dx.doi.org/10.1186/s12968-020-00666-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520984PMC
September 2020

Gadobutrol-Enhanced Cardiac Magnetic Resonance Imaging for Detection of Coronary Artery Disease.

J Am Coll Cardiol 2020 09;76(13):1536-1547

Cardiovascular Research Centre and CMR Unit at Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom.

Background: Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies.

Objectives: The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging.

Methods: Two international, single-vendor, phase 3 clinical trials of near identical design, "GadaCAD1" and "GadaCAD2," were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD.

Results: Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2.

Conclusions: Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U.S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD.
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http://dx.doi.org/10.1016/j.jacc.2020.07.060DOI Listing
September 2020

Comparability of compressed sensing-based gradient echo perfusion sequence SPARSE and conventional gradient echo sequence in assessment of myocardial ischemia.

Eur J Radiol 2020 Oct 11;131:109213. Epub 2020 Aug 11.

HELIOS Hospital Berlin-Buch, Department of Cardiology and Nephrology, Lindenberger Weg 80, 13125 Berlin, Germany. Electronic address:

Purpose: Stress perfusion imaging plays a major role in non-invasive detection of coronary artery disease. We compared a compressed sensing-based and a conventional gradient echo perfusion sequence with regard to image quality and diagnostic performance.

Method: Patients sent for coronary angiography due to pathologic stress perfusion CMR were recruited. All patients underwent two adenosine stress CMR using conventional TurboFLASH and prototype SPARSE sequence as well as quantitative coronary angiography with fractional flow reserve (FFR) within 6 weeks. Coronary angiography was considered gold standard with FFR < 0.75 or visual stenosis >90 % for identification of myocardial ischemia. Diagnostic performance of perfusion imaging was assessed in basal, mid-ventricular and apical slices by quantification of myocardial perfusion reserve (MPR) analysis utilizing the signal upslope method and a deconvolution technique using the fermi function model.

Results: 23 patients with mean age of 69.6 ± 8.9 years were enrolled. 46 % were female. Image quality was similar in conventional TurboFLASH sequence and SPARSE sequence (2.9 ± 0.5 vs 3.1 ± 0.7, p = 0,06). SPARSE sequence showed higher contrast-to-noise ratio (52.1 ± 27.4 vs 40.5 ± 17.6, p < 0.01) and signal-to-noise ratio (15.6 ± 6.2 vs 13.2 ± 4.2, p < 0.01) than TurboFLASH sequence. Dark-rim artifacts occurred less often with SPARSE (9 % of segments) than with TurboFLASH (23 %). In visual assessment of perfusion defects, SPARSE sequence detected less false-positive perfusion defects (n = 1) than TurboFLASH sequence (n = 3). Quantitative perfusion analysis on segment basis showed equal detection of perfusion defects for TurboFLASH and SPARSE with both upslope MPR analysis (TurboFLASH 0.88 ± 0.18; SPARSE 0.77 ± 0.26; p = 0.06) and fermi function model (TurboFLASH 0.85 ± 0.24; SPARSE 0.76 ± 0.30; p = 0.13).

Conclusions: Compressed sensing perfusion imaging using SPARSE sequence allows reliable detection of myocardial ischemia.
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http://dx.doi.org/10.1016/j.ejrad.2020.109213DOI Listing
October 2020

Imaging of Clinically Unrecognized Myocardial Fibrosis in Patients With Suspected Coronary Artery Disease.

J Am Coll Cardiol 2020 08;76(8):945-957

Noninvasive Cardiovascular Imaging Section, Cardiovascular Division of Department of Medicine and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address:

Background: Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia.

Objectives: This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia.

Methods: In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE).

Results: UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE.

Conclusions: In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891).
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http://dx.doi.org/10.1016/j.jacc.2020.06.063DOI Listing
August 2020

Prognostic Value of Stress CMR Perfusion Imaging in Patients With Reduced Left Ventricular Function.

JACC Cardiovasc Imaging 2020 Oct 5;13(10):2132-2145. Epub 2020 Aug 5.

Noninvasive Cardiovascular Imaging Section, Cardiovascular Division of Department of Medicine and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address:

Objectives: The aim of this study was to investigate the prognostic value of stress cardiac magnetic resonance imaging (CMR) in patients with reduced left ventricular (LV) systolic function.

Background: Patients with ischemic cardiomyopathy are at risk from both myocardial ischemia and heart failure. Invasive testing is often used as the first-line investigation, and there is limited evidence as to whether stress testing can effectively provide risk stratification.

Methods: In this substudy of a multicenter registry from 13 U.S. centers, patients with reduced LV ejection fraction (<50%), referred for stress CMR for suspected myocardial ischemia, were included. The primary outcome was cardiovascular death or nonfatal myocardial infarction. The secondary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina or congestive heart failure, and unplanned late coronary artery bypass graft surgery.

Results: Among 582 patients (mean age 62 ± 12 years, 34% women), 40% had a history of congestive heart failure, and the median LV ejection fraction was 39% (interquartile range: 28% to 45%). At median follow-up of 5.0 years, 97 patients had experienced the primary outcome, and 182 patients had experienced the secondary outcome. Patients with no CMR evidence of ischemia or late gadolinium enhancement (LGE) experienced an annual primary outcome event rate of 1.1%. The presence of ischemia, LGE, or both was associated with higher event rates. In a multivariate model adjusted for clinical covariates, ischemia and LGE were independent predictors of the primary (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.68 to 4.14; p < 0.001; and HR: 1.86; 95% CI: 1.05 to 3.29; p = 0.03) and secondary (HR: 2.14; 95% CI: 1.55 to 2.95; p < 0.001; and HR 1.70; 95% CI: 1.16 to 2.49; p = 0.007) outcomes. The addition of ischemia and LGE led to improved model discrimination for the primary outcome (change in C statistic from 0.715 to 0.765; p = 0.02). The presence and extent of ischemia were associated with higher rates of use of downstream coronary angiography, revascularization, and cost of care spent on ischemia testing.

Conclusions: Stress CMR was effective in risk-stratifying patients with reduced LV ejection fractions. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891).
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http://dx.doi.org/10.1016/j.jcmg.2020.05.034DOI Listing
October 2020

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

Magn Reson Med 2021 02 4;85(2):721-733. Epub 2020 Aug 4.

Department of Cardiology and Nephrology, 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, Berlin, Germany.

Purpose: 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]), WSS (1.5T vs. 3T [P < .05], sequence 1 vs. 2, 1 vs. 3, 2 vs. 3 [P < .001]), and peak velocity (1.5T vs. 7T, sequence 1 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.
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http://dx.doi.org/10.1002/mrm.28450DOI Listing
February 2021

Evaluation of Stress Cardiac Magnetic Resonance Imaging in Risk Reclassification of Patients With Suspected Coronary Artery Disease.

JAMA Cardiol 2020 Jul 29. Epub 2020 Jul 29.

Noninvasive Cardiovascular Imaging Section, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Importance: The role of stress cardiac magnetic resonance (CMR) imaging in clinical decision-making by reclassification of risk across American College of Cardiology/American Heart Association guideline-recommended categories has not been established.

Objective: To examine the utility of stress CMR imaging for risk reclassification in patients without a history of coronary artery disease (CAD) who presented with suspected myocardial ischemia.

Design, Setting, And Participants: A retrospective, multicenter cohort study with median follow-up of 5.4 years (interquartile range, 4.6-6.9) was conducted at 13 centers across 11 US states. Participants included 1698 consecutive patients aged 35 to 85 years with 2 or more coronary risk factors but no history of CAD who presented with suspected myocardial ischemia to undergo stress CMR imaging. The study was conducted from February 18, 2019, to March 1, 2020.

Main Outcomes And Measures: Cardiovascular (CV) death and nonfatal myocardial infarction (MI). Major adverse CV events (MACE) including CV death, nonfatal MI, hospitalization for heart failure or unstable angina, and late, unplanned coronary artery bypass graft surgery.

Results: Of the 1698 patients, 873 were men (51.4%); mean (SD) age was 62 (11) years, accounting for 67 CV death/nonfatal MIs and 190 MACE. Clinical models of pretest risk were constructed and patients were categorized using guideline-based categories of low (<1% per year), intermediate (1%-3% per year), and high (>3% year) risk. Stress CMR imaging provided risk reclassification across all baseline models. For CV death/nonfatal MI, adding stress CMR-assessed left ventricular ejection fraction, presence of ischemia, and late gadolinium enhancement to a model incorporating the validated CAD Consortium score, hypertension, smoking, and diabetes provided significant net reclassification improvement of 0.266 (95% CI, 0.091-0.441) and C statistic improvement of 0.086 (95% CI, 0.022-0.149). Stress CMR imaging reclassified 60.3% of patients in the intermediate pretest risk category (52.4% reclassified as low risk and 7.9% as high risk) with corresponding changes in the observed event rates of 0.6% per year for low posttest risk and 4.9% per year for high posttest risk. For MACE, stress CMR imaging further provided significant net reclassification improvement (0.361; 95% CI, 0.255-0.468) and C statistic improvement (0.092; 95% CI, 0.054-0.131), and reclassified 59.9% of patients in the intermediate pretest risk group (48.7% reclassified as low risk and 11.2% as high risk).

Conclusions And Relevance: In this multicenter cohort of patients with no history of CAD presenting with suspected myocardial ischemia, stress CMR imaging reclassified patient risk across guideline-based risk categories, beyond clinical risk factors. The findings of this study support the value of stress CMR imaging for clinical decision-making, especially in patients at intermediate risk for CV death and nonfatal MI.
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http://dx.doi.org/10.1001/jamacardio.2020.2834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391178PMC
July 2020

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

Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC).

Eur J Heart Fail 2020 09 21;22(9):1504-1524. Epub 2020 Aug 21.

National Heart and Lung Institute, Imperial College, London, UK.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.
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http://dx.doi.org/10.1002/ejhf.1957DOI Listing
September 2020

The EACVI survey on cardiac imaging in cardio-oncology.

Eur Heart J Cardiovasc Imaging 2020 May 28. Epub 2020 May 28.

Department of Cardiology, Oslo University Hospital, Postboks 4950 Nydalen, 0424 Oslo, Norway.

Early and late cardiovascular (CV) toxicities related to many cancer treatments may complicate the clinical course of patients, offsetting therapeutic benefits, and altering prognosis. The early detection, monitoring, and treatment of cardiotoxicity have therefore become essential parts of cancer patient care. CV imaging is a cornerstone of every cardio-oncology unit, but its use may vary across Europe because of the non-uniform availability of advanced imaging techniques and differences in the organization and logistics of cardio-oncology services. The purpose of this EACVI survey in cardio-oncology is to obtain real-world data on the current usage of cardiac imaging in cancer patients. Data from 104 centres and 35 different countries confirmed that cardiac imaging plays a pivotal role in the detection and monitoring of cardiac toxicity in oncology patients in Europe and beyond. However, it also revealed gaps between guidelines recommendations and everyday clinical practice, highlighting some of the challenges that need to be overcome in this rapidly advancing field.
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http://dx.doi.org/10.1093/ehjci/jeaa111DOI Listing
May 2020

Cost-Effectiveness Analysis of Stress Cardiovascular Magnetic Resonance Imaging for Stable Chest Pain Syndromes.

JACC Cardiovasc Imaging 2020 Jul 13;13(7):1505-1517. Epub 2020 May 13.

Noninvasive Cardiovascular Imaging Section, Cardiovascular Division of Department of Medicine and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address:

Objectives: The aim of this study was to compare, using results from the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, the incremental cost-effectiveness of a stress cardiovascular magnetic resonance (CMR)-first strategy against 4 other clinical strategies for patients with stable symptoms suspicious for myocardial ischemia: 1) immediate x-ray coronary angiography (XCA) with selective fractional flow reserve for all patients; 2) single-photon emission computed tomography; 3) coronary computed tomographic angiography with selective computed tomographic fractional flow reserve; and 4) no imaging.

Background: Stress CMR perfusion imaging has established excellent diagnostic utility and prognostic value in coronary artery disease (CAD), but its cost-effectiveness in current clinical practice has not been well studied in the United States.

Methods: A decision analytic model was developed to project health care costs and lifetime quality-adjusted life years (QALYs) for symptomatic patients at presentation with a 32.4% prevalence of obstructive CAD. Rates of clinical events, costs, and quality-of-life values were estimated from SPINS and other published research. The analysis was conducted from a U.S. health care system perspective, with health and cost outcomes discounted annually at 3%.

Results: Using hard cardiovascular events (cardiovascular death or acute myocardial infarction) as the endpoint, total costs per person were lowest for the no-imaging strategy ($16,936) and highest for the immediate XCA strategy ($20,929). Lifetime QALYs were lowest for the no-imaging strategy (12.72050) and highest for the immediate XCA strategy (12.76535). The incremental cost-effectiveness ratio for the CMR-based strategy compared with the no-imaging strategy was $52,000/QALY, whereas the incremental cost-effectiveness ratio for the immediate XCA strategy was $12 million/QALY compared with CMR. Results were sensitive to variations in model inputs for prevalence of disease, hazard rate ratio for treatment of CAD, and annual discount rate.

Conclusions: Prior to invasive XCA, stress CMR can be a cost-effective gatekeeping tool in patients at risk for obstructive CAD in the United States. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891.
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http://dx.doi.org/10.1016/j.jcmg.2020.02.029DOI Listing
July 2020

Evolution of Pulmonary Hypertension During Severe Sustained Hypoxia.

Circulation 2020 May 4;141(18):1504-1506. Epub 2020 May 4.

Institute of Aerospace Medicine, German Aerospace Center, Cologne (F.H., U.L., J.J., J.T.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.045192DOI Listing
May 2020

Standardized image interpretation and post-processing in cardiovascular magnetic resonance - 2020 update : Society for Cardiovascular Magnetic Resonance (SCMR): Board of Trustees Task Force on Standardized Post-Processing.

J Cardiovasc Magn Reson 2020 03 12;22(1):19. Epub 2020 Mar 12.

Institute for Experimental and Translational Cardiovascular Imaging, DZHK (German Centre for Cardiovascular Research) Centre for Cardiovascular Imaging, partner site RheinMain, University Hospital Frankfurt, Frankfurt am Main, Germany.

With mounting data on its accuracy and prognostic value, cardiovascular magnetic resonance (CMR) is becoming an increasingly important diagnostic tool with growing utility in clinical routine. Given its versatility and wide range of quantitative parameters, however, agreement on specific standards for the interpretation and post-processing of CMR studies is required to ensure consistent quality and reproducibility of CMR reports. This document addresses this need by providing consensus recommendations developed by the Task Force for Post-Processing of the Society for Cardiovascular Magnetic Resonance (SCMR). The aim of the Task Force is to recommend requirements and standards for image interpretation and post-processing enabling qualitative and quantitative evaluation of CMR images. Furthermore, pitfalls of CMR image analysis are discussed where appropriate. It is an update of the original recommendations published 2013.
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http://dx.doi.org/10.1186/s12968-020-00610-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066763PMC
March 2020

A multi-vendor, multi-center study on reproducibility and comparability of fast strain-encoded cardiovascular magnetic resonance imaging.

Int J Cardiovasc Imaging 2020 May 13;36(5):899-911. Epub 2020 Feb 13.

Department of Internal Medicine/Cardiology, German Heart Institute Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

Myocardial strain is a convenient parameter to quantify left ventricular (LV) function. Fast strain-encoding (fSENC) enables the acquisition of cardiovascular magnetic resonance images for strain-measurement within a few heartbeats during free-breathing. It is necessary to analyze inter-vendor agreement of techniques to determine strain, such as fSENC, in order to compare existing studies and plan multi-center studies. Therefore, the aim of this study was to investigate inter-vendor agreement and test-retest reproducibility of fSENC for three major MRI-vendors. fSENC-images were acquired three times in the same group of 15 healthy volunteers using 3 Tesla scanners from three different vendors: at the German Heart Institute Berlin, the Charité University Medicine Berlin-Campus Buch and the Theresien-Hospital Mannheim. Volunteers were scanned using the same imaging protocol composed of two fSENC-acquisitions, a 15-min break and another two fSENC-acquisitions. LV global longitudinal and circumferential strain (GLS, GCS) were analyzed by a trained observer (Myostrain 5.0, Myocardial Solutions) and for nine volunteers repeatedly by another observer. Inter-vendor agreement was determined using Bland-Altman analysis. Test-retest reproducibility and intra- and inter-observer reproducibility were analyzed using intraclass correlation coefficient (ICC) and coefficients of variation (CoV). Inter-vendor agreement between all three sites was good for GLS and GCS, with biases of 0.01-1.88%. Test-retest reproducibility of scans before and after the break was high, shown by ICC- and CoV values of 0.63-0.97 and 3-9% for GLS and 0.69-0.82 and 4-7% for GCS, respectively. Intra- and inter-observer reproducibility were excellent for both parameters (ICC of 0.77-0.99, CoV of 2-5%). This trial demonstrates good inter-vendor agreement and test-retest reproducibility of GLS and GCS measurements, acquired at three different scanners from three different vendors using fSENC. The results indicate that it is necessary to account for a possible bias (< 2%) when comparing strain measurements of different scanners. Technical differences between scanners, which impact inter-vendor agreement, should be further analyzed and minimized.DRKS Registration Number: 00013253.Universal Trial Number (UTN): U1111-1207-5874.
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http://dx.doi.org/10.1007/s10554-020-01775-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174273PMC
May 2020

Extracellular Myocardial Volume in Patients With Aortic Stenosis.

J Am Coll Cardiol 2020 01;75(3):304-316

Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom.

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.
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http://dx.doi.org/10.1016/j.jacc.2019.11.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985897PMC
January 2020

Z-score mapping for standardized analysis and reporting of cardiovascular magnetic resonance modified Look-Locker inversion recovery (MOLLI) T1 data: Normal behavior and validation in patients with amyloidosis.

J Cardiovasc Magn Reson 2020 01 20;22(1). Epub 2020 Jan 20.

Department of Internal Medicine - Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

Background: T1 mapping using modified Look-Locker inversion recovery (MOLLI) provides quantitative information on myocardial tissue composition. T1 results differ between sites due to variations in hardware and software equipment, limiting the comparability of results. The aim was to test if Z-scores can be used to compare the results of MOLLI T1 mapping from different cardiovascular magnetic resonance (CMR) platforms.

Methods: First, healthy subjects (n = 15) underwent 11 combinations of native short-axis T1 mapping (four CMR systems from two manufacturers at 1.5 T and 3 T, three MOLLI schemes). Mean and standard deviation (SD) of septal myocardial T1 were derived for each combination. T1 maps were transformed into Z-score maps based on mean and SD values using a prototype post-processing module. Second, Z-score mapping was applied to a validation sample of patients with cardiac amyloidosis at 1.5 T (n = 25) or 3 T (n = 13).

Results: In conventional T1 analysis, results were confounded by variations in field strength, MOLLI scheme, and manufacturer-specific system characteristics. Z-score-based analysis yielded consistent results without significant differences between any two of the combinations in part 1 of the study. In the validation sample, Z-score mapping differentiated between patients with cardiac amyloidosis and healthy subjects with the same diagnostic accuracy as standard T1 analysis regardless of field strength.

Conclusions: T1 analysis based on Z-score mapping provides consistent results without significant differences due to field strengths, CMR systems, or MOLLI variants, and detects cardiac amyloidosis with the same diagnostic accuracy as conventional T1 analysis. Z-score mapping provides a means to compare native T1 results acquired with MOLLI across different CMR platforms.
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http://dx.doi.org/10.1186/s12968-019-0595-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970284PMC
January 2020

Functional LGE Imaging: Cardiac Phase-Resolved Assessment of Focal Fibrosis.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:3999-4003

Cardiac Magnetic Resonance Imaging (CMR) is a central tool for diagnosis of various ischemic and non-ischemic cardiomyopathies. CMR protocols commonly comprise assessment of functional properties using cardiac phase-resolved CINE MRI and characterization of myocardial viability using late gadolinium enhancement (LGE) imaging. Conventional LGE imaging requires inversion recovery preparation with a specific inversion time to null the healthy myocardium, which restricts the acquisition to a single cardiac phase. In turn, this necessitates separate scans for cardiac function and viability. In this work, we develop a new method for functional LGE imaging in a single breath-hold using a three-step approach: 1) ECG-triggered multi-contrast data is acquired for each cardiac phase, 2) semi-quantitative relaxation maps are generated, 3) LGE imaging contrast is synthesized based on the semi-quantitative maps. The proposed functional LGE method is evaluated in four healthy subject and 20 patients at 1.5T and 3T. Thorough suppression of the healthy myocardium, as well as 40-80ms temporal resolution are achieved, with no visually apparent temporal blurring at tissue interfaces. Functional LGE in patients with focal scar demonstrates robust hyperenhancement in the scar area throughout all cardiac phases, allowing for visual assessment of scar motility. The proposed technique bears the potential to simplify and speedup common cardiac imaging protocols, while enabling improved data fusion of functional and viability information for improved evaluation of CMR.
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http://dx.doi.org/10.1109/EMBC.2019.8857759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986779PMC
July 2019

Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial.

Int J Obes (Lond) 2020 05 9;44(5):1119-1128. Epub 2019 Dec 9.

Experimental and Clinical Research Center (ECRC), a joint collaboration between the Max-Delbrück Center for Molecular Medicine and the Charité Universitätsmedizin, Berlin, Germany, and Helios Clinics Berlin, Berlin, Germany.

Background: Physical activity improves insulin sensitivity in obesity. Hypoxia training is claimed to augment this effect. We tested the hypothesis that normobaric hypoxia training would improve insulin sensitivity in obese patients with metabolic syndrome.

Methods: In a randomized controlled trial, 23 obese men with metabolic syndrome who were not informed of the FiO conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO 21%) conditions or hypoxia (n = 12; FiO 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual V̇O. Assessment of myocellular insulin sensitivity by euglycemic hyperinsulinemic clamp was performed in 21 of these subjects before and after 6 weeks of training. Comprehensive phenotyping also included biopsies of subcutaneous adipose tissues.

Results: The intermittent moderate physical exercise protocol did not substantially change the myocellular insulin sensitivity within 6 weeks under normoxic conditions (ISI: 0.035 (IQR 0.016-0.075) vs. 0.037 (IQR 0.026-0.056) mg* kg *min/(mU* l); p = 0.767). In contrast, ISI improved during hypoxia training (0.028 (IQR 0.018-0.035) vs. 0.038 (IQR 0.024-0.060) mg * kg *min/(mU *l); p < 0.05). Between group comparison of ISI change revealed a small difference between groups (Cohen's d = 0.26). Within the hypoxic group, improvement of ISI during training was associated with individual increase of circulating vascular endothelial growth factor (VEGF) levels (r = 0.678, p = 0.015), even if mean VEGF levels were not modified by any training condition. Atrial natriuretic peptide (ANP) system components were not associated with increased ISI during hypoxic training.

Conclusions: Physical training under hypoxic conditions could partially augment the favorable effects of exercise alone on myocellular insulin sensitivity in obese men with metabolic syndrome. Concomitant changes in VEGF might represent an underlying pathophysiological mechanism.
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http://dx.doi.org/10.1038/s41366-019-0504-zDOI Listing
May 2020

Distinct Subgroups in Hypertrophic Cardiomyopathy in the NHLBI HCM Registry.

J Am Coll Cardiol 2019 11;74(19):2333-2345

Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia. Electronic address:

Background: The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries.

Objectives: The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data.

Methods: Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis.

Results: A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion.

Conclusions: The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers.
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http://dx.doi.org/10.1016/j.jacc.2019.08.1057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905038PMC
November 2019

Cardiac Magnetic Resonance Stress Perfusion Imaging for Evaluation of Patients With Chest Pain.

J Am Coll Cardiol 2019 10;74(14):1741-1755

Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.

Background: Stress cardiac magnetic resonance imaging (CMR) has demonstrated excellent diagnostic and prognostic value in single-center studies.

Objectives: This study sought to investigate the prognostic value of stress CMR and downstream costs from subsequent cardiac testing in a retrospective multicenter study in the United States.

Methods: In this retrospective study, consecutive patients from 13 centers across 11 states who presented with a chest pain syndrome and were referred for stress CMR were followed for a target period of 4 years. The authors associated CMR findings with a primary outcome of cardiovascular death or nonfatal myocardial infarction using competing risk-adjusted regression models and downstream costs of ischemia testing using published Medicare national payment rates.

Results: In this study, 2,349 patients (63 ± 11 years of age, 47% female) were followed for a median of 5.4 years. Patients with no ischemia or late gadolinium enhancement (LGE) by CMR, observed in 1,583 patients (67%), experienced low annualized rates of primary outcome (<1%) and coronary revascularization (1% to 3%), across all years of study follow-up. In contrast, patients with ischemia+/LGE+ experienced a >4-fold higher annual primary outcome rate and a >10-fold higher rate of coronary revascularization during the first year after CMR. Patients with ischemia and LGE both negative had low average annual cost spent on ischemia testing across all years of follow-up, and this pattern was similar across the 4 practice environments of the participating centers.

Conclusions: In a multicenter U.S. cohort with stable chest pain syndromes, stress CMR performed at experienced centers offers effective cardiac prognostication. Patients without CMR ischemia or LGE experienced a low incidence of cardiac events, little need for coronary revascularization, and low spending on subsequent ischemia testing. (Stress CMR Perfusion Imaging in the United States [SPINS]: A Society for Cardiovascular Resonance Registry Study; NCT03192891).
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http://dx.doi.org/10.1016/j.jacc.2019.07.074DOI Listing
October 2019

Criteria for surveys: from the European Association of Cardiovascular Imaging Scientific Initiatives Committee.

Eur Heart J Cardiovasc Imaging 2019 Sep;20(9):963-966

Department of Cardiology, Oslo University Hospital, Postboks 4950 Nydalen, 0424 Oslo, Norway.

The European Association of Cardiovascular Imaging (EACVI) is committed to maintaining the highest standards of professional excellence in all aspects of cardiovascular imaging. The mission of the EACVI is to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular imaging with a particular focus on education, training, scientific initiatives, and research. The EACVI established the Scientific Initiatives Committee (SIC) in December 2018. This committee has responsibility for surveys among imagers, patients' surveys and surveys including data from clinical practice. The current document describes the aims of the EACVI SIC and the creation of the international EACVI survey network. This document summarizes the EACVI's standards for the survey questions and standards for writing the papers with the results of the surveys. These are in accordance with previous recommendations and were approved by the EACVI SIC and the EACVI Board in 2019.
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http://dx.doi.org/10.1093/ehjci/jez193DOI Listing
September 2019

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