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- Steding-Ehrenborg, K, et al.
(author)
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Hydraulic force is a novel mechanism of diastolic function that may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF
- 2021
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In: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 130:4, s. 993-1000
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Journal article (peer-reviewed)abstract
- It is a previously unrecognized physiological mechanism of the heart that diastolic filling occurs with the help of hydraulics. In patients with heart failure with preserved ejection fraction, atrial dilatation may cause the net hydraulic force to work against cardiac filling, thus further augmenting diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles, as in heart failure with reduced ejection fraction.
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- Olausson, E, et al.
(author)
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Diffuse myocardial fibrosis associates with incident ventricular arrhythmia in implantable cardioverter defibrillator recipients
- 2023
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Journal article (other academic/artistic)abstract
- BackgroundDiffuse myocardial fibrosis (DMF) quantified by extracellular volume (ECV) may represent a vulnerable phenotype and associate with life threatening ventricular arrhythmias more than focal myocardial fibrosis. This principle remains important because 1) risk stratification for implantable cardioverter defibrillators (ICD) remains challenging, and 2) DMF may respond to current or emerging medical therapies (reversible substrate).ObjectivesTo evaluate the association between quantified by ECV in myocardium without focal fibrosis by late gadolinium enhancement (LGE) with time from ICD implantation to 1) appropriate shock, or 2) shock or anti-tachycardia pacing.MethodsAmong patients referred for cardiovascular magnetic resonance (CMR) without congenital disease, hypertrophic cardiomyopathy, or amyloidosis who received ICDs (n=215), we used Cox regression to associate ECV with incident ICD therapy.ResultsAfter a median of 2.9 (IQR 1.5-4.2) years, 25 surviving patients experienced ICD shock and 44 experienced shock or anti-tachycardia pacing. ECV ranged from 20.2% to 39.4%. No patient with ECV<25% experienced an ICD shock. ECV associated with both endpoints, e.g., hazard ratio 2.17 (95%CI 1.17-4.00) for every 5% increase in ECV, p=0.014 in a stepwise model for ICD shock adjusting for ICD indication, age, smoking, atrial fibrillation, and myocardial infarction, whereas focal fibrosis by LGE and global longitudinal strain (GLS) did not.ConclusionsDMF measured by ECV associates with ventricular arrhythmias requiring ICD therapy in a dose-response fashion, even adjusting for potential confounding variables, focal fibrosis by LGE, and GLS. ECV-based risk stratification and DMF representing a therapeutic target to prevent ventricular arrhythmia warrant further investigation.Condensed AbstractAnalogous to heart failure and mortality outcomes, diffuse myocardial fibrosis (DMF) quantified by extracellular volume (ECV) may represent a more vulnerable phenotype for life-threatening ventricular arrhythmia than focal myocardial fibrosis. In patients referred for cardiovascular magnetic resonance, we identified 215 subsequently receiving implantable cardioverter defibrillators (ICD). After a median of 2.9 (IQR 1.5-4.2) years, 25 patients experienced ICD shock and 44 experienced shock or anti-tachycardia pacing. ECV associated with ICD therapy in Cox regression models. Focal fibrosis variables or global longitudinal strain did not. ECV-based risk stratification and DMF representing a therapeutic target to prevent ventricular arrhythmia warrant further investigation.
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- Tran, DL, et al.
(author)
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Exercise Intolerance, Benefits, and Prescription for People Living With a Fontan Circulation: The Fontan Fitness Intervention Trial (F-FIT)-Rationale and Design
- 2022
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In: Frontiers in pediatrics. - : Frontiers Media SA. - 2296-2360. ; 9, s. 799125-
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Journal article (peer-reviewed)abstract
- Background: Despite developments in surgical techniques and medical care, people with a Fontan circulation still experience long-term complications; non-invasive therapies to optimize the circulation have not been established. Exercise intolerance affects the majority of the population and is associated with worse prognosis. Historically, people living with a Fontan circulation were advised to avoid physical activity, but a small number of heterogenous, predominantly uncontrolled studies have shown that exercise training is safe—and for unique reasons, may even be of heightened importance in the setting of Fontan physiology. The mechanisms underlying improvements in aerobic exercise capacity and the effects of exercise training on circulatory and end-organ function remain incompletely understood. Furthermore, the optimal methods of exercise prescription are poorly characterized. This highlights the need for large, well-designed, multi-center, randomized, controlled trials.Aims and Methods: The Fontan Fitness Intervention Trial (F-FIT)—a phase III clinical trial—aims to optimize exercise prescription and delivery in people with a Fontan circulation. In this multi-center, randomized, controlled study, eligible Fontan participants will be randomized to either a 4-month supervised aerobic and resistance exercise training program of moderate-to-vigorous intensity followed by an 8-month maintenance phase; or usual care (control group). Adolescent and adult (≥16 years) Fontan participants will be randomized to either traditional face-to-face exercise training, telehealth exercise training, or usual care in a three-arm trial with an allocation of 2:2:1 (traditional:telehealth:control). Children (<16 years) will be randomized to either a physical activity and exercise program of moderate-to-vigorous intensity or usual care in a two-arm trial with a 1:1 allocation. The primary outcome is a change in aerobic exercise capacity (peak oxygen uptake) at 4-months. Secondary outcomes include safety, and changes in cardiopulmonary exercise testing measures, peripheral venous pressure, respiratory muscle and lung function, body composition, liver stiffness, neuropsychological and neurocognitive function, physical activity levels, dietary and nutritional status, vascular function, neurohormonal activation, metabolites, cardiac function, quality of life, musculoskeletal fitness, and health care utilization. Outcome measures will be assessed at baseline, 4-months, and 12-months. This manuscript will describe the pathophysiology of exercise intolerance in the Fontan circulation and the rationale and protocol for the F-FIT.
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- Fyrdahl, A., et al.
(author)
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Sector-wise golden-angle phase contrast with high temporal resolution for evaluation of left ventricular diastolic dysfunction
- 2020
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In: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 83:4, s. 1310-1321
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Journal article (peer-reviewed)abstract
- Purpose To develop a high temporal resolution phase‐contrast pulse sequence for evaluation of diastolic filling patterns, and to evaluate it in comparison to transthoracic echocardiography. Methods A phase‐contrast velocity‐encoded gradient‐echo pulse sequence was implemented with a sector‐wise golden‐angle radial ordering. Acquisitions were optimized for myocardial tissue (TE/TR: 4.4/6.8 ms, flip angle: 8º, velocity encoding: 30 cm/s) and transmitral flow (TE/TR: 4.0/6.6 ms, flip angle: 20º, velocity encoding: 150 cm/s). Shared velocity encoding was combined with a sliding‐window reconstruction that enabled up to 250 frames per cardiac cycle. Transmitral and myocardial velocities were measured in 35 patients. Echocardiographic velocities were obtained with pulsed‐wave Doppler using standard methods. Results Myocardial velocity showed a low difference and good correlation between MRI and Doppler (mean ± 95% limits of agreement 0.9 ± 3.7 cm/s, R2 = 0.63). Transmitral velocity was underestimated by MRI (P < .05) with a difference of −11 ± 28 cm/s (R2 = 0.45). The early‐to‐late ratio correlated well (R2 = 0.66) with a minimal difference (0.03 ± 0.6). Analysis of interobserver and intra‐observer variability showed excellent agreement for all measurements. Conclusions The proposed method enables the acquisition of phase‐contrast images during a single breath‐hold with a sufficiently high temporal resolution to match transthoracic echocardiography, which opens the possibility for many clinically relevant variables to be assessed by MRI.
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- Lundin, M., et al.
(author)
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Diffusely Increased Myocardial Extracellular Volume with or without Focal Late Gadolinium Enhancement: Prevalence and Associations with Left Ventricular Size and Function
- 2022
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In: Journal of Thoracic Imaging. - 0883-5993 .- 1536-0237. ; 37:1, s. 17-25
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Journal article (peer-reviewed)abstract
- Purpose: Myocardial extracellular volume fraction (ECV) using cardiovascular magnetic resonance (CMR) can identify diffuse lesions not detected by late gadolinium enhancement (LGE). We aimed to determine the prevalence of increased ECV and its relation to other CMR findings. Materials and Methods: Consecutive patients (n=609, age median [interquartile range] 53 [39 to 66] y, 62% male) underwent CMR at 1.5 T. Focal lesions on LGE images were noted. ECV in regions without focal LGE findings defined diffuse changes. Pronounced increases in left ventricular (LV) end-diastolic volume index and LV mass index, and pronounced decreases in LV ejection fraction were defined as >3 SD from the sex-specific mean in healthy volunteers. Results: Of 609 patients without amyloidosis or hypertrophic cardiomyopathy, 8% had diffusely increased ECV and 5% of all patients had diffusely increased ECV without any focal LGE findings. Multivariate analysis showed that a pronounced increase in the LV end-diastolic volume index was associated with increased ECV (P=0.001), but not LGE (P=0.52). A pronounced decrease in LV ejection fraction was associated with the presence of LGE (P<0.001), but not with increased ECV (P=0.41). Conclusions: Eight percent of patients in this clinical cohort with known or suspected heart disease had diffusely increased ECV and 60% of these lacked focal LGE findings. LV size is independently associated with increased ECV, whereas systolic dysfunction is independently associated with LGE. This image-based clinical study demonstrates that ECV-CMR provides additional information negligibly related to the results of LGE imaging, and thereby increases the diagnostic yield of CMR. © 2020 Lippincott Williams and Wilkins. All rights reserved.
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| 22. |
- Maanja, M, et al.
(author)
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An electrocardiography score predicts heart failure hospitalization or death beyond that of cardiovascular magnetic resonance imaging
- 2022
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 18364-
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Journal article (peer-reviewed)abstract
- The electrocardiogram (ECG) and cardiovascular magnetic resonance imaging (CMR) provide powerful prognostic information. The aim was to determine their relative prognostic value. Patients (n = 783) undergoing CMR and 12-lead ECG with a QRS duration < 120 ms were included. Prognosis scores for one-year event-free survival from hospitalization for heart failure or death were derived using continuous ECG or CMR measures, and multivariable logistic regression, and compared. Patients (median [interquartile range] age 55 [43–64] years, 44% female) had 155 events during 5.7 [4.4–6.6] years. The ECG prognosis score included (1) frontal plane QRS-T angle, and (2) heart rate corrected QT duration (QTc) (log-rank 55). The CMR prognosis score included (1) global longitudinal strain, and (2) extracellular volume fraction (log-rank 85). The combination of positive scores for both ECG and CMR yielded the highest prognostic value (log-rank 105). Multivariable analysis showed an association with outcomes for both the ECG prognosis score (log-rank 8.4, hazard ratio [95% confidence interval] 1.29 [1.09–1.54]) and the CMR prognosis score (log-rank 47, hazard ratio 1.90 [1.58–2.28]). An ECG prognosis score predicted outcomes independently of CMR. Combining the results of ECG and CMR using both prognosis scores improved the overall prognostic performance.
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| 23. |
- Maanja, M, et al.
(author)
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Improved evaluation of left ventricular hypertrophy using the spatial QRS-T angle by electrocardiography
- 2022
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 15106-
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Journal article (peer-reviewed)abstract
- Electrocardiographic (ECG) signs of left ventricular hypertrophy (LVH) lack sensitivity. The aim was to identify LVH based on an abnormal spatial peaks QRS-T angle, evaluate its diagnostic performance compared to conventional ECG criteria for LVH, and its prognostic performance. This was an observational study with four cohorts with a QRS duration < 120 ms. Based on healthy volunteers (n = 921), an abnormal spatial peaks QRS-T angle was defined as ≥ 40° for females and ≥ 55° for males. In other healthy volunteers (n = 461), the specificity of the QRS-T angle to detect LVH was 96% (females) and 98% (males). In patients with at least moderate LVH by cardiac imaging (n = 225), the QRS-T angle had a higher sensitivity than conventional ECG criteria (93–97% vs 13–56%, p < 0.001 for all). In clinical consecutive patients (n = 783), of those who did not have any LVH, 238/556 (43%) had an abnormal QRS-T angle. There was an association with hospitalization for heart failure or all-cause death in univariable and multivariable analysis. An abnormal QRS-T angle rarely occurred in healthy volunteers, was a mainstay of moderate or greater LVH, was common in clinical patients without LVH but with cardiac co-morbidities, and associated with outcomes.
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| 24. |
- Ramos, J. G., et al.
(author)
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Comprehensive Cardiovascular Magnetic Resonance Diastolic Dysfunction Grading Shows Very Good Agreement Compared With Echocardiography
- 2020
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In: Jacc-Cardiovascular Imaging. - : Elsevier BV. - 1936-878X .- 1876-7591. ; 13:12, s. 2530-2542
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Journal article (peer-reviewed)abstract
- OBJECTIVES The aims of this study were to develop a comprehensive cardiovascular magnetic resonance (CMR) approach to diastolic dysfunction (DD) grading and to evaluate the accuracy of CMR in the diagnosis of DD compared with echocardiography. BACKGROUND Left ventricular DD is routinely assessed using echocardiography. METHODS Consecutive clinically referred patients (n = 46; median age 59 years; interquartile range: 46 to 68 years; 33% women) underwent both conventional echocardiography and CMR. CMR diastolic transmitral velocities (E and A) and myocardial tissue velocity (e0) were measured during breath-hold using a validated high-temporal resolution radial sector-wise golden-angle velocity-encoded sequence. CMR pulmonary artery pressure was estimated from 4-dimensional flow analysis of blood flow vortex duration in the pulmonary artery. CMR left atrial volume was measured using the biplane long-axis area-length method. Both CMR and echocardiographic data were used to perform blinded grading of DD according to the 2016 joint American and European recommendations. RESULTS Grading of DD by CMR agreed with that by echocardiography in 43 of 46 cases (93%), of which 9% were normal, 2% indeterminate, 63% grade 1 DD, 4% grade 2 DD, and 15% grade 3 DD. There was a very good categorical agreement, with a weighted Cohen kappa coefficient of 0.857 (95% confidence interval: 0.73 to 1.00; p < 0.001). CONCLUSIONS A comprehensive CMR protocol for grading DD encompassing diastolic blood and myocardial velocities, estimated pulmonary artery pressure, and left atrial volume showed very good agreement with echocardiography. (C) 2020 by the American College of Cardiology Foundation.
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| 32. |
- Fyrdahl, A., et al.
(author)
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Generalization of three-dimensional golden-angle radial acquisition to reduce eddy current artifacts in bSSFP CMR imaging
- 2021
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In: Magnetic Resonance Materials in Physics Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 34, s. 109-118
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Journal article (peer-reviewed)abstract
- Purpose We propose a novel generalization of the three-dimensional double-golden-angle profile ordering, which allows for whole-heart volumetric imaging with retrospective binning and reduced eddy current artifacts. Methods A novel theory bridging the gap between the three-dimensional double golden-angle trajectory, and the two-dimensional tiny-golden-angle trajectory is presented. This enables a class of double golden-angle profile orderings with a smaller angular distance between successivek-space readouts. The novel profile orderings were evaluated through simulations, phantom experiments, and in vivo imaging. Comparisons were made to the original double-golden-angle trajectory. Image uniformity and off-resonance sensitivity were evaluated using phantom measurements, and qualitative image quality was assessed using in vivo images acquired in a healthy volunteer. Results The proposed theory successfully reduced the angular step while maintaining image uniformity after binning. Simulations revealed a slow degradation with decreasing angular steps and an increasing number of physiological bins. The phantom images showed a definite improvement in image uniformity and increased robustness to off-resonance, and in vivo imaging corroborated those findings. Conclusion Reducing the angular step in cardio-respiratory-binned golden-angle imaging shows potential for overcoming eddy current-induced image artifacts associated with 3D golden-angle radial imaging.
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| 35. |
- Grankvist, R, et al.
(author)
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Myocardial micro-biopsy procedure for molecular characterization with increased precision and reduced trauma
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 8029-
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Journal article (peer-reviewed)abstract
- Endomyocardial biopsy is a valuable tool in cardiac diagnostics but is limited by low diagnostic yield and significant complication risks. Meanwhile, recent developments in transcriptomic and proteomic technologies promise a wealth of biological data from minimal tissue samples. To take advantage of the minimal tissue amount needed for molecular analyses, we have developed a sub-millimeter endovascular biopsy device, considerably smaller than current clinical equipment, and devised a low-input RNA-sequencing protocol for analyzing small tissue samples. In in vivo evaluation in swine, 81% of biopsy attempts (n = 157) were successful. High quality RNA-sequencing data was generated from 91% of the sequenced cardiac micro-biopsy samples (n = 32). Gene expression signatures of samples taken with the novel device were comparable with a conventional device. No major complications were detected either during procedures or during 7 days’ follow-up, despite acquiring a relatively large number of biopsies (median 30) in each animal. In conclusion, the novel device coupled with RNA-sequencing provides a feasible method to obtain molecular data from the myocardium. The method is less traumatic and has a higher flexibility compared to conventional methods, enabling safer and more targeted sampling from different parts of the myocardium.
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| 36. |
- Hamilton-Craig, C, et al.
(author)
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Stress perfusion cardiovascular magnetic resonance imaging: a guide for the general cardiologist
- 2023
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In: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 109:6, s. 428-433
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Journal article (peer-reviewed)abstract
- Stress cardiovascular magnetic resonance (CMR) is an emerging non-invasive imaging technique for the assessment of known or suspected ischaemic heart disease (IHD). Stress CMR provides information on myocardial perfusion, wall motion, ventricular dimensions and volumes, as well as late gadolinium enhancement (LGE) scar imaging in a single test without ionising radiation. Data from numerous multicentre randomised studies show high diagnostic and prognostic utility, its efficacy as a gatekeeper to invasive coronary angiography and use for guiding coronary revascularisation decisions. Stress CMR is cost-effective across multiple healthcare settings, yet its uptake and usage varies worldwide and is an underutilised technology. New developments include rapid acquisition protocols, automated quantification of perfusion and myocardial blood flow, and artificial intelligence-aided automated analysis and reporting. Stress CMR is becoming more accessible and standardised around the globe and is ready for ‘prime time’ use in the non-invasive assessment of patients with suspected IHD.
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| 49. |
- Nickander, J, et al.
(author)
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Females have higher myocardial perfusion, blood volume and extracellular volume compared to males - an adenosine stress cardiovascular magnetic resonance study
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 10380-
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Journal article (peer-reviewed)abstract
- Knowledge on sex differences in myocardial perfusion, blood volume (MBV), and extracellular volume (ECV) in healthy individuals is scarce and conflicting. Therefore, this was investigated quantitatively by cardiovascular magnetic resonance (CMR). Healthy volunteers (n = 41, 51% female) underwent CMR at 1.5 T. Quantitative MBV [%] and perfusion [ml/min/g] maps were acquired during adenosine stress and at rest following an intravenous contrast bolus (0.05 mmol/kg, gadobutrol). Native T1 maps were acquired before and during adenosine stress, and after contrast (0.2 mmol/kg) at rest and during adenosine stress, rendering rest and stress ECV maps. Compared to males, females had higher perfusion, ECV, and MBV at stress, and perfusion and ECV at rest (p < 0.01 for all). Multivariate linear regression revealed that sex and MBV were associated with perfusion (sex beta −0.31, p = 0.03; MBV beta −0.37, p = 0.01, model R2 = 0.29, p < 0.01) while sex and hematocrit were associated with ECV (sex beta −0.33, p = 0.03; hematocrit beta −0.48, p < 0.01, model R2 = 0.54, p < 0.001). Myocardial perfusion, MBV, and ECV are higher in female healthy volunteers compared to males. Sex is an independent contributor to perfusion and ECV, beyond other physiological factors that differ between the sexes. These findings provide mechanistic insight into sex differences in myocardial physiology.
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| 50. |
- Nickander, J, et al.
(author)
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Increased cardiac involvement in Fabry disease using blood-corrected native T1 mapping
- 2023
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 4420-
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Journal article (peer-reviewed)abstract
- Fabry disease (FD) is a rare lysosomal storage disorder resulting in myocardial sphingolipid accumulation which is detectable by cardiovascular magnetic resonance as low native T1. However, myocardial T1 contains signal from intramyocardial blood which affects variability and consequently measurement precision and accuracy. Correction of myocardial T1 by blood T1 increases precision. We therefore deployed a multicenter study of FD patients (n = 218) and healthy controls (n = 117) to investigate if blood-correction of myocardial native T1 increases the number of FD patients with low T1, and thus reclassifies FD patients as having cardiac involvement. Cardiac involvement was defined as a native T1 value 2 standard deviations below site-specific means in healthy controls for both corrected and uncorrected measures. Overall low T1 was 135/218 (62%) uncorrected vs. 145/218 (67%) corrected (p = 0.02). With blood-correction, 13/83 previously normal patients were reclassified to low T1. This reclassification appears clinically relevant as 6/13 (46%) of reclassified had focal late gadolinium enhancement or left ventricular hypertrophy as signs of cardiac involvement. Blood-correction of myocardial native T1 increases the proportion of FD subjects with low myocardial T1, with blood-corrected results tracking other markers of cardiac involvement. Blood-correction may potentially offer earlier detection and therapy initiation, but merits further prospective studies.
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