Myocardial strain parameters in pulmonary hypertension are determined by changes in volumetric function rather than by hemodynamic alterations.

PURPOSE: To investigate associations of cardiac magnetic resonance feature-tracking-derived left (LV) and right ventricular (RV) global myocardial peak strains and strain rates with volumetric function and hemodynamic parameters to identify the major determinants of myocardial strain alterations in pulmonary hypertension (PH). METHODS: Sixty-seven patients with PH or at risk of developing PH underwent right heart catheterization (RHC) and cine realtime imaging at 3 T. RHC parameters included mean pulmonary arterial pressure (mPAP), which was used for the diagnosis of PH. LV and RV volumetric function and feature-tracking-derived global radial, circumferential, and longitudinal (GLS) peak strains, together with their strain rates, were evaluated from cine images using routine software. Furthermore, myocardial strain parameters of 24 healthy subjects were evaluated as controls. Means were compared by t-test; relationships between parameters were investigated by correlation and regression analysis. RESULTS: Compared to controls, RV-GLS, all RV systolic strain rates and the LV systolic longitudinal strain rate showed lower magnitudes in PH (RV-GLS: -21 ± 4% vs. -16 ± 5%, p < 0.0001); the strongest univariate correlate to mPAP was the RV-GLS (r = 0.59). All LV and RV strain parameters yielded stronger correlations with their respective ejection fractions. In bi-linear models using mPAP and ejection fraction as predictors, mPAP remained significant only for diastolic LV radial and circumferential strain rates. CONCLUSION: Impairment of myocardial strains is more strongly associated with alterations in LV and RV volumetric function parameters than elevated mPAP, therefore limiting diagnostic information of myocardial strain parameters in PH.

Impact of the evaluation method on 4D flow-derived diastolic transmitral and myocardial peak velocities: Comparison with echocardiography.

PURPOSE: To compare agreement of different evaluation methods of magnetic resonance (MR) 4D flow-derived diastolic transmitral and myocardial peak velocities as well as their ratios, using echocardiography as reference. METHODS: In this prospective study, 60 subjects without symptoms of cardiovascular disease underwent echocardiography and non-contrast 3 T MR 4D flow imaging of the heart. Early- (E) and late-diastolic (A) transmitral peak filling velocities were evaluated from 4D flow data using three different strategies: 1) at the mitral valve tips in short-axis orientation (SA-method), 2) between the mitral valve tips in 4-chamber orientation (4-chamber-method), and 3) as maximal velocities in the transmitral inflow volume (max-velocity-method). Septal, lateral and average early-diastolic myocardial peak velocities (e') were derived from the myocardial tissue in the vicinity of the mitral valve. 4D flow parameters were compared with echocardiography by correlation and Bland-Altman analysis. RESULTS: All 4D flow-derived E, A and E/A values correlated with echocardiography (r = 0.65-0.73, 0.75-0.83 and 0.74-0.86, respectively). While the SA- and 4-chamber-methods substantially underestimated E and A compared to echocardiography (p < 0.001), the max-velocity-method provided E (p = 0.13) and E/A (p = 0.07) without significant bias. Septal, lateral and average e' from 4D flow as well as the max-velocity-method-derived E/e' correlated with echocardiographic measurements (r = 0.64-0.81) and showed no significant bias (p = 0.26-0.54). CONCLUSION: MR 4D flow imaging allows precise and accurate evaluation of transmitral and myocardial peak velocities for characterization of LV diastolic function without significant bias to echocardiography, when transmitral velocities are assessed from the transmitral inflow volume. This enables the use of validated echocardiography threshold values.

Evaluation of left ventricular and left atrial volumetric function from native MR multislice 4D flow magnitude data.

OBJECTIVES: To assess the feasibility, precision, and accuracy of left ventricular (LV) and left atrial (LA) volumetric function evaluation from native magnetic resonance (MR) multislice 4D flow magnitude images. MATERIALS & METHODS: In this prospective study, 60 subjects without signs or symptoms of heart failure underwent 3T native cardiac MR multislice 4D flow and bSSFP-cine realtime imaging. LV and LA volumetric function parameters were evaluated from 4D flow magnitude (4D flow-cine) and bSSFP-cine data using standard software to obtain end-diastolic volume (EDV), end-systolic volume (ESV), ejection-fraction (EF), stroke-volume (SV), LV muscle mass (LVM), LA maximum volume, LA minimum volume, and LA total ejection fraction (LATEF). Stroke volumes derived from both imaging methods were further compared to 4D pulmonary artery flow-derived net forward volumes (NFV). Methods were compared by correlation and Bland-Altman analysis. RESULTS: Volumetric function parameters from 4D flow-cine and bSSFP-cine showed high to very high correlations (r = 0.83-0.98). SV, LA volumes and LATEF did not differ between methods. LV end-diastolic and end-systolic volumes were slightly underestimated (EDV: -2.9 ± 5.8 mL; ESV: -2.3 ± 3.8 mL), EF was slightly overestimated (EF: 0.9 ± 2.6%), and LV mass was considerably overestimated (LVM: 39.0 ± 11.4 g) by 4D flow-cine imaging. SVs from both methods correlated very highly with NFV (r = 0.91 in both cases) and did not differ from NFV. CONCLUSION: Native multislice 4D flow magnitude data allows precise evaluation of LV and LA volumetric parameters; however, apart from SV, LV volumetric parameters demonstrate bias and need to be referred to their respective normal values. CLINICAL RELEVANCE STATEMENT: Volumetric function assessment from native multislice 4D flow magnitude images can be performed with routinely used clinical software, facilitating the application of 4D flow as a one-stop-shop functional cardiac MR exam, providing consistent, simultaneously acquired, volume and flow data. KEY POINTS: • Native multislice 4D flow imaging allows evaluation of volumetric left ventricular and atrial function parameters. • Left ventricular and left atrial function parameters derived from native multislice 4D flow data correlate highly with corresponding standard cine-derived parameters. • Multislice 4D flow-derived volumetric stroke volume and net forward volume do not differ.

Low-grade systemic inflammation and left ventricular dysfunction in hypertensive compared to non-hypertensive hypertrophic cardiomyopathy.

BACKGROUND: Arterial hypertension (HTN) is associated with excess mortality in hypertrophic cardiomyopathy (HCM), but underlying mechanisms are largely elusive. The objective of this study was to investigate the association between HTN and markers of left ventricular (LV) dysfunction and low-grade systemic inflammation in a HCM cohort. METHODS: This was a single-center cross-sectional case-control study comparing echocardiographic and plasma-derived indices of LV dysfunction and low-grade systemic inflammation between 30 adult patients with HCM and HTN (HTN+) and 30 sex- and age-matched HCM patients without HTN (HTN-). Echocardiographic measures were assessed using post-processing analyses by blinded investigators. RESULTS: Mean age of the study population was 55.1 ± 10.4 years, 30% were women. Echocardiographic measures of systolic and diastolic dysfunction, including speckle-tracking derived parameters, did not differ between HTN+ and HTN-. Moreover, levels of N-terminal pro B-type natriuretic peptide were balanced between cases and controls. Compared with HTN-, HTN+ patients exhibited a higher white blood cell count [8.1 ± 1.8 109/l vs. 6.4 ± 1.6 109/l; p < 0.001] as well as higher plasma levels of interleukin-6 [2.8 pg/ml (2.0, 5.4) vs. 2.1 pg/ml (1.5, 3.4); p = 0.008] and high-sensitivity C-reactive protein [2.6 mg/l (1.4, 6.5) vs. 1.1 mg/l (0.9, 2.4); p = 0.004]. CONCLUSION: This study demonstrates that HTN is associated with indices of low-grade systemic inflammation among HCM patients. Moreover, this analysis indicates that the adverse impact of HTN in HCM patients is a consequence of systemic effects rather than alterations of cardiac function, as measures of LV systolic and diastolic dysfunction did not differ between HTN+ and HTN-.

MR 4D flow-derived left atrial acceleration factor for differentiating advanced left ventricular diastolic dysfunction.

OBJECTIVES: The magnetic resonance (MR) 4D flow imaging-derived left atrial (LA) acceleration factor α was recently introduced as a means to non-invasively estimate LA pressure. We aimed to investigate the association of α with the severity of left ventricular (LV) diastolic dysfunction using echocardiography as the reference method. METHODS: Echocardiographic assessment of LV diastolic function and 3-T cardiac MR 4D flow imaging were prospectively performed in 94 subjects (44 male/50 female; mean age, 62 ± 12 years). LA early diastolic peak outflow velocity (vE), systolic peak inflow velocity (vS), and early diastolic peak inflow velocity (vD) were evaluated from 4D flow data. α was calculated from α = vE / [(vS + vD) / 2]. Mean parameter values were compared by t-test; diagnostic performance of α in predicting diastolic (dys)function was investigated by receiver operating characteristic curve analysis. RESULTS: Mean α values were 1.17 ± 0.14, 1.20 ± 0.08, 1.33 ± 0.15, 1.77 ± 0.18, and 2.79 ± 0.69 for grade 0 (n = 51), indeterminate (n = 9), grade I (n = 13), grade II (n = 13), and grade III (n = 8) LV diastolic (dys)function, respectively. α differed between subjects with non-advanced (grade < II) and advanced (grade ≥ II) diastolic dysfunction (1.20 ± 0.15 vs. 2.16 ± 0.66, p < 0.001). The area under the curve (AUC) for detection of advanced diastolic dysfunction was 0.998 (95% CI: 0.958-1.000), yielding sensitivity of 100% (95% CI: 84-100%) and specificity of 99% (95% CI: 93-100%) at cut-off α ≥ 1.58. The AUC for differentiating grade III diastolic dysfunction was also 0.998 (95% CI: 0.976-1.000) at cut-off α ≥ 2.14. CONCLUSION: The 4D flow-derived LA acceleration factor α allows grade II and grade III diastolic dysfunction to be distinguished from non-advanced grades as well as from each other. CLINICAL RELEVANCE STATEMENT: As a single continuous parameter, the 4D flow-derived LA acceleration factor α shows potential to simplify the multi-parametric imaging algorithm for diagnosis of advanced LV diastolic dysfunction, thereby identifying patients at increased risk for cardiovascular events. KEY POINTS: • Detection of advanced diastolic dysfunction is typically performed using a complex, multi-parametric approach. • The 4D flow-derived left atrial acceleration factor α alone allows accurate detection of advanced left ventricular diastolic dysfunction. • As a single continuous parameter, the left atrial acceleration factor α could simplify the diagnosis of advanced diastolic dysfunction.

Left atrial acceleration factor as a magnetic resonance 4D flow measure of mean pulmonary artery wedge pressure in pulmonary hypertension.

Background: Mean pulmonary artery wedge pressure (PAWP) represents a right heart catheter (RHC) surrogate measure for mean left atrial (LA) pressure and is crucial for the clinical classification of pulmonary hypertension (PH). Hypothesizing that PAWP is related to acceleration of blood throughout the LA, we investigated whether an adequately introduced LA acceleration factor derived from magnetic resonance (MR) four-dimensional (4D) flow imaging could provide an estimate of PAWP in patients with known or suspected PH. Methods: LA 4D flow data of 62 patients with known or suspected PH who underwent RHC and near-term 1.5 T cardiac MR (ClinicalTrials.gov identifier: NCT00575692) were retrospectively analyzed. Early diastolic LA peak outflow velocity (v E) as well as systolic (v S) and early diastolic (v D) LA peak inflow velocities were determined with prototype software to calculate the LA acceleration factor (α) defined as α = v E/[(v S + v D)/2]. Correlation, regression and Bland-Altman analysis were employed to investigate the relationship between α and PAWP, α-based diagnosis of elevated PAWP (>15 mmHg) was analyzed by receiver operating characteristic curve analysis. Results: α correlated very strongly with PAWP (r = 0.94). Standard deviation of differences between RHC-derived PAWP and PAWP estimated from linear regression model (α = 0.61 + 0.10·PAWP) was 2.0 mmHg. Employing the linear-regression-derived cut-off α = 2.10, the α-based diagnosis of elevated PAWP revealed the area under the curve 0.97 with sensitivity/specificity 93%/92%. Conclusions: The very close relationship between the LA acceleration factor α and RHC-derived PAWP suggests α as potential non-invasive parameter for the estimation of PAWP and the distinction between pre- and post-capillary PH.

Automated vortical blood flow-based estimation of mean pulmonary arterial pressure from 4D flow MRI.

PURPOSE: Elevated mean pulmonary arterial pressure (mPAP), or pulmonary hypertension (PH), is associated with vortical blood flow along the main pulmonary artery. We present and validate a method for automated detection and tracking of the PH-related vortex from magnetic resonance 4D flow data that allows estimation of mPAP. METHODS: The proposed method detects the presence of a PH-related vortex in the main pulmonary artery based on geometrical properties of swirling streamlines and estimates mPAP from the PH-related vortex duration (tvortex) using a previously established model. 4D flow data of 32 subjects (19/13 with/without PH) who underwent right heart catheterization (RHC) for mPAP measurement and diagnosis of PH (mPAP >20 mmHg) were used to compare visual and automated PH-related vortex detection and to validate estimated mPAP against RHC-derived results. RESULTS: Visually and automatically determined tvortex values correlated strongly (r = 0.98); they yielded no bias, and the standard deviation of differences between them was small (5.9% of the cardiac interval). mPAP estimates from visual and automated analyses both allowed diagnosis of PH with an area under the curve of 1.00 [0.89,1.00]. For subjects with PH, neither visually nor automatically estimated mPAP differed from mPAP measured by RHC, while the standard deviation between estimated and invasively measured mPAP was lower with visual estimation (3.1 mmHg vs. 5.3 mmHg). CONCLUSION: An automated method for PH-related vortex detection and tracking from magnetic resonance 4D flow data was introduced, which demonstrated very good agreement with visual analysis and accurate estimation of elevated mPAP.

Cataract in children and adolescents with type 1 diabetes. Insights from the German/Austrian DPV registry.

OBJECTIVE: To study diabetic cataract in type 1 diabetes in a large pediatric cohort. METHODS: The 92,633 patients aged 0.5-21 years from German/Austrian multicenter diabetes registry (DPV) were analyzed. The 235 patients (0.25%) with diabetic cataract were found, 200 could be categorized: 67 with early cataract (3 months before diabetes onset - 12 months afterwards), 133 with late cataract (>12 months after diabetes onset). Regression models adjusted for age and gender were used to compare clinical parameters at diabetes onset. Regression models for patients with late cataract were implemented for the total documentation period and additionally adjusted for diabetes duration. RESULTS: Rate of cataract development shows a peak at diabetes onset and declines with longer diabetes duration. Patients with cataract showed strong female preponderance. Patients developing early cataract were older at diabetes onset (12.8 years [11.8/13.9] vs. 8.9 [8.9/9.0]; p < 0.001) and showed higher HbA1c than patients without cataract (9.0% [8.55/9.38] vs. 7.6% [7.60/7.61]; p < 0.001). They had lower height-SDS, (-0.22 [-0.48/0.04] vs. 0.25 [0.24/0.26]; p < 0.001), lower weight-SDS (-0.31 [-0.55/-0.08] vs. 0.21 [0.20/0.21]; p < 0.001) and lower BMI-SDS (-0.25 [-0.49/-0.02] vs. 0.12 [0.12/0.13); p = 0.002). Patients with late cataract showed higher HbA1c at diabetes onset (8.35% [8.08/8.62] vs. 8.04% [8.03/8.05]; p = 0.023) and higher mean HbA1c during total documentation period (8.00% [7.62/8.34] vs. 7.62% [7.61/7.63]; p = 0.048). CONCLUSIONS: Our data confirm known demographic and clinical characteristics of patients developing early cataract. Hyperglycemia-induced osmotic damage to lens fibers at diabetes onset might be the main pathomechanism. Long term glycemic control is associated with cataract development.

Cardiac Magnetic Resonance Imaging Right Ventricular Longitudinal Strain Predicts Mortality in Patients Undergoing TAVI.

Background: Right ventricular (RV) function predicts survival in numerous cardiac conditions, including left heart disease. The reference standard for non-invasive assessment of RV function is cardiac magnetic resonance imaging (CMR). The aim of this study was to investigate the association between pre-procedural CMR-derived RV functional parameters and mortality in patients undergoing transcatheter aortic valve implantation (TAVI). Methods: Patients scheduled for TAVI were recruited to undergo pre-procedural CMR. Volumetric function and global longitudinal and circumferential strain (GLS and GCS) of the RV and left ventricle (LV) were measured. The association with the primary endpoint (1-year all-cause mortality) was analyzed with Cox regression. Results: Of 133 patients undergoing CMR, 113 patients were included in the analysis. Mean age was 81.8 ± 5.8 years, and 65% were female. Median follow-up was 3.9 [IQR 2.3-4.7] years. All-cause and cardiovascular mortality was 14 and 12% at 1 year, and 28 and 20% at 3 years, respectively. One-year all-cause mortality was significantly predicted by RV GLS [HR = 1.109 (95% CI: 1.023-1.203); p = 0.012], RV ejection fraction [HR = 0.956 (95% CI: 0.929-0.985); p = 0.003], RV end-diastolic volume index [HR = 1.009 (95% CI: 1.001-1.018); p = 0.025], and RV end-systolic volume index [HR = 1.010 (95% CI: 1.003-1.017); p = 0.005]. In receiver operating characteristic (ROC) analysis for 1-year all-cause mortality, the area under the curve was 0.705 (RV GLS) and 0.673 (RV EF). Associations decreased in strength at longer follow-up. None of the LV parameters was associated with mortality. Conclusions: RV function predicts intermediate-term mortality in TAVI patients while LV parameters were not associated with outcomes. Inclusion of easily obtainable RV GLS may improve future risk scores.

A Framework for the generation of digital twins of cardiac electrophysiology from clinical 12-leads ECGs.

Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology (EP)) are digital replicas of patient hearts derived from clinical data that match like-for-like all available clinical observations. Due to their inherent predictive potential, CDTs show high promise as a complementary modality aiding in clinical decision making and also in the cost-effective, safe and ethical testing of novel EP device therapies. However, current workflows for both the anatomical and functional twinning phases within CDT generation, referring to the inference of model anatomy and parameters from clinical data, are not sufficiently efficient, robust and accurate for advanced clinical and industrial applications. Our study addresses three primary limitations impeding the routine generation of high-fidelity CDTs by introducing; a comprehensive parameter vector encapsulating all factors relating to the ventricular EP; an abstract reference frame within the model allowing the unattended manipulation of model parameter fields; a novel fast-forward electrocardiogram (Electrocardiogram (ECG)) model for efficient and bio-physically-detailed simulation required for parameter inference. A novel workflow for the generation of CDTs is then introduced as an initial proof of concept. Anatomical twinning was performed within a reasonable time compatible with clinical workflows (<4h) for 12 subjects from clinically-attained magnetic resonance images. After assessment of the underlying fast forward ECG model against a gold standard bidomain ECG model, functional twinning of optimal parameters according to a clinically-attained 12 lead ECG was then performed using a forward Saltelli sampling approach for a single subject. The achieved results in terms of efficiency and fidelity demonstrate that our workflow is well-suited and viable for generating biophysically-detailed CDTs at scale.

Differences in left ventricular and left atrial function assessed during breath-holding and breathing.

PURPOSE: To analyze differences in systolic and diastolic left ventricular (LV) as well as left atrial (LA) function parameters obtained from identical cardiac magnetic resonance (MR) imaging techniques during inspiratory breath-holding and breathing (breath-hold to breathing differences). METHOD: 56 subjects without signs of heart failure (23/33 male/female, age 58 ±â€¯14 years) underwent 3 T MR cine real-time and transmitral phase contrast imaging with the same spatial and temporal resolution during inspiratory breath-holding and free breathing. LV and LA volumetric function parameters were derived from segmentation of cine series, transmitral peak velocities and early-diastolic myocardial peak velocity from phase contrast series. Corresponding breath-hold and breathing parameters were compared by Bland-Altman analysis; repeatability of breath-hold and breathing measurements was quantified by variance component analysis. p < 0.05 was regarded as statistically significant. RESULTS: Mean differences between results obtained during inspiratory breath-holding vs. breathing were significant for LV volumetric function (end-diastolic volume=-7 mL, p = 0.002; end-systolic volume=-7 mL, p < 0.001; ejection fraction = 3 %, p < 0.001; peak ejection rate = 22 mL/s, p = 0.002; early-diastolic peak filling rate=-34 mL/s, p = 0.025), LA volumetric function (maximum volume=-6 mL, p < 0.001; total ejection fraction=-4%, p < 0.001; active ejection fraction=-2%, p = 0.013; before contraction ejection fraction=-4%, p < 0.001) and early-diastolic velocities (transmitral=-6 cm/s, p < 0.001; tissue velocity=-1.8 cm/s, p < 0.001). Standard deviations of breath-hold-to-breathing differences exceeded the corresponding repeatabilities of breath-hold and breathing measurements. CONCLUSIONS: Systolic and diastolic LV and LA function parameters acquired during inspiratory breath-holding and breathing differ, and large inter-individual breath-hold-to-breathing variations are possible. Thus, the breathing state should be taken into account, especially when comparing results in patient follow-up acquired in different respiratory states.

Impact of the Choice of Native T1 in Pixelwise Myocardial Blood Flow Quantification.

BACKGROUND: Quantification of myocardial blood flow (MBF) from dynamic contrast-enhanced (DCE) MRI can be performed using a signal intensity model that incorporates T1 values of blood and myocardium. PURPOSE: To assess the impact of T1 values on pixelwise MBF quantification, specifically to evaluate the influence of 1) study population-averaged vs. subject-specific, 2) diastolic vs. systolic, and 3) regional vs. global myocardial T1 values. STUDY TYPE: Prospective. SUBJECTS: Fifteen patients with chronic coronary heart disease. FIELD STRENGTH/SEQUENCE: 3T; modified Look-Locker inversion recovery for T1 mapping and saturation recovery gradient echo for DCE imaging, both acquired in a mid-ventricular short-axis slice in systole and diastole. ASSESSMENT: MBF was estimated using Fermi modeling and signal intensity nonlinearity correction with different T1 values: study population-averaged blood and myocardial, subject-specific systolic and diastolic, and segmental T1 values. Myocardial segments with perfusion deficits were identified visually from DCE series. STATISTICAL TESTS: The relationships between MBF parameters derived by different methods were analyzed by Bland-Altman analysis; corresponding mean values were compared by t-test. RESULTS: Using subject-specific diastolic T1 values, global diastolic MBF was 0.61 ± 0.13 mL/(min·g). It did not differ from global MBF derived from the study population-averaged T1 (P = 0.88), but the standard deviation of differences was large (0.07 mL/(min·g), 11% of mean MBF). Global diastolic and systolic MBF did not differ (P = 0.12), whereas global diastolic MBF using systolic (0.62 ± 0.13 mL/(min·g)) and diastolic T1 values differed (P < 0.05). If regional instead of global T1 values were used, segmental MBF was lower in segments with perfusion deficits (bias = -0.03 mL/(min·g), -7% of mean MBF, P < 0.05) but higher in segments without perfusion deficits (bias = 0.01 mL/(min·g), 1% of mean MBF, P < 0.05). DATA CONCLUSION: Whereas cardiac phase-specific T1 values have a minor impact on MBF estimates, subject-specific and myocardial segment-specific T1 values substantially affect MBF quantification. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Cellular contribution to left and right atrial dysfunction in chronic arterial hypertension in pigs.

AIMS: Atrial contractile dysfunction contributes to worse prognosis in hypertensive heart disease (HHD), but the role of cardiomyocyte dysfunction in atrial remodelling in HHD is not well understood. We investigated and compared cellular mechanisms of left (LA) and right atrial (RA) contractile dysfunction in pigs with HHD. METHODS AND RESULTS: In vivo electrophysiological and magnetic resonance imaging studies were performed in control and pigs treated with 11-deoxycorticosterone acetate (DOCA)/high-salt/glucose diet (12 weeks) to induce HHD. HHD leads to significant atrial remodelling and loss of contractile function in LA and a similar trend in RA (magnetic resonance imaging). Atrial remodelling was associated with a higher inducibility of atrial fibrillation but unrelated to changes in atrial refractory period or fibrosis (histology). Reduced atrial function in DOCA pigs was related to reduced contraction amplitude of isolated LA (already at baseline) and RA myocytes (at higher frequencies) due to reduced intracellular Ca release (Fura 2-AM, field stimulation). However, Ca regulation differed in LA and RA cardiomyocytes: LA cardiomyocytes showed reduced sarcoplasmic reticulum (SR) [Ca], whereas in RA, SR [Ca] was unchanged and SR Ca2+ -ATPase activity was increased. Sodium-calcium exchanger (NCX) activity was not significantly altered. We used ORM-10103 (3 µM), a specific NCX inhibitor to improve Ca availability in LA and RA cardiomyocytes from DOCA pigs. Partial inhibition of NCX increased Ca2+ transient amplitude and SR Ca in LA, but not RA cells. CONCLUSIONS: In this large animal model of HHD, atrial remodelling in sinus rhythm in vivo was related to differential LA and RA cardiomyocyte dysfunction and Ca signalling. Selective acute inhibition of NCX improved Ca release in diseased LA cardiomyocytes, suggesting a potential therapeutic approach to improve atrial inotropy in HHD.

MR 4D flow-based mean pulmonary arterial pressure tracking in pulmonary hypertension.

OBJECTIVES: Longitudinal hemodynamic follow-up is important in the management of pulmonary hypertension (PH). This study aimed to evaluate the potential of MR 4-dimensional (4D) flow imaging to predict changes in the mean pulmonary arterial pressure (mPAP) during serial investigations. METHODS: Forty-four adult patients with PH or at risk of developing PH repeatedly underwent routine right heart catheterization (RHC) and near-term MR 4D flow imaging of the main pulmonary artery. The duration of vortical blood flow along the main pulmonary artery was evaluated from MR 4D velocity fields using prototype software and converted to an MR 4D flow imaging-based mPAP estimate (mPAPMR) by a previously established model. The relationship of differences between RHC-derived baseline and follow-up mPAP values (ΔmPAP) to corresponding differences in mPAPMR (ΔmPAPMR) was analyzed by means of regression and Bland-Altman analysis; the diagnostic performance of ΔmPAPMR in predicting mPAP increases or decreases was investigated by ROC analysis. RESULTS: Areas under the curve for the prediction of mPAP increases and decreases were 0.92 and 0.93, respectively. With the natural cutoff ΔmPAPMR = 0 mmHg, mPAP increases (decreases) were predicted with an accuracy, sensitivity, and specificity of 91% (91%), 85% (89%), and 94% (92%), respectively. For patients in whom 4D flow allowed a point estimate of mPAP (mPAP > 16 mmHg), ΔmPAPMR correlated strongly with ΔmPAP (r = 0.91) and estimated ΔmPAP bias-free with a standard deviation of 5.1 mmHg. CONCLUSIONS: MR 4D flow imaging allows accurate non-invasive prediction and quantification of mPAP changes in adult patients with PH or at risk of developing PH. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00575692 and NCT01725763 KEY POINTS: • MR 4D flow imaging allows accurate non-invasive prediction of mean pulmonary arterial pressure increases and decreases in adult patients with or at risk of developing pulmonary hypertension. • In adult patients with mean pulmonary arterial pressure > 16 mmHg, MR 4D flow imaging allows estimation of longitudinal mean pulmonary arterial pressure changes without bias with a standard deviation of 5.1 mmHg.

Nuclear Magnetic Relaxation Mapping of Spin Relaxation in Electrically Stressed Glycerol.

This work discusses nuclear magnetic relaxation effects in glycerol subject to a strong electric field. The methods used are 1.5 T magnetic resonance imaging (MRI), referenced by 9.4 T nuclear magnetic resonance (NMR). While MRI allows a glycerol probe to be sampled with a high voltage (HV) of 16 kV applied to the probe, NMR provides precise molecular data from the sample, but the sample cannot be tested under HV. Using MRI, the recording of magnetic relaxation times was possible while HV was applied to the glycerol. NMR spectroscopy was used to confirm that MRI provides a reasonably accurate estimation of temperature. The applied HV was observed to have a negligible effect on the spin-lattice relaxation time T 1, which represents the energy release to the thermal bath or system enthalpy. In contrast to that, the spin-spin relaxation time T 2, which does represent the local entropy of the system, shows a lower response to temperature while the liquid is electrically stressed. These observations point toward a proton population in electrically stressed glycerol that is more mobile than that found in the bulk, an observation that is in agreement with previously published results for water.

Comprehensive Cardiovascular Magnetic Resonance Diastolic Dysfunction Grading Shows Very Good Agreement Compared With Echocardiography.

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 (e') 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.

Automated mitral valve vortex ring extraction from 4D-flow MRI.

PURPOSE: To present and validate a method for automated extraction and analysis of the temporal evolution of the mitral valve (MV) vortex ring from MR 4D-flow data. METHODS: The proposed algorithm uses the divergence-free part of the velocity vector field for Q criterion-based identification and tracking of MV vortex ring core and region within the left ventricle (LV). The 4D-flow data of 20 subjects (10 healthy controls, 10 patients with ischemic heart disease) were used to validate the algorithm against visual analysis as well as to assess the method's sensitivity to manual LV segmentation. Quantitative MV vortex ring parameters were analyzed with respect to both their differences between healthy subjects and patients and their correlation with transmitral peak velocities. RESULTS: The algorithm successfully extracted MV vortex rings throughout the entire cardiac cycle, which agreed substantially with visual analysis (Cohen's kappa = 0.77). Furthermore, vortex cores and regions were robustly detected even if a static end-diastolic LV segmentation mask was applied to all frames (Dice coefficients 0.82 ± 0.08 and 0.94 ± 0.02 for core and region, respectively). Early diastolic MV vortex ring vorticity, kinetic energy and circularity index differed significantly between healthy controls and patients. In contrast to vortex shape parameters, vorticity and kinetic energy correlated strongly with transmitral peak velocities. CONCLUSION: An automated method for temporal MV vortex ring extraction demonstrating robustness with respect to LV segmentation strategies is introduced. Quantitative vortex parameter analysis indicates importance of the MV vortex ring for LV diastolic (dys)function.

Cardiovascular magnetic resonance 4D flow analysis has a higher diagnostic yield than Doppler echocardiography for detecting increased pulmonary artery pressure.

BACKGROUND: Pulmonary hypertension is definitively diagnosed by the measurement of mean pulmonary artery (PA) pressure (mPAP) using right heart catheterization. Cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow analysis can estimate mPAP from blood flow vortex duration in the PA, with excellent results. Moreover, the peak systolic tricuspid regurgitation (TR) pressure gradient (TRPG) measured by Doppler echocardiography is commonly used in clinical routine to estimate systolic PA pressure. This study aimed to compare CMR and echocardiography with regards to quantitative and categorical agreement, and diagnostic yield for detecting increased PA pressure. METHODS: Consecutive clinically referred patients (n = 60, median [interquartile range] age 60 [48-68] years, 33% female) underwent echocardiography and CMR at 1.5 T (n = 43) or 3 T (n = 17). PA vortex duration was used to estimate mPAP using a commercially available time-resolved multiple 2D slice phase contrast three-directional velocity encoded sequence covering the main PA. Transthoracic Doppler echocardiography was performed to measure TR and derive TRPG. Diagnostic yield was defined as the fraction of cases in which CMR or echocardiography detected an increased PA pressure, defined as vortex duration ≥15% of the cardiac cycle (mPAP ≥25 mmHg) or TR velocity > 2.8 m/s (TRPG > 31 mmHg). RESULTS: Both CMR and echocardiography showed normal PA pressure in 39/60 (65%) patients and increased PA pressure in 9/60 (15%) patients, overall agreement in 48/60 (80%) patients, kappa 0.49 (95% confidence interval 0.27-0.71). CMR had a higher diagnostic yield for detecting increased PA pressure compared to echocardiography (21/60 (35%) vs 9/60 (15%), p < 0.001). In cases with both an observable PA vortex and measurable TR velocity (34/60, 56%), TRPG was correlated with mPAP (R2 = 0.65, p < 0.001). CONCLUSIONS: There is good quantitative and fair categorical agreement between estimated mPAP from CMR and TRPG from echocardiography. CMR has higher diagnostic yield for detecting increased PA pressure compared to echocardiography, potentially due to a lower sensitivity of echocardiography in detecting increased PA pressure compared to CMR, related to limitations in the ability to adequately visualize and measure the TR jet by echocardiography. Future comparison between echocardiography, CMR and invasive measurements are justified to definitively confirm these findings.

Quantitative Clinical Cardiac Magnetic Resonance Imaging. / Quantitative klinische Herz-Magnetresonanztomografie.

BACKGROUND: Cardiac magnetic resonance imaging (MRI) represents the established reference standard method for the assessment of cardiac function and non-invasive evaluation of myocardial tissue in a variety of clinical questions, wherein quantification of cardiac parameters gains growing diagnostic and differential-diagnostic importance. This review aims to summarize established and newly emerging quantitative parameters, which are assessed in routine cardiac MRI. Interrelations and interdependencies between metrics are explained, and common factors affecting quantitative results are discussed. METHOD: The review is based on a PubMed literature research using the search terms "cardiac magnetic resonance" and "quantification", "recommendations", "quantitative evaluation/assessment", "reference method", "reference/normal values", "pitfalls" or "artifacts" published between 2000-2019. RESULTS AND CONCLUSION: Quantitative functional, phase contrast, and perfusion imaging, as well as relaxation time mapping techniques give opportunity for assessment of a large number of quantitative cardiac MRI parameters in clinical routine. Application of these techniques allows for characterization of function, morphology and perfusion of the heart beyond visual analysis of images, either in primary evaluation and comparison to normal values or in patients' follow-up and treatment monitoring. However, with implementation of quantitative parameters in clinical routine, standardization is of particular importance as different acquisition and evaluation strategies and algorithms may substantially influence results, though not always immediately apparent. KEY POINTS: · Clinical cardiac MRI provides numerous functional and morphological quantitative parameters.. · Quantitative cardiac MRI enables assessment of diffuse and global myocardial alterations.. · Standardized data acquisition/evaluation is the prerequisite for diagnostic use of quantitative cardiac MRI parameters.. CITATION FORMAT: · Reiter U, Reiter C, Kräuter C et al. Quantitative Clinical Cardiac Magnetic Resonance Imaging. Fortschr Röntgenstr 2020; 192: 246 - 256.