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Cellular and Molecular Life Sciences :... Jul 2021Dystrophin is a large protein serving as local scaffolding repetitively bridging cytoskeleton and the outside of striated muscle cell. As such dystrophin is a critical... (Review)
Review
Dystrophin is a large protein serving as local scaffolding repetitively bridging cytoskeleton and the outside of striated muscle cell. As such dystrophin is a critical brick primarily in dystrophin-associated protein complex (DAGC) and in a larger submembranous unit, costamere. Accordingly, the lack of functional dystrophin laying at the root of Duchenne muscular dystrophy (DMD) drives sarcolemma instability. From this point on, the cascade inevitably leading to the death of myocyte begins. In cardiomyocytes, intracellular calcium overload and related mitochondrial-mediated cell death mainly contribute to myocardial dysfunction and dilation while other protein dysregulation and/or mislocalization may affect electrical conduction system and favor arrhythmogenesis. Although clinically DMD manifests as progressive muscle weakness and skeletal muscle symptoms define characteristic of DMD, it is the heart problem the biggest challenge that most often develop in the form of dilated cardiomyopathy (DCM). Current standards of treatment and recent progress in respiratory care, introduced in most settings in the 1990s, have improved quality of life and median life expectancy to 4th decade of patient's age. At the same time, cardiac causes of death related to DMD increases. Despite preventive and palliative cardiac treatments available, the prognoses remain poor. Direct therapeutic targeting of dystrophin deficiency is critical, however, hindered by the large size of the dystrophin cDNA and/or stochastic, often extensive genetic changes in DMD gene. The correlation between cardiac involvement and mutations affecting specific dystrophin isoforms, may provide a mutation-specific cardiac management and novel therapeutic approaches for patients with CM. Nonetheless, the successful cardiac treatment poses a big challenge and may require combined therapy to combat dystrophin deficiency and its after-effects (critical in DMD pathogenesis). This review locates the multifaceted heart problem in the course of DMD, balancing the insights into basic science, translational efforts and clinical manifestation of dystrophic heart disease.
Topics: Animals; Arrhythmias, Cardiac; Cardiomyopathies; Dystrophin; Humans; Muscular Dystrophy, Duchenne
PubMed: 34091693
DOI: 10.1007/s00018-021-03862-2 -
Frontiers in Cell and Developmental... 2022Atherosclerosis is a chronic artery disease characterized by plaque formation and vascular inflammation, eventually leading to myocardial infarction and stroke. Innate... (Review)
Review
Atherosclerosis is a chronic artery disease characterized by plaque formation and vascular inflammation, eventually leading to myocardial infarction and stroke. Innate immunity plays an irreplaceable role in the vascular inflammatory response triggered by chronic infection. Periodontitis is a common chronic disorder that involves oral microbe-related inflammatory bone loss and local destruction of the periodontal ligament and is a risk factor for atherosclerosis. Periodontal pathogens contain numerous pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide, CpG DNA, and Peptidoglycan, that initiate the inflammatory response of the innate immunity depending on the recognition of pattern-recognition receptors (PRRs) of host cells. The immune-inflammatory response and destruction of the periodontal tissue will produce a large number of damage-associated molecular patterns (DAMPs) such as neutrophil extracellular traps (NETs), high mobility group box 1 (HMGB1), alarmins (S100 protein), and which can further affect the progression of atherosclerosis. Molecular patterns have recently become the therapeutic targets for inflammatory disease, including blocking the interaction between molecular patterns and PRRs and controlling the related signal transduction pathway. This review summarized the research progress of some representative PAMPs and DAMPs as the molecular pathological mechanism bridging periodontitis and atherosclerosis. We also discussed possible ways to prevent serious cardiovascular events in patients with periodontitis and atherosclerosis by targeting molecular patterns.
PubMed: 35281098
DOI: 10.3389/fcell.2022.856118 -
Polish Journal of Radiology 2019To test the hypothesis that the prevalence of myocardial bridging varies between ethnic groups, and that the segment proximal to the myocardial bridge is more prone to...
PURPOSE
To test the hypothesis that the prevalence of myocardial bridging varies between ethnic groups, and that the segment proximal to the myocardial bridge is more prone to plaque formation.
MATERIAL AND METHODS
A total of 4500 patients who had undergone computerised tomography (CT) coronary angiography at our institute were studied for myocardial bridging. Data on the clinical profile and indication for CT coronary angiography in myocardial bridging were collected. Patients with and without proximal disease were compared using the chi-square test for ordinal variables and Student's t-test for continuous variables. The length to depth ratio (RA-MA ratio) of the bridged segment was determined.
RESULTS
The prevalence of atherosclerotic plaques in the segment proximal to the bridged segment was 37.8%, which was lower than the prevalence of 48.7% for plaques in the corresponding segments among patients without myocardial bridging. The average length of the bridged segment was 15.5 ± 5 mm, and that for patients with and without proximal plaques was 13 ± 4 and 16 ± 6 mm ( = 0.1), respectively. Similarly, the average depth of the segments with and without proximal plaques was 1.8 ± 0.6 mm and 1.4 ± 0.5 mm ( = 0.06), respectively. Only the RA-MA ratio (8 ± 3 vs. 13 ± 6, = 0.01) was significantly lower in patients with atherosclerotic plaques.
CONCLUSIONS
The prevalence in our study population was 10%, with mid left anterior descending artery (LAD) being the most common segment involved. Moreover, the prevalence and distribution of coronary plaques in LAD were similar in patients with and without myocardial bridging.
PubMed: 32082443
DOI: 10.5114/pjr.2019.90370 -
The American Journal of Cardiology Feb 2023Myocardial bridging (MB) is a congenital variant in which a segment of a coronary artery follows an atypical intramural course under a "bridge" of myocardium and is... (Meta-Analysis)
Meta-Analysis
Myocardial bridging (MB) is a congenital variant in which a segment of a coronary artery follows an atypical intramural course under a "bridge" of myocardium and is notably common in hypertrophic cardiomyopathy (HCM). This systematic review and meta-analysis explored the clinical consequences of MB in patients with HCM. A total of 3 outcome domains were investigated: cardiovascular mortality, nonfatal adverse cardiac events, and investigative indicators of myocardial ischemia. A meta-analysis was performed on 10 observational studies comparing outcomes in patients with HCM with and without MB. Studies were identified through a systematic search of 4 databases (PubMed, Scopus, Medline Complete, and Web of Science). The quality of the studies was assessed using a modified version of the Downs and Black tool, from which studies could score a maximum of 23 points. The mean score was 17.5 ± 1.3 (good). The meta-analysis showed that MB was not associated with cardiovascular mortality (odds ratio [OR] 1.70, 95% confidence interval [CI] 0.56 to 5.15, p = 0.35) or nonfatal adverse cardiac events (OR 1.80, 95% CI 0.98 to 3.28, p = 0.06) but was associated with myocardial ischemia (OR 1.89, 95% CI 1.03 to 3.44, p = 0.04). In conclusion, the potential prognostic implications of MB in HCM, especially in those with hemodynamically significant bridges and/or severe underlying disease, should not be ignored. The focus of future studies should be to establish functional and morphologic thresholds, by which MB may adversely influence prognosis by corroborating imaging findings with clinical outcome data.
Topics: Humans; Myocardial Bridging; Cardiomyopathy, Hypertrophic; Myocardium; Myocardial Ischemia
PubMed: 36512852
DOI: 10.1016/j.amjcard.2022.10.059 -
BMC Cardiovascular Disorders Mar 2023The fat attenuation index (FAI) is a radiological parameter that represents pericoronary adipose tissue (PCAT) inflammation, along with myocardial bridging (MB), which...
BACKGROUND
The fat attenuation index (FAI) is a radiological parameter that represents pericoronary adipose tissue (PCAT) inflammation, along with myocardial bridging (MB), which leads to pathological shear stress in the coronary vessels; both are associated with coronary atherosclerosis. In the present study, we assessed the predictive value of FAI values and MB parameters through coronary computed tomography angiography (CCTA) for predicting the risk of coronary atherosclerosis and vulnerable plaque in patients with MB.
METHODS
We included 428 patients who underwent CCTA and were diagnosed with MB. FAI values, MB parameters, and high-risk coronary plaque (HRP) characteristics were recorded. The subjects were classified into two groups (A and B) according to the absence or presence of coronary plaque in the segment proximal to the MB. Group B was further divided into Groups B (HRP-positive) and B (HRP-negative) according to the HRP characteristic classification method. The differences among the groups were analysed. Multiple logistic regression analysis was performed to determine the independent correlation between FAI values and MB parameters and coronary atherosclerosis and vulnerable plaque risk.
RESULTS
Compared to the subjects in Group A, those in Group B presented greater MB lengths, MB depths and muscle index values, more severe MB systolic stenosis and higher FAI values (all P < 0.05). In multivariate logistic analysis, age (OR 1.076, P < 0.001), MB systolic stenosis (OR 1.102, P < 0.001) and FAI values (OR 1.502, P < 0.001) were independent risk factors for the occurrence of coronary atherosclerosis. Compared to subjects in Group B, those in Group B presented greater MB lengths and higher FAI values (both P < 0.05). However, only the FAI value was an independent factor for predicting HRP (OR 1.641, P < 0.001).
CONCLUSION
In patients with MB, MB systolic stenosis was associated with coronary plaque occurrence in the segment proximal to the MB. The FAI value was not only closely related to coronary atherosclerosis occurrence but also associated with plaque vulnerability. FAI values may provide more significant value in the prediction of coronary atherosclerosis than MB parameters in CCTA.
Topics: Humans; Coronary Artery Disease; Computed Tomography Angiography; Constriction, Pathologic; Myocardial Bridging; Coronary Angiography; Plaque, Atherosclerotic; Adipose Tissue; Coronary Vessels; Predictive Value of Tests
PubMed: 36949394
DOI: 10.1186/s12872-023-03146-6 -
European Journal of Medical Research Nov 2023Myocardial bridges are congenital coronary artery anomalies. There are still many controversies surrounding surgical treatment strategies for myocardial bridges combined...
BACKGROUND
Myocardial bridges are congenital coronary artery anomalies. There are still many controversies surrounding surgical treatment strategies for myocardial bridges combined with other heart disorders. The purpose of this study was to evaluate the surgical treatment strategies and outcomes in patients with these conditions.
METHODS
Between March 2004 and October 2021, our institution witnessed 77 patients diagnosed with myocardial bridging who underwent surgical intervention. According to the myocardial bridge and combined heart disorder, four groups were identified: 1. isolated LAD supra-arterial myotomy group, 2. LAD CABG and(or not) myotomy group, 3. LAD supra-arterial myotomy and grafting of other branches group, and 4. LAD supra-arterial myotomy and other cardiac surgery group. The perioperative outcomes, symptoms, life quality, mortality, and major adverse cardiac events (MACEs) were analyzed.
RESULTS
There were no deaths during hospitalization and no rethoractomy for postoperative bleeding or major adverse cardiac events (MACEs). The follow-up period ranged from 2 months to 199.2 months (55.61 ± 10.21) months, the 10-year cumulative survival rates for the four groups of patients were 95.0%, 100%, 100% and 74.1%, and the 10-year freedom rates from the MACEs were 83.9%, 92.0%, 87.5% and 76.2%, respectively.
CONCLUSIONS
Supra-arterial myotomy is preferred in patients with isolated myocardial bridge, and acceptable results can be achieved by choosing supra-arterial myotomy in combination with CABG or other cardiac surgery simultaneously for patients with myocardial bridges and other heart disorders.
Topics: Humans; Coronary Artery Bypass; Coronary Artery Disease; Cardiac Surgical Procedures; Myocardium; Arteries
PubMed: 37936191
DOI: 10.1186/s40001-023-01478-9 -
Scientific Reports Mar 2022In-vivo estimation of mechanical properties of the myocardium is essential for patient-specific diagnosis and prognosis of cardiac disease involving myocardial...
In-vivo estimation of mechanical properties of the myocardium is essential for patient-specific diagnosis and prognosis of cardiac disease involving myocardial remodeling, including myocardial infarction and heart failure with preserved ejection fraction. Current approaches use time-consuming finite-element (FE) inverse methods that involve reconstructing and meshing the heart geometry, imposing measured loading, and conducting computationally expensive iterative FE simulations. In this paper, we propose a machine learning (ML) model that feasibly and accurately predicts passive myocardial properties directly from select geometric, architectural, and hemodynamic measures, thus bypassing exhaustive steps commonly required in cardiac FE inverse problems. Geometric and fiber-orientation features were chosen to be readily obtainable from standard cardiac imaging protocols. The end-diastolic pressure-volume relationship (EDPVR), which can be obtained using a single-point pressure-volume measurement, was used as a hemodynamic (loading) feature. A comprehensive ML training dataset in the geometry-architecture-loading space was generated, including a wide variety of partially synthesized rodent heart geometry and myofiber helicity possibilities, and a broad range of EDPVRs obtained using forward FE simulations. Latin hypercube sampling was used to create 2500 examples for training, validation, and testing. A multi-layer feed-forward neural network (MFNN) was used as a deep learning agent to train the ML model. The model showed excellent performance in predicting stiffness parameters [Formula: see text] and [Formula: see text] associated with fiber direction ([Formula: see text] and [Formula: see text]). After conducting permutation feature importance analysis, the ML performance further improved for [Formula: see text] ([Formula: see text]), and the left ventricular volume and endocardial area were found to be the most critical geometric features for accurate predictions. The ML model predictions were evaluated further in two cases: (i) rat-specific stiffness data measured using ex-vivo mechanical testing, and (ii) patient-specific estimation using FE inverse modeling. Excellent agreements with ML predictions were found for both cases. The trained ML model offers a feasible technology to estimate patient-specific myocardial properties, thus, bridging the gap between EDPVR, as a confounded organ-level metric for tissue stiffness, and intrinsic tissue-level properties. These properties provide incremental information relative to traditional organ-level indices for cardiac function, improving the clinical assessment and prognosis of cardiac diseases.
Topics: Animals; Heart; Heart Failure; Heart Ventricles; Humans; Machine Learning; Myocardium; Rats
PubMed: 35361836
DOI: 10.1038/s41598-022-09128-6 -
BMC Cardiovascular Disorders Apr 2021Myocardial bridging is a congenital anomaly defined as a segment of epicardial coronary arteries running through the myocardium. Various complications related to...
BACKGROUND
Myocardial bridging is a congenital anomaly defined as a segment of epicardial coronary arteries running through the myocardium. Various complications related to myocardial bridging have been reported, but at present, cardiac arrest has rarely been reported.
CASE PRESENTATION
We report one case of a patient who was successfully resuscitated from ventricular fibrillation cardiac arrest and was diagnosed with myocardial bridging accompanied by myocardial ischaemia. A 50-year-old woman who had been resuscitated from cardiac arrest transferred to our institution for evaluation and management of out-of-hospital cardiac arrest. We confirmed the diagnosis of significant myocardial bridging with evident myocardial ischaemia by coronary angiography, resting echocardiography and heart MRI. Vasospasm was thought to be a trigger factor judging from the transient ST elevation on electrocardiography. In addition, the finding of septal buckling was detected for the first time throughout the whole cardiac cycle by resting echocardiography in MB.
CONCLUSION
We report a rare case of survival after out-of-hospital cardiac arrest that might be caused by significant myocardial bridging-induced myocardial ischaemia, which was objectively confirmed by echocardiography and heart MRI. Although myocardial bridging is often overlooked as an aetiology for sudden cardiac death, this case highlights the importance of expanding the differential diagnosis to myocardial bridging in the work-up for the cause of sudden cardiac death.
Topics: Coronary Angiography; Diagnosis, Differential; Echocardiography; Electrocardiography; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Myocardial Bridging; Myocardial Ischemia; Out-of-Hospital Cardiac Arrest; Predictive Value of Tests; Resuscitation; Treatment Outcome; Ventricular Fibrillation
PubMed: 33853525
DOI: 10.1186/s12872-021-01975-x -
Herz Oct 2023Myocardial bridging (MB) and hypertrophic cardiomyopathy (HCM) are associated with the risk of fatal ventricular arrhythmias (VAs). The goal of the study was to...
BACKGROUND
Myocardial bridging (MB) and hypertrophic cardiomyopathy (HCM) are associated with the risk of fatal ventricular arrhythmias (VAs). The goal of the study was to determine the relationship between MB and fatal VAs in HCM patients with implantable cardiac defibrillators (ICD).
METHODS
A total of 108 HCM patients (mean age: 46.6 ± 13.6 years; male: 73) were enrolled in this retrospective study. All patients underwent transthoracic echocardiography and coronary computed tomography angiography. Fatal VAs including sustained ventricular tachycardia and ventricular fibrillation were documented in ICD records.
RESULTS
There were documented fatal VAs in 29 (26.8%) patients during a mean follow-up time of 71.3 ± 30.9 months. Compared with the other groups, the fatal VA group had a higher incidence of the following: presence of MB (82.8 vs. 38%, p < 0.001), deep MB (62.1 vs. 6.3%, p < 0.001), very deep MB (24.1 vs. 0%, p < 0.001), long MB (65.5 vs. 11.4%, p < 0.001), presence of > 1 MB (17.2 vs. 0%, p = 0.001), and MB of the left anterior descending artery (79.3 vs. 17.7%, p < 0.001) . Sudden cardiac death (SCD) risk score (hazard ratio: 1.194; 95% CI: 1.071-1.330; p = 0.001) and presence of MB (hazard ratio: 3.815; 95% CI: 1.41-10.284; p = 0.008) were found to be independent predictors of fatal VAs in HCM patients.
CONCLUSIONS
The current data suggest that the SCD risk score and presence of MB were independent risk factors for fatal VAs in patients with HCM. In addition to conventional risk factors, the coronary anatomical course can provide clinicians with valuable information when assessing the risk of fatal VAs in HCM patients.
Topics: Humans; Male; Adult; Middle Aged; Retrospective Studies; Myocardial Bridging; Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic; Tachycardia, Ventricular; Risk Factors; Death, Sudden, Cardiac; Defibrillators, Implantable
PubMed: 37081129
DOI: 10.1007/s00059-023-05171-9 -
Reviews in Cardiovascular Medicine Dec 2019The objective of this study was to explore the effects of myocardial bridge compression on blood flow, normal stress, circumferential stress and shear stress in mural...
The objective of this study was to explore the effects of myocardial bridge compression on blood flow, normal stress, circumferential stress and shear stress in mural coronary artery. An original mural coronary artery simulative device has been greatly improved and its measured hemodynamic parameters have been expanded from a single stress (normal stress) to multiple stresses to more fully and accurately simulate the true hemodynamic environment under normal stress, circumferential stress and shear stress. This device was used to more fully explore the relationship between hemodynamics and mural coronary atherosclerosis under the combined effects of multiple stresses. Results obtained from the mural coronary artery simulator showed stress abnormality to be mainly located in the proximal mural coronary artery where myocardial bridge compression was intensified and average and fluctuation values (maximum minus minimum) of proximal stress were significantly increased by 27.8% and 139%, respectively. It is concluded that myocardial bridge compression causes abnormalities in the proximal hemodynamics of the mural coronary artery. This is of great significance for understanding the hemodynamic mechanism of coronary atherosclerosis and has potential clinical value for the pathological effect and treatment of myocardial bridge.
Topics: Computer Simulation; Coronary Circulation; Coronary Vessels; Hemodynamics; Humans; Models, Anatomic; Models, Cardiovascular; Myocardial Bridging; Stress, Mechanical
PubMed: 31912719
DOI: 10.31083/j.rcm.2019.04.554