Correlation of mitochondrial respiration in platelets, peripheral blood mononuclear cells and muscle fibers.

There is a growing interest for the possibility of using peripheral blood cells (including platelets) as markers for mitochondrial function in less accessible tissues. Only a few studies have examined the correlation between respiration in blood and muscle tissue, with small sample sizes and conflicting results. This study investigated the correlation of mitochondrial respiration within and across tissues. Additional analyses were performed to elucidate which blood cell type would be most useful for assessing systemic mitochondrial function. There was a significant but weak within tissue correlation between platelets and peripheral blood mononuclear cells (PBMCs). Neither PBMCs nor platelet respiration correlated significantly with muscle respiration. Muscle fibers from a group of athletes had higher mass-specific respiration, due to higher mitochondrial content than non-athlete controls, but this finding was not replicated in either of the blood cell types. In a group of patients with primary mitochondrial diseases, there were significant differences in blood cell respiration compared to healthy controls, particularly in platelets. Platelet respiration generally correlated better with the citrate synthase activity of each sample, in comparison to PBMCs. In conclusion, this study does not support the theory that blood cells can be used as accurate biomarkers to detect minor alterations in muscle respiration. However, in some instances, pronounced mitochondrial abnormalities might be reflected across tissues and detectable in blood cells, with more promising findings for platelets than PBMCs.

Prognostic utility and characterization of left ventricular hypertrophy using global thickness.

Cardiovascular magnetic resonance (CMR) can accurately measure left ventricular (LV) mass, and several measures related to LV wall thickness exist. We hypothesized that prognosis can be used to select an optimal measure of wall thickness for characterizing LV hypertrophy. Subjects having undergone CMR were studied (cardiac patients, n = 2543; healthy volunteers, n = 100). A new measure, global wall thickness (GT, GTI if indexed to body surface area) was accurately calculated from LV mass and end-diastolic volume. Among patients with follow-up (n = 1575, median follow-up 5.4 years), the most predictive measure of death or hospitalization for heart failure was LV mass index (LVMI) (hazard ratio (HR)[95% confidence interval] 1.16[1.12-1.20], p < 0.001), followed by GTI (HR 1.14[1.09-1.19], p < 0.001). Among patients with normal findings (n = 326, median follow-up 5.8 years), the most predictive measure was GT (HR 1.62[1.35-1.94], p < 0.001). GT and LVMI could characterize patients as having a normal LV mass and wall thickness, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy, and the three abnormal groups had worse prognosis than the normal group (p < 0.05 for all). LV mass is highly prognostic when mass is elevated, but GT is easily and accurately calculated, and adds value and discrimination amongst those with normal LV mass (early disease).

Endurance-trained subjects and sedentary controls increase ventricular contractility and efficiency during exercise: Feasibility of hemodynamics assessed by non-invasive pressure-volume loops.

INTRODUCTION: Pressure-volume (PV) loops can be used to assess both load-dependent and load-independent measures of cardiac hemodynamics. However, analysis of PV loops during exercise is challenging as it requires invasive measures. Using a novel method, it has been shown that left ventricular (LV) PV loops at rest can be obtained non-invasively from cardiac magnetic resonance imaging (CMR) and brachial pressures. Therefore, the aim of this study was to assess if LV PV loops can be obtained non-invasively from CMR during exercise to assess cardiac hemodynamics. METHODS: Thirteen endurance trained (ET; median 48 years [IQR 34-60]) and ten age and sex matched sedentary controls (SC; 43 years [27-57]) were included. CMR images were acquired at rest and during moderate intensity supine exercise defined as 60% of expected maximal heart rate. Brachial pressures were obtained in conjunction with image acquisition. RESULTS: Contractility measured as maximal ventricular elastance (Emax) increased in both groups during exercise (ET: 1.0 mmHg/ml [0.9-1.1] to 1.1 mmHg/ml [0.9-1.2], p<0.01; SC: 1.1 mmHg/ml [0.9-1.2] to 1.2 mmHg/ml [1.0-1.3], p<0.01). Ventricular efficiency (VE) increased in ET from 70% [66-73] at rest to 78% [75-80] (p<0.01) during exercise and in SC from 68% [63-72] to 75% [73-78] (p<0.01). Arterial elastance (EA) decreased in both groups (ET: 0.8 mmHg/ml [0.7-0.9] to 0.7 mmHg/ml [0.7-0.9], p<0.05; SC: 1.0 mmHg/ml [0.9-1.2] to 0.9 mmHg/ml [0.8-1.0], p<0.05). Ventricular-arterial coupling (EA/Emax) also decreased in both groups (ET: 0.9 [0.8-1.0] to 0.7 [0.6-0.8], p<0.01; SC: 1.0 [0.9-1.1] to 0.7 [0.7-0.8], p<0.01). CONCLUSIONS: This study demonstrates for the first time that LV PV loops can be generated non-invasively during exercise using CMR. ET and SC increase ventricular efficiency and contractility and decrease afterload and ventricular-arterial coupling during moderate supine exercise. These results confirm known physiology. Therefore, this novel method is applicable to be used during exercise in different cardiac disease states, which has not been possible non-invasively before.

Fetal growth restriction followed by very preterm birth is associated with smaller kidneys but preserved kidney function in adolescence.

BACKGROUND: Preterm birth and fetal growth restriction (FGR) are associated with structural and functional kidney changes, increasing long-term risk for chronic kidney disease and hypertension. However, recent studies in preterm children are conflicting, indicating structural changes but normal kidney function. This study therefore assessed kidney structure and function in a cohort of adolescents born very preterm with and without verified FGR. METHODS: Adolescents born very preterm with FGR and two groups with appropriate birthweight (AGA) were included; one matched for gestational week at birth and one born at term. Cortical and medullary kidney volumes and T1 and T2* mapping values were assessed by magnetic resonance imaging. Biochemical markers of kidney function and renin-angiotensin-aldosterone system (RAAS) activation were analyzed. RESULTS: Sixty-four adolescents were included (13-16 years; 48% girls). Very preterm birth with FGR showed smaller total (66 vs. 75 ml/m2; p = 0.01) and medullary volume (19 vs. 24 ml/m2; p < 0.0001) compared to term AGA. Corticomedullary volume ratio decreased from preterm FGR (2.4) to preterm AGA (2.2) to term AGA (1.9; p = 0.004). There were no differences in T1 or T2* values (all p ≥ 0.34) or in biochemical markers (all p ≥ 0.12) between groups. CONCLUSIONS: FGR with abnormal fetal blood flow followed by very preterm birth is associated with smaller total kidney and medullary kidney volumes, but not with markers of kidney dysfunction or RAAS activation in adolescence. Decreased total kidney and medullary volumes may still precede a long-term decrease in kidney function, and potentially be used as a prognostic marker. A higher resolution version of the Graphical abstract is available as Supplementary information.

Higher blood pressure in adolescent boys after very preterm birth and fetal growth restriction.

BACKGROUND: Although preterm birth predisposes for cardiovascular disease, recent studies in children indicate normal blood pressure and arterial stiffness. This prospective cohort study therefore assessed blood pressure and arterial stiffness in adolescents born very preterm due to verified fetal growth restriction (FGR). METHODS: Adolescents (14 (13-17) years; 52% girls) born very preterm with FGR (preterm FGR; n = 24) and two control groups born with appropriate birth weight (AGA), one in similar gestation (preterm AGA; n = 27) and one at term (term AGA; n = 28) were included. 24-hour ambulatory blood pressure and aortic pulse wave velocity (PWV) and distensibility by magnetic resonance imaging were acquired. RESULTS: There were no group differences in prevalence of hypertension or in arterial stiffness (all p ≥ 0.1). In boys, diastolic and mean arterial blood pressures increased from term AGA to preterm AGA to preterm FGR with higher daytime and 24-hour mean arterial blood pressures in the preterm FGR as compared to the term AGA group. In girls, no group differences were observed (all p ≥ 0.1). CONCLUSIONS: Very preterm birth due to FGR is associated with higher, yet normal blood pressure in adolescent boys, suggesting an existing but limited impact of very preterm birth on cardiovascular risk in adolescence, enhanced by male sex and FGR. IMPACT: Very preterm birth due to fetal growth restriction was associated with higher, yet normal blood pressure in adolescent boys. In adolescence, very preterm birth due to fetal growth restriction was not associated with increased thoracic aortic stiffness. In adolescence, very preterm birth in itself showed an existing but limited effect on blood pressure and thoracic aortic stiffness. Male sex and fetal growth restriction enhanced the effect of preterm birth on blood pressure in adolescence. Male sex and fetal growth restriction should be considered as additional risk factors to that of preterm birth in cardiovascular risk stratification.

Noninvasive Assessment of Left Ventricular Pressure-Volume Relations: Inter- and Intraobserver Variability and Assessment Across Heart Failure Subtypes.

A novel method to derive pressure-volume (PV) loops noninvasively from cardiac magnetic resonance images has recently been developed. The aim of this study was to evaluate inter- and intraobserver variability of hemodynamic parameters obtained from noninvasive PV loops in healthy controls, subclinical diastolic dysfunction (SDD), and patients with heart failure with preserved ejection fraction, mildly reduced ejection fraction, and reduced ejection fraction. We included 75 subjects, of whom 15 were healthy controls, 15 subjects with SDD (defined as fulfilling 1 to 2 echocardiographic criteria for diastolic dysfunction), and 15 patients with preserved ejection fraction, 15 with mildly reduced ejection fraction, and 15 with reduced ejection fraction. PV loops were computed using time-resolved left ventricular volumes from cardiac magnetic resonance images and a brachial blood pressure. Inter- and intraobserver variability and intergroup differences of PV loop-derived hemodynamic parameters were assessed. Bias was low and limits of agreement were narrow for all hemodynamic parameters in the inter- and intraobserver comparisons. Interobserver difference for stroke work was 2 ± 9%, potential energy was 4 ± 11%, and maximal ventricular elastance was -4 ± 7%. Intraobserver for stroke work was -1 ± 7%, potential energy was 3 ± 4%, and maximal ventricular elastance was 1 ± 5%. In conclusion, this study presents a fully noninvasive left ventricular PV loop analysis across healthy controls, subjects with SDD, and patients with heart failure with preserved or impaired systolic function. In conclusion, the method for PV loop computation from clinical-standard manual left ventricular segmentation was rapid and robust, bridging the gap between clinical and research settings.

Kinetic energy of left ventricular blood flow across heart failure phenotypes and in subclinical diastolic dysfunction.

Kinetic energy (KE) of intracardiac blood flow reflects myocardial work spent on accelerating blood and provides a mechanistic window into diastolic filling dynamics. Diastolic dysfunction may represent an early stage in the development of heart failure (HF). Here we evaluated the hemodynamic effects of impaired diastolic function in subjects with and without HF, testing the hypothesis that left ventricular KE differs between controls, subjects with subclinical diastolic dysfunction (SDD), and patients with HF. We studied 77 subjects [16 controls, 20 subjects with SDD, 16 heart failure with preserved ejection fraction (HFpEF), 9 heart failure with mildly reduced ejection fraction (HFmrEF), and 16 heart failure with reduced ejection fraction (HFrEF) patients, age- and sex-matched at the group level]. Cardiac magnetic resonance at 1.5 T included intracardiac four-dimensional (4-D) flow and cine imaging. Left ventricular KE was calculated as 0.5 × m × v2. Systolic KE was similar between groups (P > 0.4), also after indexing to stroke volume (P = 0.25), and was primarily driven by ventricular emptying rate (P < 0.0001, R2 = 0.52). Diastolic KE was higher in patients with heart failure than in controls (P < 0.05) but similar between SDD and HFpEF (P > 0.18), correlating with inflow conditions (E-wave velocity, P < 0.0001, R2 = 0.24) and end-diastolic volume (P = 0.0003, R2 = 0.17) but not with average e' (P = 0.07). Diastolic KE differs between controls and heart failure, suggesting more work is spent filling the failing ventricle, whereas systolic KE does not differentiate between well-matched groups with normal ejection fractions even in the presence of relaxation abnormalities and heart failure. Mechanistically, KE reflects the acceleration imparted on the blood and is driven by variations in ventricular emptying and filling rates, volumes, and heart rate, regardless of underlying pathology.NEW & NOTEWORTHY Here we present the first study of left ventricular kinetic energy in individuals with subclinical diastolic dysfunction and in heart failure patients with preserved or impaired systolic function. Kinetic energy differs between groups in diastole, and reflects altered filling and emptying processes. Kinetic energy analysis should be considered in studies seeking to characterize myocardial energetics comprehensively.

Validation and quantification of left ventricular function during exercise and free breathing from real-time cardiac magnetic resonance images.

Exercise cardiovascular magnetic resonance (CMR) can unmask cardiac pathology not evident at rest. Real-time CMR in free breathing can be used, but respiratory motion may compromise quantification of left ventricular (LV) function. We aimed to develop and validate a post-processing algorithm that semi-automatically sorts real-time CMR images according to breathing to facilitate quantification of LV function in free breathing exercise. A semi-automatic algorithm utilizing manifold learning (Laplacian Eigenmaps) was developed for respiratory sorting. Feasibility was tested in eight healthy volunteers and eight patients who underwent ECG-gated and real-time CMR at rest. Additionally, volunteers performed exercise CMR at 60% of maximum heart rate. The algorithm was validated for exercise by comparing LV mass during exercise to rest. Respiratory sorting to end expiration and end inspiration (processing time 20 to 40 min) succeeded in all research participants. Bias ± SD for LV mass was 0 ± 5 g when comparing real-time CMR at rest, and 0 ± 7 g when comparing real-time CMR during exercise to ECG-gated at rest. This study presents a semi-automatic algorithm to retrospectively perform respiratory sorting in free breathing real-time CMR. This can facilitate implementation of exercise CMR with non-ECG-gated free breathing real-time imaging, without any additional physiological input.

Non-contrast-enhanced magnetic resonance imaging can be used to assess renal cortical and medullary volumes-A validation study.

BACKGROUND: Magnetic resonance imaging (MRI) biomarkers can diagnose and prognosticate kidney disease. Renal volume validation studies are however scarce, and measurements are limited by use of contrast agent or advanced post-processing. PURPOSE: To validate a widely available non-contrast-enhanced MRI method for quantification of renal cortical and medullary volumes in pigs; investigate observer variability of cortical and medullary volumes in humans; and present reference values for renal cortical and medullary volumes in adolescents. MATERIALS AND METHODS: Cortical and medullary volumes were quantified from transaxial in-vivo water-excited MR images in six pigs and 15 healthy adolescents (13-16years). Pig kidneys were excised, and renal cortex and medulla were separately quantified by the water displacement method. Both limits of agreement by the Bland-Altman method and reference ranges are presented as 2.5-97.5 percentiles. RESULTS: Agreement between MRI and ex-vivo quantification were -7 mL (-10-0 mL) for total parenchyma, -4 mL (-9-3 mL) for cortex, and -2 mL (-7-2 mL) for medulla. Intraobserver variability for pig and human kidneys were <5% for total parenchyma, cortex, and medulla. Interobserver variability for both pig and human kidneys were ≤4% for total parenchyma and cortex, and 6% and 12% for medulla. Reference ranges indexed for body surface area and sex were 54-103 mL/m2 (boys) and 56-103 mL/m2 (girls) for total parenchyma, 39-62 mL/m2 and 36-68 mL/m2 for cortex, and 16-45 mL/m2 and 17-42 mL/m2 for medulla. CONCLUSION: The proposed widely available non-contrast-enhanced MRI method can quantify cortical and medullary renal volumes and can be directly implemented clinically.

MVnet: automated time-resolved tracking of the mitral valve plane in CMR long-axis cine images with residual neural networks: a multi-center, multi-vendor study.

BACKGROUND: Mitral annular plane systolic excursion (MAPSE) and left ventricular (LV) early diastolic velocity (e') are key metrics of systolic and diastolic function, but not often measured by cardiovascular magnetic resonance (CMR). Its derivation is possible with manual, precise annotation of the mitral valve (MV) insertion points along the cardiac cycle in both two and four-chamber long-axis cines, but this process is highly time-consuming, laborious, and prone to errors. A fully automated, consistent, fast, and accurate method for MV plane tracking is lacking. In this study, we propose MVnet, a deep learning approach for MV point localization and tracking capable of deriving such clinical metrics comparable to human expert-level performance, and validated it in a multi-vendor, multi-center clinical population. METHODS: The proposed pipeline first performs a coarse MV point annotation in a given cine accurately enough to apply an automated linear transformation task, which standardizes the size, cropping, resolution, and heart orientation, and second, tracks the MV points with high accuracy. The model was trained and evaluated on 38,854 cine images from 703 patients with diverse cardiovascular conditions, scanned on equipment from 3 main vendors, 16 centers, and 7 countries, and manually annotated by 10 observers. Agreement was assessed by the intra-class correlation coefficient (ICC) for both clinical metrics and by the distance error in the MV plane displacement. For inter-observer variability analysis, an additional pair of observers performed manual annotations in a randomly chosen set of 50 patients. RESULTS: MVnet achieved a fast segmentation (<1 s/cine) with excellent ICCs of 0.94 (MAPSE) and 0.93 (LV e') and a MV plane tracking error of -0.10 ± 0.97 mm. In a similar manner, the inter-observer variability analysis yielded ICCs of 0.95 and 0.89 and a tracking error of -0.15 ± 1.18 mm, respectively. CONCLUSION: A dual-stage deep learning approach for automated annotation of MV points for systolic and diastolic evaluation in CMR long-axis cine images was developed. The method is able to carefully track these points with high accuracy and in a timely manner. This will improve the feasibility of CMR methods which rely on valve tracking and increase their utility in a clinical setting.

Atrioventricular plane displacement versus mitral and tricuspid annular plane systolic excursion: A comparison between cardiac magnetic resonance and M-mode echocardiography.

INTRODUCTION: Both echocardiography and CMR imaging are used to quantify longitudinal function. Inter-method variability for mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursion, and variability between directly measured MAPSE and TAPSE and as based on atrioventricular plane displacement (AVPD) analysis by CMR, are, however, not known. This study, therefore, assessed inter-method variability and variability between annular plane systolic excursion and AVPD-based values in a healthy adult population. METHODS: Echocardiography and CMR were performed in 111 adults (35 [32-38] years). Method comparisons were assessed with Deming regression, Bland-Altman analysis and coefficient of variation. Observer reproducibility was assessed by the concordance correlation coefficient. RESULTS: Echocardiography and semi-automatic CMR agreed on MAPSE (17 ± 2 mm vs. 17 ± 2 mm, p = 0.1) and TAPSE (25 ± 3 mm vs. 25 ± 3 mm, p = 0.5), correlated highly between methods (fitted-slope 1.22 [95% CI 1.07-1.38] and 1.12 [95% CI 0.95-1.29]) and showed low bias (0.42 [95% CI - 2.05 to 2.88] and - 0.18 [95% CI - 4.78 to 4.43]). Intra-/inter-observer reproducibility was high for both methods for both MAPSE (echocardiography 0.96/0.86; CMR 0.87/0.85) and TAPSE (echocardiography 0.96/0.95; CMR 0.97/0.96). MAPSE (16 ± 2 mm vs. 17 ± 2 mm; p < 0.001) and TAPSE (24 ± 3 vs. 25 ± 3 mm; p < 0.001) based on AVPD were similar but statistically different compared with semi-automatic CMR. CONCLUSIONS: Echocardiography and semi-automatic CMR have low variability and provide similar values for MAPSE and TAPSE and are thus interchangeable for follow-up studies. Lateral values based on tracked data from AVPD analysis are not clinically significantly different and could be used as a representation of annular displacement.

Hydraulic force is a novel mechanism of diastolic function that may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF.

A hydraulic force generated by blood moving the atrioventricular plane is a novel mechanism of diastolic function. The direction and magnitude of the force is dependent on the geometrical relationship between the left atrium and ventricle and is measured as the short-axis atrioventricular area difference (AVAD). In short, the net hydraulic force acts from a larger area toward a smaller one. It is currently unknown how cardiac remodeling affects this mechanism. The aim of the study was therefore to investigate this diastolic mechanism in patients with pathological or physiological remodeling. Seventy subjects [n = 11 heart failure with preserved ejection fraction (HFpEF), n = 10 heart failure with reduced ejection fraction (HFrEF), n = 7 signs of isolated diastolic dysfunction, n = 10 hypertrophic cardiomyopathy, n = 10 cardiac amyloidosis, n = 18 triathletes, and n = 14 controls] were included. Subjects underwent cardiac MR, and short-axis images of the left atrium and ventricle were delineated. AVAD was calculated as ventricular area minus atrial area and used as an indicator of net hydraulic force. At the onset of diastole, AVAD in HFpEF was -9.2 cm2 (median) versus -4.4 cm2 in controls, P = 0.02. The net hydraulic force was directed toward the ventricle for both but was larger in HFpEF. HFrEF was the only group with a positive median value (11.6 cm2), and net hydraulic force was throughout diastole directed toward the atrium. The net hydraulic force may impede cardiac filling throughout diastole in HFpEF, worsening diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles and aid ventricular filling.NEW & NOTEWORTHY 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.

Underfilling decreases left ventricular function in pulmonary arterial hypertension.

To evaluate the association between impaired left ventricular (LV) longitudinal function and LV underfilling in patients with pulmonary arterial hypertension (PAH). Thirty-nine patients with PAH and 18 age and sex-matched healthy controls were included. LV volume and left atrial volume (LAV) were delineated in short-axis cardiac magnetic resonance (CMR) cine images. LV longitudinal function was assessed from atrio-ventricular plane displacement (AVPD) and global longitudinal strain (GLS) was assessed using feature tracking in three long-axis views. LV filling was assessed by LAV and by pulmonary artery wedge pressure (PAWP) using right heart catheterisation. Patients had a smaller LAV, LV volume and stroke volume as well as a lower LV-AVPD and LV-GLS than controls. PAWP was 6 [IQR 5--9] mmHg in patients. LV ejection fraction did not differ between groups. LV stroke volume correlated with LV-AVPD (r = 0.445, p = .001), LV-GLS (r = - 0.549, p < 0.0001) and LAVmax (r = .585, p < 0.0001). Furthermore, LV-AVPD (r = .598) and LV-GLS (r = - 0.675) correlated with LAVmax (p < 0.0001 for both). Neither LV-AVPD, LV-GLS, LAVmax nor stroke volume correlated with PAWP. Impaired LV longitudinal function was associated with low stroke volume, low PAWP and a small LAV in PAH. Small stroke volumes and LAV, together with normal LA pressure, implies that the mechanism causing reduced LV longitudinal function is underfilling rather than an intrinsic LV dysfunction in PAH.

Free-breathing fetal cardiac MRI with doppler ultrasound gating, compressed sensing, and motion compensation.

BACKGROUND: Fetal cardiovascular MRI complements ultrasound to assess fetal cardiovascular pathophysiology. PURPOSE: To develop a free-breathing method for retrospective fetal cine MRI using Doppler ultrasound (DUS) cardiac gating and tiny golden angle radial sampling (tyGRASP) for accelerated acquisition capable of detecting fetal movements for motion compensation. STUDY TYPE: Feasibility study. SUBJECTS: Nine volunteers (gestational week 34-40). Short-axis and four-chamber views were acquired during maternal free-breathing and breath-hold. FIELD STRENGTH/SEQUENCE: 1.5T cine balanced steady-state free precession. ASSESSMENT: A self-gated reconstruction method was improved for clinical application by using 1) retrospective DUS gating, and 2) motion detection and rejection/correction algorithms for compensating for fetal motion. The free-breathing reconstructions were qualitatively and quantitatively assessed, and DUS-gating was compared with self-gating in breath-hold reconstructions. A scoring of 1-4 for overall image quality, cardiac, and extracardiac diagnostic quality was used. STATISTICAL TESTS: Friedman's test was used to assess differences in qualitative scoring between observers. A Wilcoxon matched-pairs signed rank test was used to assess differences between breath-hold and free-breathing acquisitions and between observers' quantitative measurements. RESULTS: In all cases, 111 free-breathing and 145 breath-hold acquisitions, the automatically calculated DUS-based cardiac gating signal provided reconstructions of diagnostic quality (median score 4, range 1-4). Free-breathing did not affect the DUS-based cardiac gated retrospective radial reconstruction with respect to image or diagnostic quality (all P > 0.06). Motion detection with rejection/correction in k-space produced high-quality free-breathing DUS-based reconstructions [median 3, range (2-4)], whereas free-breathing self-gated methods failed in 80 out of 88 cases to produce a stable gating signal. DATA CONCLUSION: Free-breathing fetal cine cardiac MRI based on DUS gating and tyGRASP with motion compensation yields diagnostic images. This simplifies acquisition for the pregnant woman and thus could help increase fetal cardiac MRI acceptance in the clinic. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:260-272.

Cardiovascular effects of severe late-onset preeclampsia are reversed within six months postpartum.

OBJECTIVES: Preeclampsia (PE) is a common pregnancy-related disorder associated with cardiovascular long-term disease. Eighty percent are late-onset PE, occurring after 34 gestational weeks, and can present with severe symptoms. Magnitude and reversibility rate of maternal cardiovascular changes after severe late-onset PE have not been characterized. This study therefore evaluated longitudinal dynamics of maternal cardiovascular changes after severe late-onset PE. STUDY DESIGN: Six previously normotensive women with severe late-onset PE and eight pregnant controls were included. Severe PE was defined as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 110 mmHg and proteinuria with/without evidence of end-organ dysfunction, or SBP ≥ 140 mmHg or DBP ≥ 90 mmHg with/without proteinuria and with evidence of end-organ dysfunction. Cardiovascular function was assessed by magnetic resonance imaging at 1-3 days, one week and six months postpartum. RESULTS: Left ventricular mass at 1-3 days postpartum was higher after severe late-onset PE (57 g/m2) compared to after normal pregnancy (48 g/m2; p = 0.01). Pulse wave velocity (PWV) decreased between 1 and 3 days and six months postpartum after PE (6.1 to 5.0 m/s; p = 0.028). There was no difference in PWV 1-3 days postpartum after severe PE compared after normal pregnancy (6.1 versus 5.6 m/s; p = 0.175). Blood pressure normalized within six months in all but one patient. CONCLUSIONS: Cardiac effects after severe late-onset PE were small and transient. This indicates that left ventricular hypertrophy after severe late-onset PE may be a secondary physiologic response to increased peripheral resistance in PE. Vascular mechanisms rather than persistent cardiac hypertrophy postpartum may be the culprit for increased long-term cardiovascular risk after PE.

Quantification of blood flow in the fetus with cardiovascular magnetic resonance imaging using Doppler ultrasound gating: validation against metric optimized gating.

INTRODUCTION: Fetal cardiovascular magnetic resonance (CMR) imaging is used clinically and for research, but has been previously limited due to lack of direct gating methods. A CMR-compatible Doppler ultrasound (DUS) gating device has resolved this. However, the DUS-gating method is not validated against the current reference method for fetal phase-contrast blood flow measurements, metric optimized gating (MOG). Further, we investigated how different methods for vessel delineation affect flow volumes and observer variability in fetal flow acquisitions. AIMS: To 1) validate DUS gating versus MOG for quantifying fetal blood flow; 2) assess repeatability of DUS gating; 3) assess impact of region of interest (ROI) size on flow volume; and 4) compare time-resolved and static delineations for flow volume and observer variability. METHODS: Phase-contrast CMR was acquired in the fetal descending aorta (DAo) and umbilical vein by DUS gating and MOG in 22 women with singleton pregnancy in gestational week 360 (265-400) with repeated scans in six fetuses. Impact of ROI size on measured flow was assessed for ROI:s 50-150% of the vessel diameter. Four observers from two centers provided time-resolved and static delineations. Bland-Altman analysis was used to determine agreement between both observers and methods. RESULTS: DAo flow was 726 (348-1130) ml/min and umbilical vein flow 366 (150-782) ml/min by DUS gating. Bias±SD for DUS-gating versus MOG were - 45 ± 122 ml/min (-6 ± 15%) for DAo and 19 ± 136 ml/min (2 ± 24%) for umbilical vein flow. Repeated flow measurements in the same fetus showed similar volumes (median CoV = 11% (DAo) and 23% (umbilical vein)). Region of interest 50-150% of vessel diameter yielded flow 35-120%. Bias±SD for time-resolved versus static DUS-gated flow was 33 ± 39 ml/min (4 ± 6%) for DAo and 11 ± 84 ml/min (2 ± 15%) for umbilical vein flow. CONCLUSIONS: Quantification of blood flow in the fetal DAo and umbilical vein using DUS-gated phase-contrast CMR is feasible and agrees with the current reference method. Repeatability was generally high for CMR fetal blood flow assessment. An ROI similar to the vessel area or slightly larger is recommended. A static ROI is sufficient for fetal flow quantification using currently available CMR sequences.

Transcatheter closure of atrial septal defect in adults: time-course of atrial and ventricular remodeling and effects on exercise capacity.

Investigate ventricular and atrial remodeling following atrial septal defect (ASD) closure and examine if pulmonary-to-systemic flow ratio (QP/QS) and right ventricular (RV) volume predict improvement, determined as percentage of predicted oxygen uptake (VO2%). Long-term cardiovascular magnetic resonance (CMR) data on atrial and ventricular remodeling after ASD-closure is limited and treatment effect on exercise capacity is debated. Sixteen patients undergoing transcatheter ASD closure and 16 age and sexmatched controls were studied. CMR was performed before treatment, the day after and 3 and 12 months later. Exercise test with gas analysis was performed before and 12 months after treatment. QP/QS decreased from 2.1 ± 0.5 to 1.4 ± 0.3 at day 1 and 1.1 ± 0.1 at 3 and 12 months. Left ventricular (LV) volumes increased and normalized on day 1 whereas left atrial volumes were unchanged. RV and right atrial volumes decreased the first 3 months. LV and RV volumes had not equalized at 12 months (RV/LV ratio 1.2 ± 0.1, P < 0.01) and RV ejection fraction remained decreased compared to controls. Improvement of VO2% after ASD closure (P < 0.01) was inversely related to QP/QS at rest (r = - 0.56, P < 0.05) but unrelated to RV end-diastolic volume (P = 0.16). Following transcatheter ASD closure, LV adaptation is rapid and RV adaptation is prolonged, with decreased systolic RV function. Patients with smaller shunts had larger improvement in VO2% suggesting patients with defects of borderline hemodynamic significance might benefit from closure. This may be due to impaired LV diastolic function influencing shunt size and exercise capacity following ASD closure.

A new vessel segmentation algorithm for robust blood flow quantification from two-dimensional phase-contrast magnetic resonance images.

Blood flow measurements in the ascending aorta and pulmonary artery from phase-contrast magnetic resonance images require accurate time-resolved vessel segmentation over the cardiac cycle. Current semi-automatic segmentation methods often involve time-consuming manual correction, relying on user experience for accurate results. The purpose of this study was to develop a semi-automatic vessel segmentation algorithm with shape constraints based on manual vessel delineations for robust segmentation of the ascending aorta and pulmonary artery, to evaluate the proposed method in healthy volunteers and patients with heart failure and congenital heart disease, to validate the method in a pulsatile flow phantom experiment, and to make the method freely available for research purposes. Algorithm shape constraints were extracted from manual reference delineations of the ascending aorta (n = 20) and pulmonary artery (n = 20) and were included in a semi-automatic segmentation method only requiring manual delineation in one image. Bias and variability (bias ± SD) for flow volume of the proposed algorithm versus manual reference delineations were 0·0 ± 1·9 ml in the ascending aorta (n = 151; seven healthy volunteers; 144 heart failure patients) and -1·7 ± 2·9 ml in the pulmonary artery (n = 40; 25 healthy volunteers; 15 patients with atrial septal defect). Interobserver bias and variability were lower (P = 0·008) for the proposed semi-automatic method (-0·1 ± 0·9 ml) compared to manual reference delineations (1·5 ± 5·1 ml). Phantom validation showed good agreement between the proposed method and timer-and-beaker flow volumes (0·4 ± 2·7 ml). In conclusion, the proposed semi-automatic vessel segmentation algorithm can be used for efficient analysis of flow and shunt volumes in the aorta and pulmonary artery.