Suchergebnisse

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. ; Support for this work was partially funded by Generalitat de Catalunya Grants FI-AGAUR 2014-2017 and RH040991 (to M. Sitges), the Spanish government (Plan Nacional I + D, Ministerio de Economia y Competitividad Grants DEP2010-20565, DEP2013-44923-P, and TIN2014-52923-R, cofinanced by the Fondo Europeo de Desarrollo Regional de la Unión Europea "Una manera de hacer Europa"), Instituto de Salud Carlos III Grants PI13/01580 and PI16/00703, and Centro de Investigación BIomédica en Red-Cardiovascular CB16/11/00354.

Aims: 4D flow magnetic resonance imaging (MRI) allows quantitative assessment of left ventricular (LV) function according to characteristics of the dynamic flow in the chamber. Marked abnormalities in flow components volume and kinetic energy (KE) have previously been demonstrated in moderately dilated and depressed LVs compared to healthy subjects. We hypothesized that these 4D flow-based measures would detect even subtle LV dysfunction and remodeling. Methods and Results: We acquired 4D flow and morphological MRI data from 26 patients with chronic ischemic heart disease with New York Heart Association (NYHA) class I and II and with no to mild LV systolic dysfunction and remodeling, and from 10 healthy controls. A previously validated method was used to separate the LV end-diastolic volume (LVEDV) into functional components: direct flow, which passes directly to ejection, and non-ejecting flow, which remains in the LV for at least 1 cycle. The direct flow and non-ejecting flow proportions of end-diastolic volume and KE were assessed. The proportions of direct flow volume and KE fell with increasing LVEDV-index (LVEDVI) and LVESV-index (LVESVI) (direct flow volume r = -0.64 and r = -0.74, both Pamp;lt;0.001; direct flow KE r = -0.48, P = 0.013, and r = -0.56, P = 0.003). The proportions of non-ejecting flow volume and KE rose with increasing LVEDVI and LVESVI (non-ejecting flow volume: r = 0.67 and r = 0.76, both Pamp;lt;0.001; non-ejecting flow KE: r = 0.53, P = 0.005 and r = 0.52, P = 0.006). The proportion of direct flow volume correlated moderately to LVEF (r = 0.68, P amp;lt; 0.001) and was higher in a sub-group of patients with LVEDVI amp;gt; 74 ml/m(2) compared to patients with LVEDVI amp;lt; 74 ml/m(2) and controls (both Pamp;lt;0.05). Conclusion: Direct flow volume and KE proportions diminish with increased LV volumes, while non-ejecting flow proportions increase. A decrease in direct flow volume and KE at end-diastole proposes that alterations in these novel 4D flow-specific markers may detect LV dysfunction even in subtle or subclinical LV remodeling. ; Funding Agencies|Swedish Heart Lung foundation [20140398]; Swedish Research Council [2014-6191]; European Union FP7 [223615]; Medical Research Council of Southeast Sweden [FORSS-35141, FORSS-88731, FORSS-157921]; County Council of Ostergotland/Heart and Medicine Center [20090120]

Aims Endurance athletes develop cardiac remodeling to cope with increased cardiac output during exercise. This remodeling is both anatomical and functional and shows large interindividual variability. In this study, we quantify local geometric ventricular remodeling related to long-standing endurance training and assess its relationship with cardiovascular performance during exercise. Methods We extracted 3D models of the biventricular shape from end-diastolic cine magnetic resonance images acquired from a cohort of 89 triathlon athletes and 77 healthy sedentary subjects. Additionally, the athletes underwent cardio-pulmonary exercise testing, together with an echocardiographic study at baseline and few minutes after maximal exercise. We used statistical shape analysis to identify regional bi-ventricular shape differences between athletes and non-athletes. Results The ventricular shape was significantly different between athletes and controls (p < 1e-6). The observed regional remodeling in the right heart was mainly a shift of the right ventricle (RV) volume distribution towards the right ventricular infundibulum, increasing the overall right ventricular volume. In the left heart, there was an increment of left ventricular mass and a dilation of the left ventricle. Within athletes, the amount of such remodeling was independently associated to higher peak oxygen pulse (p < 0.001) and weakly with greater post-exercise RV free wall longitudinal strain (p = 0.03). Conclusions We were able to identify specific bi-ventricular regional remodeling induced by long-lasting endurance training. The amount of remodeling was associated with better cardiopulmonary performance during an exercise test. ; Spanish Ministry of Economy and Competitiveness DEP2013-44923-P TIN201452923-R MDM2015-0502 European Union (EU) European Union under the Horizon 2020 Programme for Research, Innovation 642676 CardioFunXion Erasmus+Programme 20130040 La Caixa Foundation LCF/PR/GN14/10270005 LCF/PR/GN18/10310003 Instituto de Salud Carlos III PI14/00226 PI15/00130 PI17/00675 AGAUR 2017 SGR Grant 1531

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10−2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models. ; This paper has been partially funded by CompBioMed project, under H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant agreement n◦ 675451. FS is supported by a grant from Severo Ochoa (n◦ SEV-2015-0493-16-4), Spain. CB is supported by a grant from the Fundació LaMarató de TV3 (n◦ 20154031), Spain. TI and PI are supported by the Institute of Engineering in Medicine, USA, and the Lillehei Heart Institute, USA. ; Peer Reviewed ; Postprint (published version)

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10−2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models. ; This paper has been partially funded by CompBioMed project, under H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant agreement n◦ 675451. FS is supported by a grant from Severo Ochoa (n◦ SEV-2015-0493-16-4), Spain. CB is supported by a grant from the Fundació LaMarató de TV3 (n◦ 20154031), Spain. TI and PI are supported by the Institute of Engineering in Medicine, USA, and the Lillehei Heart Institute, USA. ; Peer Reviewed ; Postprint (published version)

Few data exist concerning the right ventricular (RV) physiological adaptation in American-style football (ASF) athletes. We aimed to analyze the RV global and regional responses among ASF-trained athletes. Fifty-nine (20 linemen and 39 non-linemen) ASF athletes were studied before and after inter-seasonal training. During this period, which lasted 7 months, all athletes were exposed to combined dynamic and static exercises. Cardiac longitudinal changes were examined using three-dimensional transthoracic echocardiography. A computational method based on geodesic distances was applied to volumetrically parcellate the RV into apical, outlet, and inlet regions. RV global and regional end-diastolic volumes increased significantly and similarly in linemen and non-linemen after training, with predominant changes in the apex and outlet regions. RV global and regional ejection fractions were preserved. Morphological changes were uniformly distributed among the four cardiac chambers, and it was independent of the field position. Assessment of RV end-diastolic global, inlet and apical volumes showed low intra-observer (3.3%, 4.1%, and 5.3%, respectively) and inter-observer (7%, 12.2%, and 9%, respectively) variability, whereas the outlet regional volumetric assessment was less reproducible. To conclude, ASF inter-seasonal training was associated with a proportionate biventricular enlargement, regardless of the field position. Regional RV analysis allowed us to quantify the amount of exercise-induced remodeling that was larger in the apical and outlet regions. ; F.T. is supported by a grant from the Fonds de Recherche du Québec—Santé (FRQS). The methodological part of this study was partly supported by the Spanish Ministry of Economy and Competitiveness (Maria de Maeztu Units of Excellence Programme—MDM-2015-0502) and the European Union under the Horizon 2020 Programme for Research, Innovation (grant agreement No. 642676 CardioFunXion).

AIMS: Ventricular remodelling following myocardial infarction progressively leads to loss of contractile capacity and heart failure. Although calcineurin promotes maladaptive cardiac hypertrophy, we recently showed that the calcineurin splicing variant, CnAβ1, has beneficial effects on the infarcted heart. However, whether this variant limits necrosis or improves remodelling is still unknown, precluding translation to the clinical arena. Here, we explored the effects and therapeutic potential of CnAβ1 overexpression post-infarction. METHODS AND RESULTS: Double transgenic mice with inducible cardiomyocyte-specific overexpression of CnAβ1 underwent left coronary artery ligation followed by reperfusion. Echocardiographic analysis showed depressed cardiac function in all infarcted mice 3 days post-infarction. Induction of CnAβ1 overexpression 1 week after infarction improved function and reduced ventricular dilatation. CnAβ1-overexpressing mice showed shorter, thicker scars, and reduced infarct expansion, accompanied by reduced myocardial remodelling. CnAβ1 induced vascular endothelial growth factor (VEGF) expression in cardiomyocytes, which resulted in increased infarct vascularization. This paracrine angiogenic effect of CnAβ1 was mediated by activation of the Akt/mammalian target of rapamycin pathway and VEGF. CONCLUSIONS: Our results indicate that CnAβ1 exerts beneficial effects on the infarcted heart by promoting infarct vascularization and preventing infarct expansion. These findings emphasize the translational potential of CnAβ1 for gene-based therapies. ; European Union [ERG-239158, CardioNeT-ITN-289600]; Spanish Ministry of Science and Innovation [BFU2009-10016, SAF2012-31451]; Regional Government of Madrid [2010-BMD-2321]; Fondo de Investigaciones Sanitarias [RD12/0042/0066]; Spanish Ministry of Economy and Competitiveness; Pro-CNIC Foundation ; Sí

Left ventricular remodeling following myocardial infarction (MI) is related to adverse outcome. It has been shown that an up-regulation of plasma soluble ST2 (sST2) levels are associated with lower pre-discharge left ventricular (LV) ejection fraction, adverse cardiovascular outcomes and mortality outcome after MI. The mechanisms involved in its modulation are unknown and there is not specific treatment capable of lowering plasma sST2 levels in acute-stage HF. We recently identified Yin-yang 1 (Yy1) as a transcription factor related to circulating soluble ST2 isoform (sST2) expression in infarcted myocardium. However, the underlying mechanisms involved in this process have not been thoroughly elucidated. This study aimed to evaluate the pathophysiological implication of miR-199a-5p in cardiac remodeling and the expression of the soluble ST2 isoform. Myocardial infarction (MI) was induced by permanent ligation of the left anterior coronary artery in C57BL6/J mice that randomly received antimiR199a therapy, antimiR-Ctrl or saline. A model of biomechanical stretching was also used to characterize the underlying mechanisms involved in the activation of Yy1/sST2 axis. Our results show that the significant upregulation of miR-199a-5p after myocardial infarction increases pathological cardiac hypertrophy by upregulating circulating soluble sST2 levels. AntimiR199a therapy up-regulates Sirt1 and inactivates the co-activator P300 protein, thus leading to Yy1 inhibition which decreases both expression and release of circulating sST2 by cardiomyocytes after myocardial infarction. Pharmacological inhibition of miR-199a rescues cardiac hypertrophy and heart failure in mice, offering a potential therapeutic approach for cardiac failure. ; This study was supported by a grant from the Seneca Foundation-Agency of Science and Technology of the Region of Murcia (20652/JLI/18) and a grant from the Instituto de Salud Carlos III (PI19/00519) which is cofinanced through the European Union's European Regional Development Fund (FEDER). Dr. Lax is a Ramon and Cajal researcher at the Department of Medicine, University of Murcia. ; Sí

Objective: To identify the presence of different cardiac phenotypes among FGR. Study Design: Fetal echocardiography was performed in 126 FGR (defined as birth weight <10th centile) and 64 adequate for gestational age (AGA). Principal component and cluster analyses were performed to identify different cardiac phenotypes among FGR cases. Results: Three different cardiac phenotypes were identified within FGR: globular, elongated and hypertrophic. Most FGR cases (54%) were characterized by a 'globular' heart with the lowest left ventricular sphericity index (controls: median 1.78 (interquartile range 1.62-1.97), FGR-elongated: 1.92 (1.78-2.09), FGR-globular 1.44 (1.36-1.52) and FGR-hypertrophic 1.65 (1.42-1.77), P=0.001), while 29% of the cases showed an 'elongated' left ventricle with nearly normal cardiac dimensions. Finally, 17% of the FGR showed a 'hypertrophic' phenotype with the highest values in left ventricular wall thickness (controls: 1.22 mm/kg (1.1-1.67), FGR-elongated: 1.52 (1.28-1.86), FGR-globular 1.65 (1.39-1.99) and FGR-hypertrophic 3.68 (3.45-4.71), P=0.001) and cardiac dimensions. The globular and elongated phenotype showed fetoplacental profile of late-onset FGR while the hypertrophic phenotype showed signs of early-onset FGR The hypertrophic cluster also showed the worst perinatal results presenting the lowest birthweight centile, gestational age at birth, Apgar score, and the highest postnatal blood pressure and carotid intima media thickness. Conclusions: FGR induces at least 3 different cardiac phenotypes, with early-onset FGR cases associated with a hypertrophic response and worse perinatal outcomes. This cardiac phenotypic classification may improve identification of those FGR cases with the highest perinatal and long-term cardiovascular risk. ; This work was supported by the Erasmus+ Programme of the European Union (grant number 2013‐0040) (this publication reflects the views of only the authors and the Commission cannot be held responsible for any use which may be made of the information contained herein); Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (grant numbers PI12/00801, PI14/00226, SAF2012‐37196 and TIN2014‐52923‐R), cofinanciado por el Fondo Europeo de Desarrollo Regional de la Unión Europea 'Una manera de hacer Europa'. The research leading to these results has received funding from 'la Caixa' Foundation, Cerebra Foundation for the Brain Injured Child and Agència de Gestió d'Ajuts Universitaris i de Recerca (grant number SGR_928). B.V.A. was supported by Programa de Ayudas Postdoctorales from Agència de Gestió d'Ajuts Universitaris i de Recerca (grant number: 2013FI_B 00667) and wishes to express her gratitude to the Mexican National Council of Science and Technology (CONACyT, Mexico City, Mexico) for partially supporting her predoctoral stay at Hospital Clínic, Barcelona, Spain.

Abstract Background: Cardiac remodeling depends on the intensity, duration, and training method. Objective: To evaluate if the training performed in a Portuguese military special operations troop increases cardiac remodeling in a sample of young individuals who previously practiced competitive sports. Methods: A prospective study involving 76 military candidates for military special operations, 45 of whom previously practiced at competitive level (> 10 hours per week). Of these military athletes, only 17 successfully completed the course. The evaluation was performed at 6 months intervals and included a complete clinical history, physical examination, vital signs, anthropometric data and echocardiographic evaluation. Statistical significance was considered when p < 0.05, with a 95% confidence interval. Results: At the end of the course, there was a decrease in the percentage of fat mass (19.1 ± 3.3% vs. 13.1 ± 3.5%; p < 0.01), an increase in the percentage of lean mass (41.3 ± 2.1% vs. 44.4 ± 1.8%; p < 0.01), and decreased systolic and diastolic blood pressure and heart rate. Regarding cardiac remodeling, there was an increase in left ventricular diastolic diameter (49.7 ± 3.2 mm vs. 52.8 ± 3.4 mm; p < 0.01), an increase trend in left atrial volume (27.3 ± 4.5 mL/m2 vs. 28.2 ± 4.1 mL/m2; p = 0.07) and increased left ventricular mass (93.1 ± 7.7 g/m2 vs. 100.2 ± 11.4 g/m2; p < 0.01). Functional variables also changed, with an increase in S' (15 (13-16) cm/s vs. 17 (16-18) cm/s; p < 0,01) and a decrease in left ventricular ejection fraction (60 ± 6% vs. 54 ± 6%; p < 0.01). Conclusion: Intense military physical training resulted in additional cardiac remodeling in athletes of competitive level, both structural and functional.

Abstract Background: Cardiac remodeling depends on the intensity, duration, and training method. Objective: To evaluate if the training performed in a Portuguese military special operations troop increases cardiac remodeling in a sample of young individuals who previously practiced competitive sports. Methods: A prospective study involving 76 military candidates for military special operations, 45 of whom previously practiced at competitive level (> 10 hours per week). Of these military athletes, only 17 successfully completed the course. The evaluation was performed at 6 months intervals and included a complete clinical history, physical examination, vital signs, anthropometric data and echocardiographic evaluation. Statistical significance was considered when p < 0.05, with a 95% confidence interval. Results: At the end of the course, there was a decrease in the percentage of fat mass (19.1 ± 3.3% vs. 13.1 ± 3.5%; p < 0.01), an increase in the percentage of lean mass (41.3 ± 2.1% vs. 44.4 ± 1.8%; p < 0.01), and decreased systolic and diastolic blood pressure and heart rate. Regarding cardiac remodeling, there was an increase in left ventricular diastolic diameter (49.7 ± 3.2 mm vs. 52.8 ± 3.4 mm; p < 0.01), an increase trend in left atrial volume (27.3 ± 4.5 mL/ m2 vs. 28.2 ± 4.1 mL/m2; p = 0.07) and increased left ventricular mass (93.1 ± 7.7 g/m2 vs. 100.2 ± 11.4 g/m2; p < 0.01). Functional variables also changed, with an increase in S' (15 (13-16) cm/s vs. 17 (16-18) cm/s; p < 0,01) and a decrease in left ventricular ejection fraction (60 ± 6% vs. 54 ± 6%; p < 0.01). Conclusion: Intense military physical training resulted in additional cardiac remodeling in athletes of competitive level, both structural and functional. (Int J Cardiovasc Sci. 2018; [online].ahead print, PP.0-0)

Abstract

Background
Cardiovascular disease is associated with higher incidence of frailty. However, the nature of the mechanisms underlying this association remain unclear. The purpose of this study is to identify cardiovascular phenotypes most associated with physical frailty and functional performance in the Multi-Ethnic Study of Atherosclerosis (MESA).


Methods
As part of the MESA study, 3045 participants underwent cardiovascular magnetic resonance and computed tomography between 2010-2012. Of these, 1743 completed a Six-Minute Walk test (6MWT) and questionnaires (follow-up Exam: 2016-2018) which were used to generate a binary combined frail/prefrail vs. robust score according to a modified FRAIL Scale (self-report questionnaire). Multivariable logistic (binary frail outcome) or linear (6MWT) regression assessed the association between frailty and cardiovascular structure and function, aortic stiffness, coronary artery calcium, and myocardial fibrosis (ECV, extracellular volume fraction).


Results
Participants were 66±8yrs, 52% female at the time of imaging, and 29.4% were classified as frail or pre-frail. Older age and female gender were associated with greater odds of being in the frail/prefrail group. Concentric left ventricular remodeling (OR 1.89,p=0.008; Coef. -52.9,p&lt;0.001), increased ECV (OR 1.10,p=0.002; Coef. -4.0,p=0.001), and worsening left atrial strain rate at early diastole (OR 1.56,p=&lt;0.001; Coef. -22.75,p=0.027) were found to be associated with a greater likelihood of being in a frail state and lower 6MWT distance (m) . All associations with 6MWT performance were attenuated with adjustments for risk factors while ECV and LA strain rate remained independently associated with frailty.


Conclusions
These findings suggest a significant overlap in pathways associated with subclinical cardiac dysfunction, cardiovascular fibrosis and physical frailty.

Background: Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity. Methods: Thirty-four dilated cardiomyopathy patients, 30 ischemic cardiomyopathy patients, and 36 controls underwent magnetic resonance including 4-dimensional flow, BNP (brain-type natriuretic peptide) measurement, functional capacity assessment (6-minute walk test), and symptom quantification. A subgroup of dilated cardiomyopathy and control subjects underwent cardiac energetic assessment. Left ventricular flow was separated into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average KE throughout the cardiac cycle was calculated. Results: Patients had reduced direct flow proportion and direct-flow average KE compared with controls (Pamp;lt;0.0001). The residual volume proportion and residual volume average KE were increased in patients (Pamp;lt;0.0001). Importantly, in a multiple linear regression model to predict the patients 6-minute walk test, the independent predictors were age (beta=-0.3015; P=0.019) and direct-flow average KE (beta=0.280, P=0.035; R-2 model, 0.466, P=0.002). In contrast, neither ejection fraction nor left ventricular volumes were independently predictive. Conclusions: This study demonstrates an independent predictive relationship between the direct-flow average KE and a prognostic measure of functional capacity. Intracardiac 4-dimensional flow parameters are novel biomarkers in heart failure and may provide additive value in monitoring new therapies and predicting prognosis. ; Funding Agencies|British Heart Foundation [FS/12/14/29354]; Medical Research Council; Oxford British Heart Foundation Centre of Research Excellence; Wellcome Trust; Royal Society [098436/Z/12/B]; National Institute for Health Research Oxford Biomedical Research Centre Programme; Swedish Research Council; Swedish Heart and Lung Foundation [20140398]; European Union [310612]