Left Ventricular Diastolic Function in Children with Atrial Septal Defects Improves After Closure by Means of Increased Hydraulic Force.

Hydraulic force aids diastolic filling of the left ventricle (LV) by facilitating basal movement of the atrioventricular plane. The short-axis atrioventricular area difference (AVAD) determines direction and magnitude of this force. Patients with atrial septal defect (ASD) have reduced LV filling due to the left-to-right shunt across the atrial septum and thus potentially altered hydraulic force. The aims were therefore to use cardiac magnetic resonance images to assess whether AVAD and thus the hydraulic force differ in children with ASD compared to healthy children, and if it improves after ASD closure. Twenty-two children with ASD underwent cardiac magnetic resonance before ASD closure. Of these 22 children, 17 of them repeated their examination also after ASD closure. Twelve controls were included. Left atrial and ventricular areas were delineated in short-axis images, and AVAD was defined as the largest ventricular area minus the largest atrial area at each time frame and normalized to body height (AVADi). At end diastole AVADi was positive in all participants, suggesting a force acting towards the atrium assisting the diastolic movement of the atrioventricular plane; however, lower in children both before (6.3 cm2/m [5.2-8.0]; p < 0.0001) and after ASD closure (8.7 cm2/m [6.6-8.5]; p = 0.0003) compared to controls (12.2 cm2/m [11.3-13.9]). Left ventricular diastolic function improves after ASD closure in children by means of improved hydraulic force assessed by AVAD. Although AVADi improved after ASD closure, it was still lower than in controls, indicating diastolic abnormality even after ASD closure. In patients where AVADi is low, ASD closure may help avoid diastolic function deterioration and improve outcome. This could likely be important also in patients with small shunt volumes, especially if they are younger, who currently do not undergo ASD closure. Changes in clinical routine may be considered pending larger outcome studies.

Atrioventricular Area Difference Aids Diastolic Filling in Patients with Repaired Tetralogy of Fallot.

A hydraulic force aids diastolic filling of the left ventricle (LV) and is proportional to the difference in short-axis area between the left ventricle and atrium; the atrioventricular area difference (AVAD). Patients with repaired Tetralogy of Fallot (rToF) and pulmonary regurgitation (PR) have reduced LV filling which could lead to a negative AVAD and a hydraulic force impeding diastolic filling. The aim was to assess AVAD and to determine whether the hydraulic force aids or impedes diastolic filling in patients with rToF and PR, compared to controls. Twelve children with rToF (11.5 [9-13] years), 12 pediatric controls (10.5 [9-13] years), 12 adults with rToF (21.5 [19-27] years) and 12 adult controls (24 [21-29] years) were retrospectively included. Cine short-axis images were acquired using cardiac magnetic resonance imaging. Atrioventricular area difference was calculated as the largest left ventricular short-axis area minus the largest left atrial short-axis area at beginning of diastole and end diastole and indexed to height (AVADi). Children and adults with rToF and PR had higher AVADi (0.3 cm2/m [- 1.3 to 0.8] and - 0.6 [- 1.5 to - 0.2]) at beginning of diastole compared to controls (- 2.7 cm2/m [- 4.9 to - 1.7], p = 0.015) and - 3.3 cm2/m [- 3.8 to - 2.8], p = 0.017). At end diastole AVADi did not differ between patients and controls. Children and adults with rToF and pulmonary regurgitation have an atrioventricular area difference that do not differ from controls and thus a net hydraulic force that contributes to left ventricular diastolic filling, despite a small underfilled left ventricle due to pulmonary regurgitation.

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.

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.

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.

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.

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.

Left and right ventricular hemodynamic forces in healthy volunteers and elite athletes assessed with 4D flow magnetic resonance imaging.

Intracardiac blood flow is driven by hemodynamic forces that are exchanged between the blood and myocardium. Previous studies have been limited to 2D measurements or investigated only left ventricular (LV) forces. Right ventricular (RV) forces and their mechanistic contribution to asymmetric redirection of flow in the RV have not been measured. We therefore aimed to quantify 3D hemodynamic forces in both ventricles in a cohort of healthy subjects, using magnetic resonance imaging 4D flow measurements. Twenty five controls, 14 elite endurance athletes, and 2 patients with LV dyssynchrony were included. 4D flow data were used as input for the Navier-Stokes equations to compute hemodynamic forces over the entire cardiac cycle. Hemodynamic forces were found in a qualitatively consistent pattern in all healthy subjects, with variations in amplitude. LV forces were mainly aligned along the apical-basal longitudinal axis, with an additional component aimed toward the aortic valve during systole. Conversely, RV forces were found in both longitudinal and short-axis planes, with a systolic force component driving a slingshot-like acceleration that explains the mechanism behind the redirection of blood flow toward the pulmonary valve. No differences were found between controls and athletes when indexing forces to ventricular volumes, indicating that cardiac force expenditures are tuned to accelerate blood similarly in small and large hearts. Patients' forces differed from controls in both timing and amplitude. Normal cardiac pumping is associated with specific force patterns for both ventricles, and deviation from these forces may be a sensitive marker of ventricular dysfunction. Reference values are provided for future studies.NEW & NOTEWORTHY Biventricular hemodynamic forces were quantified for the first time in healthy controls and elite athletes (n = 39). Hemodynamic forces constitute a slingshot-like mechanism in the right ventricle, redirecting blood flow toward the pulmonary circulation. Force patterns were similar between healthy subjects and athletes, indicating potential utility as a cardiac function biomarker.

Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic myocardial infarction even when the absolute atrioventricular plane displacement is decreased.

BACKGROUND: The majority (60%) of left ventricular (LV) stroke volume (SV) is generated by longitudinal shortening causing apical atrioventricular plane displacement (AVPD) in systole. The remaining SV is caused by radial inward motion of the epicardium both in the septal and the lateral wall. We aimed to determine if these longitudinal, septal and lateral contributions to LVSV are changed in patients with chronic myocardial infarction (MI). METHODS: Patients with a chronic (>3 months) ST-elevation MI in the left anterior descending (LAD, n = 20) or right coronary artery (RCA, n = 16) and healthy controls (n = 20) were examined with cardiovascular magnetic resonance (CMR). AVPD was quantified in long axis cine CMR images and LV volumes and dimensions in short axis cine images. RESULTS: AVPD was decreased both in patients with LAD-MI (11 ± 1 mm, p < 0.001) and RCA-MI (13 ± 1 mm, p < 0.05) compared to controls (15 ± 0 mm). However, the longitudinal contribution to SV was unchanged for both LAD-MI (58 ± 3%, p = 0.08) and RCA-MI (59 ± 3%, p = 0.09) compared to controls (64 ± 2%). The preserved longitudinal contribution despite decreased absolute AVPD was a results of increased epicardial dimensions (p < 0.01 for LAD-MI and p = 0.06 for RCA-MI). In LAD-MI the septal contribution to LVSV was decreased (5 ± 1%) compared to both controls (10 ± 1%, p < 0.01) and patients with RCA-MIs (10 ± 1%, p < 0.01). The lateral contribution was increased in LAD-MI patients (44 ± 3%) compared to both RCA-MI (35 ± 2%, p < 0.05) and controls (29 ± 2%, p < 0.001). CONCLUSION: Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic MI even when the absolute AVPD is decreased.

Physiological variation in left atrial transverse orientation does not influence orthogonal P-wave morphology.

BACKGROUND: It has previously been demonstrated that orthogonal P-wave morphology in healthy athletes does not depend on atrial size, but the possible impact of left atrial orientation on P-wave morphology remains unknown. In this study, we investigated if left atrial transverse orientation affects P-wave morphology in different populations. METHODS: Forty-seven patients with atrial fibrillation, 21 patients with arrhythmogenic right ventricular cardiomyopathy, 67 healthy athletes, and 56 healthy volunteers were included. All underwent cardiac magnetic resonance imaging or computed tomography and the orientation of the left atrium was determined. All had 12-lead electrocardiographic recordings, which were transformed into orthogonal leads and orthogonal P-wave morphology was obtained. RESULTS: The median left atrial transverse orientation was 87 (83, 91) degrees (lower and upper quartiles) in the total study population. There was no difference in left atrial transverse orientation between individuals with different orthogonal P-wave morphologies. CONCLUSIONS: The physiological variation in left atrial orientation was small within as well as between the different populations. There was no difference in left atrial transverse orientation between subjects with type 1 and type 2 P-wave morphology, implying that in this setting the P-wave morphology was more dependent on atrial conduction than orientation.

Time-resolved tracking of the atrioventricular plane displacement in Cardiovascular Magnetic Resonance (CMR) images.

BACKGROUND: Atrioventricular plane displacement (AVPD) is an indicator for systolic and diastolic function and accounts for 60% of the left ventricular, and 80% of the right ventricular stroke volume. AVPD is commonly measured clinically in echocardiography as mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE), but has not been applied widely in cardiovascular magnetic resonance (CMR). To date, there is no robust automatic algorithm available that allows the AVPD to be measured clinically in CMR with input in a single timeframe. This study aimed to develop, validate and provide a method that automatically tracks the left and right ventricular AVPD in CMR images, which can be used in the clinical setting or in applied cardiovascular research in multi-center studies. METHODS: The proposed algorithm is based on template tracking by normalized cross-correlation combined with a priori information by principal component analysis. The AVPD in each timeframe is calculated for the left and right ventricle separately using CMR long-axis cine images of the 2, 3, and 4-chamber views. The algorithm was developed using a training set (n = 40), and validated in a test set (n = 113) of healthy subjects, athletes, and patients after ST-elevation myocardial infarction from 10 centers. Validation was done using manual measurements in end diastole and end systole as reference standard. Additionally, AVPD, peak emptying velocity, peak filling velocity, and atrial contraction was validated in 20 subjects, where time-resolved manual measurements were used as reference standard. Inter-observer variability was analyzed in 20 subjects. RESULTS: In end systole, the difference between the algorithm and the reference standard in the left ventricle was (mean ± SD) -0.6 ± 1.9 mm (R = 0.79), and -0.8 ± 2.1 mm (R = 0.88) in the right ventricle. Inter-observer variability in end systole was -0.6 ± 0.7 mm (R = 0.95), and -0.5 ± 1.4 mm (R = 0.95) for the left and right ventricle, respectively. Validation of peak emptying velocity, peak filling velocity, and atrial contraction yielded lower accuracy than the displacement measures. CONCLUSIONS: The proposed algorithm show good agreement and low bias with the reference standard, and with an agreement in parity with inter-observer variability. Thus, it can be used as an automatic method of tracking and measuring AVPD in CMR.

Left ventricular atrioventricular plane displacement is preserved with lifelong endurance training and is the main determinant of maximal cardiac output.

Age-related decline in cardiac function can be prevented or postponed by lifelong endurance training. However, effects of normal ageing as well as of lifelong endurance exercise on longitudinal and radial contribution to stroke volume are unknown. The aim of this study was to determine resting longitudinal and radial pumping in elderly athletes, sedentary elderly and young sedentary subjects. Furthermore, we aimed to investigate determinants of maximal cardiac output in elderly. Eight elderly athletes (63 ± 4 years), seven elderly sedentary (66 ± 4 years) and ten young sedentary subjects (29 ± 4 years) underwent cardiac magnetic resonance imaging. All subjects underwent maximal exercise testing and for elderly subjects maximal cardiac output during cycling was determined using a dye dilution technique. Longitudinal and radial contribution to stroke volume did not differ between groups (longitudinal left ventricle (LV) 52-65%, P = 0.12, right ventricle (RV) 77-87%, P = 0.16, radial 7.9-8.6%, P = 1.0). Left ventricular atrioventricular plane displacement (LVAVPD) was higher in elderly athletes and young sedentary compared with elderly sedentary subjects (14 ± 3, 15 ± 2 and 11 ± 1 mm, respectively, P < 0.05). There was no difference between groups for RVAVPD (P = 0.2). LVAVPD was an independent predictor of maximal cardiac output (R(2) = 0.61, P < 0.01, ß = 0.78). Longitudinal and radial contributions to stroke volume did not differ between groups. However, how longitudinal pumping was achieved differed; elderly athletes and young sedentary subjects showed similar AVPD whereas this was significantly lower in elderly sedentary subjects. Elderly sedentary subjects achieved longitudinal pumping through increased short-axis area of the ventricle. Large AVPD was a determinant of maximal cardiac output and exercise capacity.

Whole-heart four-dimensional flow can be acquired with preserved quality without respiratory gating, facilitating clinical use: a head-to-head comparison.

BACKGROUND: Respiratory gating is often used in 4D-flow acquisition to reduce motion artifacts. However, gating increases scan time. The aim of this study was to investigate if respiratory gating can be excluded from 4D flow acquisitions without affecting quantitative intracardiac parameters. METHODS: Eight volunteers underwent CMR at 1.5 T with a 5-channel coil (5ch). Imaging included 2D flow measurements and whole-heart 4D flow with and without respiratory gating (Resp(+), Resp(-)). Stroke volume (SV), particle-trace volumes, kinetic energy, and vortex-ring volume were obtained from 4D flow-data. These parameters were compared between 5ch Resp(+) and 5ch Resp(-). In addition, 20 patients with heart failure were scanned using a 32-channel coil (32ch), and particle-trace volumes were compared to planimetric SV. Paired comparisons were performed using Wilcoxon's test and correlation analysis using Pearson r. Agreement was assessed as bias±SD. RESULTS: Stroke volume from 4D flow was lower compared to 2D flow both with and without respiratory gating (5ch Resp(+) 88±18 vs 97±24.0, p=0.001; 5ch Resp(-) 86±16 vs 97.1±22.7, p<0.01). There was a good correlation between Resp(+) and Resp(-) for particle-trace derived volumes (R2=0.82, 0.2±9.4 ml), mean kinetic energy (R2=0.86, 0.07±0.21 mJ), peak kinetic energy (R2=0.88, 0.14±0.77 mJ), and vortex-ring volume (R2=0.70, -2.5±9.4 ml). Furthermore, good correlation was found between particle-trace volume and planimetric SV in patients for 32ch Resp(-) (R2=0.62, -4.2±17.6 ml) and in healthy volunteers for 5ch Resp(+) (R2=0.89, -11±7 ml), and 5ch Resp(-) (R2=0.93, -7.5±5.4 ml), Average scan duration for Resp(-) was shorter compared to Resp(+) (27±9 min vs 61±19 min, p<0.05). CONCLUSIONS: Whole-heart 4D flow can be acquired with preserved quantitative results without respiratory gating, facilitating clinical use.

The relationship between longitudinal, lateral, and septal contribution to stroke volume in patients with pulmonary regurgitation and healthy volunteers.

Septal systolic motion is towards the left ventricle (LV) in healthy hearts. Patients with pulmonary regurgitation (PR) and right ventricular (RV) volume overload have systolic septal motion toward the RV. This may affect the longitudinal contribution from atrioventricular plane displacement (AVPD) and septal and lateral contribution to stroke volume (SV). The study aimed to quantify these contributions to SV in patients with PR. Cardiac magnetic resonance imaging was used for assessment of cardiac volumes. Patients (n = 30; age 9-59 yr) with PR due to surgically corrected tetralogy of Fallot and 54 healthy controls (age 10-66 yr) were studied. Longitudinal contribution to RVSV was 47 ± 2% (means ± SE) in patients with PR and 79 ± 1% in controls (P < 0.001). Lateral contribution to RVSV and LVSV was 40 ± 1 and 62 ± 2% in patients and 31 ± 1 and 36 ± 1% in controls (P < 0.001 for both). Septal motion contributed to RVSV by 8 ± 1% in patients and by 7 ± 1% to LVSV in controls (P < 0.001). PR patients have decreased longitudinal contribution to RVSV and increased lateral pumping, resulting in larger outer volume changes and septal motion towards the RV. The changes in RV pumping physiology may be explained by RV remodeling resulting in lower systolic inflow of blood into the right atrium in relation to SV. This avoids the development of pendulum volume between the caval veins and right atrium, which would occur in PR patients if longitudinal contribution to SV was preserved. Decreased AVPD suggests that tricuspid annular excursion, a marker of RV function, is less valid in these patients.

Atrial remodelling is less pronounced in female endurance-trained athletes compared with that in male athletes.

OBJECTIVES: Little data exists on atrial adaptation to training in women. Furthermore, data on right atrial (RA) volumes is lacking for both male and female athletes. The objective of this study was therefore to investigate atrial volumes in male and female athletes. DESIGN: A total of 75 athletes (33 women) and 53 controls (21 women) underwent cardiovascular magnetic resonance imaging. Left atrial (LA) and RA volumes were measured by manual delineation. The atrial appendage was included in the volumes, and pulmonary veins were excluded. RESULTS: Atrial volumes were larger in athletes compared with those in controls (males: LA 116 ± 19 ml versus 93 ± 19 ml, RA 166 ± 32 ml versus 133 ± 23 ml, p < 0.0001, females: LA 90 ± 15 ml versus 83 ± 17 ml, p < 0.05, RA 119 ± 24 ml versus 108 ± 18 ml, p = 0.07). When normalized for body surface area, atrial volumes remained larger in athletes. However, when normalized for total heart volume (THV) there were no differences between groups except for LA volumes in females where controls had higher LA/THV compared with those in athletes (p < 0.05). CONCLUSION: Atrial volumes were significantly larger in athletes. Atrial volumes normalized for THV did not differ between athletes and controls indicating a balanced enlargement. There was only a small difference between female controls and female athletes, suggesting that atrial adjustment to training is more modest in women.

Diastolic Filling in Patients After Heart Transplantation Is Impaired Due to an Altered Geometrical Relationship Between the Left Atrium and Ventricle.

BACKGROUND: The geometrical relationship between atrial and ventricular short-axis cross-sectional area determines the hydraulic forces acting on intracardiac blood. This is important for diastolic filling. In patients undergoing heart transplantation (HTx), the left atrium is often enlarged as a result of the standard surgical technique. We hypothesized that diastolic filling in HTx patients is affected by the surgery altering the geometrical relationship between atrium and ventricle. METHODS AND RESULTS: This retrospective, cross-sectional study included 25 HTx patients (median age, 52 [range, 25-70] years), 15 patients with heart failure with reduced ejection fraction (median age, 63 [range, 52-75] years), 15 patients with heart failure with preserved ejection fraction (median age, 74 [range, 56-82] years), and 15 healthy controls (median age, 64 [range, 58-67] years) who underwent cardiac magnetic resonance imaging. Left ventricular, atrial, and total heart volumes (THV) were obtained. Atrioventricular area difference at end diastole and end systole was calculated as the largest ventricular short-axis area minus the largest atrial short-axis area. Left atrial minimum volume normalized for THV (LAmin/THV) was larger in HTx patients (median, 0.13 [range, 0.07-0.19]) compared with controls (median, 0.05 [range, 0.03-0.08], P <0.001), whereas left ventricular volume normalized for THV (left ventricular end-diastolic volume/THV) was similar between HTx and controls (median, 0.19 [range, 0.12-0.24] and median, 0.22 [range, 0.20-0.25], respectively). At end diastole, when atrioventricular area difference reached its largest positive value in controls, 11 HTx patients (44%) had a negative atrioventricular area difference, indicating impaired diastolic filling. CONCLUSIONS: Diastolic filling is impaired in HTx patients due to an altered geometrical relationship between the left atrium and ventricle. When performing cardiac transplantation, a surgical technique that creates a smaller left atrium may improve diastolic filling by aiding hydraulic forces.

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.

Moderate intensity supine exercise causes decreased cardiac volumes and increased outer volume variations: a cardiovascular magnetic resonance study.

BACKGROUND: The effects on left and right ventricular (LV, RV) volumes during physical exercise remains controversial. Furthermore, no previous study has investigated the effects of exercise on longitudinal contribution to stroke volume (SV) and the outer volume variation of the heart. The aim of this study was to determine if LV, RV and total heart volumes (THV) as well as cardiac pumping mechanisms change during physical exercise compared to rest using cardiovascular magnetic resonance (CMR). METHODS: 26 healthy volunteers (6 women) underwent CMR at rest and exercise. Exercise was performed using a custom built ergometer for one-legged exercise in the supine position during breath hold imaging. Cardiac volumes and atrio-ventricular plane displacement were determined. Heart rate (HR) was obtained from ECG. RESULTS: HR increased during exercise from 60±2 to 94±2 bpm, (p<0.001). LVEDV remained unchanged (p=0.81) and LVESV decreased with -9±18% (p<0.05) causing LVSV to increase with 8±3% (p<0.05). RVEDV and RVESV decreased by -7±10% and -24±14% respectively, (p<0.001) and RVSV increased 5±17% during exercise although not statistically significant (p=0.18). Longitudinal contribution to RVSV decreased during exercise by -6±15% (p<0.05) but was unchanged for LVSV (p=0.74). THV decreased during exercise by -4±1%, (p<0.01) and total heart volume variation (THVV) increased during exercise from 5.9±0.5% to 9.7±0.6% (p<0.001). CONCLUSIONS: Cardiac volumes and function are significantly altered during supine physical exercise. THV becomes significantly smaller due to decreases in RVEDV whilst LVEDV remains unchanged. THVV and consequently radial pumping increases during exercise which may improve diastolic suction during the rapid filling phase.

Longitudinal strain from velocity encoded cardiovascular magnetic resonance: a validation study.

BACKGROUND: Regional myocardial function is typically evaluated by visual assessment by experienced users, or by methods requiring substantial post processing time. Visual assessment is subjective and not quantitative. Therefore, the purpose of this study is to develop and validate a simple method to derive quantitative measures of regional wall function from velocity encoded cardiovascular magnetic resonance (CMR), and provide associated normal values for longitudinal strain. METHOD: Both fast field echo (FFE) and turbo field echo (TFE) velocity encoded CMR images were acquired in three long axis planes in 36 healthy volunteers (13 women, 23 men), age 35±12 years. Strain was also quantified in 10 patients within one week after myocardial infarction. The user manually delineated myocardium in one time frame and strain was calculated as the myocardium was tracked throughout the cardiac cycle using an optimization formulation and mechanical a priori assumptions. A phantom experiment was performed to validate the method with optical tracking of deformation as an independent gold standard. RESULTS: There was an excellent agreement between longitudinal strain measured by optical tracking and longitudinal strain measured with TFE velocity encoding. Difference between the two methods was 0.0025 ± 0.085 (ns). Mean global longitudinal strain in the 36 healthy volunteers was -0.18 ± 0.10 (TFE imaging). Intra-observer variability for all segments was 0.00 ± 0.06. Inter-observer variability was -0.02 ± 0.07 (TFE imaging). The intra-observer variability for radial strain was high limiting the applicability of radial strain. Mean longitudinal strain in patients was significantly lower (-0.15± 0.12) compared to healthy volunteers (p<0.05). Strain (expressed as percentage of normal strain) in infarcted regions was lower compared to remote areas (p<0.01). CONCLUSION: In conclusion, we have developed and validated a robust and clinically applicable technique that can quantify longitudinal strain and regional myocardial wall function and present the associated normal values for longitudinal strain.