Changes In Myocardial Function Research Articles

Alterations of Myocardial Mitochondrial Morphology and Function in a Canine Model of Premature Ventricular Contractions-Induced Cardiomyopathy.

Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM. Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson's trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all p < 0.01 vs the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all p < 0.05). We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.

Mesenchymal Stem Cells (MSCs) Alleviate Mouse Sepsis Induced Cardiomyopathy (SICM) by Inhibiting the NR1D2/LCN2 Pathway

Sepsis is characterized as a systemic inflammatory response syndrome resulting from infection, leading to the development of multiple organ dysfunction syndrome. Sepsis induced cardiomyopathy (SICM) is a frequently encountered condition in clinical settings. Mesenchymal stem cells (MSCs) possess inherent immunomodulatory and anti-inflammatory attributes, rendering them a promising therapeutic approach to reestablish the equilibrium between anti-inflammatory and pro-inflammatory systems in septic patients. Consequently, MSCs are frequently employed in clinical investigations.In this study, the author established a mouse SICM model through cecal ligation and puncture (CLP) and administered MSCs via the tail vein. Following successful modeling, the myocardial function and histopathological changes were detected by echocardiography, HE staining, TUNEL staining, ELISA and other experiments. As a result, MSCs demonstrated the ability to enhance myocardial function, promote cardiac tissue repair, suppress inflammatory response, reduce levels of myocardial injury markers, and mitigate oxidative stress. Additionally, transcriptome and proteome analyses were conducted. Through differential expression analysis, functional enrichment analysis and multi omics association analysis, revealed that the transcriptional factors nuclear receptor subfamily 1 (NR1D2) and target gene lipocalin 2 (LCN2) played key roles in mediating the effects of MSCs on SICM. JASPAR website and ChIP-qPCR experiment were used to predict and confirm the targeting relationship between them. Subsequent cell co-culture experiments and a series of experiments confirmed that MSCs attenuated cardiomyocyte injury by downregulating the expression of NR1D2 and its downstream target gene LCN2. In conclusion, MSCs alleviate mice SICM via inhibiting NR1D2/LCN2 pathway.

Effect of tafamidis on left atrial function of patients with transthyretin amyloid cardiomyopathy.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by the functional and structural effects of amyloid infiltration, predominantly within the ventricles, causing biventricular wall thickening. Amyloid infiltration can be observed in the left atrium in ATTR-CM patients, but the association of left atrial (LA) myocardial function with cardiovascular events and of changes in LA myocardial function with tafamidis administration have not yet been clarified. Our aim was, therefore, to use speckle-tracking strain for investigating LA myocardial function in patients with ATTR-CM treated with tafamidis. We studied 55 patients with biopsy-proven ATTR-CM who had been treated with tafamidis (age: 76 ± 2years, male: 93%). For speckle-tracking analysis of LA myocardial function, the systolic LA strain (LA reservoir function) was defined for this study as LA myocardial function from the apical 4-chamber view. The primary endpoint was defined as a composite comprising cardiovascular death and/or heart failure hospitalization after tafamidis administration over a median follow-up period of 28 ± 4months. Patients with baseline LA strain < 8.6% (median value) experienced significantly more cardiovascular events than those without (log-rank P = 0.002). Moreover, LA strain in 26 patients worsened after tafamidis administration, and multivariate logistic regression analysis showed age, global longitudinal strain and relative apical longitudinal strain index were identified as independent determinants of deterioration of LA strain after tafamidis administration. In conclusion, baseline LA reservoir function is closely associated with cardiovascular events after tafamidis administration, and could be an additional parameter for the management of patients with ATTR-CM.

Assessment of cardiac adverse events following COVID-19 vaccination by speckle tracking echocardiography

Cardiac discomfort has been reported periodically in COVID-19-vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests, electrocardiogram (ECG), and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomforts, such as chest tightness, palpitations, dyspnea, and chest pain. The ECG readings exhibited both premature ventricular contractions and premature atrial contractions (n = 24, 36.4%), while none of the individuals in the control group manifested signs of cardiac arrhythmia. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) was reduced in the symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to the control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable the evaluation of subtle changes in myocardial function after vaccination.

Left ventricular strain changes at high altitude in rats: a cardiac magnetic resonance tissue tracking imaging study

BackgroundLong-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment.Methods6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan.ResultsThe plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05).ConclusionsAfter 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.

Usability of myocardial work parameters to demonstrate subclinical myocardial involvement in normotensive individuals with exaggerated hypertensive response in treadmill exercise testing.

Early determination of changes in myocardial functions is essential for the protection of cardiovascular diseases. This study aimed to evaluate myocardial work parameters in healthy individuals who developed an exaggerated hypertensive response during the treadmill exercise test procedure. The study included a total of 64 patients for whom an exercise electrocardiography test was planned for functional capacity evaluation. The study population was divided according to the presence of exaggerated hypertensive response to exercise (EBPRE) (SBP/DBP ≥210/105mmHg in males ≥190/105mmHg in females) and normal blood pressure response to exercise (NBPRE). Patients' echocardiographic evaluations were made at rest, and myocardial work parameters were calculated. There was no statistical difference between the groups (NBPRE vs. EBPRE, respectively) in terms of left ventricular 2,3 and 4 chamber strains and global longitudinal strain (GLS) values (-20.6±-2.3, -19.7±-1.9, p:.13; -21.3±-2.7, -21±-2.4, p:.68; -21.2±-2.2, -21.2±-2.3, p:.93; and -20.8±-1.5, -20.4±-1.5, p:.23, respectively). Global constrictive work (GCW), global waste work (GWW), and global work efficiency (GWE) were not statistically different between the two groups (2374±210, 2465±204, p:.10; 142±64, 127±42, p:.31; 94.3±2.5, 95.1±1.5, p:.18, respectively). In contrast, global work index (GWI) parameters were different between the two groups (2036±149, 2147±150, p<.001). The GWI was independently associated with EBPRE (odds ratio with 95% 3.32 (1.02-11.24), p=.03). The partial effect plots were used for GWI to predict EBPRE, according to the results, an increase in GWI predicts probability of exaggerated hypertensive response. In conclusion, Myocardial work analyses might be used to identify early signs of myocardial involvement in normotensive patients with EBPRE.

Discrimination of myocardial function changes: Evolution of chronic kidney disease or hemodialysis effect?

Discrimination of myocardial function changes: Evolution of chronic kidney disease or hemodialysis effect?

Perioperative hyperoxia- impact on myocardial biomarkers, strain and outcome in high-risk patients undergoing non-cardiac surgery: Protocol for a prospective randomized controlled trial

BackgroundSupplemental oxygen is used during every general anesthesia. However, for the maintenance phase of a general anesthesia, in most cases the longest part of anesthesia, only scarce evidence of dosing supplemental oxygen exists. Oxygen is a well-known coronary vasoconstrictor and thus may contribute to cardiovascular complications especially in vulnerable high-risk patients with coronary artery disease undergoing major non-cardiac surgery. Myocardial biomarkers are early indicators of myocardial injury. Oxygen supply demand mismatches due to coronary artery disease aggravated by hyperoxia might be displayed by changes from the biomarker's baseline-values. This study is designed to detect changes in myocardial biomarkers levels associated with perioperative hyperoxia. MethodsThis prospective randomized controlled interventional trial investigates the impact of maintaining perioperative high oxygen supplementation in high-risk patients undergoing non-cardiac vascular surgery on cardiac biomarkers, myocardial strain and outcome in 110 patients. Patients are allocated to be supplemented with either 0.3 (normal) or 0.8 (high) fraction of inspired oxygen (FiO2) perioperatively. Included is a short crossover phase during which transesophageal echocardiography is used to evaluate myocardial function at FiO2 0.3 and 0.8 by strain analysis in each patient. Patients will be followed up for complications at 30 days and 1 year. ConclusionThe trial is designed to evaluate perioperative changes from baseline myocardial biomarkers associated with perioperative FiO2. Furthermore, exploration and correlation of changes in biomarkers, acute early changes in myocardial function and clinical outcomes induced by different FiO2 may be possible.

Echocardiographic evaluation of myocardial structural and functional changes in patients with stage 5 chronic kidney disease before and after kidney transplantation

Introduction. Chronic kidney disease, stage 5, leads to structural remodeling of the myocardium, and heart failure. Kidney transplantation promotes normalization of structural and functional parameters of the myocardium through reverse remodeling with an improvement of its systolic function.Aim. To evaluate structural and functional changes of the myocardium in patients before and after kidney transplantation, using echocardiography.Material and methods. A retrospective cross-sectional study included 111 individuals of whom 36 patients underwent evaluation for kidney transplant waiting list placement program (Group I), and 51 patients received kidney transplants from deceased donors (Group II). Group III consisted of 24 individuals without kidney pathology. All patients underwent transthoracic two-dimensional echocardiography using the Phillips Epiq 7 device to determine the structural and functional parameters of the heart, including the use of speckle-tracking technique to assess longitudinal and circumferential myocardial deformation of the left ventricle.Results. There were no statistically significant differences in transthoracic echocardiography results between patients in Group I and Group II. When compared to the parameters of patients in Group III, statistically significant differences were found in the following parameters: volume and volume index of the left atrium, end-diastolic volume index, left ventricular mass index, interventricular septum thickness and posterior wall thickness of the left ventricle, as well as diastolic function parameters (E/A). Patients in Group I and Group II had significantly higher values of left atrium diameter: 32 (26.0;38.0) mmHg and 31.0 (27.3;40.0) mmHg, respectively, (p1-2=0.949), while in Group III this parameter value was 22.5 (20.8;25.3) mmHg (p1-3&lt;0.001, p2-3&lt;0.001). Correlation analysis revealed statistically significant correlations between left ventricular mass index and global circumferential strain (r=0.41, p=0.0027), as well as between E/e' ratio and left ventricular mass index (r=0.323, p=0.00197). It was found that after 3 months post kidney transplantation, there was a decrease in the left atrium diameter, volume, and volume index. The values of left atrium diameter immediately after kidney transplantation and after 3 months were 40 (32.5;45) mmHg and 35 (25.5;41.0) mmHg (p=0.049); those of the left atrium volume were 62.5 (50.0;77.3) and 51.5 (47.5;64.5) ml (p=0.03); and those of the left atrium volume index were 33.4 (29.3;40.2) and 28.3 (25.5;33.6) ml/m2 (p=0.01) respectively.Conclusions. Patients with chronic kidney disease stage 5 have a high incidence of functional and structural abnormalities of the left heart chambers; left ventricular mass index positively correlates with E/e' and global circumferential strain. At 3 months after kidney transplantation, there was a slight positive trend manifested in the form of a decrease in left atrium diameter and a decrease in left ventricle volume. Further dynamic study of this group of patients in the long term after kidney transplantation is planned.

Structure of cardiac rhythm disorders in patients with obesity and associated with it dyslipidemia as an arrhythmogenic factor

Obesity is a global public health problem in the twenty-first century. The most adverse it’s effects are associated with visceral type, with accumulation of epicardial fat, showing high metabolic activity, dysfunction and important role in the development of lipotoxic cardiomyopathy linked with significant morphological and functional myocardial changes, accompanying by high risk of heart rhythm disorders. The aim of the study: to identify structure (frequency and character) of cardiac arrhythmias in men of employable age with visceral obesity, to establish the relationship of arrhythmias with features of the blood lipid spectrum of these patients. Material and methods. 98 men with abdominal obesity and 46 overweight patients were examined. The control group consisted of 40 healthy patients with normal body weight. All the patients were undergone ECG monitoring, echocardiography and analysis of serum lipid levels. Results. The presence of obesity is statistically significantly associated with the risk of supraventricular couplets, frequent ventricular extrasystoles, sinus arrhythmia and atrial fibrillation. The increase in the severity of obesity was accompanied by a tendency to a greater frequency of arrhythmias: in obesity of I degree, the frequency of atrial fibrillation was 12.3%, II–III degree — 21.2%, p = 0.25; frequent ventricular extrasystoles with similar degrees of obesity — 13.8% and 21.1%, respectively. Atrial fibrillation was significantly more often detected against the background of lipid disorders, mainly with a decrease in HDLP. Conclusion. The main type of heart rhythm disturbance in patients with obesity are supraventricular arrhythmias, mainly atrial fibrillation, the frequency of which increases in proportion to the increase in the patient's body weight. Abdominal obesity leads to an increase in ventricular ectopic activity. Dyslipidemia is the one of risk factors for arrhythmias in these patients.

Elevated levels of alcohol dehydrogenase aggravate ethanol-evoked cardiac remodeling and contractile anomalies through FKBP5-yap-mediated regulation of ferroptosis and ER stress

Alcohol intake provokes severe organ injuries including alcoholic cardiomyopathy with hallmarks of cardiac remodeling and contractile defects. This study examined the toxicity of facilitated ethanol metabolism in alcoholism-evoked changes in myocardial morphology and contractile function, insulin signaling and various cell death domains using cardiac-selective overexpression of alcohol dehydrogenase (ADH). WT and ADH mice were offered an alcohol liquid diet for 12 weeks prior to assessment of cardiac geometry, function, ER stress, apoptosis and ferroptosis. Alcohol intake provoked pronounced glucose intolerance, cardiac remodeling and contractile anomalies with apoptosis, ER stress, and ferroptosis, the effects were accentuated by ADH with the exception of global glucose intolerance. Hearts from alcohol ingesting mice displayed dampened insulin-stimulated phosphorylation of insulin receptor (tyr1146) and IRS-1 (tyrosine) along with elevated IRS-1 serine phosphorylation, the effect was augmented by ADH. Alcohol challenge dampened phosphorylation of Akt and GSK-3β, and increased phosphorylation of c-Jun and JNK, the effects were accentuated by ADH. Alcohol challenge promoted ER stress, FK506 binding protein 5 (FKBP5), YAP, apoptosis and ferroptosis, the effects were exaggerated by ADH. Using a short-term ethanol challenge model (3 g/kg, i.p., twice in three days), we found that inhibition of FKBP5-YAP signaling or facilitated ethanol detoxification by Alda-1 alleviated ethanol cardiotoxicity. In vitro study revealed that the ethanol metabolite acetaldehyde evoked cardiac contractile anomalies, lipid peroxidation, and apoptosis, the effects of which were mitigated by Alda-1, inhibition of ER stress, FKBP5 and YAP. These data suggest that facilitated ethanol metabolism via ADH exacerbates alcohol-evoked myocardial remodeling, functional defects, and insulin insensitivity possibly through a FKBP5-YAP-associated regulation of ER stress and ferroptosis.

So close, yet so far away: the relationship between MAM and cardiac disease.

Mitochondria-associated membrane (MAM) serve as crucial contact sites between mitochondria and the endoplasmic reticulum (ER). Recent research has highlighted the significance of MAM, which serve as a platform for various protein molecules, in processes such as calcium signaling, ATP production, mitochondrial structure and function, and autophagy. Cardiac diseases caused by any reason can lead to changes in myocardial structure and function, significantly impacting human health. Notably, MAM exhibits various regulatory effects to maintain cellular balance in several cardiac diseases conditions, such as obesity, diabetes mellitus, and cardiotoxicity. MAM proteins independently or interact with their counterparts, forming essential tethers between the ER and mitochondria in cardiomyocytes. This review provides an overview of key MAM regulators, detailing their structure and functions. Additionally, it explores the connection between MAM and various cardiac injuries, suggesting that precise genetic, pharmacological, and physical regulation of MAM may be a promising strategy for preventing and treating heart failure.

Left ventricle function and post-transcriptional events with exercise training in pigs.

Standardized exercise protocols have been shown to improve overall cardiovascular fitness, but direct effects on left ventricular (LV) function, particularly diastolic function and relation to post-transcriptional molecular pathways (microRNAs (miRs)) are poorly understood. This project tested the central hypothesis that adaptive LV remodeling resulting from a large animal exercise training protocol, would be directly associated with specific miRs responsible for regulating pathways relevant to LV myocardial stiffness and geometry. Pigs (n = 9; 25 Kg) underwent a 4 week exercise training protocol (10 degrees elevation, 2.5 mph, 10 min, 5 days/week) whereby LV chamber stiffness (KC) and regional myocardial stiffness (rKm) were measured by Doppler/speckle tracking echocardiography. Age and weight matched non-exercise pigs (n = 6) served as controls. LV KC fell by approximately 50% and rKm by 30% following exercise (both p < 0.05). Using an 84 miR array, 34 (40%) miRs changed with exercise, whereby 8 of the changed miRs (miR-19a, miR-22, miR-30e, miR-99a, miR-142, miR-144, miR-199a, and miR-497) were correlated to the change in KC (r ≥ 0.5 p < 0.05) and mapped to matrix and calcium handling processes. Additionally, miR-22 and miR-30e decreased with exercise and mapped to a localized inflammatory process, the inflammasome (NLRP-3, whereby a 2-fold decrease in NLRP-3 mRNA occurred with exercise (p < 0.05). Chronic exercise reduced LV chamber and myocardial stiffness and was correlated to miRs that map to myocardial relaxation processes as well as local inflammatory pathways. These unique findings set the stage for utilization of myocardial miR profiling to identify underlying mechanisms by which exercise causes changes in LV myocardial structure and function.

Ultrasound study of right ventricular myocardial perfusion and functional changes in hypertrophic cardiomyopathy.

To evaluate the changes of right ventricular (RV) myocardial perfusion and function in patients with hypertrophic cardiomyopathy (HCM) by myocardial contrast echocardiography (MCE) and speckle tracking (2D-STE), and to explore the relationship between RV myocardial perfusion and strain. Conventional ultrasound, MCE and 2D-STE were performed on 29 HCM patients and 21 healthy subjects to analyze RV myocardial perfusion, RV global strain, RV free wall strain, and strain of each segment. The correlation between RV myocardial perfusion and strain was further analyzed in HCM patients. MCE results showed that the regional myocardial perfusion of the RV in HCM patients was decreased. Compared with the normal control group, the mean slope (β) in the middle and apical segments of the RV free wall, and the peak intensity (A), β, myocardial blood flow (MBF) of the ventricular septum decreased in HCM patients (P < 0.05). RV function was impaired in HCM patients. The RV global strain (RV GLS), and the strain of RV free wall and each segment were lower than those in the normal control group (P < 0.05). Correlation analysis showed that there was a certain correlation between RV myocardial perfusion and strain, such as the β of the whole RV in HCM group had a positive correlation with the strain of the middle segment of the interventricular septum (r = 0.550, P = 0.002). The regional myocardial perfusion and strain of the RV in HCM patients are reduced, and there is a positive correlation between them, suggesting that the reduction of myocardial strain may be related to the impairment of myocardial microcirculation.

Early left ventricular microvascular dysfunction in diabetic pigs: a longitudinal quantitative myocardial perfusion CMR study

BackgroundMicrovascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique.MethodsTwelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function.ResultsWith the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = − 0.353, P = 0.022), LV remodeling index (r = − 0.312, P = 0.033), fasting blood glucose (r = − 0.313, P = 0.043), and HbA1c (r = − 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration.ConclusionsMyocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling.

The crucial relationship between miRNA-27 and CSE/H2S, and the mechanism of action of GLP-1 in myocardial hypertrophy.

Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II. Molecular alterations in the myocardium were quantified using quantitative real time PCR (qRT-PCR), Western blotting, and ELISA. Morphological changes were characterized by hematoxylin and eosin (HE) staining and Masson's trichrome staining. Functional myocardial changes were assessed using echocardiography. Our results demonstrated that miR-27a levels were elevated, while H2S levels were reduced in TAC mice and myocardial hypertrophy. Further luciferase and target scan assays confirmed that cystathionine-γ-lyase (CSE) was a direct target of miR-27a and was negatively regulated by it. Notably, enhancement of H2S expression in the heart was observed in mice injected with recombinant adeno-associated virus vector 9 (rAAV9)-anti-miR-27a and in cells transfected with a miR-27a inhibitor during cardiac hypertrophy. However, this effect was abolished by co-transfection with CSE siRNA and the miR-27a inhibitor. Conversely, injecting rAAV9-miR-27a yielded opposite results. Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H2S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H2S pathway in the management of cardiac hypertrophy.

Myocardial structural and functional changes in cardiac amyloidosis - insights from a prospective observational patient registry

Abstract Background Within the last decade, cardiac amyloidosis (CA) has been acknowledged as a significant cause of heart failure and patients who are affected face a dismal prognosis, especially in later stages of the disease. The pathophysiological hallmark of cardiac amyloidosis (CA) is the deposition of amyloid within the myocardium. Consequently, extracellular volume (ECV) of affected patients increases. However, studies on ECV progression over time and its' impact on prognosis are lacking. Objectives We aimed to investigate the progression of ECV and its prognostic impact in CA patients. Methods Serial cardiac magnetic resonance (CMR) examinations, including ECV quantification were performed in consecutive CA patients. Results Between 2012 and 2021, 103 CA patients underwent baseline and follow-up CMR, including ECV quantification. Median ECVs at baseline of the total (n = 103), transthyretin [(ATTR) n = 80], and [light chain (AL) n = 23] CA cohorts were 48.0%, 49.0%, and 42.6%. During a median follow-up period of 12 months, ECV increased significantly in all cohorts (48.0% to 50.5%, p&amp;lt;0.001; 49.0% to 50.5%, p&amp;lt;0.001; 42.6% to 50.6%, p = 0.026). Separate analyses for treatment-naïve (n = 14) and treated (n = 66) ATTR patients revealed that the median change of ECV from baseline to follow-up was significantly higher among untreated patients (5.5% versus 2.7%, p = 0.035). Survival analyses demonstrated that median change of ECV was an independent (adjusted for troponin t and NT-proBNP) predictor of outcome in all CA cohorts [total: hazard ratio (HR): 1.114, 95% confidence-interval (CI): 1.045 – 1.189, p&amp;lt;0.001; ATTR: HR: 1.099, 95% CI: 1.014 – 1.192, p = 0.022; AL: HR: 1.142, 95% CI: 1.006 – 1.297, p = 0.040]. Conclusions The present study demonstrates that ECV, quantified by CMR T1 mapping, increases significantly in CA patients over the course of 12 months. While ECV increased, irrespective of amyloid type our analyses showed the highest increase among untreated ATTR patients. Moreover, the change of ECV was an independent predictor of adverse outcomes in AL, as well as ATTR patients emphasizing the usefulness of CMR T1 mapping in the management of CA patients.Figure 1.Dot PlotsFigure 2.Kaplan Meier Curves

Association Between Type 2 Diabetes and Changes in Myocardial Structure, Contractile Function, Energetics, and Blood Flow Before and After Aortic Valve Replacement in Patients With Severe Aortic Stenosis.

Type 2 diabetes (T2D) is associated with an increased risk of left ventricular dysfunction after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Persistent impairments in myocardial energetics and myocardial blood flow (MBF) may underpin this observation. Using phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance, this study tested the hypothesis that patients with severe AS and T2D (AS-T2D) would have impaired myocardial energetics as reflected by the phosphocreatine to ATP ratio (PCr/ATP) and vasodilator stress MBF compared with patients with AS without T2D (AS-noT2D), and that these differences would persist after AVR. Ninety-five patients with severe AS without coronary artery disease awaiting AVR (30 AS-T2D and 65 AS-noT2D) were recruited (mean, 71 years of age [95% CI, 69, 73]; 34 [37%] women). Thirty demographically matched healthy volunteers (HVs) and 30 patients with T2D without AS (T2D controls) were controls. One month before and 6 months after AVR, cardiac PCr/ATP, adenosine stress MBF, global longitudinal strain, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and 6-minute walk distance were assessed in patients with AS. T2D controls underwent identical assessments at baseline and 6-month follow-up. HVs were assessed once and did not undergo 6-minute walk testing. Compared with HVs, patients with AS (AS-T2D and AS-noT2D combined) showed impairment in PCr/ATP (mean [95% CI]; HVs, 2.15 [1.89, 2.34]; AS, 1.66 [1.56, 1.75]; P<0.0001) and vasodilator stress MBF (HVs, 2.11 mL min g [1.89, 2.34]; AS, 1.54 mL min g [1.41, 1.66]; P<0.0001) before AVR. Before AVR, within the AS group, patients with AS-T2D had worse PCr/ATP (AS-noT2D, 1.74 [1.62, 1.86]; AS-T2D, 1.44 [1.32, 1.56]; P=0.002) and vasodilator stress MBF (AS-noT2D, 1.67 mL min g [1.5, 1.84]; AS-T2D, 1.25 mL min g [1.22, 1.38]; P=0.001) compared with patients with AS-noT2D. Before AVR, patients with AS-T2D also had worse PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.66 [1.56, 1.75]; P=0.04) and vasodilator stress MBF (AS-T2D, 1.25 mL min g [1.10, 1.41]; T2D controls, 1.54 mL min g [1.41, 1.66]; P=0.001) compared with T2D controls at baseline. After AVR, PCr/ATP normalized in patients with AS-noT2D, whereas patients with AS-T2D showed no improvements (AS-noT2D, 2.11 [1.79, 2.43]; AS-T2D, 1.30 [1.07, 1.53]; P=0.0006). Vasodilator stress MBF improved in both AS groups after AVR, but this remained lower in patients with AS-T2D (AS-noT2D, 1.80 mL min g [1.59, 2.0]; AS-T2D, 1.48 mL min g [1.29, 1.66]; P=0.03). There were no longer differences in PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.51 [1.34, 1.53]; P=0.12) or vasodilator stress MBF (AS-T2D, 1.48 mL min g [1.29, 1.66]; T2D controls, 1.60 mL min g [1.34, 1.86]; P=0.82) between patients with AS-T2D after AVR and T2D controls at follow-up. Whereas global longitudinal strain, 6-minute walk distance, and NT-proBNP all improved after AVR in patients with AS-noT2D, no improvement in these assessments was observed in patients with AS-T2D. Among patients with severe AS, those with T2D demonstrate persistent abnormalities in myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function after AVR; AVR effectively normalizes myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function in patients without T2D.

Dynamic changes in myocardial oxygenation and function during induction of general anaesthesia: Quantification by cardiovascular magnetic resonance imaging

Dynamic changes in myocardial oxygenation and function during induction of general anaesthesia: Quantification by cardiovascular magnetic resonance imaging

Loss and recovery of myocardial mitochondria in mice under different tail suspension time: Apoptosis and mitochondrial fission, fusion and autophagy.

Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.