Myocardial Contraction Research Articles

Kiosk 2R-FA-01 - Comparison of Myocardial Contraction FBaction in Hypertrophic Cardiomyopathy Patients via Multimodality Imaging and Its Effect on Clinical Outcome

Kiosk 2R-FA-01 - Comparison of Myocardial Contraction FBaction in Hypertrophic Cardiomyopathy Patients via Multimodality Imaging and Its Effect on Clinical Outcome

Kiosk 4R-FC-04 - Discordance Between Myocardial Contraction FBaction by Volumetric versus Geometric Formula-based Methods

Kiosk 4R-FC-04 - Discordance Between Myocardial Contraction FBaction by Volumetric versus Geometric Formula-based Methods

Study of Serum Magnesium, Potassium and Calcium in Acute Myocardial Infarction Patients

Introduction: A myocardial infarction happens when blood flow stops or decreases to the coronary arteries of the myocardial muscle, resulting in damage to the heart muscle. Magnesium is important electrolyte plays vital role in suppressing arrhythmias during myocardial ischemia and during reperfusion. Potassium is the most abundant cation of intracellular fluid. A significant correlation between hypokalemia and ventricular fibrillation is recorded. Calcium plays a vital role in myocardial muscle contraction. Aim: To study serum levels of magnesium, potassium and calcium in acute myocardial infarction patients. Material and methods: This was a prospective case control study conducted in Prathima Institute of medical sciences Nagunur, Karimnagar, Telangana state, India between January 2015 to December 2015. A total 50 acute myocardial infarction patients and 50 normal age and sex matched healthy controls selected for study. Serum magnesium estimated by colorimetric xylidyl blue complex method, serum potassium estimated by ion selective electrode method and serum calcium by OCPC method. Statistical analysis carried out using statistical software SPSS version 16 and p-value < 0.05 considered statistically significant. Results: Serum levels of magnesium, potassium and calcium were significantly decreased in acute myocardial infarction patients when compared healthy controls and is statistically significant (<0.05) Conclusion: The above study suggested decreased serum level of key elements such as magnesium, potassium and calcium in acute myocardial infarction patients when compared to healthy controls. Estimation and correction of these elements may play a pivotal role in management of patients with acute myocardial infarction

Integrated analysis reveals ceRNA network of cardiac remodeling by SGLT2 inhibitor in middle-aged hypertensive rats

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent an innovative class of antidiabetic agents that have demonstrated promise in mitigating cardiac remodeling. However, the transcriptional regulatory mechanisms underpinning their impact on blood pressure and the reversal of hypertension-induced cardiac remodeling remain largely unexplored. Given this context, our study concentrated on comparing the cardiac expression profiles of lncRNAs and mRNAs between Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). To validate our results, we performed blood pressure measurements, tissue staining, and qRT-PCR. The treatment led to a significant reduction in systolic blood pressure and improved cardiac remodeling by reducing myocardial fibrosis and regulating the inflammatory response. Our examination disclosed that ventricular tissue mRNA, regulated by hypertension, was primarily concentrated in the complement and coagulation cascades and cytokine-cytokine receptor interactions. Compared with SHR, the SGLT2i treatment group was associated with myocardial contraction. Investigation into the lncRNA-mRNA regulatory network and competing endogenous RNA (ceRNA) network suggested that the potential roles of these differentially expressed (DE) lncRNAs and mRNAs were tied to processes such as collagen fibril organization, inflammatory response, and extracellular matrix (ECM) modifications. We found that the expression of Col3a1, C1qa, and lncRNA NONRATT007139.2 were altered in the SHR group and that SGLT2i treatment reversed these changes. Our results suggest that dapagliflozin effectively reverses hypertension-induced myocardial remodeling through a lncRNA-mRNA transcriptional regulatory network, with immune cell-mediated ECM deposition as a potential regulatory target. This underlines the potentiality of SGLT2i and genes related to immunity as promising targets for the treatment of hypertension.

Evaluation of myocardial contraction fraction in transcatheter aortic valve replacement

Evaluation of myocardial contraction fraction in transcatheter aortic valve replacement

PDE2 is cardioprotective in chronic heart failure

Abstract Background Patients with chronic heart failure (HF) often develop life-threatening arrhythmia due to structural and electrophysiological cardiac remodelling. The chronic activation of the sympathetic nervous system is initially able to compensate the reduced myocardial contraction. Finally, long-term activation of the β-adrenergic pathway leads to deleterious activation of cAMP-dependent kinases and dysregulation of intracellular Ca2+ handling promoting HF progression and development of arrhythmia. Interestingly, phosphodiesterase 2 (PDE2), an enzyme to hydrolyze cAMP, is upregulated in human HF. Thus, PDE2 might reduce enhanced cAMP levels and pro-arrhythmic Ca2+ releases in HF. Purpose We investigated the effects of genetic PDE2 deletion on cardiac function, cellular contraction and arrhythmia occurrence in murine HF model. Methods HF was induced via high fat (60 %) diet (HFD) and the treatment with NO-synthase inhibitor L-NAME (0.5 g/l) for 5 weeks in cardiomyocyte-specific PDE2-knockout mice (KO) and control mice (WT). We characterized cardiac function by echocardiography, arrhythmia development by ECG-telemetry, cellular contraction by video-based analysis of sarcomere-shortening and cellular Ca2+ releases using Ca2+ imaging techniques. Results After 5 weeks HFD and L-NAME, mice gained weight, displayed increased blood pressure and reduced systolic and diastolic cardiac function. Interestingly, PDE2 KO showed reduced contractility and ejection fraction compared to WT mice after 5 weeks HF. On cellular level, the contraction of isolated cardiomyocytes slightly increased in HF indicating cardiac hypertrophy. However, the β-adrenergic stimulation with isoprenaline (ISO) enhanced cellular contraction only in non-failing WT mice, but was blunted in cells from failing WT hearts reflecting a desensitization of the β-adrenergic pathway. In contrast, the ISO-induced increase in cellular contraction was preserved in failing hearts from KO mice. Interestingly, PDE2 inhibition with BAY 60-7550 increased the ISO-induced cellular contraction in HF from WT, which was not observed in cells from non-failing mice. In HF, the expression of Ca2+ cycling proteins like phospholamban (PLB) were affected. Failing PDE2 KO mice showed higher phosphorylation levels of PLB compared to WT mice with HF. In diseased hearts, pro-arrhythmic triggers like spontaneous Ca2+ waves and Ca2+ sparks were increased. Importantly, diseased PDE2 KO mice developed more arrhythmia in-vivo upon arrhythmia provocation than WT animals. Conclusion Cardiac PDE2 deletion was detrimental in HF showing reduced cardiac function and higher number of arrhythmia. PDE2 stimulation might serve as potential therapeutical target in HF limiting the consequences of chronic β-adrenergic hyperactivation.

Abstract 13340: Contractility and Local Stress Patterns Depend on Directionality of Fibrosis Progression: Insights From Microscale Biomechanical Simulations

Introduction: Cardiac fibrosis, a common pathological process in heart disease, leads to reduced contractility and increased myocardial stiffness. However, it remains unclear how various cellular and subcellular events individually contribute to these changes. Hypothesis: Tissue-scale biomechanical effects resulting from cellular and subcellular changes, such as myocyte loss and increased ECM stiffness, are anisotropic and depend on the prevailing direction of fibrosis progression. Methods: We used a mechanical modeling framework allowing for explicit geometrical representation of individual myocytes embedded in ECM. We used a transversely isotropic hyperelastic formulation for the cells while assuming the ECM to be isotropic. Contraction was imposed in each cell using an active stress model. In a simulated tissue domain (6х12 cells), we explored different cellular configurations (Fig. 1A) representing longitudinal, transverse, and random fibrosis progression (i.e., myocyte loss). In each configuration, we examined tissue shortening and stress distributions subject to original and 10х increased ECM stiffness. Results: Myocyte loss perpendicular to the myofiber direction had the largest impact on contractility (Fig. 1B and 1C; as low as 10.8% shortening vs. 15.4% at baseline). In particular, transverse stresses were greatly perturbed in areas near where remaining cells met replacement matrix. Longitudinal and random fibrosis progression had less impact on contractility but led to dramatic heterogeneity in stress distributions. Increased matrix stiffness (Fig. 1C) led to increased magnitude of all stress values. Conclusions: Tissue-scale changes depend on both ECM stiffening and the directionality of myocyte loss. Our model predicts that transverse fibrosis progression has the greatest impact on myocardial contraction, while longitudinal and random progression induce higher local maxima in myocardial stress distributions.

Abstract 17495: Protein Kinase A Activity in Heart Failure Spectrums

Introduction: Protein Kinase A (PKA) signaling is activated by β-adrenergic receptor (BAR) stimulation and regulates myocardial contraction and cellular functions. Chronic PKA overactivation can lead to apoptosis, structural dysfunction and arrhythmias. Heart failure (HF) is associated with increased BAR stimulation and downstream detrimental cellular effects likely mediated by increased PKA activation, but it remains unclear whether PKA is uniformly increased across HF spectrums. We aimed to determine the extent of PKA activity in HF phenotypes. Methods: Serum from HF patients (age 18-89, 66% male) (acute systolic HF, n=19, HF with reduced ejection fraction HFrEF (n=58) and HF with preserved ejection fraction-HFpEF (n=10) were collected. PKA assay: H9c2 rat heart cells (ATCC) were plated overnight and serum samples (1:100 dilution) were incubated with cells for 1 hour. Specific activity of the enzyme in pmol/min/ng was calculated (% above the basal PKA rate). For comparison, healthy controls (n=35, age 18-69, 59% male) were tested. In 3 HFrEF subjects, serum PKA signaling was inhibited by anti-IgG beads, specific antigens or Propranolol. Mann Whitney U test was performed to determine differences between groups. Results: Median PKA activation was 76% (acute HF), 49% in HFrEF, 39% in HFpEF and 9% in healthy controls. Compared to controls, PKA activity was significantly higher across all HF phenotypes (p<0.05). No statistical difference was noted between HF phenotypes although acute HF sera demonstrated numerically higher PKA activation in the heart cells. PKA activity was attenuated with anti-IgG beads or Propranolol in HFrEF, which suggests circulating IgG autoantibodies lead to induction of PKA signaling via BAR pathway in HF. Conclusion: PKA activity is increased across HF spectrums compared with healthy controls. Acute systolic HF appears to be associated with highest PKA activation. Further studies are underway to corroborate these findings.

Abstract 15928: D-dimer as a New Biomarker of Aortic Stenosis Progression and Outcomes: Results From the PROGRESSA Study

Background: Aortic stenosis (AS) induces left ventricular (LV) remodeling and hypertrophy, which are key markers of the transition to heart failure. The present study aimed to evaluate the association between D-dimer plasma levels, LV hypertrophy and mortality with AS. Method: One-hundred and forty-six asymptomatic patients (mean age 65±13, men 76%) with mild or moderate AS prospectively recruited in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent Doppler-echocardiography annually to measure AS severity, LV mass indexed to body surface area (LVMi) and myocardial contraction fraction (MCF). The annualized changes in LVMi and MCF were calculated between baseline and last follow up. Results: Higher plasma levels of D-dimers at baseline were significantly associated with faster progression rate of LVMi and MCF (r 2 =0.18 and -0.22, respectively; all p<0.01). On multivariable analysis adjusted for age, sex, comorbidities, creatinine level, peak aortic jet velocity at baseline, D-dimers remained significantly associated with faster change in LVMi and MCF (all, p<0.01). Moreover, in multivariate analysis adjusted for age, sex, AS severity at baseline, higher levels of D-dimer were significantly associated with the progression to a higher grade of AS severity (HR [95% CI] 1.67 [1.14-2.46], p=0.009). During a median follow-up of 8.1 (5.6-9.9) years, 38 (26%) patients died. On multivariable Cox regression analysis, higher levels of D-dimer were associated with an increased risk of all-cause mortality (HR [95% CI]: 1.97 [0.98-1.97], p=0.05). Conclusion: Higher levels of D-dimer are associated with faster progression of AS severity, LV hypertrophy and dysfunction, and increased risk of mortality in patients with AS. This new blood biomarker may improve risk stratification and management of asymptomatic patients with AS. Further studies are needed to determine the mechanisms underlying this association between D-dimer and outcomes in AS.

Abstract 12000: Prolonged Arterial Phase is Caused of the Chest Pain in Takotsubo Cardiomyopathy A Dynamics Angiography and Artificial Intelligence Analysis

Introduction: Takotsubo Cardiomyopathy (TCM) known as “Broken Heart Syndrome” is triggered by extreme emotional or physical stress. The typical TCM patient features chest pain, ST elevation, elevated troponin, reduced ejection fraction (EF), patent coronary artery, and apical ballooning. Hypothesis: Could abnormal coronary flow explain chest pain in Takotsubo patients? Methods: The patient with severe chest pain, elevated troponin, ST change, patent coronary arteries, and apical ballooning underwent angiography and review with a new dynamic recording technique. Ten patients without ACS, normal EF, and no coronary artery disease served as control. At first, the angiographic recording started when the contrast was injected into the coronary artery. Then the recording continued with the blood in white color moving in until all contrast disappeared from the arteries. The angiogram was recorded at 15 images per second. The review of coronary images focused on the blood flow in white on top of a background of black contrast. The arterial phase (AP) calculation began when the blood moved in and ended when all the contrast was flushed out of the distal arterial vasculature. The two-layer artificial intelligence program was built based on U-net and Densenet-121. The first layer, with a segmentation model and Convolutional neural network is responsible for detecting the starting frame of AP with a full index of contrast. The second layer with a segmentation model will detect the ending frame of AP. All TCM patient was followed up in one year. Results: Fifteen TCM patients met the criteria (12/15 female). The AP in the TCM group was 3.17 +/- 0.53 seconds compared with 1.62 +/- 0.26 seconds in the control group (P<0.001). The TCM group had a mean EF 33.9 +/- 7.6 %, and all recovered to 58.8 +/- 12.6 % after two weeks. At one year follow-up, all patients had no chest pain and no re-admission, except for one case of non-cardiovascular mortality associated with septic shock from pneumonia 3 months after the index event. Conclusions: Chest pain in TCM was caused by slow flow (measured as prolonged arterial phase) which was detrimental to myocardial contraction. Their prognosis was benign because all patients recovered.

Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy.

Sepsis is a medical condition characterized by acute organ dysfunction and uncontrolled inflammation. Organ dysfunction in sepsis is the primary cause of mortality in patients with myocardial dysfunction. Levosimendan is a vasodilating and inotropic agent used in patients with acute heart failure and has resulted in decreased morbidity and mortality in these patients. Our main objective is to examine levosimendan's efficacy in treating severe sepsis complicated with septic cardiomyopathy. We systematically searched five databases, PubMed, Web of Science, Embase, Cochrane Library and BioMed Central, for articles and publications from their inception to 2023. Our study adopted the PICOS approach in identifying suitable publications during the systematic search. Inclusion criteria included randomized, controlled trials utilizing levosimendan in adult patients diagnosed with septic shock or severe sepsis. We excluded non-English publications and non-randomized controlled trials. The Newcastle-Ottawa scale (NOS) scale was used to assess the methodological quality, while the risk of bias was assessed through the Cochrane Risk of bias tool. All statistical analyses were performed using RevMan version 5.4. Eight studies met the eligibility criteria and were included in the analysis. There was a statistically significant positive effect on cardiac input in patients treated with levosimendan compared to those treated with dobutamine (p < 0.001). Similarly, there were positive effects on left ventricular ejection fraction (LVEF) (p < 0.001) and left ventricular stroke work index (LVSWI) (p < 0.001). We observed a significant reduction in mortality (p < 0.01) and serum levels of lactic acid (p < 0.01). Levosimendan is a calcium sensitizer associated with an influx of calcium ions and activation of ATP-dependent potassium channels that increases myocardial contractility contractions, enhances vasodilation and improves oxygen supply to the cells and tissues. Levosimendan is highly efficacious and safe in the management of sepsis and sepsis-induced cardiomyopathy.

Regulation of cardiac calcium signaling by newly identified calcium pump modulators

In cardiomyocytes, the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) is a central component of intracellular Ca2+ regulation. Several heart diseases, including heart failure, are associated with reduced myocardial contraction due to SERCA2a downregulation. Therefore, the need for developing new drugs that could improve SERCA2a function is high. We have recently identified SERCA2a modulators (Compounds 6 and 8) from our screening campaigns and confirmed activation of biochemical SERCA2a ATPase activity and Ca2+ uptake activity. In this study, confocal microscopy and in-cell Ca2+ imaging were used to characterize the effects of these SERCA2a activators on Ca2+ regulation in mouse ventricular myocytes and endoplasmic reticulum (ER) Ca2+ uptake in a HEK293 cell expressing human SERCA2a. Analysis of cytosolic Ca2+ dynamics in cardiomyocytes revealed that both Compounds (6 and 8) increase the action potential-induced Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ load. While Compound 6 induced a negligible effect on Ca2+ transients invoked by the L-type Ca2+ channel (LTCC) current, Compound 8 increased Ca2+ transients during LTCC activation, suggesting an off-target protein interaction of Compound 8. Analysis of ER Ca2+ transport by human SERCA2a in HEK cells showed that only Compound 6 increased both ER Ca2+ uptake and ER Ca2+ load significantly, whereas Compound 8 had no effect on SERCA2a Ca2+ transport. This study revealed that Compound 6 exhibits promising characteristics that can improve intracellular Ca2+ dynamics by selectively enhancing SERCA2a Ca2+ uptake.

EVALUATION OF THYROID PROFILE AND ITS PROGNOSTIC VALUE IN PATIENTS OF ACUTE CORONARY SYNDROME

Objective: The objective of the study is to study the association of thyroid dysfunction with acute coronary syndrome (ACS), its complications and duration of hospital stay. Methods: This prospective comparative study was done on 100 patients divided equally into ACS patients with control (normal thyroid function) and ACS patients with thyroid dysfunction admitted in a tertiary care center, Udaipur, Rajasthan with ACS during the period of February 2021–July 2022. We studied the prevalence, prognostic factor of thyroid hormone in these patients. Results: The mean ejection fraction of the control group was 51.16±11.72%, of hypothyroid group was 49.00±13.55% and of hyperthyroid group was 51.12±13.78%. 29 cases of cardiac failures, 38 cases of arrhythmias, and 32 cases of major adverse cardiac events were observed. 56% of patients required thrombolysis, out of which 67.86% were from the subclinical hypothyroid group. The mean hospital stay in control group was 4.53±1.55, in hypothyroid group was 5.27±1.84 and in hyperthyroid group was 7.00±1.92.18% mortality. Conclusion: Patients with acute myocardial infarction, initially develop alteration in thyroid hormone levels, which is possibly a compensatory mechanism to reduce the metabolic demand of the heart, by reducing myocardium contraction and cardiac output but may cause cardiac failure and higher rates of cardiovascular complications like arrhythmias and death in some of the patients. Thyroid dysfunctions in patients with ACS may also need a longer duration of intensive care and close monitoring during follow-up.

Echocardiographic and Angiographic Assessment of Right Ventricular Function and Right Coronary Artery Stenosis in Acute Inferior Wall Myocardial Infarction.

Cardiovascular diseases (CVDs) are a global concern. CVD remains a primary cause of death despite reduced coronary heart disease death rates. Acute coronary syndrome (ACS) involves myocardial infarction (MI) and unstable angina, sharing mechanisms such as plaque instability. Our study assesses the right ventricular (RV) function's predictive value in acute inferior wall MI (IWMI) to identify high-risk patients with an elevated likelihood of experiencing severe cardiac complications, hemodynamic instability, or a higher mortality risk following an acute IWMI. The research was conductedin the Department of Cardiology at theRajendra Institute of Medical Sciences (RIMS), Ranchi, from July 2021 to June 2022, following the necessary ethical approval. A cohort of 140 patients with IWMI, carefully chosen according to rigorous criteria, clearly understood the study's objectives before providing informed consent. The evaluations were conducted in the following order: clinical assessments, followed by blood testing, then echocardiography, and finally, coronary angiography. Furthermore, the study examined risk factors and utilized statistical methods to elucidate the associations between qualities and results. The study included 140 participants, with 61% being male and 39% female. Among the participants, 14% were aged 30-45, 50% were aged 46-60, and 30% were over 60. Age shows significant proportions in different categories. Diabetes, dyslipidemia, hypertension, and smoking/tobacco addiction did not differ among stenosis groups. Proximal right coronary artery (RCA) stenosis patients had elevated jugular venous pressure (JVP). The echocardiograms were performed within 48 hours of post-percutaneous coronary intervention, and significant differences between groups were observed. Participants with proximal stenosis had lower tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC), which showedcompromised RV systolic function. Proximal stenosis patients had reduced systolic motion velocity (Sm), indicating impaired myocardial contraction. Echocardiographic parameters such as early diastolic velocity (Em), atrial contraction velocity (Am), Em/Am ratio (a marker of diastolic function), isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) between groups were different, indicating distinct cardiac functions. Proximal stenosis increased the myocardial performance index (MPI), indicating cardiac impairment. The left ventricular ejection fraction (LVEF) was comparable in the two stenosis groups, indicating similar left ventricular performance. Echocardiography showed significant RV function differences in acute inferior wall ST-segment elevation myocardial infarction (STEMI) patients with proximal and distal RCA lesions. RV dysfunction is linked to right ventricle myocardial infarction (RVMI), and echocardiographic markers can provide valuable insights. Results emphasizethat acute inferior wall STEMI is diagnosed by electrocardiogram (ECG) criteria, particularly ST-segment elevation. However, these markers emphasize the importance of RV assessment in RCA involvement assessment. These findings suggest that RV function can help diagnose acute inferior wall STEMI RCA involvement. In acute inferior STEMIs, RV function echocardiography is essential for RCA lesion location.

Assessment of Prevalence, Clinical Characteristics, and Risk Factors Associated With “Low Flow State” Using Cardiac Magnetic Resonance

ObjectiveTo assess prevalence, clinical characteristics, and risk factors associated with low flow state (LFS) in a multiethnic population with normal left ventricular ejection fraction (LVEF). Patients and MethodsThe study included 4398 asymptomatic participants undergoing cardiac magnetic resonance from July 17, 2000, to August 29, 2002. Left ventricular (LV) mass, volume, and myocardial contraction fraction were assessed. Low flow state was defined as stroke volume index (SVi of <35 mL/m2). Clinical characteristics, cardiac risk factors, and cardiac magnetic resonance findings were compared between LFS and normal flow state (NFS) groups (NFS: SVi of ≥35 mL/m2). ResultsThere were significant differences in the prevalence of LFS in different ethnic groups. Individuals with LFS were older (66±9.6 vs 61±10 years; P<.0001). The prevalence of LFS was 19% in the group aged older than 70 years. The logistic multivariable regression analysis found that age was independently associated with LFS. The LFS group had significantly higher prevalence of diabetes (30% vs 24%; P=.001), LV mass-volume ratio (1.13±0.22 vs 0.91±0.15; P<.0001), inflammatory markers, a lower LV mass index (59±10 vs 65±11 kg/m2; P<.001), lower myocardial contraction fraction (58.1±10.6% vs 75.7±13%; P<.001), and a lower left atrial size index (32.2±4.6 vs 36.7±5.9 mm/m2; P<.0001) than NFS. ConclusionLow flow state may be considered an under-recognized clinical entity associated with increasing age, multiple risk factors, increased inflammatory markers, a lower LV mass index, and suboptimal myocardial performance despite the presence of normal LVEF and absence of valvular disease.

Cooperative mechanisms underlie differences in myocardial contractile dynamics between large and small mammals.

Ca2+ binding to troponin C (TnC) and myosin cross-bridge binding to actin act in a synergistic cooperative manner to modulate myocardial contraction and relaxation. The responsiveness of the myocardial thin filament to the activating effects of Ca2+ and myosin cross-bridge binding has been well-characterized in small mammals (e.g., mice). Given the nearly 10-fold difference in resting heart rates and twitch kinetics between small and large mammals, it is unlikely that the cooperative mechanisms underlying thin filament activation are identical in these two species. To test this idea, we measured the Ca2+ dependencies of steady-state force and the rate constant of force redevelopment (ktr) in murine and porcine permeabilized ventricular myocardium. While murine myocardium exhibited a steep activation-dependence of ktr, the activation-dependent profile of ktr was significantly reduced in porcine ventricular myocardium. Further insight was attained by examining force-pCa and ktr-pCa relationships. In the murine myocardium, the pCa50 for ktr was right-shifted compared with the pCa50 for force, meaning that increases in steady-state force occurred well before increases in the rate of force redevelopment were observed. In the porcine myocardium, we observed a tighter coupling of the force-pCa and ktr-pCa relationships, as evidenced by near-maximal rates of force redevelopment at low levels of Ca2+ activation. These results demonstrate that the molecular mechanisms underlying the cooperative activation of force are a dynamic property of the mammalian heart, involving, at least in part, the species- and tissue-specific expression of cardiac myosin heavy chain isoforms.

The physiological response during optogenetic-based cardiac pacing in awake freely moving mice.

There are several methods to control a heart rate, such as electrical stimulation and drug administration. However, these methods may be invasive or affect other organs. Recently, an optogenetic-based cardiac pacing method has enabled us to stimulate the cardiac muscle in non-contact. In many previous studies, the pacing was applied ex vivo or in anesthetized animals. Therefore, the physiologic response of animals during optogenetic pacing remains unclear. Here, we established a method of optogenetic-based cardiac pacing in awake, freely moving mice and simultaneously measured electrocardiogram, blood pressure, and respiration. As a result, light-induced myocardial contraction produces blood flow and indirectly affects the respiration rhythm. Additionally, light illumination enabled heart rate recovery in bradycardic mice. These findings may be employed for further research that relates a heartbeat state to animal behavior. Together, this method may drive the development of less invasive pacemakers without pacing leads.

Biomarkers of Collagen Metabolism Are Associated with Left Ventricular Function and Prognosis in Dilated Cardiomyopathy: A Multi-Modal Study.

Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM. DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5-8). In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = -0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = -0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002-1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004). The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients.

Photopolymerizable Hydrogel for Enhanced Intramyocardial Vascular Progenitor Cell Delivery and Post-Myocardial Infarction Healing.

Cell transplantation success for myocardial infarction (MI) treatment is often hindered by low engraftment due to washout effects during myocardial contraction. A clinically viable biomaterial that enhances cell retention can optimize intramyocardial cell delivery. In this study, a therapeutic cell delivery method is developed for MI treatment utilizing a photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. Human vascular progenitor cells, capable of forming functional vasculatures upon transplantation, are combined with an in situ photopolymerization approach and injected into the infarcted zones of mouse hearts. This strategy substantially improves acute cell retention and promoteslong-term post-MI cardiac healing, including stabilized cardiac functions, preserved viable myocardium, and reduced cardiac fibrosis. Additionally, engrafted vascular cells polarize recruited bone marrow-derived neutrophils toward a non-inflammatory phenotype via transforming growth factor beta (TGFβ) signaling, fostering a pro-regenerative microenvironment. Neutrophil depletion negates the therapeutic benefits generated by cell delivery in ischemic hearts, highlighting the essential role of non-inflammatory, pro-regenerative neutrophils in cardiac remodeling. In conclusion, this GelMA hydrogel-based intramyocardial vascular cell delivery approach holds promise for enhancing the treatment of acute myocardial infarction.

Quantification of Myocardial Contraction Fraction with Three-Dimensional Automated, Machine-Learning-Based Left-Heart-Chamber Metrics: Diagnostic Utility in Hypertrophic Phenotypes and Normal Ejection Fraction.

Aims: The differentiation of left ventricular (LV) hypertrophic phenotypes is challenging in patients with normal ejection fraction (EF). The myocardial contraction fraction (MCF) is a simple dimensionless index useful for specifically identifying cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) when calculated by cardiac magnetic resonance. The purpose of this study was to evaluate the value of MCF measured by three-dimensional automated, machine-learning-based LV chamber metrics (dynamic heart model [DHM]) for the discrimination of different forms of hypertrophic phenotypes. Methods and Results: We analyzed the DHM LV metrics of patients with CA (n = 10), hypertrophic cardiomyopathy (HCM, n = 36), isolated hypertension (IH, n = 87), and 54 healthy controls. MCF was calculated by dividing LV stroke volume by LV myocardial volume. Compared with controls (median 61.95%, interquartile range 55.43-67.79%), mean values for MCF were significantly reduced in HCM-48.55% (43.46-54.86% p < 0.001)-and CA-40.92% (36.68-46.84% p < 0.002)-but not in IH-59.35% (53.22-64.93% p < 0.7). MCF showed a weak correlation with EF in the overall cohort (R2 = 0.136) and the four study subgroups (healthy adults, R2 = 0.039 IH, R2 = 0.089; HCM, R2 = 0.225; CA, R2 = 0.102). ROC analyses showed that MCF could differentiate between healthy adults and HCM (sensitivity 75.9%, specificity 77.8%, AUC 0.814) and between healthy adults and CA (sensitivity 87.0%, specificity 100%, AUC 0.959). The best cut-off values were 55.3% and 52.8%. Conclusions: The easily derived quantification of MCF by DHM can refine our echocardiographic discrimination capacity in patients with hypertrophic phenotype and normal EF. It should be added to the diagnostic workup of these patients.