Cardiac performance after an endurance open water swimming race.

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.

Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise.

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.

Understanding the Aortic Isthmus Doppler Profile and Its Changes with Gestational Age Using a Lumped Model of the Fetal Circulation.

OBJECTIVE: The aortic isthmus (AoI) blood flow has a characteristic shape with a small end-systolic notch observed during the third trimester of pregnancy. However, what causes the appearance of this notch is not fully understood. We used a lumped model of the fetal circulation to study the possible factors causing the end-systolic notch and the changes of AoI flow through gestation. METHODS: A validation of the model was performed by fitting patient-specific data from two normal fetuses. Then, different parametric analyses were performed to evaluate the major determinants of the appearance of the end-systolic notch. The changes in the AoI flow profile through gestation were assessed. RESULTS: Our model allows to simulate the AoI waveform. The delay in the onset of ejection together with the longer ejection duration of the right ventricle are the most relevant factors in the origin of the notch. It appears around 25 weeks of gestation and becomes more pronounced with advancing gestation. DISCUSSION: We demonstrated that the end-systolic notch on the AoI flow occurs mainly as a result of a delayed and longer ejection of the right ventricle. Our findings improve the understanding of hemodynamic changes in the fetal circulation and the interpretation of clinical imaging.

A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

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.

Atrial functional and geometrical remodeling in highly trained male athletes: for better or worse?

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.

An in vitro phantom study on the influence of tear size and configuration on the hemodynamics of the lumina in chronic type B aortic dissections.

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.

Right Ventricular Electromechanical Dyssynchrony and Its Relation to Right Ventricular Remodeling, Dysfunction, and Exercise Capacity in Ebstein Anomaly.

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 VO2 (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.

Relationship between endocardial activation sequences defined by high-density mapping to early septal contraction (septal flash) in patients with left bundle branch block undergoing cardiac resynchronization therapy.

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.

Machine-learning-based exploration to identify remodeling patterns associated with death or heart-transplant in pediatric-dilated cardiomyopathy.

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.

Assessment of aortic stiffness in marfan syndrome using two-dimensional and Doppler echocardiography.

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.

Impaired biventricular deformation in Marfan syndrome: a strain and strain rate study in adult unoperated patients.

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 ß-stiffness index. RESULTS: EF (%) was reduced in MFS patients (59 ± 5 vs 72 ± 4, P < 0.001), whereas ß-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). ß-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.

Feasibility of estimating regional mechanical properties of cerebral aneurysms in vivo.

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.

Cardiac injuries in blunt chest trauma.

Blunt chest traumas are a clinical challenge, both for diagnosis and treatment. The use of cardiovascular magnetic resonance can play a major role in this setting. We present two cases: a 12-year-old boy and 45-year-old man. Late gadolinium enhancement imaging enabled visualization of myocardial damage resulting from the trauma.

Velocity and deformation imaging for the assessment of myocardial dysfunction.

Recent developments in echocardiographic imaging technology and processing enabled the quantification of myocardial motion and deformation in a clinical setting. Echocardiographic strain (-rate) imaging provides a relatively easy way to study myocardial deformation. However, although (local) deformation is clearly linked to cardiac (dys-) function, it is important to understand how this information can be used in clinical practice and how specific deformation patterns should be interpreted. This review paper first discusses which issues are important to address when assessing cardiac function and how (regional) deformation and myocardial contractility are related. The use and interpretation of deformation profiles is further illustrated for some typical cardiac pathologies. The observed deformation patterns are discussed in light of the changes in regional contractility (ischemia), timing of contractile force development (LBBB and heart failure), pressure/volume overload, and assessing diastolic function.

Biventricular and atrial diastolic function assessment using conventional echocardiography and tissue-Doppler imaging in adults with Marfan syndrome.

AIMS: Previous studies provided evidence about left ventricular systolic and diastolic dysfunction in adults with Marfan syndrome (MFS). However, in the literature, data on right ventricular and bi-atrial diastolic function are limited. We aimed to investigate whether, in the absence of significant valvular disease, diastolic dysfunction is present not only in both ventricles but also in the atrial cavities. METHODS AND RESULTS: Seventy-two adult unoperated MFS patients and 73 controls without significant differences in age, sex, and body surface area from the patient group were studied using two-dimensional, pulsed, and colour-Doppler and tissue-Doppler imaging (TDI). Biventricular early filling measurements were significantly decreased in MFS patients when compared with controls (P < 0.001). Pulsed TDI early filling measurements obtained from five mitral annular regions and over the lateral tricuspid valve corner were significantly reduced in the patient group (P < 0.001). Indices reflecting atrial function at the reservoir, conduit and contractile phases were also significantly decreased in MFS patients (P < 0.001). CONCLUSION: This study demonstrated significant biventricular diastolic and biatrial systolic and diastolic dysfunction in MFS patients. Our findings suggest that MFS affects diastolic function independently. Diastolic abnormalities could be attributed to fibrillin-1 deficiency and dysregulation of transforming growth factor-beta activity in the cardiac extracellular matrix.

Early impairment of left ventricular long-axis systolic function demonstrated by reduced atrioventricular plane displacement in patients with Marfan syndrome.

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.

Machine Learning Analysis of Left Ventricular Function to Characterize Heart Failure With Preserved Ejection Fraction.

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.

Characterization of myocardial motion patterns by unsupervised multiple kernel learning.

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.

3D membrane segmentation and quantification of intact thick cells using cryo soft X-ray transmission microscopy: A pilot study.

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.