Ventricular Shortening Research Articles

Clinical significance of myocardial deformation of a left ventricle in children with hypertrophic cardiomyopathy

Purpose: to evaluate the clinical significance of left ventricular myocardial deformation indicators, their relationship with the degree of heart failure and left ventricular hypertrophy in children with hypertrophic cardiomyopathy (HCM). Materials and methods. 61 patients with primary genetically confirmed asymmetric HCM aged 7 to 17 years underwent a comprehensive clinical and echocardiography. Echocardiography determined indicators of left ventricular systolic function: ejection and shortening fractions, global longitudinal, circular and radial myocardial deformations and deformations rates. The assessment of myocardial hypertrophy of left ventricular segments was performed taking into account absolute values in systole and diastole depending on age, recalculated per standard deviation units in the population (Z-score factor). Results. A more pronounced degree of heart failure, a decrease in ejection and shortening fractions, and indicators of left ventricular myocardial deformation were established in all children with non-obstructive and obstructive forms of HCM and an extreme degree of myocardial hypertrophy, in contrast to the non-obstructive form of the disease with a less pronounced degree of hypertrophy. An earlier decrease in myocardial deformation indices was revealed in comparison with ejection and shortening fractions, longitudinal deformation and its speed in comparison with radial and circular, their speeds. Conclusions. 1. In children with HCM and extreme degrees of left ventricular myocardial hypertrophy, compared with mild and moderate hypertrophy, a more pronounced degree of heart failure is observed, which is accompanied by a decrease in left ventricular systolic function. Among them, a decrease in myocardial deformation rates and their velocities is more sensitive compared to left ventricular ejection fractions and shortening. 2. Reduction of left ventricular myocardial deformation in children with HCM depends on the degree of hypertrophy. The earliest, manifesting itself even with a mild degree of hypertrophy, is a decrease in longitudinal deformation and its speed compared to circular and radial deformations and their speeds. 3. Determining the indicators of left ventricular myocardial deformation in children with HCM in comparison with the degree of myocardial hypertrophy is of great clinical importance in assessing the systolic function of the left ventricle to optimize administration tactics and timely treatment of the disease.

Cross-sectional Study of the Association between Plasma Brain Natriuretic Peptide Levels and Left Ventricular Shortening Fraction in Fukuyama Congenital Muscular Dystrophy.

Cross-sectional Study of the Association between Plasma Brain Natriuretic Peptide Levels and Left Ventricular Shortening Fraction in Fukuyama Congenital Muscular Dystrophy.

Left Ventricular Strains and Right Ventricular Longitudinal Shortening Are Associated in Healthy Adults-A Detailed Analysis from the Three-Dimensional Speckle-Tracking Echocardiographic MAGYAR-Healthy Study.

The right ventricle (RV) lies on the left ventricle (LV), and their shapes and movements are characteristic and significantly different. The aim of the present study was to investigate the relationship between three-dimensional speckle-tracking echocardiography (3DSTE)-derived LV strains, which represent LV contractility as quantitative features, and tricuspid annular plane systolic excursion (TAPSE) as determined by M-mode echocardiography, which represents the longitudinal movement of the RV, in healthy adults. A total of 79 healthy adults (mean age: 28.1 ± 6.3 years; 33 men) were enrolled in the present study. After two-dimensional Doppler echocardiography, 3DSTE-derived data acquisition was carried out in all cases, and detailed 3DSTE-based analysis was performed offline at a later date. Reduced TAPSE was associated with increased global and basal LV radial strain (RS). Increased TAPSE was also associated not only with increased global and basal LV-RS but also with global LV longitudinal strain (LS). An increase in global LV-RS and global LV circumferential strain (CS) showed associations with other strains except for global LV-LS. An increase in global LV-LS did not show associations with other strains. Increased global LV-RS was associated with reduced TAPSE, while the degree of global LV-LS and global LV-CS did not show associations with TAPSE. Three-dimensional speckle-tracking echocardiography-derived LV-RS and LV-LS are associated with the longitudinal shortening of the RV represented by TAPSE in healthy adults.

Mechanism and Impact of Left Atrial Dyssynchrony on Long-Term Clinical Outcome During Cardiac Resynchronization Therapy

BackgroundLeft bundle branch block (LBBB) causes left atrial (LA) dyssynchrony. It is unknown if LA dyssynchrony impacts long-term prognosis. ObjectivesThe purpose of this study was to determine mechanisms of LA dyssynchrony in LBBB and if LA dyssynchrony impacts long-term prognosis. MethodsIn a prospective multicenter study of 168 heart failure patients with LBBB, echocardiographic strain imaging was done before and after 6 months with cardiac resynchronization therapy (CRT). Outcome was assessed after 6 years. Dyssynchrony was measured relative to septum as delay in left ventricular (LV) lateral wall shortening and LA lateral wall stretch. Response to CRT was defined as at least 15% reduction in LV end-systolic volume. ResultsBefore CRT, there was marked LA dyssynchrony of 105 ± 76 ms, which decreased to 37 ± 68 ms in CRT-responders (P < 0.001), whereas nonresponders showed only a modest reduction in LA dyssynchrony (P < 0.05). There was strong association between LA and LV dyssynchrony (r = 0.70), consistent with direct LV-LA mechanical interaction. CRT caused modest increase in LA reservoir strain (P < 0.01) and marked increase of LV filling time (P < 0.001) in responders. Mortality after 6 years was 21% (35 deaths). LA dyssynchrony did not independently predict mortality. However, the combination of preserved LA reservoir strain (≥18%) and resolved LA dyssynchrony (≤53 ms) after 6 months with CRT was associated with excellent long term-prognosis: HR: 0.11 (95% CI: 0.03-0.42) vs preserved reservoir strain and persistent LA dyssynchrony. ConclusionsLA dyssynchrony in LBBB was attributed to direct LV-LA mechanical interactions. CRT improved diastolic function by increasing LV filling time. Patients with preserved LA reservoir strain and resolution of LA dyssynchrony by CRT had excellent long-term prognosis. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185)

Partial deletion of the Akap1 gene promotes abnormalities in gut barrier function, gut microbiota composition and cardiac function during cardiovascular aging in mice

Abstract Background Cardiovascular aging is characterized by mitochondrial dysfunction, changes in intestinal permeability and microbiota composition. Mitochondria-targeted A-kinase anchoring proteins (mitoAKAPs) are a group of structurally diverse proteins binding the regulatory subunits of protein kinase A (PKA), and targeting PKA at discrete intracellular locations. We analyzed the effects of global partial genetic deletion of Akap1 on intestinal barrier permeability, microbiota composition, inflammation, and cardiac function during aging in mice. Purpose The proposal of this study was to determine the role of mitoAKAPs in the gut-heart axis during cardiovascular aging. Methods Young (4-6-month) and old (18-24-month) genetically modified Akap1+/+ and Akap1+/− mice of either sex underwent evaluation of cardiac function by transthoracic echocardiography. To evaluate gut barrier integrity, we analyzed expression levels of intestinal junction proteins occludin (Ocln), zonulin (Tjp1) in colonic samples and FITC-dextran permeability in vivo, circulating levels of Tumor Necrosis Factor-alpha (TNF-alpha), Lipopolysaccharide (LPS), Interleukin-1 (IL-1) and Interleukin-10 (IL-10). Fecal microbial composition was evaluated by Illumina Mi-Seq, Gut microbiota differences based on 16S rDNA sequencing at genus and species taxonomic levels were identified using linear discriminant analysis (LDA) combined with effect size (LEfSe) algorithm. Finally, faecal microbiota transplantation (FMT) was performed for five weeks to test whether modification of gut microbiota composition can affect cardiac function. Results A reduction in % left ventricular shortening (FS%) was observed in young and old Akap1+/- mice compared to Akap1+/+ mice. This finding was associated to increased intestinal permeability, as indicated by reduced mRNA levels of Ocln and Tjp1, increased LPS traslocation across intestinal epitelium into blood in 24m Akap1+/- mice compared to Akap1+/+. Through the analysis of the microbial signature, we observed the different bacterial species present in the microbiota of the experimental groups. FMT of bacteria species from old Akap1+/− to young Akap1+/+ mice induced gut abnormalities and cardiac dysfunction, while FMT from young Akap1+/+ donors ameliorated cardiac dysfunction in old Akap1+/+ mice. Conclusions MitoAKAPs play a crucial role in the maintenance of intestinal barrier function, gut microbiota composition and cardiac function during aging. Modulation of the composition of the intestinal microbiota influences intestinal permeability and cardiac function. MitoAKAPs could represent an important diagnostic and therapeutic target for cardiac and intestinal dysfunction.

Phloridzin prevents diabetic cardiomyopathy by reducing inflammation and oxidative stress

Oxidative stress and inflammation significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Persistent inflammatory stimuli drive the progression of myocardial fibrosis and impaired cardiac function. Phloridzin (Phl), a natural compound, demonstrates both anti-inflammatory and antioxidant properties. Nevertheless, its therapeutic potential and underlying mechanisms in DCM remain unclear. This study aimed to elucidate the mechanisms through which Phl inhibited myocardial fibrosis and exerted its antioxidative effects. The impact of Phl on DCM was evaluated using a high-fat/high-sugar diet combined with streptozotocin to induce an animal model and an in vitro H9C2 cell model stimulated by high glucose (HG). Untargeted metabolomics identified potential mechanisms underlying myocardial fibrosis. Phl treatment significantly enhanced left ventricular ejection fraction (EF%) and shortening fraction (FS%), while reducing myocardial injury markers, such as lactate dehydrogenase and creatine phosphokinase-MB, and suppressing myocardial collagen fiber accumulation. Simultaneously, Phl attenuated myocardial inflammation via inhibition of MyD88/NF-κB signaling, modulated the Nrf2/GPX4 axis to counter oxidative stress, and mitigated ferroptosis. In vitro, Phl inhibited high glucose-induced myocardial hypertrophy and fibrosis in H9C2 cells, while also repressing NF-κB activation in cardiomyocytes. Metabolomic profiling revealed that Phl ameliorated DCM through modulation of glycerophospholipid metabolic pathways, linking these metabolic shifts to enhanced antioxidant capacity, thereby reflecting its ability to reduce oxidative stress in the myocardium. Collectively, Phl provides cardioprotective effects by alleviating inflammation and oxidative damage.

Omega-3 supplementation attenuates doxorubicin-induced cardiotoxicity but is not related to the ceramide pathway.

Cardiotoxicity is the serious side effect of doxorubicin treatment. Ceramides are formed from the degradation of sphingolipids in cell membranes and play an important role in signaling and modulating biological processes. There is evidence that omega-3 fatty acid administration can act on this pathway. To evaluate the role of the ceramide pathway in the pathophysiology of doxorubicin-induced cardiotoxicity and the effect of omega-3 fatty acid supplementation in the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. Sixty male Wistar rats were divided into four groups: Control (C), Doxorubicin (D), Omega-3 fatty acids (W), and Doxorubicin + Omega-3 fatty acids (DW). The groups received omega-3 fatty acids (400 mg/kg/day, via gavage) or water for 6 weeks and doxorubicin (3.5 mg/kg, intraperitoneal) or saline once a week for 4 weeks. Doxorubicin-treated animals showed increases in left atrium and left ventricle diameters, serum triglycerides and cholesterol, malondialdehyde, and protein carbonylation. We also observed a decrease in left ventricular shortening fraction and nSMase1 expression in the heart. Omega-3 fatty acid supplementation attenuated the structural and functional alterations caused by doxorubicin and decreased protein carbonylation. In contrast to doxorubicin, omega-3 fatty acids increased neutral nSMase activity in animals that both received and did not receive doxorubicin but with no effect on nSMase1 protein expression. Omega-3 fatty acid supplementation attenuated the cardiotoxicity caused by doxorubicin. The ceramide pathway may be involved in the pathophysiology of cardiotoxicity, but it is not the mechanism by which omega-3 fatty acids attenuated cardiac dysfunction.

Clinical effect of recombinant human brain natriuretic peptide in the treatment of heart failure in elderly patients

BackgroundHeart failure in elderly individuals poses significant challenges due to the decline in cardiac function associated with aging. This study aimed to investigate the clinical efficacy of recombinant human brain natriuretic peptide (rhBNP) for the treatment of heart failure, especially in elderly patients.MethodsThis was a retrospective case control study of the medical records of 60 elderly patients with heart failure admitted to our hospital between December 2020 and December 2023. Patients were divided into two groups based on treatment. The control group (n = 30) received diuretics, digitalis, and β receptor blockers, while the observation group (n = 30) received lyophilized rhBNP in addition to the control group treatment. Changes in BNP levels and clinical outcomes were compared between the two groups.ResultsPosttreatment BNP levels were significantly lower in the observation group than in the control group (p < 0.05), and the total clinical effective rate was greater in the observation group (p < 0.05). Additionally, the left ventricular diameter, left atrial diameter, left ventricular shortening fraction, diastolic flow signal and cardiac output in the observation group were lower than those in the control group (p < 0.05), while the thickness of the aortic root diameter in the observation group was greater than that in the control group (p < 0.05).ConclusionRhBNP demonstrated ideal clinical efficacy in elderly patients with heart failure, improving symptoms and indicating potential for widespread use in the future.

Inversion of Left Ventricular Axial Shortening: In Silico Proof of Concept for Treatment of HFpEF.

Left ventricular (LV) longitudinal function is mechanically coupled to the elasticity of the ascending aorta (AA). The pathophysiologic link between a stiff AA and reduced longitudinal strain and the subsequent deterioration in longitudinal LV systolic function is likely relevant in heart failure with preserved ejection fraction (HFpEF). The proposed therapeutic effect of freeing the LV apex and allowing for LV inverse longitudinal shortening was studied in silico utilizing the Living Left Heart Human Model (Dassault Systémes Simulia Corporation). LV function was evaluated in a model with (A) an elastic AA, (B) a stiff AA, and (C) a stiff AA with a free LV apex. The cardiac model simulation demonstrated that freeing the apex caused inverse LV longitudinal shortening that could abolish the deleterious mechanical effect of a stiff AA on LV function. A stiff AA and impairment of the LV longitudinal strain are common in patients with HFpEF. The hypothesis-generating model strongly suggests that freeing the apex and inverse longitudinal shortening may improve LV function in HFpEF patients with a stiff AA.

Right ventricular longitudinal shortening and right atrial volumes are not associated in healthy adults-detailed analysis from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

There is a close relationship between volumes of the right atrium (RA) and dimensions and derived functional sphincter-like features of the tricuspid annulus (TA). However, its relation to longitudinal TA motion is not clear, which can even be considered to be a characteristic of the longitudinal shortening of the right ventricle (RV) and represented by TA plane systolic excursion (TAPSE). Therefore, the aim of this cohort study was to perform a detailed analysis of the relationship of three-dimensional speckle-tracking echocardiography (3DSTE)-derived RA volumes and RV longitudinal shortening in healthy individuals. These parameters were also examined in case of average values and larger/smaller than mean values. The present study comprised 93 healthy adults (mean age: 27.7±6.3 years, 46 men), who participated in a complete medical investigation including two-dimensional, TAPSE, Doppler and 3DSTE-derived RA volumetric echocardiographic assessments. RA volumes, stroke volumes and emptying fractions were not related to TAPSE. In case of low, mean and high TAPSE, maximum [50.4±22.4 vs. 49.5±15.5 vs. 49.0±15.8 mL, P= not significant (ns)], preatrial contraction (36.9±16.8 vs. 34.5±10.4 vs. 35.6±10.5 mL, P= ns) and minimum (28.7±13.6 vs. 27.2±9.4 vs. 26.6±9.3 mL, P= ns) RA volumes did not differ. Higher RA volumes showed no associations with TAPSE either. 3DSTE-derived RA volumes and M-mode echocardiography-derived TAPSE representing RV longitudinal shortening are not associated in healthy adults. None of the RA volumes showed correlations with TAPSE.

Cerebral Ischemia and Reperfusion-Induced Changes in Left Ventricular Function and Electrocardiogram in Mice

Background: Stroke may produce functional and electrical heart disturbances. The underlying characteristics and mechanisms have not been fully elucidated. Objectives: To evaluate whether acute cerebral ischemia (I) and reperfusion (R) may cause cardiac dysfunction and electrocardiographic alterations in an experimental mice model. Methods: Male mice that underwent cerebral ischemia and reperfusion (I/R) were evaluated by electrocardiography (ECG) and echocardiography. Heart rate, corrected QT (QTc) interval, T-wave peak to T-wave end (Tp-Te) interval, left ventricular ejection fraction (LVEF), shortening fraction (SF) and isovolumetric relaxation time (IVRT) were analyzed. Cerebral infarct size was calculated, and neurological deficit was assessed with the Longa scale. Results: Twenty-four hours after R, a statistically significant decrease in LVEF (I/R: 66.5±1.5% vs. sham: 74.3±0.9%; p=0.002) and in SF (I/R: 42.9±1.7% vs sham: 52.3±1.7%; p=0.004) was observed. QTc interval prolongation was observed during I/R (baseline: 125.1±4.3 ms; 60 min after I: 143.8±5.2 ms; 24 h after R: 170.3±5.8 ms; p=0.002). Tp-Te interval was not prolonged during I (baseline: 25.9±1.3 ms vs. 60 min after I: 23.8±1.4 ms; p=0.999) but it was prolonged during R (24 h after R: 32.0±2.3 ms; p=0.049). Cerebral infarct size was 34.9±2.5% and survival in the I/R group was 43.3%. Conclusion: Acute cerebral ischemia induces mild left ventricular dysfunction and disturbances in ventricular repolarization which intensify within the first 24 hours after reperfusion.

Balloon Valvuloplasty in Congenital Critical Aortic Valve Stenosis in Neonates and Infants: A Rescue Procedure for the Left Ventricle.

Congenital critical aortic valve stenosis (CAVS) is a life-threatening disease requiring urgent treatment. First-line therapy is still controversial. The aim of our study was (1) to analyze retrospectively the patients of our institution who underwent balloon aortic valvuloplasty (BAV) due to CAVS and (2) describe the techniques for improved feasibility of intervention using microcatheters and retrieval loops. Twelve patients underwent 23 BAVs: 1 BAV was performed in 3 patients, 2 BAVs were performed in 7 patients, and 3 BAVs were performed in 2 patients. The peak trans-valvular pressure gradient (Δp) and left ventricular shortening fraction (LVSF) improved significantly in the first two interventions. In the first BAV, Δp decreased from 73.7 ± 34.5 mmHg to 39.8 ± 11.9 mmHg (p = 0.003), and the LVSF improved from 22.3 ± 13.5% to 31.6 ± 10.2% (p = 0.001). In the second BAV, Δp decreased from 73.2 ± 33.3 mmHg to 35.0 ± 20.2 mmHg (p < 0.001), and the LVSF increased from 26.7 ± 9.6% to 33.3 ± 7.4% (p = 0.004). Cardiac surgery during the neonatal period was avoided for all children. The median time to valve surgery was 5.75 years. Few complications occurred, namely mild-to-moderate aortic regurgitation, one remediable air embolism, and one intimal injury to the ascending aorta. We conclude that BAV is a successful emergency treatment for CAVS, resulting in left ventricular relief, clinical stabilization, and a time gain until cardiac surgery.

Design and Analysis of a Polymeric Left Ventricular Simulator via Computational Modelling.

Preclinical testing of medical devices is an essential step in the product life cycle, whereas testing of cardiovascular implants requires specialised testbeds or numerical simulations using computer software Ansys 2016. Existing test setups used to evaluate physiological scenarios and test cardiac implants such as mock circulatory systems or isolated beating heart platforms are driven by sophisticated hardware which comes at a high cost or raises ethical concerns. On the other hand, computational methods used to simulate blood flow in the cardiovascular system may be simplified or computationally expensive. Therefore, there is a need for low-cost, relatively simple and efficient test beds that can provide realistic conditions to simulate physiological scenarios and evaluate cardiovascular devices. In this study, the concept design of a novel left ventricular simulator made of latex rubber and actuated by pneumatic artificial muscles is presented. The designed left ventricular simulator is geometrically similar to a native left ventricle, whereas the basal diameter and long axis length are within an anatomical range. Finite element simulations evaluating left ventricular twisting and shortening predicted that the designed left ventricular simulator rotates approximately 17 degrees at the apex and the long axis shortens around 11 mm. Experimental results showed that the twist angle is 18 degrees and the left ventricular simulator shortens 5 mm. Twist angles and long axis shortening as in a native left ventricle show it is capable of functioning like a native left ventricle and simulating a variety of scenarios, and therefore has the potential to be used as a test platform.

Fetal left and right ventricular strain parameters using speckle tracking in congenital heart diseases.

Assessment of fetal ventricular function is mostly subjective, and currently, for the objective assessment left ventricular shortening fraction is obtained. However, this by itself is not very reliable. Hence, more tools that can provide an objective assessment are needed to increase the confidence of functional assessment. Speckle tracking imaging can provide one such tool. In this study we sought to establish the normative value of global longitudinal and circumferential strain for our fetal patients and for two major forms of congenital heart diseases, namely atrioventricular canal defects (AVC) and uncorrected dextro-transposition of the great arteries (dTGA) to act as a benchmark. The study was completed via a single center retrospective analysis on 72 fetal echocardiograms (26 normal, 15 dTGA, and 31 AVC). Tomtec Arena™ echocardiography analysis software was used for analysis. In normal fetuses, mean left ventricular (LV) global longitudinal strain (GLS) was - 22.6% (95% CI -24, -21.1) and mean right ventricular (RV) GLS was - 22.1% (95% CI -23.6, -20.6). In AVC patients LV GLS was-26.6% (95% CI -28,-25.3) and mean RV GLS was - 26.5% (95% CI -27.9,-25.2). In dTGA patients LV GLS was - 22.9% (95% CI of -24.8, -21) and RV GLS was - 21.3% (95% CI was - 23.4, -20.8). There was good intra-rater reliability though poor to fair inter-rater reliability. Notwithstanding its current limitations, strain imaging can provide useful information that can increase confidence of cardiac functional assessment in fetal patients. However, to be reliable across the board, further automation and standardization is required.

Dimethyl phthalate induced cardiovascular developmental toxicity in zebrafish embryos by regulating MAPK and calcium signaling pathways

Dimethyl phthalate (DMP), the lowest-molecular-weight phthalate ester (PAE), is one of the most commonly detected persistent organic pollutants in the environment, but its toxic effects, especially cardiovascular developmental toxicity, are largely unknown. In this study, zebrafish embryos were exposed to sublethal concentrations of DMP from 4 to 96 hpf. Our results showed that DMP treatment induced yolk retention, pericardial edema, and swim bladder deficiency, as well as increased SV-BA distance and decreased heart rate, stroke volume, ventricular axis shortening rate and ejection fraction. In addition, oxidative stress and apoptosis were found to be highly involved in this process. The results of transcriptome sequencing and mRNA expression of related genes indicated that MAPK and calcium signaling pathways were perturbed by DMP. These findings have the potential to provide new insights into the potential developmental toxicity and cardiovascular disease risk of DMP.

Feasibility Value of Right Ventricular Longitudinal Shortening Fraction and the Prognostic Implications in Patients With Heart Transplantation.

Right ventricular longitudinal shortening fraction (RVLSF) is a 2-dimensional speckle tracking echocardiography parameter based on tricuspid annular displacement analysis that could be used to assess right ventricular (RV) systolic function. The value of RVLSF in the assessment of RV systolic function in recipients of heart transplantation (HT) and whether RVLSF can replace strain parameters remains unknown. A total of 153 adult patients who underwent HT were consecutively enrolled in this prospective longitudinal study. All subjects were examined by conventional transthoracic 2-dimensional echocardiography and 2-dimensional speckle tracking echocardiography to evaluate the RV end-diastolic basal diameter, RV end-diastolic area, fractional area change, peak systolic velocity of tricuspid annulus, tricuspid annular plane systolic excursion, RV free wall strain, and RVLSF. Cox proportional hazards regression was used to test if the parameters of interest had independent prognostic value for adverse outcome prediction in patients who underwent HT. A significant positive correlation was found between the measurements of RVLSF and RV free wall strain (r=0.927, P<0.001). Compared with the event-free group, the adverse outcome group displayed reduced RVLSF and RV free wall strain and higher age (P<0.001, <0.001, =0.016, respectively) in patients who underwent HT. RVLSF and RV free wall strain were independently associated with poor prognosis in multivariable analysis (both P<0.001). RVLSF assessment provides an effective evaluation of RV longitudinal systolic function in the transplanted hearts and has prognostic value for adverse outcomes in patients undergoing HT.

Electroacupuncture pretreatment mediates sympathetic nerves to alleviate myocardial ischemia–reperfusion injury via CRH neurons in the paraventricular nucleus of the hypothalamus

BackgroundMyocardial ischemia–reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia–reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVNCRH neurons.MethodsIntegrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVNCRH neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot.ResultsOur data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVNCRH neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVNCRH neurons can counteract this protective effect.ConclusionEA pretreatment can inhibit PVNCRH neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.

The IAAM LTBP4 Haplotype is Protective Against Dystrophin-Deficient Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes. We retrospectively collected 3138 echocardiographic measurements of left ventricular ejection fraction (EF), shortening fraction (SF), and end-diastolic volume (EDV) from 819 DMD participants, 541 from an Italian multicentric cohort and 278 from the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS). Using generalized estimating equation (GEE) models, we estimated the yearly rate of decrease of EF (-0.80%) and SF (-0.41%), while EDV increase was not significantly associated with age. Utilizing a multivariate generalized estimating equation (GEE) model we observed that mutations preserving the expression of the C-terminal Dp71 isoform of dystrophin were correlated with decreased EDV (-11.01 mL/m2, p = 0.03) while for dp116 were correlated with decreased EF (-4.14%, p = <0.001). The rs10880 genotype in the LTBP4 gene, previously shown to prolong ambulation, was also associated with increased EF and decreased EDV (+3.29%, p = 0.002, and -10.62 mL/m2, p = 0.008) with a recessive model. We quantitatively describe the progression of systolic dysfunction progression in DMD, confirm the effect of distal dystrophin isoform expression on the dystrophin-deficient heart, and identify a strong effect of LTBP4 genotype of DCM in DMD.

Prognostic Value of a New Right Ventricular-to-Pulmonary Artery Coupling Parameter Using Right Ventricular Longitudinal Shortening Fraction in Patients Undergoing Transcatheter Aortic Valve Replacement: A Prospective Echocardiography Study.

Introduction: Right-ventricular-to-pulmonary artery (RV-PA) coupling, measured as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP), has emerged as a predictor factor in patients undergoing transcatheter aortic valvular replacement (TAVR). Right ventricular longitudinal shortening fraction (RV-LSF) outperformed TAPSE as a prognostic parameter in several diseases. We aimed to compare the prognostic ability of two RV-PA coupling parameters (TAPSE/PASP and the RV-LSF/PASP ratio) in identifying MACE occurrences. Method: A prospective and single-center study involving 197 patients who underwent TAVR was conducted. MACE (heart failure, myocardial infarction, stroke, and death within six months) constituted the primary outcome. ROC curve analysis determined cutoff values for RV-PA ratios. Multivariable Cox regression analysis explored the association between RV-PA ratios and MACE. Results: Forty-six patients (23%) experienced the primary outcome. No significant difference in ROC curve analysis was found (RV-LSF/PASP with AUC = 0.67, 95%CI = [0.58-0.77] vs. TAPSE/PASP with AUC = 0.62, 95%CI = [0.49-0.69]; p = 0.16). RV-LSF/PASP < 0.30%.mmHg-1 was independently associated with the primary outcome. The 6-month cumulative risk of MACE was 59% (95%CI = [38-74]) for patients with RV-LSF/PASP < 0.30%.mmHg-1 and 17% (95%CI = [12-23]) for those with RV-LSF/PASP ≥ 0.30%.mmHg-1; (p < 0.0001). Conclusions: In a contemporary cohort of patients undergoing TAVR, RV-PA uncoupling defined by an RV-LSF/PASP < 0.30%.mmHg-1 was associated with MACE at 6 months.

Right Ventricular Longitudinal Shortening is not Associated with Left Ventricular Rotational Mechanics in Healthy Adults - Insights from the Three-dimensional Speckle-tracking Echocardiographic MAGYAR-Healthy Study.

The left ventricle (LV) not only contracts, but its rotational mechanics have a significant role in systolic ejection, whereas the right ventricle (RV) is substantially different in shape and function, and its contractility is not accompanied by rotational features. Simple M-mode echocardiography-based tricuspid annular plane systolic excursion (TAPSE) reflects RV longitudinal contraction or shortening. The aim of the present study was to examine the relationship between the parameters characterizing the rotational mechanics of the LV as assessed by three-dimensional speckle-tracking echocardiography (3DSTE) and the TAPSE. The effects of different degrees of these parameters on each other were also examined. The present retrospective analysis evaluated the results of 80 healthy adult individuals with an average age of 28.1 6.3 years (33 males) with LV rotational mechanics being directed normally. All cases have undergone complete two-dimensional Doppler echocardiography with the measurement of TAPSE and 3DSTE. None of the LV volumes and rotational parameters showed any differences in healthy cases with TAPSE 18-21 mm vs. TAPSE 22 mm. Similarly, right atrial (RA) volumetric parameters did not differ either. TAPSE showed no associations with the degree of basal LV rotation. RA volumes were slightly increased with higher basal LV rotation. Similar to basal LV rotation, TAPSE did not change with the degree of apical LV rotation and a tendentious increase of RA volumes could be demonstrated with increasing apical LV rotation. No correlation could be demonstrated between apical and basal LV rotations and TAPSE. 3DSTE-derived LV rotational parameters and TAPSE are not associated suggesting that LV twist is independent of RV longitudinal shortening in healthy circumstances.