Biventricular shape modes discriminate pulmonary valve replacement in tetralogy of Fallot better than imaging indices.

Current indications for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) rely on cardiovascular magnetic resonance (CMR) image-based indices but are inconsistently applied, lead to mixed outcomes, and remain debated. This study aimed to test the hypothesis that specific markers of biventricular shape may discriminate differences between rTOF patients who did and did not require subsequent PVR better than standard imaging indices. In this cross-sectional retrospective study, biventricular shape models were customized to CMR images from 84 rTOF patients. A statistical atlas of end-diastolic shape was constructed using principal component analysis. Multivariate regression was used to quantify shape mode and imaging index associations with subsequent intervention status (PVR, n = 48 vs. No-PVR, n = 36), while accounting for confounders. Clustering analysis was used to test the ability of the most significant shape modes and imaging indices to discriminate PVR status as evaluated by a Matthews correlation coefficient (MCC). Geometric strain analysis was also conducted to assess shape mode associations with systolic function. PVR status correlated significantly with shape modes associated with right ventricular (RV) apical dilation and left ventricular (LV) dilation (p < 0.01), RV basal bulging and LV conicity (p < 0.05), and pulmonary valve dilation (p < 0.01). PVR status also correlated significantly with RV ejection fraction (p < 0.05) and correlated marginally with LV end-systolic volume index (p < 0.07). Shape modes discriminated subsequent PVR better than standard imaging indices (MCC = 0.49 and MCC = 0.28, respectively) and were significantly associated with RV and LV radial systolic strain. Biventricular shape modes discriminated differences between patients who did and did not require subsequent PVR better than standard imaging indices in current use. These regional features of cardiac morphology may provide insight into adaptive vs. maladaptive types of structural remodeling and point toward an improved quantitative, patient-specific assessment tool for clinical use.

Right-left ventricular shape variations in tetralogy of Fallot: associations with pulmonary regurgitation.

BACKGROUND: Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas. METHODS: In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8-24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole. RESULTS: PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p < 0.05). Increasing PRV was associated with RV dilation and basal bulging, in conjunction with decreased LV septal-lateral dimension (LV flattening) and systolic septal motion towards the RV (all p < 0.05). Increased global RV radial, longitudinal, circumferential and LV radial systolic strains were significantly associated with increased PRV (all p < 0.05). CONCLUSION: A biventricular atlas of rTOF patients quantified multivariate relationships between left-right ventricular morphometry and wall motion with pulmonary regurgitation. Regional RV dilation, LV reduction, LV septal-lateral flattening and increased RV strain were all associated with increased pulmonary regurgitant volume. Morphometric scores provide simple metrics linking mechanisms for structural and functional alteration with important clinical indices.

Right Ventricular Flow Vorticity Relationships With Biventricular Shape in Adult Tetralogy of Fallot.

Remodeling in adults with repaired tetralogy of Fallot (rToF) may occur due to chronic pulmonary regurgitation, but may also be related to altered flow patterns, including vortices. We aimed to correlate and quantify relationships between vorticity and ventricular shape derived from atlas-based analysis of biventricular shape. Adult rToF (n = 12) patients underwent 4D flow and cine MRI imaging. Vorticity in the RV was computed after noise reduction using a neural network. A biventricular shape atlas built from 95 rToF patients was used to derive principal component modes, which were associated with vorticity and pulmonary regurgitant volume (PRV) using univariate and multivariate linear regression. Univariate analysis showed that indexed PRV correlated with 3 modes (r = -0.55,-0.50, and 0.6, all p < 0.05) associated with RV dilatation and an increase in basal bulging, apical bulging and tricuspid annulus tilting with more severe regurgitation, as well as a smaller LV and paradoxical movement of the septum. RV outflow and inflow vorticity were also correlated with these modes. However, total vorticity over the whole RV was correlated with two different modes (r = -0.62,-0.69, both p < 0.05). Higher vorticity was associated with both RV and LV shape changes including longer ventricular length, a larger bulge beside the tricuspid valve, and distinct tricuspid tilting. RV flow vorticity was associated with changes in biventricular geometry, distinct from associations with PRV. Flow vorticity may provide additional mechanistic information in rToF remodeling. Both LV and RV shapes are important in rToF RV flow patterns.

Estimation of myocardial strain from non-rigid registration and highly accelerated cine CMR.

Sparsely sampled cardiac cine accelerated acquisitions show promise for faster evaluation of left-ventricular function. Myocardial strain estimation using image feature tracking methods is also becoming widespread. However, it is not known whether highly accelerated acquisitions also provide reliable feature tracking strain estimates. Twenty patients and twenty healthy volunteers were imaged with conventional 14-beat/slice cine acquisition (STD), 4× accelerated 4-beat/slice acquisition with iterative reconstruction (R4), and a 9.2× accelerated 2-beat/slice real-time acquisition with sparse sampling and iterative reconstruction (R9.2). Radial and circumferential strains were calculated using non-rigid registration in the mid-ventricle short-axis slice and inter-observer errors were evaluated. Consistency was assessed using intra-class correlation coefficients (ICC) and bias with Bland-Altman analysis. Peak circumferential strain magnitude was highly consistent between STD and R4 and R9.2 (ICC = 0.876 and 0.884, respectively). Average bias was -1.7 ± 2.0 %, p < 0.001, for R4 and -2.7 ± 1.9 %, p < 0.001 for R9.2. Peak radial strain was also highly consistent (ICC = 0.829 and 0.785, respectively), with average bias -11.2 ± 18.4 %, p < 0.001, for R4 and -15.0 ± 21.2 %, p < 0.001 for R9.2. STD circumferential strain could be predicted by linear regression from R9.2 with an R2 of 0.82 and a root mean squared error of 1.8 %. Similarly, radial strain could be predicted with an R2 of 0.67 and a root mean squared error of 21.3 %. Inter-observer errors were not significantly different between methods, except for peak circumferential strain R9.2 (1.1 ± 1.9 %) versus STD (0.3 ± 1.0 %), p = 0.011. Although small systematic differences were observed in strain, these were highly consistent with standard acquisitions, suggesting that accelerated myocardial strain is feasible and reliable in patients who require short acquisition durations.

In-line automated tracking for ventricular function with magnetic resonance imaging.

An efficient nonrigid registration algorithm was implemented on the image reconstruction computer to enable in-line automatic tracking of features in steady-state free precession cine images. Four-dimensional left ventricle function analysis was performed with and without use of the in-line automatic tracking result. The method was tested in 30 patients referred for cardiac magnetic resonance imaging for a variety of clinical assessments. The time required for in-line tracking was 10 +/- 2 s per slice using an image reconstructor with dual Advanced Micro Devices single-core Opteron 248 CPUs (2.2 GHz) and 8GB random access memory. The precision of clinical estimates of left ventricular volumes was significantly improved relative to the ground truth research estimates with automatic tracking versus without (6 ml vs. 9 ml in end-diastolic volume; 5 ml vs. 10 ml in end-systolic volume; both p < 0.05). In-line automatic tracking of image features shows promise for facilitating clinical analysis of ventricular function.

Giant congenital coronary artery aneurysm in pulmonary atresia with intact septum.

Congenital coronary artery fistula is frequently associated with pulmonary atresia and intact ventricular septum (PA/IVS). Aneurysmal dilatation is rare, and can be complicated by rupture, distal thrombi and myocardial ischaemia.

Mapping of mitral regurgitant defects by cardiovascular magnetic resonance in moderate or severe mitral regurgitation secondary to mitral valve prolapse.

PURPOSE: In mitral valve prolapse, determining whether the valve is suitable for surgical repair depends on the location and mechanism of regurgitation. We assessed whether cardiovascular magnetic resonance (CMR) could accurately identify prolapsing or flail mitral valve leaflets and regurgitant jet direction in patients with known moderate or severe mitral regurgitation. METHODS: CMR of the mitral valve was compared with trans-thoracic echocardiography (TTE) in 27 patients with chronic moderate to severe mitral regurgitation due to mitral valve prolapse. Contiguous long-axis high temporal resolution CMR cines perpendicular to the valve commissures were obtained across the mitral valve from the medial to lateral annulus. This technique allowed systematic valve inspection and mapping of leaflet prolapse using a 6 segment model. CMR mapping was compared with trans-oesophageal echocardiography (TOE) or surgical inspection in 10 patients. RESULTS: CMR and TTE agreed on the presence/absence of leaflet abnormality in 53 of 54 (98%) leaflets. Prolapse or flail was seen in 36 of 54 mitral valve leaflets examined on TTE. CMR and TTE agreed on the discrimination of prolapse from flail in 33 of 36 (92%) leaflets and on the predominant regurgitant jet direction in 26 of the 27 (96%) patients. In the 10 patients with TOE or surgical operative findings available, CMR correctly classified presence/absence of segmental abnormality in 49 of 60 (82%) leaflet segments. CONCLUSION: Systematic mitral valve assessment using a simple protocol is feasible and could easily be incorporated into CMR studies in patients with mitral regurgitation due to mitral valve prolapse.

The prevalence of coronary arterial abnormalities in pulmonary atresia with intact ventricular septum and their influence on surgical results.

BACKGROUND: The relatively high mortality in patients with pulmonary atresia and intact ventricular septum may be related to the presence of significant coronary arterial anomalies. This retrospective review of cineangiocardiograms was undertaken to further elucidate the types and variety of such coronary arterial abnormalities, and to assess their effect on postoperative survival. MATERIAL AND RESULTS: Details regarding coronary arterial anatomy and abnormalities were assessed in 116 patients. We noted the site and severity of lesions, and the presence of fistulous communications from the right ventricle to the coronary arteries, assessing the proportion of left ventricular myocardium affected by coronary arterial interruptions or significant stenoses, in other words, the amount dependent on coronary circulation from the right ventricle. We also measured diameters of the tricuspid and mitral valves. Fistulas were found in 87 patients (75%), interruptions of major coronary arteries in 40 patients (34%), lack of connections between the coronary arteries and the aorta in 18 patients (16%), and single origin of a coronary artery, with the right coronary artery arising from the left, in 6 patients (5%). We found increased mortality in 47 patients (40%) who had a right ventricular-dependent coronary arterial circulation. The presence of fistulas in itself was not associated with higher mortality, but the presence of coronary arterial interruptions (p = 0.05), and a higher myocardial score (p = 0.0009), were. CONCLUSION: We encountered a higher prevalence of both coronary arterial abnormalities and right ventricular-dependent circulation than previously reported. Awareness of the severity of the coronary arterial abnormalities should assist in planning treatment.

Midwall shortening after coarctation repair: the effect of through-plane motion on single-plane indices of left ventricular function.

Left ventricular midwall function is increased after repair of coarctation of the aorta (CoA). The cause is unclear. This study aimed to examine the variance between fiber shortening derived from 3-dimensional models of myocardial deformation, and 1- and 2-dimensional indices of left ventricular systolic function. In all, 15 young adults after CoA and 15 matched control subjects were recruited. Endocardial and midwall fractional shortening were calculated using M-mode echocardiography. Ejection fraction, midwall fractional shortening, and myocardial deformation were calculated or measured from magnetic resonance (MR) imaging. Echocardiographic and cine-MR imaging midwall fractional shortening were increased after CoA (P = .02 and < .001). In contrast, 3-dimensional MR tagging demonstrated normal midwall circumferential shortening and decreased longitudinal shortening in the CoA group (P < .01). Cine MR midwall shortening, recalculated to allow for through-plane motion, was similar to tagged midwall shortening, with no difference between the CoA and control groups. After CoA, measures of left ventricular function systematically overestimate midwall fiber shortening unless the methodology accounts for through-plane motion.

Congenital arteriovenous fistula between an intercostal artery and the left brachiocephalic vein.

Congenital arteriovenous fistulas between the thoracic arteries and the systemic veins are rare, and in clinical terms may mimic patency of the arterial duct. We present a neonate with a large arteriovenous fistula between the left sixth intercostal artery and the left brachiocephalic vein, to the best of our knowledge a unique site of drainage. To our knowledge, ours is also the earliest presentation and treatment of a thoracic arteriovenous fistula.

Three-dimensional assessment of left ventricular systolic strain in patients with type 2 diabetes mellitus, diastolic dysfunction, and normal ejection fraction.

Left ventricular (LV) diastolic dysfunction often occurs in patients with type 2 diabetes mellitus (DM) independent of atherosclerotic coronary artery disease, myocardial ischemia, and regional wall motion anomalies. Limited information exists on LV myocardial tissue strain in this patient group. We measured 3-dimensional (3-D) parameters of LV systolic and diastolic functions in 28 patients who had type 2 DM (age 33 to 70 years), standard echocardiographic evidence of LV diastolic dysfunction, and normal LV ejection fraction, and 31 normal control subjects (age 19 to 74 years) who had no evidence of cardiac disease, with multislice cine anatomic and tagged magnetic resonance imaging. Three-dimensional analysis of the resulting images showed that peak systolic mitral valve plane displacement was 12% smaller (p = 0.040) and peak diastolic mitral valve plane velocity was 21% lower (p = 0.008) in patients who had DM than in normal controls. Peak systolic circumferential and longitudinal strains and principal 3-D shortening strain were 14%, 22%, and 10% smaller, respectively, in the DM group (p <0.001 for each). Peak diastolic rate of relaxation of circumferential and longitudinal strains and principal 3-D shortening strain were 35%, 32%, and 33% lower, respectively, in the DM group (p <0.001 for each). Thus, LV systolic circumferential, longitudinal and 3-D principal strains, and diastolic strain rates are impaired in patients who have type 2 DM, LV diastolic dysfunction, and normal LV ejection fraction.

Regeneration of the heart in diabetes by selective copper chelation.

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Although altered systemic regulation of transition metals in diabetes has been the subject of previous investigation, it is not known whether changed transition metal metabolism results in heart disease in common forms of diabetes and whether metal chelation can reverse the condition. We found that administration of the Cu-selective transition metal chelator trientine to rats with streptozotocin-induced diabetes caused increased urinary Cu excretion compared with matched controls. A Cu(II)-trientine complex was demonstrated in the urine of treated rats. In diabetic animals with established heart failure, we show here for the first time that 7 weeks of oral trientine therapy significantly alleviated heart failure without lowering blood glucose, substantially improved cardiomyocyte structure, and reversed elevations in left ventricular collagen and beta(1) integrin. Oral trientine treatment also caused elevated Cu excretion in humans with type 2 diabetes, in whom 6 months of treatment caused elevated left ventricular mass to decline significantly toward normal. These data implicate accumulation of elevated loosely bound Cu in the mechanism of cardiac damage in diabetes and support the use of selective Cu chelation in the treatment of this condition.

Age-related changes in myocardial relaxation using three-dimensional tagged magnetic resonance imaging.

PURPOSE: Marked changes in left ventricular diastolic filling occur with advancing age, but alterations in myocardial movement accompanying these findings have not been previously documented. We aimed to identify differences in myocardial motion during relaxation and diastole using magnetic resonance imaging (MRI), with tagging, which uniquely allows accurate, noninvasive assessment of myocardial movement in three dimensions. METHODS: Tagged MRI images from two groups of normal individuals were analyzed using dedicated computer software to provide values for group comparison of apical rotation, torsion, and circumferential and longitudinal strain throughout the cardiac cycle. RESULTS: The mean age of the younger group was 22 years, (n = 15) and that of the older group was 69 years, (n = 16). In the older group, peak apical rotation and torsion were increased during systole and significantly more apical rotation, torsion, circumferential, and longitudinal strain persisted during myocardial relaxation and diastole. In addition, peak normalized reversal of apical rotation was reduced (-5.1 +/- 1.2 degrees s-1 vs. -6.7 +/- 1.2 degrees s-1, p = 0.001), and there were slower peak rates of circumferential lengthening (76.2 +/- 28% s-1 vs. 142.5 +/- 17% s-1, p < 0.001) and longitudinal lengthening (62.7 +/- 21% s-1 vs. 122.5 +/- 20% s-1, p < 0.001). CONCLUSIONS: Tagged MRI is a unique, noninvasive imaging method that can identify significant prolongation and reduction of myocardial relaxation in older compared with young normal individuals.

Aging alters patterns of regional nonuniformity in LV strain relaxation: a 3-D MR tissue tagging study.

Although age-related impairment of diastolic function is well documented, patterns of regional tissue relaxation impairment with age have not been characterized. MRI tissue tagging with a regional three-dimensional (3-D) analysis was performed in 15 younger (age 19-26 yr) and 16 older (age 60-74 yr) normal, healthy volunteers. The peak rate of relaxation of circumferential strain (RC) was decreased in the older group (on average, 105 +/- 28 vs. 163 +/- 18 %/s for older vs. younger, mean +/- SD, P < 0.001) to a greater extent in the lateral wall than in the septum (P = 0.016) and to a greater extent in the apex than in the base (P < 0.001). Peak rate of relaxation of longitudinal strain (RL) was also reduced with age (94 +/- 27 vs. 155 +/- 18 %/s, P < 0.001) to a greater extent in the apex than in the base (P < 0.001). Both RC and RL were greater in the apex than in the base only in the younger subjects (P < 0.001 for each). Peak rate of torsion reversal (RT) was reduced with age (74 +/- 16 vs. 91 +/- 15 degrees/s, P = 0.006) to a greater extent in the base than in the apex (P = 0.035). An increase in regional asynchrony in time to RC and time to RL (P < 0.001 for each), but not time to RT, occurred with age. Thus patterns of regional nonuniformity of myocardial relaxation are altered in a consistent fashion with aging.

Temporal evolution of left ventricular strain late after repair of coarctation of the aorta using 3D MR tissue tagging.

PURPOSE: Following repair of coarctation of the aorta (CoA), LV mass is increased along with morbidity and mortality. Previous studies have reported increased shortening indices and impaired diastolic function. However, direct measurements of local material motion and temporal evolution of strain have been lacking. METHODS: Magnetic resonance (MR) tissue tagging was used to quantify regional three-dimensional myocardial deformation throughout systole and much of diastole in 14 patients (aged 19-23) who had CoA repair 17-23 years previously, and 15 age-, sex- and BSA-matched normal volunteers (NV). RESULTS: Mass to end-diastolic volume ratio was increased in the CoA group (1.23 +/- 0.12 g/mL CoA vs. 1.14 +/- 0.10 g/mL NV, p = 0.039), together with ejection fraction (65.3 +/- 4.4 vs. 60.8 +/-1.9%, p = 0.001) and systolic blood pressure (132.5 +/- 14.5 vs. 117.3 +/- 11.6 mmHg, p = 0.004). At end-systole, circumferential shortening was normal, but longitudinal shortening was decreased (14.9 +/- 1.3 vs. 16.8 +/- 1.4%, p < 0.001). Although systolic strain rates were not significantly different, early diastolic strain rate (EDSR) in the CoA group was increased in the circumferential direction (-71 +/- 23 vs. -52 +/- 20%/sec, p = 0.029), but decreased in the longitudinal direction (-27 +/- 12 vs. -39 +/- 11%/sec, p = 0.015). Longitudinal shortening and circumferential EDSR were related to right arm-leg pressure gradient (R2 = 0.20, p = 0.016 and R2 = 0.38, p < 0.001, respectively) and to mass index (R2 = 0.18, p = 0.024 and R2 = 014, p = 0.049, respectively). CONCLUSIONS: MR tagging allows quantitative information on the temporal evolution of myocardial deformation. Directionally dependent changes in strain evolution are seen late after CoA repair. These changes are related to both persistent arm-leg pressure gradient and degree of hypertrophy and may be indicators of developing dysfunction.