Myocardial Disease Research Articles

ENDOGENOUS β 3 -ADRENERGIC RECEPTOR ACTIVATION ALLEVIATES SEPSIS-INDUCED CARDIOMYOCYTE APOPTOSIS VIA PI3K/AKT SIGNALING PATHWAY.

β 3 -adrenergic receptor (β 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of β 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of β 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. We found that β 3 -AR existed both in adult rat ventricular myocytes (ARVMs) and H9c2 cells. The expression of β 3 -AR was upregulated in LPS-treated ARVMs and the heart of CLP rats. Pretreatment with β 3 -AR agonist, BRL37344, inhibited LPS-induced cardiomyocyte apoptosis and caspase-3, -8, and -9 activation in ARVMs. BRL37344 also reduced apoptosis and increased the protein levels of PI3K, p-Akt Ser473 and p-eNOS Ser1177 in LPS-treated H9c2 cells. Inhibition of PI3K using LY294002 abolished the inhibitory effect of BRL37344 on LPS-induced caspase-3, -8, and -9 activation in H9c2 cells. Furthermore, administration of β 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9, and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous β 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.

The "arrhythmic" presentation of peripartum cardiomyopathy: case series and critical review of the literature.

Peripartum Cardiomyopathy (PPCM) is a polymorphic myocardial disease occurring late during pregnancy or early after delivery. While reduced systolic function and heart failure (HF) symptoms have been widely described, there is still a lack of reports about the arrhythmic manifestations of the disease. Most importantly, a broad range of unidentified pre-existing conditions, which may be missed by general practitioners and gynecologists, must be considered in differential diagnosis. The issue is relevant since some arrhythmias are associated to sudden cardiac death occurring in young patients, and the overall risk does not cease during the early postpartum period. This is why multimodality diagnostic workup and multidisciplinary management are highly suggested for these patients. We reported a series of 16 patients diagnosed with PPCM following arrhythmic clinical presentation. Both inpatients and outpatients were identified retrospectively. We performed several tests to identify the arrhythmic phenomena, inflammation and fibrosis presence. Cardiomyopathies phenotypes were reclassified in compliance with the updated ESC guidelines recommendations. Arrhythmias were documented in all the patients during the first cardiological assessment. PVC were the most common recorder arrhythmias, followed by VF, NSVT, AF, CSD.

Role Played by Biochemical and Hematological Parameters in the Prediction of Cardiovascular Risk

Introduction: The term “cardiovascular diseases” (CVDs) refers to any disease affecting the heart or blood vessels. CVDs are the most common cause of death worldwide and the most responsible reason for 10% of deaths in the early 20th century. These CVDs can emerge as myocardial infarction or ischemic heart disease, stroke, and congestive heart failure. For diagnosing CVDs, physical, radiological investigations, and laboratory investigations for cardiac enzymes and lipid profile are used. In clinical practices, cardiovascular risk prediction models are very important in the identification, prevention, and staging of the severity of CVDs. Framingham Risk Score-coronary heart disease, Framingham Risk Score-cardiovascular disease, QRESEARCH-cardiovascular risk algorithm, Joint British Society risk-calculator-3, WHO/ISH CVD risk prediction charts, and Atherosclerotic Cardiovascular Disease risk-estimator are some of the available CVD risk estimators. However, many of these estimators can be used only to evaluate individuals more than 40 years and to assess the risk for 10-years. Therefore, new risk estimators are needed to overcome the deficiencies of the available risk estimators. Research have been done in novel directions; on ratios of routinely performing hematological and biochemical laboratory parameters such as Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR), and Aspartate aminotransferase to Alanine aminotransferase ratio (AST/ALT). The outcomes indicate a relationship between the above-said ratios and the risk for CVDs. 
 Conclusion: On such grounds, this review describes the importance of developing a CVD risk estimator by amalgamating some of the biochemical and hematological parameters, including NLR, PLR, and AST/ALT ratios, aiming to overcome the existing shortcomings.

One Endothelium-Targeted Combined Nucleic Acid Delivery System for Myocardial Infarction Therapy.

Acute myocardial infarction (MI) and ischemic heart disease are the leading causes of heart failure and mortality. Currently, research on MI treatment is focused on angiogenic and anti-inflammatory therapies. Although endothelial cells (ECs) are critical for triggering inflammation and angiogenesis, no approach has targeted them for the treatment of MI. In this study, we proposed a nonviral combined nucleic acid delivery system consisting of an EC-specific polycation (CRPPR-grafted ethanolamine-modified poly(glycidyl methacrylate), CPC) that can efficiently codeliver siR-ICAM1 and pCXCL12 for the treatment of MI. Animals treated with the combination therapy exhibited better cardiac function than those treated with each nucleic acid alone. In particular, the combination therapy of CPC/siR-ICAM1 and CPC/pCXCL12 significantly improved cardiac systolic function, anti-inflammatory responses, and angiogenesis compared to the control group. In conclusion, CPC-based combined gene delivery systems show impressive performance in the treatment of MI and provide a programmed strategy for the development of codelivery systems for various EC-related diseases.

The influence of left bundle branch block on myocardial T1 mapping

Tissue characterisation using T1 mapping has become an established magnetic resonance imaging (MRI) technique to detect myocardial diseases. This retrospective study aimed to determine the influence of left bundle branch block (LBBB) on T1 mapping at 1.5 T. Datasets of 36 patients with LBBB and 27 healthy controls with T1 mapping (Modified Look-Locker inversion-recovery (MOLLI), 5(3)3 sampling) were included. T1 relaxation times were determined on mid-cavity short-axis images. R2 maps were generated as a pixel-wise indicator for the goodness of the fit of T1 maps. R2 values were significantly lower in patients with LBBB than in healthy controls (whole myocardium/septum, 0.997, IQR, 0.00 vs. 0.998, IQR, 0.00; p = 0.008/0.998, IQR, 0.00 vs. 0.999, IQR, 0.00; p = 0.027). Manual correction of semi-automated evaluation tended to improve R2 values but not significantly. Strain analysis was performed and the systolic dyssynchrony index (SDIglobal) was calculated as a measure for left ventricular dyssynchrony. While MRI is generally prone to artefacts, lower goodness of the fit in LBBB may be mainly attributable to asynchronous contraction. Therefore, careful checking of the source data and, if necessary, manual post-processing is important. New techniques might improve the goodness of the fit of T1 mapping by reducing sampling in the motion prone diastole of LBBB patients.

Endomyocardial biopsy in clinical practice: the diagnostic yield and insights from a 5-year single-center experience

ObjectivesEndomyocardial biopsy (EMB) is a diagnostic tool for evaluating various cardiac conditions, such as myocarditis and myocardial infiltrative diseases. It is also the gold standard screening technique for detecting allograft rejection after heart transplantation. Despite advances in noninvasive imaging modalities for myocardial tissue characterization, EMB is still necessary for making a definitive diagnosis and determining treatment for certain conditions. Herein, we report our recent experience using EMB and its diagnostic yield. Methods and ResultsWe retrospectively reviewed EMBs performed at our institution from March 2018 through March 2023. Clinical data, including patient characteristics, indication and diagnostic yield of EMB, and procedure-related complications, were collected. Histopathological findings of the biopsies were recorded and classified based on the degree to which they matched the clinical diagnosis and cardiac magnetic resonance imaging (CMR) findings. A total of 212 EMBs obtained in 178 consecutive patients were retrospectively analyzed, with 42 biopsies performed for allograft rejection surveillance (10 patients) and the remaining performed for presumptive diagnosis of acute myocarditis or unexplained cardiomyopathy. Among the non-heart transplant cases, 54.7% of EMBs provided a clear diagnosis. The most common diagnosis was myocarditis (69%), followed by cardiac amyloidosis (CA) (26%). EMB was also helpful in detecting several rare cardiac conditions, such as eosinophilic granulomatosis with polyangiitis (EGPA), Fabry disease, and cardiac sarcoidosis. In a cohort of 101 patients who underwent both CMR and EMB, the results were concordant in 66% of cases. However, in 24.7% of patients, EMB was able to identify pathological conditions where CMR results were inconclusive, highlighting its complementary role in determining an accurate diagnosis. No complications were reported in any of the 212 EMBs performed. ConclusionsWith advances in cardiac imaging modalities, EMB is not routinely indicated for the diagnosis of cardiomyopathy. However, EMB is still an important tool for diagnosing specific cardiac diseases and could be crucial for confirming the diagnosis. EMB is generally safe if performed at experienced centers.

SwinUNet: a multiscale feature learning approach to cardiovascular magnetic resonance parametric mapping for myocardial tissue characterization.

Objective.Cardiovascular magnetic resonance (CMR) can measure T1 and T2 relaxation times for myocardial tissue characterization. However, the CMR procedure for T1/T2 parametric mapping is time-consuming, making it challenging to scan heart patients routinely in clinical practice. This study aims to accelerate CMR parametric mapping with deep learning.Approach. A deep-learning model, SwinUNet, was developed to accelerate T1/T2 mapping. SwinUNet used a convolutional UNet and a Swin transformer to form a hierarchical 3D computation structure, allowing for analyzing CMR images spatially and temporally with multiscale feature learning. A comparative study was conducted between SwinUNet and an existing deep-learning model, MyoMapNet, which only used temporal analysis for parametric mapping. The T1/T2 mapping performance was evaluated globally using mean absolute error (MAE) and structural similarity index measure (SSIM). The clinical T1/T2 indices for characterizing the left-ventricle myocardial walls were also calculated and evaluated using correlation and Bland-Altman analysis.Main results. We performed accelerated T1 mapping with ≤4 heartbeats and T2 mapping with 2 heartbeats in reference to the clinical standard, which required 11 heartbeats for T1 mapping and 3 heartbeats for T2 mapping. SwinUNet performed well in all the experiments (MAE < 50 ms, SSIM > 0.8, correlation > 0.75, and Bland-Altman agreement limits < 100 ms for T1 mapping; MAE < 1 ms, SSIM > 0.9, correlation > 0.95, and Bland-Altman agreement limits < 1.5 ms for T2 mapping). When the maximal acceleration was used (2 heartbeats), SwinUNet outperformed MyoMapNet and gave measurement accuracy similar to the clinical standard.Significance. SwinUNet offers an optimal solution to CMR parametric mapping for assessing myocardial diseases quantitatively in clinical cardiology.

New mechanisms: From lactate to lactylation to rescue heart failure.

Lactylation of α-myosin heavy chain (α-MHC) has recently been reported to preserve sarcomeric structure and function and attenuate the development of heart failure. Specifically, lactylation enhanced the interaction of α-MHC with the sarcomeric protein Titin, thereby maintaining normal sarcomeric structure and myocardial contractile function. Furthermore, the administration of lactate or inhibition of lactate efflux potentially treats heart failure by restoring lactylation of α-MHC and the interaction of α-MHC with Titin. This finding highlights the significant role of α-MHC lactylation in myocardial diseases and presents a new therapeutic target for the treatment of heart failure.

Sudden Death Due to Concurrent Arrhythmogenic Cardiomyopathy and Myocarditis: An Autopsy Case

Arrhythmogenic cardiomyopathy (ACM) is a rare genetically determined myocardial disease characterized by fibrofatty substitution of the myocardium which predisposes the patient to sudden cardiac death (SCD). In addition to the classic pathology seen in ACM, inflammatory infiltrates have been occasionally reported, suggesting a close pathophysiological relationship between ACM and inflammation. Evidence indicates that this inflammation is related to electrical instability resulting in ventricular tachycardia and SCD. This is an autopsy case of a 52-year-old female who died suddenly of concomitant ACM and myocarditis, fulfilling both histological and immunohistochemical diagnostic criteria. With the features of fatty variant ACM, the inflammatory infiltrate was prominent in the subendocardial layer of the left ventricle and was composed of mostly CD3-positive lymphocytes as well as some neutrophils and macrophages. In forensic practice, this case highlights the necessity of collecting multiple representative portions of cardiac tissue to search for inflammation, which can easily explain the cause of death and the dying process in ACM.

Evaluation of Electrocardiogram Parameters and Heart Rate Variability During Blood Pressure Elevation by Phenylephrine in Cirrhotic Rats.

Cirrhotic cardiomyopathy is a myocardial disease that may go undetected in the early stages due to peripheral vasodilatation. The aim of the study was to evaluate the electrocardiogram (ECG) and heart rate variability (HRV) after raising blood pressure by phenylephrine injection in rats with liver cirrhosis. Twenty male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 44days, animals were anesthetized and the right femoral artery and vein catheterized. After a steady-state period, a bolus injection of phenylephrine (PHE, 10μg/μl/IV, baroreflex maneuver) was followed by a slow injection of PHE (100μg/ml/5min/IV, sustained maneuver). Rapid and slow injections of PHE resulted in a greater increase in mean arterial pressure (MAP) and a weaker bradycardia response in the CBDL group than in the Sham group. ECG analysis showed increased QT, QTc, JT, and T peak to T end in the CBDL group, which remained unchanged after PHE injection. On the other hand, the parasympathetic indices of the HF band and RMSSD, and the sympathetic index of the LF band after PHE injection were lower in the CBDL group than in the Sham group.ECG data indicated prolonged ventricular depolarization and repolarization, independent of blood pressure levels in cirrhosis. On the other hand, after PHE injection, the parasympathetic and sympathetic components of HRV decreased, regardless of the duration of elevated blood pressure. We suggest that HRV analysis can provide a useful approach to assess cardiac dysfunction associated with elevated blood pressure in cirrhosis.

Analysis of genetic variant associated with heart failure mortality implicates thymic stromal lymphopoietin as mediator of strain-induced myocardial fibroblast-mast cell crosstalk and fibrosis.

Heart failure (HF) is a leading cause of death and disability globally. Heritable factors and the extent and pattern of myocardial fibrosis are important determinants of outcomes in patients with HF. In a genome-wide association study of mortality in HF, we recently identified a genetic polymorphism on chromosome 5q22 associated with HF mortality. Here, we sought to study the mechanisms by which this variant may influence myocardial disease processes. We find that the risk allele is located in an enhancer motif upstream of the TSLP gene (encoding thymic stromal lymphopoietin), conferring increased binding of the transcription factor nescient helix-loop helix 1 (NHLH1) and increased TSLP expression in human heart. Further, we find that increased strain of primary human myocardial fibroblasts results in increased TSLP expression and that the TSLP receptor is expressed in myocardial mast cells in human single nuclei RNA sequence data. Finally, we show that TSLP overexpression induces increased transforming growth factor β expression in myocardial mast cells and tissue fibrosis. Collectively, our findings based on follow-up of a human genetic finding implicate a novel pathway in myocardial tissue homeostasis and remodeling.

Myocarditis in children.Etiology. Pathogenesis. Epidemiology. Clinical presentation

Readers will be presented with a series of articles on myocarditis in children, which are based on clinical guidelines developed by a group of authors on this topic. Myocarditis is an inflammatory myocardial disease characterized by a wide range of clinical manifestations — from minor to sudden cardiac death. Given the absence of pathognomonic symptoms, as well as the similarity of manifestations in the onset with common childhood diseases such as respiratory distress, gastrointestinal diseases, infectious pathology, specialists often overlook the likelihood of a diagnosis of “myocarditis”, which causes a late start of therapy and an adverse outcome. Considering that myocarditis accounts for 12% of cases of sudden cardiac death in adolescents and young adults, suspicion of this disease in differential diagnosis in children with nonspecific symptoms and disease progression may be the key to the formation of a proper treatment strategy. Despite significant advances in the study of myocarditis in both adults and children, there are still many unresolved issues. The purpose of this article is to highlight the current view of the etiology, pathogenesis, epidemiology and clinical features in children with various types of myocarditis in order to increase the knowledge of practitioners for better clinical management of patients with myocarditis.

Assessment of left ventricular dysfunction by strain echo in primary hyperparathyroidism and its reversal after parathyroidectomy.

Strain echocardiography is a highly sensitive modality for detecting myocardial disease at an early stage. Therefore, we aim to evaluate subclinical left ventricular dysfunction in primary hyperparathyroidism (PHPT) patients with myocardial strain imaging in addition to conventional echocardiography and to look for its reversal after parathyroidectomy (PTx). Thirty patients who underwent curative parathyroidectomy for PHPT were included. All patients were evaluated with M mode echo, 2D echo and strain imaging before and 6months after PTx. Left ventricular ejection fraction, left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH), Global Longitudinal Strain (GLS) and global circumferential strain (GCS) were recorded. On M mode echo, LVH was present in 15 patients and 8 of them improved completely after PTx (p<0.038). Incidence of systolic and diastolic dysfunction on 2D echo was 10% and 13.3% respectively; while myocardial strain imaging showed impaired systolic function in 46.7% patients. Hence, compared to conventional 2D echo, strain imaging showed 36.7% high detection rate of subnormal cardiac function. There was improvement in left ventricle dysfunction (p = 0.083), GLS and GCS (p = 0.034) after PTx. Serum parathormone demonstrated a strong positive correlation with change in GLS and GCS (p = 0.013, p = 0.126) while serum calcium showed a weak correlation with change in GLS and GCS following surgery. Myocardial strain imaging should be considered for all PHPT patients as early identification of subclinical ventricle dysfunction provides an opportunity for an early intervention and thereby preventing development of irreversible LV dysfunction.

HIV, HIV-Specific Factors, and Myocardial Disease in Women.

People with human immunodeficiency virus (HIV) (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation, and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men. We investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (fibrosis), and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers. Among 261 women with HIV (WWH, N = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 69.4% failed to achieve persistent viral suppression (40.7% with peak viral load <200 cp/mL). Overall, WWH showed higher nT1 than women without HIV after full adjustment. This higher nT1 was more pronounced in those with antecedent or current viremia or nadir CD4+ count <200 cells/μL, with the latter also associated with higher extracellular volume fraction. WWH and current CD4+ count <200 cells/μL had less cardiomyocyte steatosis. Cumulative exposure to specific ART showed no associations. Compared with sociodemographically similar women without HIV, WWH on ART exhibit higher myocardial fibro-inflammation, which is more prominent with unsuppressed viremia or CD4+ lymphopenia. These findings support the importance of improved ART adherence strategies, along with better understanding of latent infection, to mitigate cardiac end-organ damage in this population.

Distinct cytoskeletal regulators of mechanical memory in cardiac fibroblasts and cardiomyocytes.

Recognizing that cells "feel" and respond to their mechanical environment, recent studies demonstrate that many cells exhibit a phenomenon of "mechanical memory" in which features induced by prior mechanical cues persist after the mechanical stimulus has ceased. While there is a general recognition that different cell types exhibit different responses to changes in extracellular matrix stiffening, the phenomenon of mechanical memory within myocardial cell types has received little attention to date. To probe the dynamics of mechanical memory in cardiac fibroblasts (CFs) and cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs), we employed a magnetorheological elastomer (MRE) cell culture substrate with tunable and reversible stiffness spanning the range from normal to diseased myocardium. In CFs, using increased cell area and increases in α-smooth muscle actin as markers of cellular responses to matrix stiffening, we found that induction of mechanical memory required seven days of stiff priming. Both induction and maintenance of persistent CF activation were blocked with the F-actin inhibitor cytochalasin D, while inhibitors of microtubule detyrosination had no impact on CFs. In iPSC-CMs, mechanical memory was invoked after only 24h of stiff priming. Moreover, mechanical memory induction and maintenance were microtubule-dependent in CMs with no dependence on F-actin. Overall, these results identify the distinct temporal dynamics of mechanical memory in CFs and iPSC-CMs with different cytoskeletal mediators responsible for inducing and maintaining the stiffness-activated phenotype. Due to its flexibility, this model is broadly applicable to future studies interrogating mechanotransduction and mechanical memory in the heart and might inform strategies for attenuating the impact of load-induced pathology and excess myocardial stiffness.

Noninvasive Prediction of Pulmonary Capillary Wedge Pressure in Patients With Normal Left Ventricular Ejection Fraction: Comparison of Cardiac Magnetic Resonance With Comprehensive Echocardiography

Cardiac magnetic resonance (CMR) was recently reported to predict mean pulmonary capillary wedge pressure (PCWP). However, there is a paucity of data on its accuracy for estimation of PCWP in patients with normal left ventricular (LV) ejection fraction (EF). We sought to examine its accuracy against the invasive gold standard and to compare it with the accuracy of comprehensive echocardiography. Stable patients with EF of ≥50% who underwent right heart catheterization, CMR, and echocardiographic imaging within 1week were included. Pulmonary capillary wedge pressure was estimated by CMR using a previously validated equation where PCWP is estimated based on the left atrial maximum volume and LV mass. Echocardiographic estimation of PCWP was based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines, taking into account the presence of myocardial disease. The mean age of the 79 patients was 55±15years, and 58.2% were female. There were 33 patients with PCWP >15mm Hg by right heart catheterization. Cardiac magnetic resonance prediction of PCWP had an area under the curve (AUC)=0.72. In comparison, echocardiographic prediction of PCWP showed a higher accuracy (AUC=0.87 vs AUC=0.72; P=.008). In patients with normal LV EF, CMR estimation of mean PCWP based on LV mass and left atrial volume has modest accuracy for detecting patients with mean PCWP >15mm Hg. Comprehensive echocardiography predicts elevated PCWP with higher accuracy in comparison with CMR.

Cardiac MRI in diagnosis, prognosis, and follow-up of hypertrophic cardiomyopathy in children: current perspectives.

Hypertrophic Cardiomyopathy (HCM) is an inherited myocardial disease characterised by left ventricular hypertrophy, which carries an increased risk of life-threatening arrhythmias and sudden cardiac death. The age of presentation and the underlying aetiology have a significant impact on the prognosis and quality of life of children with HCM, as childhood-onset HCM is associated with high mortality risk and poor long-term outcomes. Accurate cardiac assessment and identification of the HCM phenotype are therefore crucial to determine the diagnosis, prognostic stratification, and follow-up. Cardiac magnetic resonance (CMR) is a comprehensive evaluation tool capable of providing information on cardiac morphology and function, flow, perfusion, and tissue characterisation. CMR allows to detect subtle abnormalities in the myocardial composition and characterise the heterogeneous phenotypic expression of HCM. In particular, the detection of the degree and extent of myocardial fibrosis, using late-gadolinium enhanced sequences or parametric mapping, is unique for CMR and is of additional value in the clinical assessment and prognostic stratification of paediatric HCM patients. Additionally, childhood HCM can be progressive over time. The rate, timing, and degree of disease progression vary from one patient to the other, so close cardiac monitoring and serial follow-up throughout the life of the diagnosed patients is of paramount importance. In this review, an update of the use of CMR in childhood HCM is provided, focussing on its clinical role in diagnosis, prognosis, and serial follow-up.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

Hybrid Magnetic Resonance Positron Emission Tomography Is Associated With Cardiac-Related Outcomes in Cardiac Sarcoidosis

BackgroundImaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18F-fluorodeoxyglucose (18F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+). ObjectivesThis study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes. MethodsA total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR−), presence/absence of 18F-FDG (PET+/PET−), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(−), MR(−)PET(+)FOCAL, MR(−)PET(+)DIFFUSE, MR(−)PET(−). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/−)5.7%. Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints. ResultsPatients designated MR(+)5.7%PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL, and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint. ConclusionsHybrid MR/PET image–based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image–based classification may have use in prognostication and treatment management in CS.

Construction of A Prediction Model for Atrial Fibrillation in Patients with Dilated Cardiomyopathy and Heart Failure

Dilated cardiomyopathy (DCM) is a common myocardial disease characterized by enlargement of the heart cavity and decreased systolic function, often leading to heart failure (HF) and arrhythmia. The occurrence of atrial fibrillation (AF) is closely related to the progression and prognosis of the disease. In recent years, with the advancement of medical imaging and biomarkers, models for predicting the occurrence of AF in DCM patients have gradually become a research hotspot. This article aims to review the current situation of AF in DCM patients and explore the importance and possible methods of constructing predictive models to provide reference for clinical prevention and treatment. We comprehensively analyzed the risk factors for AF in DCM patients from epidemiological data, pathophysiological mechanisms, clinical and laboratory indicators, electrocardiogram and imaging parameters, and biomarkers, and evaluated the effectiveness of existing predictive models. Through analysis of existing literature and research, this article proposes a predictive model that integrates multiple parameters to improve the accuracy of predicting AF in DCM patients and provide a scientific basis for personalized treatment.