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BMJ (Clinical Research Ed.) Jun 2024
Topics: Humans; Death, Sudden, Cardiac; Risk Assessment; Death, Sudden; Risk Factors
PubMed: 38936846
DOI: 10.1136/bmj.q1396 -
ACS Applied Materials & Interfaces Jun 2024Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle...
Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle loses strength for contraction, producing arrhythmias and fainting, and entails a high risk of sudden death. Permanent implantable conductive hydrogels that can restore contraction strength and conductivity appear to be promising candidates for myocardium functional recovery. In this work, we present a printable cardiac hydrogel that can exert functional effects on networks of cardiac myocytes. The hydrogel matrix was designed from poly(vinyl alcohol) (PVA) dynamically cross-linked with gallic acid (GA) and the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The resulting patches exhibited excellent electrical conductivity, elasticity, and mechanical and contractile strengths, which are critical parameters for reinforcing weakened cardiac contraction and impulse propagation. Furthermore, the PVA-GA/PEDOT blend is suitable for direct ink writing via a melting extrusion. As a proof of concept, we have proven the efficiency of the patches in propagating the electrical signal in adult mouse cardiomyocytes through recordings of intracellular Ca transients during cell stimulation. Finally, the patches were implanted in healthy mouse hearts to demonstrate their accommodation and biocompatibility. Magnetic resonance imaging revealed that the implants did not affect the essential functional parameters after 2 weeks, thus showing great potential for treating cardiomyopathies.
PubMed: 38936818
DOI: 10.1021/acsami.4c03784 -
Heart Rhythm Jun 2024Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic...
BACKGROUND
Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood.
OBJECTIVES
We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression.
METHODS
Following exposure to 20Gy of X-rays in a single fraction, neonatal rat ventricular cardiomyocytes (NRVCs) were analyzed 24 and 96h post-radiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration (APD) in both monolayers and single cells. Additionally, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and mRNA levels.
RESULTS
Following irradiation with 20Gy, NRVCs exhibited increased beat rate and conduction velocities 24 and 96h after treatment. mRNA and protein levels of ion channels were altered, with the most significant changes observed at the 96h-mark. Upregulation of Cacna1c (Ca1.2), Kcnd3 (K4.3), Kcnh2 (K11.1), Kcnq1 (K7.1), Kcnk2 (K2.1), Kcnj2 (K2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 (RYR2) and Slc8a1 (NCX) expression and altered properties 96h post-treatment. Fibroblast and myofibroblast levels remained unchanged.
CONCLUSIONS
CSBRT modulates expression of various ion channels, calcium handling proteins, and gap-junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed following cSBRT.
PubMed: 38936449
DOI: 10.1016/j.hrthm.2024.06.043 -
JACC. Clinical Electrophysiology Jun 2024Ventricular tachycardia (VT), which can lead to sudden cardiac death, occurs frequently in patients after myocardial infarction. Radiofrequency catheter ablation (RFA)...
BACKGROUND
Ventricular tachycardia (VT), which can lead to sudden cardiac death, occurs frequently in patients after myocardial infarction. Radiofrequency catheter ablation (RFA) is a modestly effective treatment of VT, but it has limitations and risks. Cardiac magnetic resonance (CMR)-based heart digital twins have emerged as a useful tool for identifying VT circuits for RFA treatment planning. However, the CMR resolution used to reconstruct these digital twins may impact VT circuit predictions, leading to incorrect RFA treatment planning.
OBJECTIVES
This study sought to predict RFA targets in the arrhythmogenic substrate using heart digital twins reconstructed from both clinical and high-resolution 2-dimensional CMR datasets and compare the predictions.
METHODS
High-resolution (1.35 × 1.35 × 3 mm), or oversampled resolution (Ov-Res), short-axis late gadolinium-enhanced CMR was acquired by combining 2 subsequent clinical resolution (Clin-Res) (1.35 × 1.35 × 6 mm) short-axis late gadolinium-enhanced CMR scans from 6 post-myocardial infarction patients undergoing VT ablation and used to reconstruct a total of 3 digital twins (1 Ov-Res, 2 Clin-Res) for each patient. Rapid pacing was used to assess VT circuits and identify the optimal ablation targets in each digital twin. VT circuits predicted by the digital twins were compared with intraprocedural electroanatomic mapping data and used to identify emergent VT.
RESULTS
The Ov-Res digital twins reduced partial volume effects and better predicted unique VT circuits compared with the Clin-Res digital twins (66.6% vs 54.5%; P < 0.01). Only the Ov-Res digital twin successfully identified emergent VT after a failed initial ablation.
CONCLUSIONS
Digital twin infarct geometry and VT circuit predictions depend on the magnetic resonance resolution. Ov-Res digital twins better predict VT circuits and emergent VT, which may improve RFA outcomes.
PubMed: 38934970
DOI: 10.1016/j.jacep.2024.04.032 -
Indian Journal of Community Medicine :... 2024[This corrects the article on p. 279 in vol. 49, PMID: 38665450.].
[This corrects the article on p. 279 in vol. 49, PMID: 38665450.].
PubMed: 38933782
DOI: 10.4103/IJCM.IJCM_266_24 -
Cureus May 2024Left ventricular non-compaction cardiomyopathy (LVNC), or non-compaction cardiomyopathy (NCCM), is defined by pronounced left ventricular trabeculations and deep...
Left ventricular non-compaction cardiomyopathy (LVNC), or non-compaction cardiomyopathy (NCCM), is defined by pronounced left ventricular trabeculations and deep intertrabecular recesses connecting with the ventricular cavity. Patients with NCCM can be asymptomatic or have severe complications, including heart failure, arrhythmias, thromboembolism, and sudden cardiac death. Our case discusses a patient with shortness of breath who was found to have a newly decreased ejection fraction. The workup revealed non-ischemic cardiomyopathy and cardiac MRI showed hyper-trabeculations consistent with NCCM. The patient was started on oral anticoagulation and guideline-directed medical therapy (GDMT) and discharged with an event monitor. NCCM stands as a relatively rare and enigmatic condition, often veiled in ambiguity. The absence of standardized diagnostic and management protocols further complicates its clinical landscape. While echocardiography is the primary diagnostic tool, its tendency for under-diagnosis poses a significant challenge. Conversely, advanced imaging modalities like cardiac MRI may lead to instances of overdiagnosis. Treatment approaches are non-specific, incorporating GDMT, anticoagulation, implantable cardioverter-defibrillator placement, and genetic testing paired with counseling. Prioritizing genetic research is crucial to uncover tailored therapeutic interventions. Establishing consensus guidelines and refining diagnostic accuracy are pivotal steps toward mitigating the risks associated with under and over-diagnosis.
PubMed: 38933642
DOI: 10.7759/cureus.61142 -
Annals of Pediatric Cardiology 2024Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy associated with fibrofatty tissue replacement of the ventricular tissue. The disease can cause...
Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy associated with fibrofatty tissue replacement of the ventricular tissue. The disease can cause ventricular dysfunction and arrhythmias and can increase the risk of sudden cardiac death. This cardiomyopathy can have variable clinical presentations, especially in the pediatric and young adult populations. In this report, we describe the case of an 18-year-old female with myocarditis as the initial presentation of ACM. She presented following a resuscitated cardiac arrest due to ventricular arrhythmia. On arrival, myocardial edema and delayed gadolinium enhancement were present on cardiac magnetic resonance imaging, with no ventricular changes observed, making the diagnosis consistent with myocarditis. Genetic testing revealed a pathogenic mutation in the desmoplakin gene consistent with ACM. Given the unconventional initial presentation of this patient's disease, early consideration of genetic testing may be beneficial to aid in the early diagnosis and management of ACM in young patients.
PubMed: 38933053
DOI: 10.4103/apc.apc_122_23 -
International Journal of Molecular... Jun 2024The aim of the Special Issue "Molecular study of sudden cardiac death" was to gather new studies on the molecular biology of cardiac death, from both a fundamental and...
The aim of the Special Issue "Molecular study of sudden cardiac death" was to gather new studies on the molecular biology of cardiac death, from both a fundamental and clinical perspective [...].
Topics: Humans; Death, Sudden, Cardiac
PubMed: 38928072
DOI: 10.3390/ijms25126366 -
Biomedicines Jun 2024Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator...
Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator (ICD) should be considered in patients with an estimated 5-year risk of malignant ventricular arrhythmia (MVA) of ≥10%. The risk prediction score for MVA includes non-missense LMNA mutations, despite their role as an established risk factor for sudden cardiac death (SCD) has been questioned in several studies. The purpose of this study is to investigate cardiac features and find gene-phenotype correlations that would contribute to the evidence on the prognostic implications of non-missense vs. missense mutations in a cohort of LMNA mutant patients. An observational, prospective study was conducted in which 54 patients positive for a Lamin A/C mutation were enrolled, and 20 probands (37%) were included. The median age at first clinical manifestation was 41 (IQR 19) years. The median follow-up was 8 years (IQR 8). The type of gene mutation was distributed as follows: missense in 26 patients (48%), non-frameshift insertions in 16 (30%), frameshift deletions in 5 (9%), and nonsense in 7 (13%). Among the missense mutation carriers, two (8%) died and four (15%) were admitted onto the heart transplant list or underwent transplantation, with a major adverse cardiovascular event (MACE) rate of 35%. No statistically significant differences in MACE prevalence were identified according to the missense and non-missense mutation groups ( value = 0.847). Our data shift the spotlight on this considerable topic and could suggest that some missense mutations may deserve attention regarding SCD risk stratification in real-world clinical settings.
PubMed: 38927500
DOI: 10.3390/biomedicines12061293 -
Biomedicines May 2024The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity... (Review)
Review
The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity contribute to myocarditis pathogenesis, regardless of its infectious or non-infectious nature and across different histological and clinical subtypes. The heterogeneity of myocarditis etiologies and molecular effectors is one of the determinants of its clinical variability, manifesting as a spectrum of disease phenotype and progression. This spectrum ranges from a fulminant presentation with spontaneous recovery to a slowly progressing, refractory heart failure with ventricular dysfunction, to arrhythmic storm and sudden cardiac death. In this review, we first examine the updated definition and classification of myocarditis at clinical, biomolecular and histopathological levels. We then discuss recent insights on the role of specific immune cell populations in myocarditis pathogenesis, with particular emphasis on established or potential therapeutic applications. Besides the well-known immunosuppressive agents, whose efficacy has been already demonstrated in human clinical trials, we discuss the immunomodulatory effects of other drugs commonly used in clinical practice for myocarditis management. The immunological complexity of myocarditis, while presenting a challenge to simplistic understanding, also represents an opportunity for the development of different therapeutic approaches with promising results.
PubMed: 38927363
DOI: 10.3390/biomedicines12061156