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AIMS: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene. It has been observed that FBN1 deficient mice have reduced left ventricular (LV) systolic function which is correlated to increased transforming growth factor-beta activity. This study aimed to ascertain LV functional abnormalities in MFS patients using M-mode and tissue Doppler imaging (TDI). METHODS AND RESULTS: In 66 (15-58 years) MFS patients and 61 normal controls, ejection fraction (EF) was evaluated by Simpson's biplane method. Atrioventricular plane displacement (AVPD) obtained from five mitral annular regions was also assessed using M-mode and TDI techniques. To overcome limitations associated with conventional M-mode echocardiography, anatomical and colour anatomical M-mode were also utilized. Ejection fraction was significantly reduced in MFS patients when compared to controls (66.3 +/- 0.74 vs. 71.9 +/- 0.56, P < 0.001), although it was within the normal range. M-mode and TDI AVPD measurements obtained from lateral, septal, inferior, anterior and posterior mitral annular regions were also significantly reduced in MFS patients in comparison to controls (P <0.001, for all measurements). CONCLUSION: Left ventricular long-axis systolic function is significantly reduced in MFS patients. This data suggests that LV function should be monitored in MFS and appropriate treatment applied if necessary. [ABSTRACT FROM AUTHOR]

Background: Abnormal atrioventricular and intraventricular electrical conduction and dysfunction of the functional right ventricle (fRV) are common in Ebstein anomaly (EA). However, fRV mechanical dyssynchrony and its relation to fRV function are poorly characterized. We evaluated fRV mechanical dyssynchrony in EA patients in relation to fRV remodeling, dysfunction, and exercise intolerance., Methods: We retrospectively analyzed data from nonoperated EA patients and age-matched controls who underwent echocardiography, cardiovascular magnetic resonance imaging, and cardiopulmonary exercise testing to quantify right ventricular (RV) remodeling, dysfunction, and exercise capacity. The relation of these to fRV dyssynchrony was retrospectively investigated. Right ventricular mechanical dyssynchrony was defined by early fRV septal activation (right-sided septal flash), RV lateral wall prestretch/late contraction, postsystolic shortening, and intra-RV delay using two-dimensional strain echocardiography. The SD of time to peak shortening among the fRV segments was calculated as a parameter of mechanical dispersion., Results: Thirty-five EA patients (10 of whom were <18 years of age) and 35 age-matched controls were studied. Ebstein anomaly patients had worse RV function and increased intra-RV dyssynchrony versus controls. Nineteen of 35 (54%) EA patients had early septal activation with simultaneous stretch and consequent late activation and postsystolic shortening of RV lateral segments. Intra-fRV mechanical delay correlated with fRV end-diastolic volume index (r = 0.43, P < .05) and fRV end-systolic volume index (r = 0.63, P < .001). The fRV ejection fraction was lower in EA with versus without right-sided septal flash (44.9 ± 11.0 vs 54.2 ± 8.2, P = .012). The fRV mechanical dispersion correlated with the percentage of predicted peak VO 2 (r = -0.35, P < .05)., Conclusions: In EA, fRV mechanical dyssynchrony is associated with fRV remodeling, dysfunction, and impaired exercise capacity. Mechanical dyssynchrony as a therapeutic target in selected EA patients warrants further study., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: We investigated left ventricular (LV) remodeling, mechanics, systolic and diastolic function, combined with clinical characteristics and heart-failure treatment in association to death or heart-transplant (DoT) in pediatric idiopathic, genetic or familial dilated cardiomyopathy (DCM), using interpretable machine-learning., Methods and Results: Echocardiographic and clinical data from pediatric DCM and healthy controls were retrospectively analyzed. Machine-learning included whole cardiac-cycle regional longitudinal strain, aortic, mitral and pulmonary vein Doppler velocity traces, age and body surface area. We used unsupervised multiple kernel learning for data dimensionality reduction, positioning patients based on complex conglomerate information similarity. Subsequently, k-means identified groups with similar phenotypes. The proportion experiencing DoT was evaluated. Pheno-grouping identified 5 clinically distinct groups that were associated with differing proportions of DoT. All healthy controls clustered in groups 1 to 2, while all, but one, DCM subjects, clustered in groups 3 to 5; internally validating the algorithm. Cluster-5 comprised the oldest, most medicated patients, with combined systolic and diastolic heart-failure and highest proportion of DoT. Cluster-4 included the youngest patients characterized by severe LV remodeling and systolic dysfunction, but mild diastolic dysfunction and the second-highest proportion of DoT. Cluster-3 comprised young patients with moderate remodeling and systolic dysfunction, preserved apical strain, pronounced diastolic dysfunction and lowest proportion of DoT., Conclusions: Interpretable machine-learning, using full cardiac-cycle systolic and diastolic data, mechanics and clinical parameters, can potentially identify pediatric DCM patients at high-risk for DoT, and delineate mechanisms associated with risk. This may facilitate more precise prognostication and treatment of pediatric DCM., Competing Interests: Disclosure statement The authors report no conflict of interest. Patricia Garcia-Canadilla has received funding from the postdoctoral fellowships program Beatriu de Pinos (2018-BP-00201), funded by the Secretary of Universities and Research (Goverment of Catalonia) and by the Horizon 2020 programme of research and innovation of the European Union under the Marie Skłodowska-Curie grant agreement Nº 801370. Pablo Miki Martí-Castellote has received funding from the predoctoral fellowships program FI-SDUR (2020-FISDU-00169) from AGAUR., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Endurance exercise competitions have shown a transient negative effect on global right ventricular (RV) performance. Most published studies are based on terrestrial sports. The aim of our study was to evaluate the cardiac effects after an open water swimming race., Methods: We evaluated 33 healthy swimmers (mean age 40.9 ± 7.2) participating in a 9.5 km open water swimming race. All subjects underwent a standard transthoracic echocardiography including an evaluation of dimensions and myocardial ventricular deformation. Echocardiography was performed 24 h before and within the first hour of arrival at the finish line. Cardiac troponin I (cTn I), NT-ProBNP and leukocytes were also evaluated., Results: No changes in left ventricle (LV) ejection fraction or LV global longitudinal strain were observed. A significant increase in RV end-diastolic area (RVEDA) was noted after the race (RVEDA at baseline 15.12 ± 1.86; RVEDA after race 16.06 ± 2.27, p < 0.05), but no changes were seen in RV fractional area change or RV global longitudinal strain. Cardiac biomarkers and leukocytes significantly increased. No association was detected between the increase in cTn I or NT-proBNP and the RV acute dilatation or LV performance. A significant association was observed between cTn I and leukocytes (r = 0.375, p < 0.05)., Conclusions: An acute RV dilatation but without an impairment in RV deformation was observed after participating in an endurance swimming race. The correlation between the increase in cTn I and leukocytes, but not with ventricular performance, may support the hypothesis of an exercise-induced increase in myocardial sarcolemmal permeability due to an inflammatory response rather than myocardial injury.

Background: Current diagnosis of heart failure with preserved ejection fraction (HFpEF) is suboptimal. We tested the hypothesis that comprehensive machine learning (ML) of left ventricular function at rest and exercise objectively captures differences between HFpEF and healthy subjects., Methods and Results: One hundred fifty-six subjects aged >60 years (72 HFpEF+33 healthy for the initial analyses; 24 hypertensive+27 breathless for independent evaluation) underwent stress echocardiography, in the MEDIA study (Metabolic Road to Diastolic Heart Failure). Left ventricular long-axis myocardial velocity patterns were analyzed using an unsupervised ML algorithm that orders subjects according to their similarity, allowing exploration of the main trends in velocity patterns. ML identified a continuum from health to disease, including a transition zone associated to an uncertain diagnosis. Clinical validation was performed (1) to characterize the main trends in the patterns for each zone, which corresponded to known characteristics and new features of HFpEF; the ML-diagnostic zones differed for age, body mass index, 6-minute walk distance, B-type natriuretic peptide, and left ventricular mass index ( P <0.05) and (2) to evaluate the consistency of the proposed groupings against diagnosis by current clinical criteria; correlation with diagnosis was good (κ, 72.6%; 95% confidence interval, 58.1-87.0); ML identified 6% of healthy controls as HFpEF. Blinded reinterpretation of imaging from subjects with discordant clinical and ML diagnoses revealed abnormalities not included in diagnostic criteria. The algorithm was applied independently to another 51 subjects, classifying 33% of hypertensive and 67% of breathless controls as mild-HFpEF., Conclusions: The analysis of left ventricular long-axis function on exercise by interpretable ML may improve the diagnosis and understanding of HFpEF., (© 2018 American Heart Association, Inc.)

Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): -2.9 ± 0.5 vs. -3.3 ± 0.6 s -1 , SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: -3.3 ± 0.6 vs. -3.0 ± 0.4 s -1 and basal SR: -3.3 ± 0.7 vs. -2.7 ± 0.6 s -1 , MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive. NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right ventricular adaptation to physical activity follows a biphasic, dose-dependent, and segmentary pattern. Moderate exercise promotes a mild systolic function enhancement at the right ventricular apex and more intense exercise impairs systolic and diastolic function., (Copyright © 2017 the American Physiological Society.)

Structural analysis of biological membranes is important for understanding cell and sub-cellular organelle function as well as their interaction with the surrounding environment. Imaging of whole cells in three dimension at high spatial resolution remains a significant challenge, particularly for thick cells. Cryo-transmission soft X-ray microscopy (cryo-TXM) has recently gained popularity to image, in 3D, intact thick cells (∼10μm) with details of sub-cellular architecture and organization in near-native state. This paper reports a new tool to segment and quantify structural changes of biological membranes in 3D from cryo-TXM images by tracking an initial 2D contour along the third axis of the microscope, through a multi-scale ridge detection followed by an active contours-based model, with a subsequent refinement along the other two axes. A quantitative metric that assesses the grayscale profiles perpendicular to the membrane surfaces is introduced and shown to be linearly related to the membrane thickness. Our methodology has been validated on synthetic phantoms using realistic microscope properties and structure dimensions, as well as on real cryo-TXM data. Results demonstrate the validity of our algorithms for cryo-TXM data analysis.

Aortic wall stiffness, tear size and location and the presence of abdominal side branches arising from the false lumen (FL) are key properties potentially involved in FL enlargement in chronic aortic dissections (ADs). We hypothesize that temporal variations on FL flow patterns, as measured in a cross-section by phase-contrast magnetic resonance imaging (PC-MRI), could be used to infer integrated information on these features. In 33 patients with chronic descending AD, instantaneous flow profiles were quantified in the FL at diaphragm level by PC-MRI. We used a lumped-parameter model to assess the changes in flow profiles induced by wall stiffness, tear size/location, and the presence of abdominal side branches arising from the FL. Four characteristic FL flow patterns were identified in 31/33 patients (94%) based on the direction of flow in systole and diastole: BA = systolic biphasic flow and primarily diastolic antegrade flow (n = 6); BR = systolic biphasic flow and primarily diastolic retrograde flow (n = 14); MA = systolic monophasic flow and primarily diastolic antegrade flow (n = 9); MR = systolic monophasic flow and primarily diastolic retrograde flow (n = 2). In the computational model, the temporal variation of flow directions within the FL was highly dependent on the position of assessment along the aorta. FL flow patterns (especially at the level of the diaphragm) showed their characteristic patterns due to variations in the cumulative size and the spatial distribution of the communicating tears, and the incidence of visceral side branches originating from the FL. Changes in wall stiffness did not change the temporal variation of the flows whereas it importantly determined intraluminal pressures. FL flow patterns implicitly codify morphological information on key determinants of aortic expansion in ADs. This data might be taken into consideration in the imaging protocol to define the predictive value of FL flows., Competing Interests: The authors have declared that no competing interests exist.

We propose an independent objective method to characterize different patterns of functional responses to stress in the heart failure with preserved ejection fraction (HFPEF) syndrome by combining multiple temporally-aligned myocardial velocity traces at rest and during exercise, together with temporal information on the occurrence of cardiac events (valves openings/closures and atrial activation). The method builds upon multiple kernel learning, a machine learning technique that allows the combination of data of different nature and the reduction of their dimensionality towards a meaningful representation (output space). The learning process is kept unsupervised, to study the variability of the input traces without being conditioned by data labels. To enhance the physiological interpretation of the output space, the variability that it encodes is analyzed in the space of input signals after reconstructing the velocity traces via multiscale kernel regression. The methodology was applied to 2D sequences from a stress echocardiography protocol from 55 subjects (22 healthy, 19 HFPEF and 14 breathless subjects). The results confirm that characterization of the myocardial functional response to stress in the HFPEF syndrome may be improved by the joint analysis of multiple relevant features., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: This study sought to understand and characterize the acute atrial response to endurance exercise and the influence of the amount of exercise performed., Background: Endurance exercise seems to be recognized as a risk factor for developing atrial arrhythmia. Atrial geometrical and functional remodeling may be the underlying substrate., Methods: Echocardiography was performed in 55 healthy adults at baseline and after a 3-stage trail race: a short race (S) (14 km), n = 17; a medium race (M) (35 km), n = 21; and a long race (L) (56 km), n = 17. Analysis consisted of standard, speckle-tracking assessment of both the left ventricle (LV) and right ventricle (RV) and both the left atrium (LA) and the right atrium (RA): a-wave strain (Sa) and strain rate (Ra) as a surrogate for atrial contractile function and s-wave strain (St) and strain rate (SR) as reservoir function., Results: After the race, RA reservoir function decreased in group M (Δ% SRs: -12.5) and further in group L (Δ% SRs: -15.4), with no changes in group S. RA contractile function decreased in group L (Δ% SRa: -9.3), showed no changes in group M (Δ% SRa: +0.7), and increased in group S (Δ% SRa: +14.8). A similar trend was documented in LA reservoir and contractile function but with less pronounced changes. The decrease in RA reservoir after the race correlated with the decrease in RV global longitudinal strain (GLS) (Δ% RVGLS vs. RASt and RASRs: +0.44; p < 0.05 and +0.41, respectively; p < 0.05)., Conclusions: During a trail-running race, an acute exercise-dose dependent impairment in atrial function was observed, mostly in the RA, which was related to RV systolic dysfunction. The impact on atrial function of long-term endurance training might lead to atrial remodeling, favoring arrhythmia development., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Highly trained athletes show an increased risk of atrial arrhythmias. Little is known about atrial volumes and function during exercise in this population. Our aim was to analyze atrial size and contractile function during exercise. Fifty endurance athletes with 11 ± 8 h of training per week and 30 sedentary control subjects were included. Echocardiography was performed at baseline and during exercise. Left (LA) and right atrial (RA) size and function were assessed by two-dimensional echocardiography. Peak negative strain (Sa) during atrial contraction and active atrial emptying volume (AEV) were measured. Athletes and control subjects showed a significant increment of deformation and AEV of both atria with exercise (P < 0.01 vs baseline for LA and RA). Among athletes, a subgroup with significant LA (n = 8)/RA (n = 15) dilatation (≥40 mL/m 2 ) showed a significantly lower increment in AEV with exercise (LA∆AEV: 1.4 ± 1.1 mL/m 2 vs 2.1 ± 0.9 mL/m 2 , P = 0.04; RA∆AEV: 0.9 ± 0.8 mL/m 2 vs 2.3 ± 1.1 mL/m 2 , P < 0.01) and lower increment in deformation vs other athletes (LA∆Sa: -3.2 ± 2.9% vs -9.5 ± 4.4%, P < 0.01; RA∆Sa: -2.5 ± 3.3% vs. -9.8 ± 3.3%, P < 0.01). During exercise, active atrial strain increases, but less in athletes compared to controls, but due to larger atrial volumes, they reached similar increases in atrial emptying volume. However, this overall lesser deformation increases from a subgroup with significant atrial dilatation showing impairment in atrial contractile reserve., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Right ventricle (RV) dysfunction has been described in athletes after endurance races. We aimed to understand and characterize the RV response to endurance exercise, the impact of individual variability and the effects of the amount of exercise., Methods and Results: Echocardiography was performed in 55 healthy adults at baseline and after a three-stage trail race: short (14 km; n = 17); medium (35 km; n = 21); and long (56 km; n = 17). Standard and speckle tracking echocardiographic assessment of the RV was performed with global and separate analysis of the RV basal (inflow) and apical regions. Although no change was observed in the short distance runners, the RV systolic deformation decreased significantly (p < 0.05) after both the medium length and long races (Δ% RV global strain -7.6 ± 20.1 and -8.7 ± 21.8, respectively) with significant RV dilatation (Δ% RV volume +10.6 ± 9.9 and +15.3 ± 12.8, respectively). The RV basal segment made a major contribution to stroke volume during exercise, showing larger increases in size and strain compared with the apex. Various patterns of RV adaptation to exercise, ranging from increases in both RV segmental strains and sizes to an insufficient increase in size and a decrease in strain, were identified; this individual variability was not correlated with prior training., Conclusion: An acute RV impairment was demonstrated after a trail-running race and was related to the amount of exercise. A high inter-individual variability was observed. Differences in RV adaptation patterns were independent of prior training, suggesting the influence was due to other individual factors., (© The European Society of Cardiology 2015.)

Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular interactions in right ventricular pressure overload, demonstrating distinct differences between pediatric pulmonary arterial hypertension (iPAH) and pulmonary stenosis (PS). Altered timing of right ventricular free wall contraction and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency, independent of right ventricular systolic pressure., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Introduction: Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood-flow redistribution in order to maintain perfusion to the brain. However, some hemodynamic parameters that might be more directly related to staging of the disease cannot be measured non-invasively in clinical practice. For this, we developed a patient-specific model of the fetal circulation to estimate vascular properties of each individual., Methods: A lumped model of the fetal circulation was developed and personalized using measured echographic data from 37 normal and IUGR fetuses to automatically estimate model-based parameters. A multivariate regression analysis was performed to evaluate the association between the Doppler pulsatility indices (PI) and the model-based parameters. The correlation between model-based parameters and the placental lesions was analyzed in a set of 13 IUGR placentas. A logistic regression analysis was done to assess the added value of the model-based parameters relative to Doppler indices, for the detection of fetuses with adverse perinatal outcome., Results: The estimated model-based placental and brain resistances were respectively increased and reduced in IUGR fetuses while placental compliance was increased in IUGR fetus. Umbilical and middle cerebral arteries PIs were most associated with both placental resistance and compliance, while uterine artery PI was more associated with the placental compliance. The logistic regression analysis showed that the model added significant information to the traditional analysis of Doppler waveforms for predicting adverse outcome in IUGR., Discussion: The proposed patient-specific computational model seems to be a good approach to assess hemodynamic parameters than cannot be measured clinically., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Descending aortic dissection (DAD) is associated with high morbidity and mortality rates. Aortic wall stiffness is a variable often altered in DAD patients and potentially involved in long-term outcome. However, its relevance is still mostly unknown. To gain more detailed knowledge of how wall elasticity (compliance) might influence intraluminal haemodynamics in DAD, a lumped-parameter model was developed based on experimental data from a pulsatile hydraulic circuit and validated for 8 clinical scenarios. Next, the variations of intraluminal pressures and flows were assessed as a function of wall elasticity. In comparison with the most rigid-wall case, an increase in elasticity to physiological values was associated with a decrease in systolic and increase in diastolic pressures of up to 33% and 63% respectively, with a subsequent decrease in the pressure wave amplitude of up to 86%. Moreover, it was related to an increase in multidirectional intraluminal flows and transition of behaviour as 2 parallel vessels towards a vessel with a side-chamber. The model supports the extremely important role of wall elasticity as determinant of intraluminal pressures and flow patterns for DAD, and thus, the relevance of considering it during clinical assessment and computational modelling of the disease.

Time-to-peak measurements and single-parameter observations are cumbersome and often confusing for quantifying local changes in myocardial function. Recent spatiotemporal normalization techniques can provide a global picture of myocardial motion and strain patterns and overcome some of these limitations. Despite these advances, the quantification of pattern changes remains descriptive, which limits their relevance for longitudinal studies. Our paper provides a new perspective to the longitudinal analysis of myocardial motion. Non-rigid registration (diffeomorphic registration via currents) is used to match pairs of patterns, and pattern changes are inferred from the registration output. Scalability is added to the different components of the input patterns in order to tune up the contributions of the spatial, temporal and magnitude dimensions to data changes, which are of interest for our application. The technique is illustrated on 2D echocardiographic sequences from 15 patients with hypertrophic obstructive cardiomyopathy. These patients underwent biventricular pacing, which aims at provoking mechanical dyssynchrony to reduce left ventricular outflow tract (LVOT) obstruction. We demonstrate that our method can automatically quantify timing and magnitude changes in myocardial motion between baseline (non-paced) and 1 year follow-up (pacing on), resulting in a more robust analysis of complex patterns and subtle changes. Our method helps confirming that the reduction of LVOT pressure gradient actually comes from the induction of the type of dyssynchrony that was expected., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We propose a technique for myocardial motion estimation based on image registration using both B-mode echocardiographic images and tissue Doppler sequences acquired interleaved. The velocity field is modeled continuously using B-splines and the spatiotemporal transform is constrained to be diffeomorphic. Images before scan conversion are used to improve the accuracy of the estimation. The similarity measure includes a model of the speckle pattern distribution of B-mode images. It also penalizes the disagreement between tissue Doppler velocities and the estimated velocity field. Registration accuracy is evaluated and compared to other alternatives using a realistic synthetic dataset, obtaining mean displacement errors of about 1 mm. Finally, the method is demonstrated on data acquired from six volunteers, both at rest and during exercise. Robustness is tested against low image quality and fast heart rates during exercise. Results show that our method provides a robust motion estimate in these situations.

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid clinical follow up.

Purpose: Highly trained athletes have an increased risk of atrial arrhythmias. Atrial geometrical and functional remodeling may be the underlying substrate. We analyze and relate atrial size, deformation and performance in professional handball players compared with non-sportive subjects., Methods: 24 Professional handball players and 20 non-sportive males were compared. All subjects underwent an echocardiographic study with evaluation of left (LA), right atrial (RA) dimensions and deformation by strain (Sa) and strain rate (SRa). Atrial performance was assessed from the atrial stroke volume (SV). With computational geometrical models, we studied the relation between atrial volumes, strains and SV and compared atrial working conditions. We estimated the functional reserve and a resulting average wall stress., Results: LA and RA volumes were larger in athletes than in controls (35.2 ± 8.8 vs. 24.8 ± 4.3 ml/m(2), p < 0.01 and 29.0 ± 8.4 vs. 19.0 ± 5.1 ml/m(2), p < 0.01 respectively). LASa and RASa during active atrial contraction were decreased in athletes (-12.2 ± 2.0 vs. -14.5 ± 2.1%, p < 0.01 and -12.1 ± 1.8 vs. -14.2 ± 1.5%, p < 0.01 respectively). LASV was similar between groups (6.6 ± 1.4 vs. 7.3 ± 1.1 ml, p = 0.19) and RASV was lower in athletes (6.2 ± 1.3 vs. 7.2 ± 1.1 ml, p < 0.01). Computational models showed that this different operational mode potentially increases performance reserve, but at the cost of higher atrial wall stress., Conclusion: A proportion of athletes with enlarged LA and RA showed different atrial contractile performance, likely resulting in atria working at higher wall stress.

Objective: Management and follow-up of chronic aortic dissections continue to be a clinical challenge due to progressive dilatation and subsequent rupture. To predict complications, guidelines suggest follow-up of aortic diameter. However, dilatation is triggered by hemodynamic parameters (pressures/wall shear stresses) and geometry of false (FL) and true lumen (TL), information not captured by diameter alone. Therefore, we aimed at better understanding the influence of dissection anatomy on TL and FL hemodynamics., Methods: In vitro studies were performed using pulsatile flow in realistic dissected latex/silicone geometries with varying tear number, size, and location. We assessed three different conformations: (1) proximal tear only; (2) distal tear only; (3) both proximal and distal tears. All possible combinations (n = 8) of small (10% of aortic diameter) and large (25% of aortic diameter) tears were considered. Pressure, velocity, and flow patterns were analyzed within the lumina (at proximal and distal sections) and at the tears. We also computed the FL mean pressure index (FPI(mean)%) as a percentage of the TL mean pressure, to compare pressures among models., Results: The presence of large tears equalized FL/TL pressures compared with models with only small tears (proximal FPI(mean)% 99.85 ± 0.45 vs 92.73 ± 3.63; distal FPI(mean)% 99.51 ± 0.80 vs 96.35 ± 1.96; P < .001). Thus, large tears resulted in slower velocities through the tears (systolic velocity <180 cm/s) and complex flows within the FL, whereas small tears resulted in lower FL pressures, higher tear velocities (systolic velocity >290 cm/s), and a well-defined flow. Additionally, both proximal and distal tears act as entry and exit. During systole, flow enters the FL through all tears simultaneously, while during diastole, flow leaves through all communications. Flow through the FL, from proximal to distal tears or vice versa, is minimal., Conclusions: Our results suggest that FL hemodynamics heavily depends on cumulative tear size, and thus, it is an important parameter to take into account when clinically assessing chronic aortic dissections., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

We present a registration framework that combines both tissue Doppler and B-mode echocardiographic sequences. The estimated spatiotemporal transform is diffeomorphic, and calculated by modeling its corresponding velocity field using continuous B-splines. A new cost function using both B-mode image voxel intensities and Doppler velocities is also proposed. Registration accuracy was evaluated on synthetic data with known ground truth. Results showed that our method allows quantifying wall motion with higher accuracy than when using a single modality. On patient data, both displacement and velocity curves were compared with the ones obtained from widely used commercial software using either B-mode images or TDI. Our method demonstrated to be more robust to image noise while being independent from the beam angle.

Aims: Early inward motion and thickening/thinning of the ventricular septum associated with left bundle branch block is known as the septal flash (SF). Correction of SF corresponds to response to cardiac resynchronization therapy (CRT). We hypothesized that SF was associated with a specific left ventricular (LV) activation pattern predicting a favourable response to CRT. We sought to characterize the spatio-temporal relationship between electrical and mechanical events by directly comparing non-contact mapping (NCM), acute haemodynamics, and echocardiography., Methods and Results: Thirteen patients (63 ± 10 years, 10 men) with severe heart failure (ejection fraction 22.8 ± 5.8%) awaiting CRT underwent echocardiography and NCM pre-implant. Presence and extent of SF defined visually and with M-mode was fused with NCM bull's eye plots of endocardial activation patterns. LV-dP/dt(max) was measured during different pacing modes. Five patients had a large SF, four small SF, and four no SF. Large SF patients had areas of conduction block in non-infarcted regions, whereas those with small or no SF did not. Patients with large SF had greater acute response to LV and biventricular (BIV) pacing vs. those with small/no SF (% increase dP/dt 28 ± 14 vs. 11 ± 19% for LV pacing and 42 ± 28 vs. 22 ± 21% for BIV pacing) (P < 0.05). This translated into a more favourable chronic response to CRT. The lines of conduction block disappeared with LV/BIV pacing while remaining with right ventricle pacing., Conclusion: A strong association exists between electrical activation and mechanical deformation of the septum. Correction of both mechanical synchrony and the functional conduction block by CRT may explain the favourable response in patients with SF.

Image registration has been proposed as an automatic method for recovering cardiac displacement fields from tagged Magnetic Resonance Imaging (tMRI) sequences. Initially performed as a set of pairwise registrations, these techniques have evolved to the use of 3D+t deformation models, requiring metrics of joint image alignment (JA). However, only linear combinations of cost functions defined with respect to the first frame have been used. In this paper, we have applied k-Nearest Neighbors Graphs (kNNG) estimators of the α-entropy (H(α)) to measure the joint similarity between frames, and to combine the information provided by different cardiac views in an unified metric. Experiments performed on six subjects showed a significantly higher accuracy (p<0.05) with respect to a standard pairwise alignment (PA) approach in terms of mean positional error and variance with respect to manually placed landmarks. The developed method was used to study strains in patients with myocardial infarction, showing a consistency between strain, infarction location, and coronary occlusion. This paper also presents an interesting clinical application of graph-based metric estimators, showing their value for solving practical problems found in medical imaging., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The clinical assessment of left atrial function during atrial fibrillation is challenging and often inaccurate because of the beat-to-beat variability in the cycle length. The aim of this study was to validate the use of an index beat, the beat following two preceding cardiac cycles of equal duration, for the measurement of left atrial functional indices, including area, volume, and expansion index. The index beat was compared with the conventional but time-consuming method of averaging multiple consecutive cardiac cycles., Methods: Thirty patients with persistent or permanent atrial fibrillation were studied using two-dimensional echocardiography, and left atrial indices were measured from the average of 17 consecutive cardiac cycles compared with that of an index beat taken from outside of these 17 cycles., Results: The index beat showed good correlation with the averaging technique, and comparison of the two methods showed them to be interchangeable. Clinically, the differences in left atrial functional indices between the two methods were minor., Conclusions: Use of the index beat to measure dynamic left atrial function in atrial fibrillation can easily be performed and is as accurate as and less time consuming than the onerous method of averaging of multiple cardiac cycles.

In this paper, we present a new method for the automatic comparison of myocardial motion patterns and the characterization of their degree of abnormality, based on a statistical atlas of motion built from a reference healthy population. Our main contribution is the computation of atlas-based indexes that quantify the abnormality in the motion of a given subject against a reference population, at every location in time and space. The critical computational cost inherent to the construction of an atlas is highly reduced by the definition of myocardial velocities under a small displacements hypothesis. The indexes we propose are of notable interest for the assessment of anomalies in cardiac mobility and synchronicity when applied, for instance, to candidate selection for cardiac resynchronization therapy (CRT). We built an atlas of normality using 2D ultrasound cardiac sequences from 21 healthy volunteers, to which we compared 14 CRT candidates with left ventricular dyssynchrony (LVDYS). We illustrate the potential of our approach in characterizing septal flash, a specific motion pattern related to LVDYS and recently introduced as a very good predictor of response to CRT., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: To investigate the presence of any regional myocardial deformation abnormalities in Marfan syndrome (MFS) and determine the benefits of using advanced echocardiography compared to conventional techniques., Background: Myocardial dysfunction in MFS may be caused by extracellular matrix remodeling thus, resulting in uniform reduced functionality. However, increased aortic stiffness may cause segmental ventricular abnormalities. Strain rate imaging (SRI) constitutes a validated technique to assess regional deformation in various clinical conditions. With this in mind, we aimed to investigate biventricular function in MFS using SRI., Methods: Forty-four MFS patients (mean age 30 ± 12 years, 26 men) and 49 controls without valvular disease were examined using SRI. Ejection fraction (EF) was calculated by the Simpson's biplane method. Biventricular deformation was assessed by measuring strain/strain rate. Strain values were divided by left ventricular (LV) end-diastolic volume to adjust LV deformation for geometry changes providing a strain index (SI). Aortic stiffness was evaluated using the β-stiffness index., Results: EF (%) was reduced in MFS patients (59 ± 5 vs 72 ± 4, P < 0.001), whereas β-stiffness was increased (P < 0.001). LV radial and LV and right ventricular (RV) long-axis strain values (%) were reduced in the patient group (70 ± 17 vs 93 ± 10; 19 ± 2 vs 25 ± 2; 30 ± 9 vs 36 ± 8, respectively, P < 0.001). Strain rate measurements were also reduced (P < 0.001). In a multiple regression analysis, MFS diagnosis was negatively associated with LV SI (-0.262 [-0.306, -0.219], P < 0.001). β-Stiffness was negatively associated with SI obtained from the septum, inferior and anterior walls. ROC analyses demonstrated that SRI, when compared with conventional echocardiography, had higher sensitivity and specificity in predicting biventricular dysfunction in MFS., Conclusions: Our study showed a uniform reduction in biventricular deformation in MFS. These findings suggest that assessment of myocardial function using advanced echocardiographic techniques could be more accurate in MFS patient evaluation than conventional echocardiography alone., (© 2011, Wiley Periodicals, Inc.)

Background: Extracellular matrix remodeling in the aortic wall results in increased aortic stiffness (AoS) in Marfan syndrome (MFS). Pulsed-wave velocity (PWV) constitutes the best indirect AoS measurement. We aimed to assess PWV in MFS patients using two-dimensional (2D) and Doppler echocardiography., Methods: Thirty-one MFS patients, (mean age 31 ± 14 years, 16 men) and 31 controls were examined. Blood flow was recorded in the aorta near the aortic valve and immediately after in the descending aorta with simultaneous electrocardiography. PWV was calculated by dividing the distance between the two sample volume positions (D) by the time difference (TD) between the intervals from the QRS start to the ascending and descending aortic flow onsets. B-stiffness was also measured., Results: TD (described in "Methods" section) and, aortic arch length were significantly increased in MFS patients, P < 0.001. Thus, PWV values were significantly higher in patients when compared with controls, 7.20 m/s (5.12, 9.43) versus 4.64 m/s (3.37, 6.24), P < 0.001. B-stiffness was also significantly increased in MFS patients; 5.15 (3.69, 7.65) versus 2.44 (1.82, 3.66), P < 0.001. Multiple regression analysis showed a positive association with MFS diagnosis and age, (P = 0.002 and 0.009, respectively). Reproducibility of PWV measurements was <5%., Conclusions: AoS was significantly higher in MFS patients as expected. Our data demonstrated that PWV measurements can be performed, in the absence of serious musculoskeletal abnormalities in MFS adults, as part of a cardiac ultrasound scan. This technique can be helpful in diagnosis and management in MFS., (© 2011, Wiley Periodicals, Inc.)

Simulated magnetic resonance imaging brain studies have been generated for over a decade. Despite their useful potential, simulated cardiac studies are only emerging. This article focuses on the realistic simulation of cardiac magnetic resonance imaging datasets. The methodology is based on the XCAT phantom, which is modified to increase realism of the simulated images. Modifications include the modeling of trabeculae and papillary muscles based on clinical measurements and published data. To develop and evaluate our approach, the clinical database included 40 patients for anatomical measurements, 10 patients for papillary muscle modeling, and 10 patients for local gray value statistics. The virtual database consisted of 40 digital voxel phantoms. Histograms from different tissues were obtained from the real datasets and compared with histograms of the simulated datasets with the Chi-square dissimilarity metric (χ(2)) and Kullback-Leibler divergence. For the original phantom, χ(2) values averaged 0.65 ± 0.06 and Kullboek-Leibler values averaged 0.69 ± 0.38. For the modified phantom, χ(2) values averaged 0.34 ± 0.12 and Kullboek-Leibler values averaged 0.32 ± 0.15. The proposed approach demonstrated a noticeable improvement of the local appearance of the simulated images with respect to the ones obtained originally., (© 2010 Wiley-Liss, Inc.)

Introduction and Objectives: In hypertrophic cardiomyopathy (HCM), it has been suggested that regional fiber disarray produces segments that exhibit no or severely reduced deformation, and that these segments are distributed nonuniformly within the left ventricle (LV). This contrasts with observations in other types of hypertrophy, such as in athlete's heart or hypertensive left ventricular hypertrophy (HLVH), in which abnormal cardiac deformation may exist but the reduction is not so severe that some segments exhibit no deformation. Our aim was to use the strain distribution to study deformation in HCM., Methods: We used tagged magnetic resonance imaging to reconstruct LV systolic deformation in 12 controls, 10 athletes, 12 patients with HCM, and 10 patients with HLVH. Deformation was quantified using a fast nonrigid registration algorithm and peak radial and circumferential systolic strain values were determined in 16 LV segments., Results: Patients with HCM had significantly lower average strain values than individuals in other groups. However, while the deformation observed in healthy subjects and HLVH patients clustered around the mean, in HCM patients, segments with normal contraction coexisted with segments exhibiting no or significantly reduced deformation, which resulted in a greater heterogeneity of strain values. Moreover, some nondeforming segments were observed even when fibrosis and hypertrophy were absent., Conclusions: The strain distribution characterized specific patterns of myocardial deformation in patients with LVH due to different etiologies. Patients with HCM had significantly lower mean strain values and a greater heterogeneity in strain values than controls, athletes and HLVH patients. In addition, they had nondeforming regions.

Introduction: several studies have documented increased aortic stiffness in patients with Marfan syndrome (MFS) using echocardiography and magnetic resonance imaging. Recent studies have also shown primary myocardial impairment in MFS. We investigated whether left ventricular (LV) function could be further impaired when acting against a stiff vascular system., Methods: twenty-six MFS patients (mean age 30 ± 2 years, 17 males) and 30 normal controls were examined. Mitral annular displacement, as a surrogate for LV systolic function, was evaluated from septal, anterolateral, anterior and inferior regions using M-mode and tissue Doppler imaging. Septal/anterolateral and anterior/inferior M-mode displacement measurements were normalised by dividing them by the longitudinal inner distance obtained at end diastole from the 4- and 2-chamber views, respectively. Carotid-femoral and carotid-radial (CF and CR) pulse wave velocities (PWV) were determined using an automated applanation tonometry device. Central aortic pressure was assessed by recording radial waveforms with the tonometer and central waveforms were reconstructed using a generalised transfer function., Results: CF- and CR-PWV were significantly increased in the patient group (p<0.001), whilst mitral annular displacement measurements were significantly reduced (p<0.001, all regions). Regression analysis demonstrated that the disease status and CF-PWV were strongly associated with reduced LV systolic function (p<0.001, p=0.002, respectively)., Conclusions: our study showed reduced LV systolic function and increased aortic stiffness in MFS patients. The efficiency of a fibrillin-1 deficient heart may be further reduced by ejection into a stiff vascular system. Care should be taken to ensure that any treatment regime addresses both increased aortic stiffness and myocardial dysfunction in MFS.

Echocardiography has a leading role in the routine assessment and diagnosis of hypertrophic ventricles. However, the use of M-mode echocardiography and measurement of global left ventricular function may be misleading. Traditionally, systolic function was thought to be preserved in patients with hypertrophic myopathies until the late stages of the disease, and hypertrophic myopathies were thought to affect the myocardium more diffusely than ischemic heart disease. Ultrasound deformation imaging, either by Doppler myocardial imaging or speckle tracking, provides more-sensitive detection of regional myocardial motion and deformation than standard echocardiography. Basic and clinical studies that apply these techniques have revealed early, often subclinical impairment in systolic function. This information allows the detection and treatment of myocardial dysfunction at an early stage, which is of high clinical importance. Physiological hypertrophic remodeling seen in athletes differs from pathological myocardial hypertrophy, which can be caused by compensatory reactive hypertrophy owing to pressure overload in patients with aortic stenosis or hypertension, as well as amyloidosis, Fabry disease or Friedreich ataxia. Each of the etiologies associated with hypertrophy demonstrate distinct regional changes in myocardial deformation, which allows identification of the underlying processes, and will improve the assessment and follow-up of patients with hypertrophic myopathies.

Heart failure leads to gross cardiac structural changes. While cardiac resynchronization therapy (CRT) is a recognized treatment for restoring synchronous activation, it is not clear how changes in cardiac shape and size affect the electrical pacing therapy. This study used a human heart computer model which incorporated anatomical structures such as myofiber orientation and a Purkinje system (PS) to study how pacing affected failing hearts. The PS was modeled as a tree structure that reproduced its retrograde activation feature. In addition to a normal geometry, two cardiomyopathies were modeled: dilatation and hypertrophy. A biventricular pacing protocol was tested in the context of atrio-ventricular block. The contribution of the PS was examined by removing it, as well as by increasing endocardial conductivity. Results showed that retrograde conduction into the PS was a determining factor for achieving intraventricular synchrony. Omission of the PS led to an overestimate of the degree of electrical dyssynchrony while assessing CRT. The activation patterns for the three geometries showed local changes in the order of activation of the lateral wall in response to the same pacing strategy. These factors should be carefully considered when determining lead placement and optimizing device parameters in clinical practice.

Purpose: In this article, the authors studied the feasibility of estimating regional mechanical properties in cerebral aneurysms, integrating information extracted from imaging and physiological data with generic computational models of the arterial wall behavior., Methods: A data assimilation framework was developed to incorporate patient-specific geometries into a given biomechanical model, whereas wall motion estimates were obtained from applying registration techniques to a pair of simulated MR images and guided the mechanical parameter estimation. A simple incompressible linear and isotropic Hookean model coupled with computational fluid-dynamics was employed as a first approximation for computational purposes. Additionally, an automatic clustering technique was developed to reduce the number of parameters to assimilate at the optimization stage and it considerably accelerated the convergence of the simulations. Several in silico experiments were designed to assess the influence of aneurysm geometrical characteristics and the accuracy of wall motion estimates on the mechanical property estimates. Hence, the proposed methodology was applied to six real cerebral aneurysms and tested against a varying number of regions with different elasticity, different mesh discretization, imaging resolution, and registration configurations., Results: Several in silico experiments were conducted to investigate the feasibility of the proposed workflow, results found suggesting that the estimation of the mechanical properties was mainly influenced by the image spatial resolution and the chosen registration configuration. According to the in silico experiments, the minimal spatial resolution needed to extract wall pulsation measurements with enough accuracy to guide the proposed data assimilation framework was of 0.1 mm., Conclusions: Current routine imaging modalities do not have such a high spatial resolution and therefore the proposed data assimilation framework cannot currently be used on in vivo data to reliably estimate regional properties in cerebral aneurysms. Besides, it was observed that the incorporation of fluid-structure interaction in a biomechanical model with linear and isotropic material properties did not have a substantial influence in the final results.