Impact of aortic valve stenosis on myocardial deformation in different left ventricular levels: A three-dimensional speckle tracking echocardiography study.

BACKGROUND: Global systolic left ventricular (LV) myocardial function progressively declines as degenerative aortic valve stenosis (AS) progresses. Whether this results in uniformly distributed deformation changes from base to apex has not been investigated. METHODS: Eighty-five AS patients underwent three-dimensional (3D) echocardiography in this cross-sectional study. Patients were grouped by peak jet velocity into mild (n = 32), moderate (n = 31), and severe (n = 22) AS. 3D speckle tracking derived strain, rotation, twist, and torsion were obtained to assess global LV function and myocardial function at the apical, mid, and basal levels. RESULTS: Global longitudinal strain (GLS) was lower in patients with severe AS (-16.1 ± 2.4% in mild, -15.5 ± 2.5% in moderate, and -13.5 ± 3.0% in severe AS [all p < .01]). Peak basal and mid longitudinal strain (LS), basal rotation and twist from apical to basal level followed the same pattern, while peak apical LS was higher in moderate AS compared to severe AS (all p < .05). In multivariate analyses, lower GLS was particularly associated with male sex, higher body mass index and peak aortic jet velocity, lower basal LS with higher filling pressure (E/e') and LV mass, lower mid LS with higher RWT and presence of AS symptoms, and lower apical LS with male sex and higher systolic blood pressure, respectively (all p < .05). CONCLUSION: Using 3D speckle tracking echocardiography reveals regional and global changes in LV mechanics in AS related to the severity of AS, LV remodeling and presence of cardiovascular risk factors.

Myocardial strain imaging: how useful is it in clinical decision making?

Myocardial strain is a principle for quantification of left ventricular (LV) function which is now feasible with speckle-tracking echocardiography. The best evaluated strain parameter is global longitudinal strain (GLS) which is more sensitive than left ventricular ejection fraction (LVEF) as a measure of systolic function, and may be used to identify sub-clinical LV dysfunction in cardiomyopathies. Furthermore, GLS is recommended as routine measurement in patients undergoing chemotherapy to detect reduction in LV function prior to fall in LVEF. Intersegmental variability in timing of peak myocardial strain has been proposed as predictor of risk of ventricular arrhythmias. Strain imaging may be applied to guide placement of the LV pacing lead in patients receiving cardiac resynchronization therapy. Strain may also be used to diagnose myocardial ischaemia, but the technology is not sufficiently standardized to be recommended as a general tool for this purpose. Peak systolic left atrial strain is a promising supplementary index of LV filling pressure. The strain imaging methodology is still undergoing development, and further clinical trials are needed to determine if clinical decisions based on strain imaging result in better outcome. With this important limitation in mind, strain may be applied clinically as a supplementary diagnostic method.

Mitral valve analysis adding a virtual semi-transparent annulus plane for detection of prolapsing segments.

BACKGROUND: We hypothesized that a novel three-dimensional virtual semi-transparent annulus plane (3D VSAP) presented on a holographic screen can be used to visualize the prolapsing tissue in degenerative mitral valve disease and furthermore, provide us with geometrical data of the mitral valve apparatus. Phantom and patient studies were designed to demonstrate the feasibility of creating a semi-automatic, semi-transparent mitral annulus plane visualized on a holographic display. METHODS: Ten pipe cleaners mimicking the mitral annulus with different shapes and three types of annuloplasty rings served as phantoms. We obtained 3D transoesophageal examination of the phantoms in a special designed box filled with water. Recordings were converted to the holographic display and a 3D VSAP was created. The ratio of the major and minor axes as well as the non-planar angles were calculated and compared with direct measures of the phantoms. Forty patients with degenerative mitral valve disease were then analyzed with 3D transthoracic echocardiography (TTE) and a 3D VSAP was created on the holographic display. A total of 240 segments were analyzed by two independent observers, one echo expert (observer I), and the other novice with limited echo experience (observer II). The two observers created the 3D VSAP in each patient before suggesting the valve pathology. RESULTS: The major/minor axes ratio and non-planar angles by 3D VSAP correlated with direct measurements by r = 0.65, p < 0.02 and r = 0.99, p < 0.0001, respectively. The sensitivity and specificity of the 3D VSAP method in patients was 81 and 97%, respectively (observer I) and for observer II 77 and 96%, respectively. The accuracy and precisions were 93.9 and 89.4%, respectively (observer I), 92.3 and 85.1% (observer II). Mitral valve analysis adding a 3D VSAP was feasible with high accuracy and precision, providing a quick and less subjective method for diagnosing mitral valve prolapse. This novel method may improve preoperative diagnostics and may relieve a better understanding of the pathophysiology of mitral valve disease. Thus, based on the specific findings in each patient, a tailored surgical repair can be planned and hopefully enhance long-term repair patency in the future.

Neutral impact on systolic and diastolic cardiac function of 2 years of intensified multi-intervention in type 2 diabetes: the randomized controlled Asker and Bærum Cardiovascular Diabetes (ABCD) study.

BACKGROUND: Patients with type 2 diabetes (T2D) are prone to develop preclinical myocardial dysfunction, but no single strategy to prevent progression to heart failure has been established. We aimed to assess whether intensified global cardiovascular (CV) risk factor control would improve left ventricular (LV) systolic and diastolic function as compared with standard of care. METHODS: A total of 100 patients with ≥1 CV risk factor (29% female, mean ± SD age 58 ± 10 years, LV ejection fraction 63 ± 8%, 16% with LV diastolic dysfunction) were randomized to 2 years of intensified CV risk multi-intervention (INT, n = 50) or standard care (STAND, n = 50). Echocardiography, including tissue Doppler imaging, and maximum exercise test were performed at baseline and study end. Multi-intervention comprised lifestyle intervention and pharmacologic treatment to reach strict prespecified CV risk factor goals, whereas STAND group received current guideline care. RESULTS: Greater reductions were observed for hemoglobin A1c and total cholesterol in the INT group (P < .001 and P = .021, respectively), whereas blood pressure reduction was similar. Work capacity increased in INT and decreased in STAND (P = .014). There was no significant between-group difference in the change in any of the echocardiographic parameters. CONCLUSIONS: Two years of intensified multi-intervention in patients with T2D improved work capacity and glycemic and lipid control and had no significant benefit or harm on resting cardiac function.

Automatic measurement of aortic annulus diameter in 3-dimensional transoesophageal echocardiography.

BACKGROUND: Transcatheter aortic valve implantation involves percutaneously implanting a biomechanical aortic valve to treat severe aortic stenosis. In order to select a proper device, precise sizing of the aortic valve annulus must be completed. METHODS: In this paper, we describe a fully automatic segmentation method to measure the aortic annulus diameter in patients with aortic calcification, operating on 3-dimensional transesophageal echocardiographic images. The method is based on state estimation of a subdivision surface representation of the left ventricular outflow tract and aortic root. The state estimation is solved by an extended Kalman filter driven by edge detections normal to the subdivision surface. RESULTS: The method was validated on echocardiographic recordings of 16 patients. Comparison against two manual measurements showed agreements (mean ±SD) of -0.3 ± 1.6 and -0.2 ± 2.3 mm for perimeter-derived diameters, compared to an interobserver agreement of -0.1 ± 2.1 mm. CONCLUSIONS: With this study, we demonstrated the feasibility of an efficient and fully automatic measurement of the aortic annulus in patients with aortic disease. The algorithm robustly measured the aortic annulus diameter, providing measurements indistinguishable from those done by cardiologists.

Quantified planar collagen distribution in healthy and degenerative mitral valve: biomechanical and clinical implications.

Degenerative mitral valve disease is a common valvular disease with two arguably distinct phenotypes: fibroelastic deficiency and Barlow's disease. These phenotypes significantly alter the microstructures of the leaflets, particularly the collagen fibers, which are the main mechanical load carriers. The predominant method of investigation is histological sections. However, the sections are cut transmurally and provide a lateral view of the microstructure of the leaflet, while the mechanics and function are determined by the planar arrangement of the collagen fibers. This study, for the first time, quantitatively examined planar collagen distribution quantitatively in health and disease using second harmonic generation microscopy throughout the thickness of the mitral valve leaflets. Twenty diseased samples from eighteen patients and six control samples were included in this study. Healthy tissue had highly aligned collagen fibers. In fibroelastic deficiency they are less aligned and in Barlow's disease they are completely dispersed. In both diseases, collagen fibers have two preferred orientations, which, in contrast to the almost constant one orientation in healthy tissues, also vary across the thickness. The results indicate altered in vivo mechanical stresses and strains on the mitral valve leaflets as a result of disease-related collagen remodeling, which in turn triggers further remodeling.

Characterisation of global and regional mitral annular strains in an acute porcine model.

OBJECTIVES: This study aimed to explore regional mitral annular strain using a novel computational method. METHODS: Eight pigs underwent implantation with piezoelectric transducers around the mitral annulus. Interventions of pre- and afterload were performed by inferior vena cava constriction and endovascular balloon occlusion of the descending aorta. The mitral annulus was reconstructed in a mathematical model and divided into 6 segments. Global and segmental annular strain were calculated from a discrete mathematical representation. RESULTS: Global annular strain gradually decreased after isovolumetric contraction until late systole. Mitral annular end-systolic strain demonstrated shortening in all segments except the anterior segment, which showed the least deformation. The P2 annular segment demonstrated the most end-systolic shortening (-7.6 ± 1.1% at baseline, P < 0.001 compared to anterior segment). Systolic global annular strain showed no significant change in response to load interventions but correlated positively with left ventricular contractility at baseline and after preload reduction. CONCLUSIONS: Mitral annular systolic strain demonstrates cyclical variations with considerable regional heterogeneity, with the most pronounced deformation in posterior annular segments. Measurements appear independent of changes to pre- and afterload.

Sex differences in left atrial volumes, mechanics, and stiffness in primary mitral regurgitation-a combined 2D and 3D echocardiographic study.

AIMS: Mitral regurgitation (MR) causes left atrial (LA) enlargement and impaired reservoir function. We assessed whether changes in LA size, strain, and stiffness in significant (moderate or greater) primary MR are sex-specific. METHODS AND RESULTS: In the 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation study, 111 patients with primary MR were prospectively investigated with 2D and 3D echocardiography. MR was severe if the 3D regurgitant fraction was ≥50%. LA size was assessed by maximum, minimum, and pre-A 3D volume (LAV), mechanics by peak reservoir (LASr) and contractile strain, and stiffness by the ratio: mitral peak E-wave divided by the annular e' velocity (E/e')/LASr. Women were older, had higher heart rate, and lower body mass index and MR regurgitant volumes (P < 0.05). 3D LAV indexed for body surface area and LA contractile strain did not differ by sex, while LASr was lower (22.2 vs. 25.0%) and LA stiffness higher in women (0.56 vs. 0.44) (P < 0.05). In linear regression analysis, female sex was associated with higher LA stiffness independent of age, minimum LAV, left ventricular global longitudinal strain, diabetes, and coronary artery disease (R2 = 0.56, all P < 0.05). In logistic regression analysis, women had a four-fold (95% CI 1.2-13.1, P = 0.02) higher adjusted risk of increased LA stiffness than men. CONCLUSION: Women with significant primary MR have more impaired LA reservoir mechanics and increased LA stiffness compared with men despite lower MR regurgitant volumes and similar indexed LA size. The findings reveal sex-specific features of LA remodeling in MR. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04442828.

Exercise-Induced Cardiac Troponin I Elevation Is Associated With Regional Alterations in Left Ventricular Strain in High-Troponin Responders.

BACKGROUND: The implications of exercise-induced cardiac troponin elevation in healthy individuals are unclear. This study aimed to determine if individuals with a high exercise-induced cardiac troponin I (cTnI) response have alterations in myocardial function following high-intensity endurance exercise compared with normal-cTnI responders. METHODS AND RESULTS: Study individuals were recruited from previous participants in a 91-km mountain bike cycling race (the North Sea Race) and were classified as high- (n=34) or normal-cTnI responders (n=25) based on maximal cTnI values after the recruitment race. The present study exposed all participants to 2 prolonged high-intensity exercises: a combined lactate threshold and cardiopulmonary exercise test and repeated participation in the North Sea Race. Echocardiography was performed before, immediately after, and 24 hours following exercise. All study individuals (n=59) had normal coronary arteries, and were aged 51±10 years; 46 (74%) were men. There were no differences in baseline characteristics between the high- and normal-cTnI responders. Maximal cTnI levels 3 hours after exercise were significantly higher in the high- compared with normal-cTnI group (P<0.001-0.027). Following exercise, there were no differences in global ventricular function between the 2 groups. In contrast, high-cTnI responders had significantly lower regional strain in the anteroseptal segments following exercise, with more profound changes after the race. CONCLUSIONS: High-cTnI responders had lower anteroseptal segmental strain shortly after exercise than normal-cTnI responders. However, there were no permanent alterations in myocardial strain, indicating no short- or long-term adverse consequences of these exercise-induced alterations in myocardial function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.

Correlation between Murmurs and Echocardiographic Findings; From an Imaging Cardiologist Point of View.

A heart murmur in adults is a common reason for referral for echocardiography at most general cardiology clinics in Europe. A murmur may indicate either a mild age-related valvular calcification or regurgitation, or represent a significant heart valve disease requiring valvular intervention. Generally, the correlation between murmurs by auscultation and severity of heart valve disease by echocardiography is poor. Particularly, the severity and characterization of diastolic murmurs by auscultation may poorly correlate with echocardiographic findings. This narrative review aims to summarize the differential diagnoses of physiological and pathological murmurs, describes the current referral practice of murmur patients for echocardiography, and presents a single-center experience on the correlation of auscultation and echocardiographic findings with a particular focus on aortic and mitral valve diseases. A careful auscultation of the heart prior to the echocardiogram is mandatory and may help to predict the echocardiographic findings and their interpretation in view of the clinical information. The correlation between clinical examination, point of care ultrasound and standard echocardiography is a matter of continued exploration.

Echocardiography Assessment of Rheumatic Heart Disease: Implications for Percutaneous Balloon Mitral Valvuloplasty.

Echocardiography is an important diagnostic imaging modality in recognizing rheumatic heart disease, a chronic sequelae of acute rheumatic fever. Left-sided heart valves, especially the mitral valve is typically affected, with stenosis or regurgitation as a consequence. Although assessment of valve area by 2D planimetry is the reference method for mitral stenosis severity, 3D planimetry provides more accurate measurement and diagnostic value. Careful selection of patients in terms of echocardiographic criteria is essential to ensure safety and success of the intervention and better long-term outcomes. Several echocardiographic scores based upon mitral valve mobility, thickening, calcification, and subvalvular thickening are developed to assess mitral valve anatomy and the feasibility of percutaneous mitral commissurotomy. 3D transesophageal echocardiography (TEE) provides detailed information of the mitral anatomy (commissural fusions, and subvalvular apparatus) before intervention. In addition, 3D TEE planimetry provides a more accurate measurement of the valve area compared with 2D echocardiography. Generally, huge annular calcification and lack of commissural fusion are unfavorable echocardiographic markers that increase the risk of complications and preclude the feasibility of percutaneous balloon mitral valvuloplasty. More contemporary prospective echocardiography research studies on patients with RHD from low- and middle-income countries are needed.

In silico analysis provides insights for patient-specific annuloplasty in Barlow's disease.

Objective: To predict the required mitral annular area reduction in patients with Barlow's disease to obtain a predefined leaflet area index by a novel in silico modeling method. Methods: Three-dimensional echocardiography was used to create patient-specific mitral valve models of 8 patients diagnosed with Barlow's disease and bileaflet prolapse preoperatively. Six patients were also studied postoperatively in a finite element framework, to quantify the optimal coaptation area index. For the patient-specific finite element analyses, realistic papillary muscle and annular motion are incorporated, also for the in silico annuloplasty analyses. The annuloplasty ring size is reduced moderately until the optimal coaptation area index is achieved for each patient. Results: The mean mitral annular area at end-diastole was reduced by 58 ± 7% postoperatively (P < .001), resulting in a postoperative coaptation area index of 20 ± 5%. To achieve the same coaptation area index with moderate annular reductions and no leaflet resection the annular reduction was 31 ± 6% (P < .001). Conclusions: In silico analysis in selected patients diagnosed with Barlow's disease demonstrates that annuloplasty with only moderate annular reduction may be sufficient to achieve optimal coaptation as compared to conventional surgical procedures.

Mechanical behavior and collagen structure of degenerative mitral valve leaflets and a finite element model of primary mitral regurgitation.

Degenerative mitral valve disease is the main cause of primary mitral regurgitation with two phenotypes: fibroelastic deficiency (FED) often with localized myxomatous degeneration and diffuse myxomatous degeneration or Barlow's disease. Myxomatous degeneration disrupts the microstructure of the mitral valve leaflets, particularly the collagen fibers, which affects the mechanical behavior of the leaflets. The present study uses biaxial mechanical tests and second harmonic generation microscopy to examine the mechanical behavior of Barlow and FED tissue. Three tissue samples were harvested from a FED patient and one sample is from a Barlow patient. Then we use an appropriate constitutive model by excluding the collagen fibers under compression. Finally, we built an FE model based on the echocardiography of patients diagnosed with FED and Barlow and the characterized material model and collagen fiber orientation. The Barlow sample and the FED sample from the most affected segment showed different mechanical behavior and collagen structure compared to the other two FED samples. The FE model showed very good agreement with echocardiography with 2.02±1.8 mm and 1.05±0.79 mm point-to-mesh distance errors for Barlow and FED patients, respectively. It has also been shown that the exclusion of collagen fibers under compression provides versatility for the material model; it behaves stiff in the belly region, preventing excessive bulging, while it behaves very softly in the commissures to facilitate folding. STATEMENT OF SIGNIFICANCE: This study quantifies for the first time the collagen microstructure and mechanical behavior of degenerative mitral valve (DMV) leaflets. These data will then be used for the first disease-specific finite element (FE) model of DMV. While current surgical repair of DMV is based on surgical experience, FE modeling has the potential to support decision-making and make outcomes predictable. We adopt a constitutive model to exclude collagen fiber under compressions, an important consideration when modeling the mitral valve, where the leaflets are folded to ensure complete closure. The results of this study provide essential data for understanding the relationship between collagen microstructure and degenerative mitral valve mechanics.

Mitral annular dynamics are influenced by left ventricular load and contractility in an acute animal model.

The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High-fidelity catheters measured left ventricular pressures and the slope of the end-systolic pressure-volume relationship (Ees ) determined LV contractility. Adjustments of pre- and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi ), annular circularity index (ACI), and non-planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (-Δr) and average deformational velocity (- v ¯ $$ \overline{v} $$ ) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi -Δr and MAAi - v ¯ $$ \overline{v} $$ (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.

Three-dimensional ultrasound in cardiological diagnostics.

BACKGROUND: Diagnostic ultrasonography plays an important part in cardiology. New technological advances such as three-dimensional representation of the heart now make an important supplement to today's standard echocardiography. MATERIAL AND METHOD: An overview based on PubMed literature studies and the authors' own experience is provided of the opportunities three-dimensional echocardiography offers for present and future diagnosis of heart disease. RESULTS: Three-dimensional echocardiography is an important supplement to today's standard echocardiography. The best documentation is available for calculating left ventricular volume and ejection fraction and for diagnosing mitral valve disease. Theoretically, the method can also be used to advantage to assist in catheter-directed interventions and in the diagnosis of cardiomyopathies and complex congenital heart defects. INTERPRETATION: With improved technology and hence improved imaging, three-dimensional echocardiography will be an even more important supplement to today's standard echocardiography. More accurate preoperative diagnostics in connection with heart valve defects are particularly important for directing the choice of surgical procedure.

Mitral Annular Elasticity Determines Severity of Regurgitation in Barlow's Mitral Valve Disease.

OBJECTIVES: Barlow's mitral valve disease with late systolic mitral regurgitation provides diagnostic and therapeutic challenges. The mechanisms of the regurgitation are still unclear. We hypothesized that the onset and the severity of late systolic regurgitation are determined by annulus dynamics and the mechanical stresses imposed by the left ventricle. METHODS: Ten patients with Barlow's mitral valve disease and mitral annulus disjunction (MAD) were compared with 10 healthy controls. Resting blood pressure was measured, and transthoracic three-dimensional echocardiography was analyzed using a holographic display that allows tracking and measurements of mitral annulus surface area (ASA) throughout the cardiac cycle. A novel annulus elastance index (dASA/dP) was calculated between aortic valve opening and onset of mitral regurgitation. Severity of MAD was quantified as the disjunction index (mm × degree). Leaflet coaptation area was calculated using a finite element model. RESULTS: Peak systolic ASAs in controls and patients were 9.3 ± 0.6 and 21.1 ± 3.1 cm2, respectively (P < .001). In patients, the ASA increased rapidly during left ventricular ejection, and onset of mitral regurgitation coincided closely with peak upslope of annulus area change (dASA/dt). The finite element model showed a close association between rapid annulus displacement and coaptation area deficit in Barlow's mitral valve disease. Systolic annulus elastance index (0.058 ± 0.036 cm2/mm Hg) correlated strongly with disjunction index (r = 0.91, P < .0001). Moreover, regurgitation volume showed a positive correlation with systolic blood pressure (r = 0.80, P < .01). CONCLUSION: The present pilot study supports the hypothesis that annulus dilatation may accentuate mitral valve regurgitation in patients with Barlow's mitral valve disease. A novel annulus elastance index may predict the severity of mitral valve regurgitation in selected patients.

Finite element analysis of mitral valve annuloplasty in Barlow's disease.

Barlow's Disease affects the entire mitral valve apparatus causing mitral regurgitation. Standard annuloplasty procedures lead to an average of 55% annular area reduction of the end diastolic pre-operative annular area in Barlow's diseased valves. Following annular reduction, mitral valvuloplasty may be needed, usually with special focus on the posterior leaflet. An in silico pipeline to perform annuloplasty by utilizing the pre- and -postoperative 3D echocardiographic recordings was developed. Our objective was to test the hypothesis that annuloplasty ring sizes based on a percentage (10%-25%) decrease of the pre-operative annular area at end diastole can result in sufficient coaptation area for the selected Barlow's diseased patient. The patient specific mitral valve geometry and finite element model were created from echocardiography recordings. The post-operative echocardiography was used to obtain the artificial ring geometry and displacements, and the motion of the papillary muscles after surgery. These were used as boundary conditions in our annuloplasty finite element analyses. Then, the segmented annuloplasty ring was scaled up to represent a 10%, 20% and 25% reduction of the pre-operative end diastolic annular area and implanted to the end diastolic pre-operative finite element model. The pre-operative contact area decrease was shown to be dependent on the annular dilation at late systole. Constraining the mitral valve from dilating excessively can be sufficient to achieve proper coaptation throughout systole. The finite element analyses show that the selected Barlow's diseased patient may benefit from an annuloplasty ring with moderate annular reduction alone.

Comparison of ultrasound vector flow imaging and CFD simulations with PIV measurements of flow in a left ventricular outflow trackt phantom - Implications for clinical use and in silico studies.

In this study we have compared two modalities for flow quantification from measurement data; ultrasound (US) and shadow particle image velocimetry (PIV), and a flow simulation model using computational fluid dynamics (CFD). For the comparison we have used an idealized Quasi-2D phantom of the human left ventricular outflow tract (LVOT). The PIV data will serve as a reference for the true flow field in our setup. Furthermore, the US vector flow imaging (VFI) data has been post processed with model-based regularization developed to both smooth noise and sharpen physical flow features. The US VFI flow reconstruction results in an underestimation of the flow velocity magnitude compared to PIV and CFD. The CFD results coincide very well with the PIV flow field maximum velocities and curl intensity, as well as with the detailed vortex structure, however, this correspondence is subject to exact boundary conditions.

Myocardial inefficiency is an early indicator of exercise-induced myocardial fatigue.

Background: The effect of prolonged, high-intensity endurance exercise on myocardial function is unclear. This study aimed to determine the left ventricular (LV) response to increased exercise duration and intensity using novel echocardiographic tools to assess myocardial work and fatigue. Materials and methods: LV function was assessed by echocardiography before, immediately, and 24 h after a cardiopulmonary exercise test (CPET) and a 91-km mountain bike leisure race. Cardiac Troponin I (cTnI) was used to assess myocyte stress. Results: 59 healthy recreational athletes, 52 (43-59) years of age, 73% males, were included. The race was longer and of higher intensity generating higher cTnI levels compared with the CPET (p < 0.0001): Race/CPET: exercise duration: 230 (210, 245)/43 (40, 45) minutes, mean heart rate: 154 ± 10/132 ± 12 bpm, max cTnI: 77 (37, 128)/12 (7, 23) ng/L. Stroke volume and cardiac output were higher after the race than CPET (p < 0.005). The two exercises did not differ in post-exercise changes in LV ejection fraction (LVEF) or global longitudinal strain (GLS). There was an increase in global wasted work (p = 0.001) following the race and a persistent reduction in global constructive work 24 h after exercise (p = 0.003). Conclusion: Increased exercise intensity and duration were associated with increased myocardial wasted work post-exercise, without alterations in LVEF and GLS from baseline values. These findings suggest that markers of myocardial inefficiency may precede reduction in global LV function as markers of myocardial fatigue.

High-molecular-weight von Willebrand Factor multimer ratio differentiates true-severe from pseudo-severe classical low-flow, low-gradient aortic stenosis.

AIMS: Upon high wall shear stress, high-molecular-weight (HMW) von Willebrand Factor (VWF) multimers are degraded, thus, HMW VWF multimer deficiency mirrors haemodynamics at the site of aortic stenosis (AS). The aim of the present study was to analyse the role of HMW VWF multimer ratio for subcategorization of classical low-flow, low-gradient (LF/LG) AS. METHODS AND RESULTS: Eighty-three patients with classical LF/LG AS were prospectively recruited and HMW VWF multimer pattern was analysed using a densitometric quantification of western blot bands. Patients were subclassified into true-severe (TS) and pseudo-severe (PS) classical LF/LG AS based on dobutamine stress echocardiography (DSE). Positive and negative predictive values (PPV/NPV) of HMW VWF multimer ratio for diagnosis of the TS subtype were calculated. HMW VWF multimer ratio in TS classical LF/LG AS was significantly decreased compared to PS classical LF/LG AS (0.86 ± 0.27 vs. 1.06 ± 0.09, P < 0.001). HMW VWF multimer deficiency occurred exclusively in the TS subtype with an optimal PPV of 1.000 and NPV of 0.379. HMW VWF multimer ratio showed a strong correlation with mean transvalvular pressure gradients during DSE (r = -0.616; P < 0.001). HMW VWF multimer ratio measured at baseline was higher compared to levels measured after DSE (0.87 ± 0.27 vs. 0.84 ± 0.31; P = 0.031) indicating DSE-induced increased proteolysis. CONCLUSION: HMW VWF multimer ratio represents a valuable biomarker for classical LF/LG AS subclassification and mirrors haemodynamics during DSE. HMW VWF multimer ratio identifies the TS subtype without the use of other imaging techniques.