Diastolic Length Research Articles

Which echocardiographic measure of longitudinal function is most informative?

Abstract Background The longitudinal function of the left ventricle can be quantified by measuring the myocardial excursion with or without normalising by the diastolic length to derive strain. Furthermore, these lengths can be determined from the curved myocardial length or in a straight-line from the mid-annulus to the apex parallel to the long axis. All four combinations have been advocated and used, but the optimal is unknown. Purpose Compare the prognostic information contained by these four measures of longitudinal function in a large retrospective cohort, with measurements performed by AI. Methods The cohort consisted of echocardiograms performed during 2015 at our institution for which mortality data were available. Our previously published AI based view classifier selected the apical 4-, 2-, and 3-chamber views from each study, before the endocardial contour and annular and apical points were segmented by another neural network. From this the curved and long-axis excursion was calculated, and then strain was derived using the diastolic length. Nested non-linear Cox-models including age and sex and each of the longitudinal measures were constructed, and the information contained by each variable was quantified via Chi-Square and compared using bootstrap methods. Results 1733 patient studies were included, the median age was 64 (IQR 49 to 75) years and 51% were male. A total of 213 (14%) deaths occurred. The median excursion and strains were 3.25 cm (IQR 2.68 to 3.81) and -17% (IQR -20% to -14%) along the endocardial curve and 2.36 cm (IQR 1.88 to 2.87) and -14% (IQR -17% to -11%) along the long axis. All four longitudinal measures significantly added to a base model containing age and sex (p=0.003, p=0.005, p=0.005, p=0.002). Whilst the simple long axis excursion was numerically the most prognostic, none of the measures were significantly different from each other. Conclusions In this head-to-head AI-assisted retrospective cohort study using mortality as the endpoint, there was no good evidence that more complex measures of longitudinal function had better prognostic performance.Information provided by model componentsLong axis excursion calibration curve

Papillary Muscle Infarction by Cardiac MRI in Patients With Mitral Regurgitation.

Papillary muscle (PM) infarction (PMI) detected by cardiac magnetic resonance imaging (CMR) is associated with poor outcomes. Whether PM parameters provide more value for mitral regurgitation (MR) management currently remains unclear. Therefore, we examined the prognostic value of PMI using CMR in patients with MR. Between March 2018 and July 2023, we retrospectively enrolled 397 patients with MR undergoing CMR. CMR was used to detect PMI qualitatively and quantitively. We also collected baseline clinical, echocardiography, and follow-up data. Of the 397 patients with MR (52.4 ± 13.9 years), 117 (29.5%) were assigned to the PMI group, with 280 (70.5%) in the non-PMI group. PMI was demonstrated more in the posteromedial PM (PM-PM, 98/117) than in the anterolateral PM (AL-PM, 45/117). Compared with patients without PMI, patients with PMI had a decreased AL-PM (41.5 ± 5.4 vs. 45.6 ± 5.3)/PM-PM diastolic length (35.0 ± 5.2 vs. 37.9 ± 4.0), PM-longitudinal strain (LS, 20.4 ± 6.1 vs. 24.9 ± 4.6), AL-PM-LS (19.7 ± 6.8 vs. 24.7 ± 5.6)/PM-PM-LS (21.2 ± 7.9 vs. 25.2 ± 6.0), and increased inter-PM distance (25.7 ± 8.0 vs. 22.7 ± 6.2, all p < 0.001). Multiple logistic regression analyses identified male sex (odds ratio [OR] = 3.65, 95% confidence interval = 1.881-7.081, p < 0.001) diabetes mellitus (OR/95% CI/p = 2.534/1.13-5.68/0.024), AL-PM diastolic length (OR/95% CI/p = 0.841/0.77-0.92/< 0.001), PM-PM diastolic length (OR/95% CI/p = 0.873/0.79-0.964/0.007), inter-PM distance (OR/95% CI/p = 1.087/1.028-1.15/0.003), AL-PM-LS (OR/95% CI/p = 0.892/0.843-0.94/< 0.001), and PM-PM-LS (OR/95% CI/p = 0.95/0.9-0.992/0.021) as independently associated with PMI. Over a 769 ± 367-day follow-up, 100 (25.2%) patients had arrhythmia. Cox regression analyses indicated that PMI (hazard ratio [HR]/95% CI/p = 1.644/1.062-2.547/0.026), AL-PM-LS (HR/95% CI/p = 0.937/0.903-0.973/0.001), and PM-PM-LS (HR/95% CI/p = 0.933/0.902-0.965/< 0.001) remained independently associated with MR. The CMR-derived PMI and LS parameters improve the evaluation of PM dysfunction, indicating a high risk for arrhythmia, and provide additive risk stratification for patients with MR.

The role of epicardial obesity in the development of left ventricular diastolic dysfunction

To study the effect of epicardial adipose tissue on risk of left ventricular (LV) diastolic dysfunction (DD) in patients with visceral obesity. Obesity leads to the development of LV DD and is a major cause of heart failure with preserved LV ejection fraction (HFpEF). However, the contribution of epicardial adipose tissue to DD is understudied. This study included 101 men with general obesity (body weight index, 32.9±3.6 kg /m2). Based on severity of epicardial obesity (EO), two groups were formed: group 1, patients with an epicardial adipose tissue thickness (EATt) &gt;7 mm (n=70), and group 2, patients with EATt &lt;7 mm (n=31). Arterial hypertension, diabetes mellitus, coronary atherosclerosis, and disorders of LV diastolic function according to echocardiography (EchoCG) were the exclusion criteria. Diastolic function and LV mechanics were evaluated by speckle-tracking EchoCG for all patients at the start of the study and again at 4.7±0.3 years. At baseline, none of the patients of either group had significant differences in EchoCG characteristics of LV diastolic function (left atrial volume index, LV early diastolic longitudinal lengthening velocity, peak tricuspid regurgitation velocity, and the ratio of diastolic transmitral flow velocity to mean mitral annular velocity (E / e'). However, there were significant increases in the LV untwisting velocity to -122.11 [-142.0; -116.0 degrees /s -1] degrees/s and the time to LV peak untwisting velocity to 472.3 ms. Repeated EchoCG showed an increase in left atrial volume index in group 1 to 35.04 [33.0; 39.7] ml /m2. Repeated evaluation of the LV mechanics revealed increases in the times to LV peak untwisting and twisting and decreases in the LV twisting and untwisting velocities. The logistic regression analysis showed that EATt was a risk factor for LV DD in obesity. Furthermore, the ROC analysis determined the optimal EATt cut-off threshold of ≥9 mm as a predictor for LV DD development. EO facilitates the development of LV DD and, thus, represents a major cause for HFpEF. An EATt value of ≥9 mm can be considered as a risk factor for LV DD development in patients with EO.

Echocardiographic assessment of right ventricular function and right ventriculoarterial coupling in tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background Echocardiographic evaluation of the cardiopulmonary unit may be difficult in the presence of tricuspid regurgitation (TR) and combined echocardiographic parameters could therefore be useful in such patients. Purpose To assess the variation of simple and combined echocardiographic parameters analysing the cardiopulmonary unit according to the severity of TR. Methods Echocardiographic images were reviewed in 179 patients to assess TR grade according to Hahn’s 5 grades classification. Classical morphological (right ventricle (RV) end diastolic (ED) length and area), function (tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), S’ wave, RV free wall longitudinal strain (RVFWS)) and load (TR Time-velocity integral (TR TVI), pulmonary artery systolic pressure (PASP)) parameters analysing RV were assessed. Combined parameters of function and load (TAPSE/PASP, TR TVI x RVFWS), morphology and load (load adaptation index (LAI) = TR TVI x RVED length/area) and morphology, load, and function (myomechanical index (MMI = RV-RA mean pressure gradient x RVFWS/indexed RAED area x 10–2 ) and morphology-load-function index (MLF = RVED length/area x TR TVI x RVFWS)) were calculated. We used receiver operating characteristic (ROC) curve analysis to analyze the diagnostic value of echocardiographic parameters to predict potential high (&amp;gt;3) or low (&amp;lt;6) surgical risk of mortality according to TRISCORE. Results Simple parameters were significatively different among groups with a nonlinear progression between the 5 levels of severity of TR. Combined parameters were also significatively different among groups. Among them, MMI and MLF had a linear progression between the 5 groups (MMI: grade 1: 0.20±0.09; grade 2: 0.15±0.08; grade 3: 0.10±0.05, grade 4: 0.09±0.08; grade 5: 0.05±0.04 p = 0.000; MLF: grade 1: 7.56±2.06; grade 2: 6.57±2.14; grade 3: 4.85±2.29, grade 4: 4.79±3.17; grade 5: 3.06±1.82 p = 0.000) and had the best predictive value for TRISCORE high and low risk (MMI: AUC =0.889 p = 0.000 for low risk, 0.855 p = 0.000 for high risk; MLF: AUC =0.873 p = 0.000 for low risk, 0.822 p = 0.000 for high risk). Conclusion Combined parameters are relevant to evaluate cardiopulmonary unit in a population presenting with TR, especially when combining morphology, function and load parameters. Their good predictive value for TRISCORE risk suggests a potential role of such parameters in the prognostic assessment of TR patients and in the selection for new percutaneous repair techniques.

Echocardiographic assessment of right ventricular function and right ventriculoarterial coupling in tricuspid regurgitation

Echographic evaluation of the cardiopulmonary unit may be difficult in the presence of TR. Purpose: To assess the variation of simple and combined echographic parameters analysing the cardiopulmonary unit according to the severity of TR. Echographic images were reviewed in 179 patients to assess TR grade according to Hahn's 5 grades classification. Classical morphological (RV end diastolic length and area), function [TAPSE, RVFAC, S’,RVFWS (RV free wall longitudinal strain)] and load [PASP,TRTVI (TR Time-velocity integral)] parameters analysing RV were assessed. Combined parameters of function and load (TAPSE/PASP, TR TVI × RVFWS), morphology and load (load adaptation index = TRTVIxRVED length/area) and morphology, load, and function [myomechanical index (MMI = RV-RA mean pressure gradient × RVFWS/indexed RAED area × 10–2) and morphology-load-function index (MLF = RVED length/area xTRTVIx RVFWS)] were calculated. We used ROC curves to analyze the diagnostic value of echocardiographic parameters to predict potential high (> 3) or low (< 6) surgical risk of mortality according to TRISCORE. Simple parameters were significatively different among groups with a nonlinear progression between the 5 levels of TR. Combined parameters were also significatively different. Among them, MMI and MLF had a linear progression (MMI: grade 1: 0.20 ± 0.09; grade 2: 0.15 ± 0.08; grade 3: 0.10 ± 0.05, grade 4: 0.09 ± 0.08; grade 5: 0.05 ± 0.04 P = 0.000; MLF: grade 1: 7.56 ± 2.06; grade 2: 6.57 ± 2.14; grade 3: 4.85 ± 2.29, grade 4: 4.79 ± 3.17; grade 5: 3.06 ± 1.82 P = 0.000) and had the best predictive value for TRISCORE (MMI: AUC = 0.889 P = 0.000 for low risk, 0.855 P = 0.000 for high risk; MLF: AUC = 0.873 P = 0.000 and 0.822 P = 0.000). Combined parameters are relevant to evaluate cardiopulmonary unit in a population presenting with TR, especially when combining morphology, function and load (Fig. 1).

Effect of spironolactone on vascular stiffness in hemodialysis patients: a randomized crossover trial.

BackgroundThe role of spironolactone treatment in hemodialysis patients is debated, but a survival benefit is suggested. Mineralocorticoids and chronic kidney disease have been linked to cardiovascular fibrosis. Therefore, we hypothesized that spironolactone would affect vascular stiffness, cardiac systolic, and diastolic function in hemodialysis patients.MethodsThis was a randomized crossover study in hemodialysis patients supplemented with an echocardiographic case series. All outcomes reported here were secondary in the trial and were assessed without blinding. Block randomization and allocation determined treatment order. Participants received 50 mg spironolactone daily for 12 weeks and untreated observation for another 12 weeks. Pulse wave velocity (PWV) was measured before and after treatment and observation. Doppler-echocardiography was conducted before and after treatment. Systemic arterial compliance indexed to body surface area (SACi), left ventricular ejection fraction (LVEF), the peak early diastolic mitral inflow velocity (E), the peak late diastolic mitral inflow velocity (A), and the peak early diastolic myocardial lengthening velocity (E’) were measured. E/A and E/E’ were then calculated. Statistical analyses were conducted per protocol. A generalized linear mixed model with random participant effects was used for PWV. The Wilcoxon signed-rank test was used for echocardiographic variables.ResultsThirty participants were recruited, 18 completed follow-up, and 17 were included in PWV-analyses. Spironolactone treatment showed a tendency toward an increase in PWV of 1.34 (95% confidence interval: −0.11 to 2.78) m/s, which was not statistically significant (P = 0.07). There were no significant changes in any of the other variables (LVEF, E/A, E/Eʹ, or SACi).ConclusionsWe found no evidence supporting an effect of 12-week administration of spironolactone 50 mg daily on vascular stiffness, cardiac systolic, or diastolic function in hemodialysis patients.

Staged left ventricular recruitment facilitated by Sano conduit upsizing

Staged left ventricular recruitment facilitated by Sano conduit upsizing

Carotid Reservoir Pressure Decrease After Prolonged Head Down Tilt Bed Rest in Young Healthy Subjects Is Associated With Reduction in Left Ventricular Ejection Time and Diastolic Length.

BackgroundThe arterial pressure waveform reflects the interaction between the heart and the arterial system and carries potentially relevant information about circulatory status. According to the commonly accepted ‘wave transmission model’, the net BP waveform results from the super-position of discrete forward and backward pressure waves, with the forward wave in systole determined mainly by the left ventricular (LV) ejection function and the backward by the wave reflection from the periphery, the timing and amplitude of which depend on arterial stiffness, the wave propagation speed and the extent of downstream admittance mismatching. However, this approach obscures the ‘Windkessel function’ of the elastic arteries. Recently, a ‘reservoir-excess pressure’ model has been proposed, which interprets the arterial BP waveform as a composite of a volume-related ‘reservoir’ pressure and a wave-related ‘excess’ pressure.MethodsIn this study we applied the reservoir-excess pressure approach to the analysis of carotid arterial pressure waveforms (applanation tonometry) in 10 young healthy volunteers before and after a 5-week head down tilt bed rest which induced a significant reduction in stroke volume (SV), end-diastolic LV volume and LV longitudinal function without significant changes in central blood pressure, cardiac output, total peripheral resistance and aortic stiffness. Forward and backward pressure components were also determined by wave separation analysis.ResultsCompared to the baseline state, bed rest induced a significant reduction in LV ejection time (LVET), diastolic time (DT), backward pressure amplitude (bP) and pressure reservoir integral (INTPR). INTPR correlated directly with LVET, DT, time to the peak of backward wave (bT) and stroke volume, while excess pressure integral (INTXSP) correlated directly with central pressure. Furthermore, Δ.INTPR correlated directly with Δ.LVET, and Δ.DT, and in multivariate analysis INTPR was independently related to LVET and DT and INTXSP to central systolic BP.ConclusionThis is an hypothesis generating paper which adds support to the idea that the reservoir-wave hypothesis applied to non-invasively obtained carotid pressure waveforms is of potential clinical usefulness.

Intelligent Prediction of Cryptogenic Stroke Using Patent Foramen Ovale from TEE Imaging Data and Machine Learning Methods

In spite of the popularity of random forests (RF) as an efficient machine learning algorithm, methods for constructing the potential association for between patent foramen ovale (PFO) and cryptogenic stroke (CS) using this technique are still barely. For the vital regional study areas (atrial septum), RF was used to predict CS in patients with PFO using partial clinical data of patients and remotely sensed imaging examination data obtained from Tee imaging. We validated our method on a dataset of 151 consecutive patients with detected PFO at a large grade A hospital in China from November 2018 to December 2020, we obtained an area under the relative operating characteristic curve of 0.816, with 65% specificity at 73% sensitivity. The RF models accurately represented the relationship between the CS and remotely sensed predictor variables. Therein, maximum mobility, large right-to-left shunt during Valsalva maneuver, size of PFO in diastole and systole, and diastolic length of the tunnel present higher predictive value in CS. Our findings suggest that multi-Doppler sensor data by transesophageal echocardiography (TEE)-detected morphologic and functional characteristics of PFO may play important roles in the occurrence of CS. These results indicate that the established random forest model has the potential to predict CS in patients with PFO and great promise for application to clinical practice.

Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype.

The role that mechanical forces play in shaping the structure and function of the heart is critical to understanding heart formation and the etiology of disease but is challenging to study in patients. Engineered heart tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes have the potential to provide insight into these adaptive and maladaptive changes. However, most EHT systems cannot model both preload (stretch during chamber filling) and afterload (pressure the heart must work against to eject blood). Here, we have developed a new dynamic EHT (dyn-EHT) model that enables us to tune preload and have unconstrained contractile shortening of >10%. To do this, three-dimensional (3D) EHTs were integrated with an elastic polydimethylsiloxane strip providing mechanical preload and afterload in addition to enabling contractile force measurements based on strip bending. Our results demonstrated that dynamic loading improves the function of wild-type EHTs on the basis of the magnitude of the applied force, leading to improved alignment, conduction velocity, and contractility. For disease modeling, we used hiPSC-derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy due to mutations in the desmoplakin gene. We demonstrated that manifestation of this desmosome-linked disease state required dyn-EHT conditioning and that it could not be induced using 2D or standard 3D EHT approaches. Thus, a dynamic loading strategy is necessary to provoke the disease phenotype of diastolic lengthening, reduction of desmosome counts, and reduced contractility, which are related to primary end points of clinical disease, such as chamber thinning and reduced cardiac output.

The Preterm Heart-Brain Axis in Young Adulthood: The Impact of Birth History and Modifiable Risk Factors.

People born preterm are at risk of developing both cardiac and brain abnormalities. We aimed to investigate whether cardiovascular physiology may directly affect brain structure in young adulthood and whether cardiac changes are associated with modifiable biomarkers. Forty-eight people born preterm, followed since birth, underwent cardiac MRI at age 25.1 ± 1.4 years and brain MRI at age 33.4 ± 1.0 years. Term born controls were recruited at both time points for comparison. Cardiac left and right ventricular stroke volume, left and right ventricular end diastolic volume and right ventricular ejection fraction were significantly different between preterm and term born controls and associated with subcortical brain volumes and fractional anisotropy in the corpus callosum in the preterm group. This suggests that cardiovascular abnormalities in young adults born preterm are associated with potentially adverse future brain health. Associations between left ventricular stroke volume indexed to body surface area and right putamen volumes, as well as left ventricular end diastolic length and left thalamus volumes, remained significant when adjusting for early life factors related to prematurity. Although no significant associations were found between modifiable biomarkers and cardiac physiology, this highlights that cardiovascular health interventions may also be important for brain health in preterm born adults.

Abstract 15658: Anatomical Characteristics of the Cavotricuspid Isthmus and Their Correlation With Obstructive Sleep Apnea

Introduction: Macro-reentrant arrhythmias involving the cavo-tricuspid isthmus (CTI) are common in patients with atrial fibrillation (AF). Bidirectional CTI block is the ablation strategy of choice, but it can be surprisingly difficult to obtain at times. Objective: Aim of this study was to systematically assess the characteristics of the CTI to determine its most common anatomical variants to be anticipated for ablation. Methods: This is a prospective observational study in which intracardiac echocardiography (ICE) was used to visualize the CTI of patients undergoing AF ablation. The presence of anatomical variants was recorded, and length was measured along the central CTI in atrial systole. CTI systolic shortening measured in sinus rhythm and defined as: [(diastolic length - systolic length)/(diastolic length)]x100. Results: 180 patients (65±9 years old, 31% female, 37% paroxysmal AF) are included in the study. Mean CTI length was 31±9 mm, with a systolic shortening of 25±13%. A prominent Eustachian ridge was present in 32%, a Chiari network in 11%, and at least one pouch-like recess in 35%, with a mean depth of 5.3±2.5 mm (Figure). A longer CTI was observed in patients with non-PAF compared with patients with PAF (33 vs. 27 mm, P&lt;0.0001) and in patients with known obstructive sleep apnea (OSA; 37 vs. 32 mm, P=0.0077). Of note, after excluding patients with heart failure, ROC analysis showed that a CTI length ≥ 33 mm was predictive of the presence of OSA (67 % sensitivity and specificity, AUC = 0.71). Less CTI systolic shortening was observed in patients with non-PAF compared those with PAF (22 vs. 32%; P&lt;0.0001). Conclusion: Anatomical variants of the CTI are common and should be anticipated in case of a challenging CTI ablation. A long CTI is associated with OSA and might warrant further clinical screening to identify this common AF comorbidity. CTI systolic shortening correlates with the type of AF and could represent a measure of right atrial contractility.

Glycolaldehyde-Derived High-Molecular-Weight Advanced Glycation End-Products Induce Cardiac Dysfunction through Structural and Functional Remodeling of Cardiomyocytes.

High-molecular-weight advanced glycation end-products (HMW-AGEs) are abundantly present in our Western diet. There is growing evidence reporting that HMW-AGEs contribute to the development of cardiovascular dysfunction in vivo, next to the well-known low-molecular-weight AGEs. The goal of our study is to assess the ultrastructure and function of cardiomyocytes after chronic exposure to HMW-AGEs. A better understanding of underlying mechanisms is essential to create new opportunities for further research on the specific role of HMW-AGEs in the development and progression of cardiovascular diseases. Adult male rats were randomly assigned to daily intraperitoneal injection for six weeks with either HMW-AGEs (20 mg/kg/day) or a control solution. Hemodynamic measurements were performed at sacrifice. Single cardiomyocytes from the left ventricle were obtained by enzymatic dissociation through retrograde perfusion of the aorta. Unloaded cell shortening, time to peak and time to 50% relaxation were measured during field stimulation and normalized to diastolic length. L-type Ca2+ current density (ICaL) and steady-state inactivation of ICaL were measured during whole-cell ruptured patch clamp. Myofilament functional properties were measured in membrane-permeabilized cardiomyocytes. Ultrastructural examination of cardiac tissue was performed using electron microscopy. Rats injected with HMW-AGEs displayed in vivo cardiac dysfunction, characterized by significant changes in left ventricular peak rate pressure rise and decline accompanied with an increased heart mass. Single cardiomyocytes isolated from the left ventricle revealed concentric hypertrophy, indicated by the increase in cellular width. Unloaded fractional cell shortening was significantly reduced in cells derived from the HMW-AGEs group and was associated with slower kinetics. Peak L-type Ca2+ current density was significantly decreased in the HMW-AGEs group. L-type Ca2+ channel availability was significantly shifted towards more negative potentials after HMW-AGEs injection. The impact of HMW-AGEs on myofilament function was measured in membrane-permeabilized cardiomyocytes showing a reduction in passive force, maximal Ca2+ activated force and rate of force development. Ultrastructural examination of cardiac tissue demonstrated adverse structural remodeling in HMW-AGEs group characterized by a disruption of the cyto-architecture, a decreased mitochondrial density and altered mitochondrial function. Our data indicate that HMW-AGEs induce structural and functional cellular remodeling via a different working mechanism as the well-known LMW-AGEs. Results of our research open the door for new strategies targeting HMW-AGEs to improve cardiac outcome.

Long-term athletic training does not alter age-associated reductions of left-ventricular mid-diastolic lengthening or expansion at rest

PurposeThe interaction of ageing and exercise training status on left-ventricular (LV) peak strain is unclear. Additionally, strain analysis across the entire cardiac cycle facilitates a more detailed assessment of deformation, yet this has not been implemented to characterize the ageing LV and in association with training status. This study investigated healthy ageing and training status on LV systolic and diastolic strain utilizing novel echocardiographic applications.MethodsForty healthy males were included and allocated into four groups; young recreationally active (YRA,n = 9; 28 ± 5 years), old recreationally active (ORA, n = 10; 68 ± 6), young trained (YT,n = 10; 27 ± 6 years), and old trained (OT, n = 11, 64 ± 4 years) groups. Two-dimensional speckle-tracking echocardiography was performed to ascertain peak LV longitudinal and circumferential strain (base and apex) strain within each myocardial layer and at 5% increments across the cardiac cycle.ResultsOlder groups had lower diastolic longitudinal lengthening and circumferential expansion between 40–85% mid-diastole, regardless of training status (P < 0.05). Whereas, strain throughout systole was similar between groups (P > 0.05). Longitudinal and circumferential (base and apex) peak and layer-specific strain did not differ between groups (P > 0.05).ConclusionNovel applications of diastolic strain revealed lower age-associated LV longitudinal lengthening and circumferential expansion in older age. Yet, diastolic strain profiles did not differ based on chronic habits of exercise training and, thus, older trained men did not demonstrate an attenuation of age-associated differences in mid-diastolic LV strain.

Влияние комбинации короткодействующих β2-агониста и M-холинолитика на эффективность коронарного кровотока по данным аппланационной тонометрии у пациентов с хронической обструктивной болезнью легких

Background: bronchodilators are the major class of drugs prescribed for chronic obstructive pulmonary disease (COPD). Meanwhile, treatment strategies for obstructive lung disease using bronchodilators are continually discussed and reviewed, in particular, with regard to their potential effect on cardiovascular system. Aim: to evaluate the effect of the combination of a short-acting β2-agonist plus an anticholinergic medication (fenoterol 50 μg/dose + ipratropium bromide 20 μg/dose, 2 doses) on the efficacy of coronary blood flow in COPD patients. Patients and Methods: spirometry with bronchodilator testing (at least 12 hours after using the medication) was performed in 30 COPD patients. The efficacy of coronary blood flow was assessed by central subendocardial viability ratio (C_SEVR) measured by applanation tonometry which was performed before and 15, 30, and 60 min after using the bronchodilator. Oxygen saturation was measured at all stages of the study. Results: the combination of fenoterol and ipratropium bromide resulted in the increase of C_SEVR by 9.5 [3.3; 10.8]% in patients with low oxygen saturation at baseline due to heart rate reduction, diastolic lengthening, and oxygen level improvement. The timing of the effect was determined by the reversibility of bronchial obstruction. No effects of the combination of fenoterol and ipratropium bromide on central and peripheral blood pressure were reported. Conclusion: low oxygen saturation at baseline and reversible bronchial obstruction in COPD patients allow for a favorable predicted systemic effect of the combination of fenoterol and ipratropium bromide. When using in therapeutic dosages and according to recommended dosage regimen, this combination improves bronchopulmonary function, oxygen saturation, and the efficacy of coronary blood flow measured by applanation tonometry. KEYWORDS: chronic obstructive pulmonary disease, applanation tonometry, central subendocardial viability ratio, SEVR, bronchial obstruction, oxygen saturation. FOR CITATION: Punin D.A. Effect of the combination of a short-acting β2-agonist plus an anticholinergic drug on the efficacy of coronary blood flow measured by applanation tonometry in chronic obstructive pulmonary disease. Russian Medical Inquiry. 2020;4(4):199–206. DOI: 10.32364/2587-6821-2020-4-4-199-206.

Superior cardiac mechanics without structural adaptations in pre-adolescent soccer players.

This study aimed to evaluate left ventricular structure, function and mechanics, in highly-trained, pre-adolescent soccer players compared with age- and sex-matched controls. The study design was a prospective, cross-sectional comparison of left ventricular structure, function and mechanics. Twenty-two male soccer players from two professional youth soccer academies (age: 12.0 ± 0.3 years) and 22 recreationally active controls (age: 11.7 ± 0.3 years) were recruited. Two-dimensional conventional and speckle tracking echocardiography were used to quantify left ventricular structure, function and peak/temporal values for left ventricular strain and twist, respectively. End-diastolic volume index was larger in soccer players (51 ± 8 mm/(m2)1.5vs. 45 ± 6 mm/(m2)1.5; p = 0.007) and concentricity was lower in soccer players (4.3 ± 0.7 g/(mL)0.667vs. 4.9 ± 1.0 g/(mL)0.667; p = 0.017), without differences in mean wall thickness between groups (6.0 ± 0.4 mm vs. 6.1 ± 0.5 mm; p = 0.754). Peak circumferential strain at the base (-22.2% ± 2.5% vs. -20.5% ± 2.5%; p = 0.029) and papillary muscle levels (-20.1% ± 1.5% vs. -18.3% ± 2.5%; p = 0.007) were greater in soccer players. Peak left ventricular twist was larger in soccer players (16.92° ± 7.55° vs. 12.34° ± 4.99°; p = 0.035) and longitudinal early diastolic strain rate was greater in soccer players (2.22 ± 0.40 s-1vs. 2.02 ± 0.46 s-1; p = 0.025). Highly-trained soccer players demonstrated augmented cardiac mechanics with greater circumferential strains, twist and faster diastolic lengthening in the absence of differences in wall thickness between soccer players and controls.

Histopathology of the right ventricular outflow tract and the relation to hemodynamics in patients with repaired tetralogy of Fallot

ObjectiveTo evaluate the relationship between myocardial histopathology and tissue Doppler imaging (TDI) variables of the right ventricle and postoperative peak systolic right-to-left ventricular pressure ratio (Prv/Plv) in patients undergoing intracardiac repair for tetralogy of Fallot (TOF). MethodsOperatively resected crista supraventricularis muscle specimens from 93 patients undergoing intracardiac repair for TOF, aged 18 months to 26 years (mean, 7.02 ± 5.35 years) were subjected to light microscopy. TDI-derived parameters between the normal and abnormal categories of myocardium, the evolution of Prv/Plv, and its relationship to TDI-derived variables were tested using generalized linear random effects model using xtreg command. ResultsThe incidence of myocyte hypertrophy, myocytolysis, and perivascular fibrosis was 89.2%, 83.8%, and 77.4%, respectively. Although tricuspid annular peak systolic excursion, peak myocardial velocity during systole (s′), and early diastolic basal lengthening of right ventricle (e′) continued to improve among patients with myocardial hypertrophy, myocytolysis, and perivascular fibrosis, there was an absence of improvement of the late diastolic relaxation of right ventricular free wall (a′) in patients with perivascular fibrosis. Although there was improvement of postoperative Prv/Plv in patients with myocardial fibrosis as compared with normal histology, the values were not statistically significant (β [standard error] −0.07 [0.08], P = .3). ConclusionsThe great majority of myocardial tissues in cyanotic TOF indicate pre-existing hypertrophic, degenerative, and fibrotic changes. Perivascular fibrosis affects the diastolic compliance of the right ventricle and may account for the absence of improvement of late diastolic relaxation (a′) and greater postoperative Prv/Plv in the absence of a residual surgical lesion.

Aging and the relationships between long-axis systolic and early diastolic excursion, isovolumic relaxation time and left ventricular length-Implications for the interpretation of aging effects on e`.

BackgroundBoth the left ventricular (LV) long-axis peak early diastolic lengthening velocity (e`) and long-axis early diastolic excursion (EDExc) decrease with age, but the mechanisms underlying these decreases are not fully understood. The aim of this study was to investigate the relative contributions to aging-related decreases in e`and EDExc from LV long-axis systolic excursion (SExc), isovolumic relaxation time (IVRT, as a measure of the speed of relaxation) and LV end-diastolic length (LVEDL).MethodsThe study group was 50 healthy adult subjects of ages 17–75 years with a normal LV ejection fraction. SExc, EDExc, e`and IVRT were measured from pulsed wave tissue Doppler signals acquired from the septal and lateral walls. Multivariate modelling was performed to identify independent predictors of EDExc and e`which were consistent for the septal and lateral walls.ResultsEDExc decreased with age and the major determinant of EDExc was SExc, which also decreased with age. There was also a decrease of e`with age, and the major determinant of e`was EDExc. IVRT decreased with age and on univariate analysis was not only inversely correlated with EDExc and e`, but also with SExc. IVRT was only a minor contributor to models of EDExc which included SExc, and was an inconsistent contributor to models of e`which included EDExc. LVEDL decreased with age independent of sex and body size, and was positively correlated with SExc, EDExc and e`.ConclusionMajor mechanisms underlying the decrease in e`seen during aging are the concomitant decreases in long-axis contraction and early diastolic excursion, which are in turn related in part to long-axis remodelling of the left ventricle. After adjusting for the extent of systolic and early diastolic excursion, slowing of relaxation, as reflected in prolongation of the IVRT, makes no more than a minor contribution to aging-related decreases in EDExc and e`.

Abstract 440: The Cardiomyocyte Diastolic Stiffness and Contractility are Inversely Related to the Size of Titin: A Cellular Work Loop Study of Single Intact Cardiomyocytes

Studying cardiac titin under physiological conditions can be at the level of the left ventricular (LV) chamber and the multicellular muscle level. However, those preparations are influenced by neurohormonal reflex, preload-afterload status and extracellular matrix. In this study, cellular work loop force measurement of the single intact cardiomyocyte was conducted under physiological conditions. Intact cell experiments were performed at 37°C under field-stimulation at 2 Hz frequency. The cell was attached to the force transducer and the piezo length controller which modulates the cell length by the feedback control system based on developed force. The force length relation (cellular work loop) of the single cell was generated. The end diastolic force length relation (EDFLR), the end systolic force length relation (ESFLR) and the preload recruitable stroke work (PRSW) were obtained. The Ttn ΔIAjxn -/- ( IA -/- ) mice, in which the I-band/A-band region of titin’s spring has been deleted were studied in comparison to α-MHC-Cre ; cRbm20 ΔRRM +/- ( cRbm20 +/- ) mice which are deficient in titin splicing and express large titin isoforms in the heart. The cellular diastolic stiffness (slope of EDFLR) was increased in IA -/- and was reduced in cRbm20 +/- (151.3, 104.0 and 91.5 μN/mm 2 in IA -/- , WT and cRbm20 +/- respectively). The contractility (slopes of ESFLR and PRSW) were 233.5 and 1215.6 uN/mm 2 in WT, and were increased in IA -/- (371.2 and 2076 μN/mm 2 ) but attenuated in cRbm20 +/- (202.9 and 907.7 μN/mm 2 ). Cellular work loop studies were also conducted in intact cells isolated from the mice that underwent transverse aortic constriction (TAC) surgery with deoxycorticosterone acetate (DOCA) implantation. TAC DOCA mice developed diastolic dysfunction at the LV chamber level. The result showed that the cells from TAC DOCA hearts had increased slopes of EDFLR, ESFLR and PRSW ( 157.9, 378.9 and 1699.0 μN/mm 2 ) compared to the cells from sham mice (98.6, 230.3, and 1203.9 μN/mm 2 ). Conclusions: Cellular work loops recapitulated the cardiac physiology at the LV chamber level. The result showed that the cellular diastolic stiffness and contractility were inversely related to the size of titin and that titin stiffness plays an important roles in both diastolic and systolic function.

Abstract 243: Modeling of Diastolic Dysfunction in Induced Pluripotent Stem Cell-derived Cardiomyocytes From Hypertrophic Cardiomyopathy Patients

Aims: Diastolic dysfunction (DD) is common among hypertrophic cardiomyopathy (HCM) patients, causing major morbidity and mortality. Yet its cellular mechanisms are not fully understood, and presently, there is no effective treatment. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold great potential for investigating the mechanisms underlying DD and as a platform for drug discovery. Methods and results: In the present study, beating iPSC-CMs were generated from healthy recruits and HCM patients with evident DD. Micropatterned iPSC-CMs from HCM patients showed impaired diastolic function, as evidenced by prolonged relaxation time, retarded relaxation rate, and shortened diastolic sarcomere length. Ratiometric Ca 2+ imaging indicated elevated diastolic [Ca 2+ ] i and abnormal Ca 2+ handling in HCM iPSC-CMs, which were exacerbated by β-adrenergic challenge. Combining Ca 2+ imaging and traction force microscopy (TFM), we observed enhanced myofilament Ca 2+ sensitivity (measured as dF/Δ[Ca 2+ ] i ) in HCM iPSC-CMs. These results indicated that cytosolic diastolic Ca 2+ overload, slowed [Ca 2+ ] i decline and increased myofilament Ca 2+ sensitivity, collectively impair the relaxation of HCM cells. Treating HCM iPSC-CMs with partial blockade of Ca 2+ or late Na + current reset diastolic Ca 2+ homeostasis, restored diastolic function and improved long-term survival, suggesting disturbed Ca 2+ signaling is an important cellular pathological mechanism of DD. Further investigation showed increased expression of L-type calcium channel (LTCC) and transient receptor potential channels (TRPCs) in HCM iPSC-CMs, which likely contribute to diastolic [Ca 2+ ] i overload. Conclusion: In summary, this study recapitulated DD at the single cell level, and revealed novel mechanisms and potential therapeutic targets of DD using HCM iPSC-CMs.