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Cureus Mar 2024Takotsubo syndrome is a non-ischemic cardiomyopathy characterized by transient left ventricular (LV) apical ballooning, which typically occurs after exposure to...
Takotsubo syndrome is a non-ischemic cardiomyopathy characterized by transient left ventricular (LV) apical ballooning, which typically occurs after exposure to emotional or physical stress in elderly women. An 85-year-old woman with hypertension presented with a recent onset of palpitation and exertional dyspnea. The patient had a long-standing history of alcohol consumption, and transthoracic echocardiography revealed diffuse LV hypokinesia including apical area with an ejection fraction of 30%. The patient was suspected of alcoholic cardiomyopathy and was recommended to quit alcohol consumption. Six weeks after the first admission, the patient presented to the emergency department with a three-day history of dyspnea. Based on newly developed negative T-waves and LV apical akinesia in the absence of significant coronary artery disease, the patient was diagnosed with takotsubo syndrome combined with suspected alcoholic cardiomyopathy. Clinicians should be aware that takotsubo syndrome can occur even in the presence of reduced LV ejection fraction, leading to further LV systolic dysfunction.
PubMed: 38681458
DOI: 10.7759/cureus.57175 -
HGG Advances Apr 2024Biallelic loss-of-function variants in the MUSK gene result in two allelic disorders: (1) congenital myasthenic syndrome (CMS; OMIM: 616325), a neuromuscular disorder...
Biallelic loss-of-function variants in the MUSK gene result in two allelic disorders: (1) congenital myasthenic syndrome (CMS; OMIM: 616325), a neuromuscular disorder that has a range of severity from severe neonatal-onset weakness to mild adult-onset weakness, and (2) fetal akinesia deformation sequence (OMIM: 208150), a form of pregnancy loss characterized by severe muscle weakness in the fetus. The MUSK gene codes for muscle-specific kinase (MuSK), a receptor tyrosine kinase involved in the development of the neuromuscular junction. Here, we report a case of neonatal-onset MUSK-related CMS in a patient harboring compound heterozygous deletions in the MUSK gene, including (1) a deletion of exons 2-3 leading to an in-frame MuSK protein lacking the immunoglobulin 1 (Ig1) domain and (2) a deletion of exons 7-11 leading to an out-of-frame, truncated MuSK protein. Individual domains of the MuSK protein have been elucidated structurally; however, a complete MuSK structure generated by machine learning algorithms has clear inaccuracies. We modify a predicted AlphaFold structure and integrate previously reported domain-specific structural data to suggest a MuSK protein that dimerizes in two locations (Ig1 and the transmembrane domain). We analyze known pathogenic variants in MUSK to discover domain-specific genotype-phenotype correlations; variants that lead to a loss of protein expression, disruption of the Ig1 domain, or Dok-7 binding are associated with the most severe phenotypes. A conceptual model is provided to explain the severe phenotypes seen in Ig1 variants and the poor response of our patient to pyridostigmine.
PubMed: 38566418
DOI: 10.1016/j.xhgg.2024.100288 -
Frontiers in Cardiovascular Medicine 2024Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial...
BACKGROUND AND AIMS
Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function.
METHODS AND RESULTS
Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding.
CONCLUSION
IPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.
PubMed: 38559672
DOI: 10.3389/fcvm.2024.1376367 -
Revista de La Facultad de Ciencias... Mar 2024to describe a patient with myocardial ischemia with multiple causes.
OBJECTIVE
to describe a patient with myocardial ischemia with multiple causes.
CLINICAL CASE
This clinical case describes a 58-year-old man with a history of hypertension, dyslipidemia, COPD and previous myocardial infarction (AMI). He went to the emergency room with chest pain and dyspnea. Findings included bibasal crackles, electrocardiogram with old anterior fibrosis, elevated NT-ProBNP, and echocardiogram with septoapical akinesia. During hospitalization, he experienced tachyarrhythmia and hemodynamic deterioration, undergoing electrical cardioversion (CVE). Non-ST segment elevation acute coronary syndrome (NSTEACS) complicated with ventricular arrhythmia and acute pulmonary edema was diagnosed. Coronary angiography revealed coronary ectasias without obstructive lesions, but with mild stenosis in three vessels. The patient was successfully treated with non-invasive ventilation, diuretics, vasodilators and anticoagulation. The discharge was granted with the plan to further studies to optimize and guide treatment and finally the diagnosis of Myocardial Infarction with Non-Obstructive Arteries (MINOCA) and the presence of coronary ectasias was addressed.
CONCLUSION
it is important to highlight the non-ischemic causes in MINOCA and the association between coronary ectasia and cardiovascular events, which is why we emphasize the need for more studies to better understand the relationship between these phenomena.
Topics: Humans; Dilatation, Pathologic; MINOCA; Retrospective Studies
PubMed: 38537091
DOI: 10.31053/1853.0605.v81.n1.43231 -
The American Journal of Cardiology Feb 2024Alcohol septal ablation (ASA) is a well-established procedure for septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy, significant at rest...
Alcohol septal ablation (ASA) is a well-established procedure for septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy, significant at rest or provocable outflow tract gradients, and medically refractory symptoms. This percutaneous approach to relief of obstruction and eventual cardiac remodeling involves the infusion of a small quantity of ethanol into an appropriately targeted septal artery that is feeding the basal septum to create an iatrogenic and controlled focal infarction. Early akinesia is followed by subsequent thinning and remodeling, which widens the outflow tract, reducing or eliminating the obstruction. Historically, the use of ASA was reserved primarily for high-risk surgical candidates; however, more contemporary data suggest similar outcomes in the short-term and long-term safety of the procedure and overall effectiveness in relieving obstructive symptoms when it is performed in broader populations at experienced centers. Therefore, the current guidelines published in 2020 support ASA as a class 1 indication, similar to its open-heart surgical counterpart, surgical myectomy, when no concomitant significant coronary or valve surgical indication exists. This article summarizes contemporary management of patients with hypertrophic cardiomyopathy who were selected for ASA and details procedural methods and outcomes.
Topics: Humans; Treatment Outcome; Heart Septum; Ethanol; Cardiomyopathy, Hypertrophic; Cardiac Surgical Procedures; Ablation Techniques
PubMed: 38368036
DOI: 10.1016/j.amjcard.2023.10.064 -
Brazilian Journal of Medical and... 2024This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups:...
This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups: normal saline control and rotenone control were administered saline or rotenone (ROT), respectively, orally; sterubin 10 received ROT + sterubin 10 mg/kg po; and sterubin alone was administered to the test group (10 mg/kg). Rats of the normal saline and sterubin alone groups received sunflower oil injection (sc) daily, 1 h after receiving the treatments cited above, while rats of the other groups received rotenone injection (0.5 mg/kg, sc). The treatment was continued over the course of 28 days daily. On the 29th day, catalepsy and akinesia were assessed. The rats were then euthanized, and the brain was extracted for estimation of endogenous antioxidants (MDA: malondialdehyde, GSH: reduced glutathione, CAT: catalase, SOD: superoxide dismutase), nitrative (nitrite) stress markers, neuroinflammatory cytokines, and neurotransmitter levels and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)). Akinesia and catatonia caused by ROT reduced the levels of endogenous antioxidants (GSH, CAT, and SOD), elevated the MDA level, and altered the levels of nitrites, neurotransmitters, and their metabolites. Sterubin restored the neurobehavioral deficits, oxidative stress, and metabolites of altered neurotransmitters caused by ROT. Results demonstrated the anti-Parkinson's activities of sterubin in ROT-treated rats.
Topics: Rats; Animals; Parkinson Disease; Antioxidants; Rotenone; Saline Solution; Neuroprotective Agents; Oxidative Stress; Neurotransmitter Agents; Superoxide Dismutase; Disease Models, Animal
PubMed: 38359270
DOI: 10.1590/1414-431X2023e12829 -
Scientific Reports Jan 2024Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group of inherited disorders characterised by...
Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group of inherited disorders characterised by impaired neuromuscular transmission. Most CMS originate from defects in the muscle nicotinic acetylcholine receptor, but the underlying molecular pathogenesis is only poorly understood. Here we show that RNAi-mediated silencing of FADS-related proteins rapsyn and NUP88 in foetal fibroblasts alters organisation of the actin cytoskeleton. We show that fibroblasts from two independent FADS individuals have enhanced and shorter actin stress fibre bundles, alongside with an increased number and size of focal adhesions, with an otherwise normal overall connectivity and integrity of the actin-myosin cytoskeleton network. By proximity ligation assays and bimolecular fluorescence complementation, we show that rapsyn and NUP88 localise nearby adhesion plaques and that they interact with the focal adhesion protein paxillin. Based on these findings we propose that a respective deficiency in rapsyn and NUP88 in FADS alters the regulation of actin dynamics at focal adhesions, and thereby may also plausibly dictate myofibril contraction in skeletal muscle of FADS individuals.
Topics: Humans; Actins; Arthrogryposis; Receptors, Nicotinic; Myasthenic Syndromes, Congenital
PubMed: 38242956
DOI: 10.1038/s41598-023-50615-1 -
Frontiers in Cardiovascular Medicine 2023The aim was to characterize the electrovectorcardiographic pattern of ventricular aneurysms in ischemic cardiopathy by analyzing the cardiac ventricular repolarization....
The aim was to characterize the electrovectorcardiographic pattern of ventricular aneurysms in ischemic cardiopathy by analyzing the cardiac ventricular repolarization. The medical records of 2,670 individuals were analyzed in this cross-sectional study. A test phase included 33 patients who underwent transthoracic echocardiogram with ultrasonic enhancing agent, electrocardiogram, and vectorcardiogram (aneurysm group - = 22, and akinesia group - = 11). In the validation phase, cardiac magnetic resonance imaging established the left ventricle segmental contractility in 16 patients who underwent electrocardiographic and vectorcardiographic tests (aneurysm group, = 8, and akinesia group, = 8). The variables studied were the presence of the T-wave plus-minus pattern and the T-wave loop anterior-posterior pattern in V2-V4. The diagnostic indices used were sensitivity, specificity, and predictive values, with their respective 95% confidence intervals. During the test and validation phases, the analysis of the presence of the T-wave plus-minus pattern identified the aneurysm group with a sensitivity of 91% vs. 87% and specificity of 91% vs. 87% ( < 0.0001 vs. = 0.01), respectively. Meanwhile, the T-wave loop anterior-posterior pattern evidenced sensitivity of 95% vs. 77% and specificity of 91% vs. 87% ( < 0.0001 vs. = 0.04), respectively. The electrovectorcardiographic parameters showed high accuracy for recognizing left ventricular aneurysms in ischemic heart disease.
PubMed: 38155984
DOI: 10.3389/fcvm.2023.1275194