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International Journal of Molecular... Jan 2024Mitral valve prolapse (MVP) is a common valvular disease, affecting 2-3% of the adult human population and is a degenerative condition. A total of 5-10% of the afflicted...
Mitral valve prolapse (MVP) is a common valvular disease, affecting 2-3% of the adult human population and is a degenerative condition. A total of 5-10% of the afflicted will develop severe mitral regurgitation, cardiac dysfunction, congestive heart failure, and sudden cardiac death. Naturally occurring myxomatous MVP in dogs closely resembles MVP in humans structurally, and functional consequences are similar. In both species, valvular interstitial cells (VICs) in affected valves exhibit phenotype consistent with activated myofibroblasts with increased alpha-smooth muscle actin (αSMA) expression. Using VICs collected from normal and MVP-affected valves of dogs, we analyzed the miRNA expression profile of the cells and their associated small extracellular vesicles (sEV) using RNA sequencing to understand the role of non-coding RNAs and sEV in MVP pathogenesis. was shown to be upregulated in both the affected VICs and sEV, and overexpression of by mimic transfection in quiescent VIC recapitulates the activated myofibroblastic phenotype. Concurrently, KLF4 expression was noted to be suppressed by , confirming the -KLF4-αSMA axis. Targeting this axis may serve as a potential therapy in controlling pathologic abnormalities found in MVP valves.
Topics: Adult; Animals; Dogs; Humans; Aortic Valve; Aortic Valve Stenosis; Cells, Cultured; MicroRNAs; Mitral Valve Prolapse; Actins; Kruppel-Like Factor 4
PubMed: 38338749
DOI: 10.3390/ijms25031468 -
Zhonghua Wai Ke Za Zhi [Chinese Journal... Mar 2024To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA). This is a retrospective case series study. From...
To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA). This is a retrospective case series study. From January 2016 to July 2023, 24 cases of high-risk AAOCA underwent surgical treatment in Department of Cardiac Surgery, Guangdong Provincial People's Hospital. There were 18 males and 6 females, operatively aged ( (IQR)) 13 (26) years (range: 0.3 to 57.0 years). They were confirmed by cardiac ultrasound and cardiac CT, all of which had anomalous coronary running between the aorta and the pulmonary artery. There were 15 cases of the right coronary artery from the left aortic sinus of Valsalva, 6 cases of left coronary artery from the right aortic sinus of Valsalva, 3 cases of the sigle coronary artery. Only 3 patients had no obvious related symptoms (2 cases were complicated with a positive exercise stress test and 1 case with other intracardiac malformations), 21 cases had a history of chest tightness, chest pain, or syncope after exercise. Three patients suffered syncope after exercise and underwent cardiopulmonary resuscitation (2 cases were treated with an extracorporeal membrane oxygenerator (ECMO)). The gap from the first symptom to the diagnosis was 4.0 (11.5) months (range: 0.2 to 84.0 months). The detection rate of coronary artery abnormalities suggested by the first cardiac ultrasound was only 37.5% (9/24). Seven patients were complicated with other cardiac diseases (4 cases with congenital heart defects, 2 cases with coronary atherosclerotic heart disease, 1 case with mitral valve disease). All 24 patients underwent surgical treatment (23 cases underwent abnormal coronary artery unroofing, 1 case underwent coronary artery bypass grafting), and 5 patients underwent other intracardiac malformation correction at the same time. There were no death or surgery related complications in the hospital for 30 days after the operation. A patient with preoperative extracorporeal cardiopulmonary resuscitation was continuously assisted by ECMO after emergency AAOCA correction and had complications such as limb ischemia necrosis and renal dysfunction after the operation. During the follow-up of 2.2 (3.3) years (range: 1 month to 7.2 years), one patient who previously underwent percutaneous transluminal coronary angioplasty with a stent implant experienced significant postoperative symptomatic relief, and the other discharged patients had no related symptoms. The accurate rate of initial diagnosis for high-risk AAOCA is still low, but the risk of cardiovascular accidents is high. For sports-related chest pain and other symptoms, more attention should be paid to the detection of AAOCA, especially for adolescents. Exercise stress testing can be helpful in evaluating the cardiovascular risk of asymptomatic AAOCA. Instant surgical treatment can achieve satisfactory curative effects.
Topics: Male; Adolescent; Female; Humans; Retrospective Studies; Coronary Vessel Anomalies; Aorta; Chest Pain; Syncope
PubMed: 38291641
DOI: 10.3760/cma.j.cn112139-20230721-00021 -
Journal of Investigative Medicine High... 2024Shone complex (SC) is a rare congenital heart disease characterized by four obstructive anomalies, including parachute mitral valve (PMV), left atrial supra-valvular...
Shone complex (SC) is a rare congenital heart disease characterized by four obstructive anomalies, including parachute mitral valve (PMV), left atrial supra-valvular ring, subaortic stenosis, and coarctation of the aorta. Typically, SC manifests early in life. However, we encountered a 52-year-old female with a history of hypertension diagnosed at 26 years and left-sided weakness poststroke. She presented with worsening dyspnea and palpitations, prompting a thorough investigation. Echocardiography revealed a heavily calcified bicuspid aortic valve with severe aortic stenosis and parachute mitral valve with severe mitral stenosis and preserved ejection fraction, raising suspicions regarding the presence of SC. Cardiac catheterization, aortic-angiography, and noncontrast chest computed tomography (CT) revealed abrupt occlusion of the postductal aorta, giving a picture of aortic coarctation with well-established collateral vessels including prominent right and left internal mammary arteries. So, she was diagnosed with an incomplete SC at the age of 52. Shone complex is a rare congenital heart disease that typically presents in early childhood, but late presentations due to misdiagnosis or incomplete work up are possible. This case emphasizes the rarity of late presentations of SC and highlights the importance of early diagnosis and intervention to improve outcomes. An incomplete SC should be considered in adult patients presenting with left-sided obstructive lesions.
Topics: Female; Humans; Middle Aged; Aortic Coarctation; Echocardiography; Heart Defects, Congenital; Mitral Valve; Mitral Valve Stenosis
PubMed: 38288715
DOI: 10.1177/23247096231218636 -
Cureus Dec 2023Thyrotoxicosis is a clinical condition characterized by inappropriately elevated thyroid hormone levels in the bloodstream, leading to systemic effects on the body. In...
Thyrotoxicosis is a clinical condition characterized by inappropriately elevated thyroid hormone levels in the bloodstream, leading to systemic effects on the body. In fact, the thyrotoxic state has tight regulatory control over the cardiovascular system through genomic and non-genomic mechanisms. This study highlights a rare presentation of thyrotoxic cardiomyopathy (TCM), which, to the best of our knowledge, is one of the very few case reports involving heart failure with preserved ejection fraction (HFpEF) and only atrial involvement, compared to the previous literature. A 37-year-old female presented to the outpatient clinic with abdominal distention and neglected signs and symptoms consistent with thyrotoxicosis for a year. Investigations revealed high N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels of 1788 pg/mL. Cardiac MRI and trans-thoracic echocardiogram (TTE) revealed bilateral atrial dilatation, a left ventricular ejection fraction (LVEF) of 60%, and diastolic dysfunction. Additionally, severe free-flowing tricuspid and mitral valve regurgitation were observed, with no evidence of pericardial effusion or ventricular abnormalities. Therefore, a diagnosis of TCM was suspected and eventually confirmed by excluding other differential diagnoses. Besides a diffuse goiter on ultrasonography, the thyroid panel test revealed low thyroid-stimulating hormone (TSH) levels of <0.01 mIU/L, a free thyroxine T4 of >100 pmol/L, and positive anti-thyroid peroxidase (TPO) and TSH receptor antibodies. Accordingly, a team of endocrinologists, cardiologists, and internists managed the patient with anti-thyroid medications alongside symptomatic treatment. A few days later, she was discharged in good condition, and a follow-up visit was arranged with the endocrinology and cardiology clinics. It is crucial to maintain a high level of suspicion to detect and treat TCM promptly, and a multidisciplinary approach should ideally be employed. This is not only important for the prevention of but also reversing potentially life-threatening cardiovascular complications.
PubMed: 38283537
DOI: 10.7759/cureus.51172 -
Current Problems in Cardiology Apr 2024Limited data exists on the prognostic impact of valvular heart disease in cardiac amyloidosis (CA). We therefore sought to define the prevalence of valvular disease in... (Review)
Review
BACKGROUND
Limited data exists on the prognostic impact of valvular heart disease in cardiac amyloidosis (CA). We therefore sought to define the prevalence of valvular disease in patients with CA and assess the effects of significant valve disease on survival.
METHODS
This multi-center retrospective cohort study included consecutive patients with confirmed transthyretin (TTR) or light chain (AL) amyloidosis. Echocardiographic data closest to the date of amyloid diagnosis was reviewed, and severity was graded according to ASE guidelines. Kaplan-Meier survival analysis was performed to compare survival between patients with moderate or greater valve disease against those with mild or less disease.
RESULTS
We included 345 patients (median age 76 years; 73 % men; 110 AL, 235TTR). The median survival for the total patient cohort with cardiac amyloidosis was 2.92 years, with 30 % of patients surviving at five years after their diagnosis. Median survival comparing AL vs ATTR was 2.58 years vs 2.82 years (p = 0.67) The most common valvular abnormalities in the total cohort were mitral (62 %) and tricuspid (66 %).regurgitation There was a statistically significant difference in median survival between patients with no or mild MR compared to those with moderate or severe MR (2.92 years vs 3.35 years, p = 0.0047) (Fig. 5). There was a statistically significant difference in median survival in patients with no or mild TR compared to those with moderate or severe TR (3.35 years vs 2.3 years, p = 0.015).
CONCLUSION
Our study demonstrates a significant prevalence of mitral and tricuspid regurgitation in CA, with patients with moderate to severe MR and TR having a poorer prognosis.
Topics: Male; Humans; Aged; Female; Mitral Valve Insufficiency; Retrospective Studies; Prevalence; Heart Valve Diseases; Amyloidosis; Multicenter Studies as Topic
PubMed: 38280494
DOI: 10.1016/j.cpcardiol.2024.102417 -
Genes Jan 2024The gene encodes lamin A and lamin C, which play important roles in nuclear organization. Pathogenic variants in cause laminopathies, a group of disorders with diverse...
The gene encodes lamin A and lamin C, which play important roles in nuclear organization. Pathogenic variants in cause laminopathies, a group of disorders with diverse phenotypes. There are two main groups of disease-causing variants: missense variants affecting dimerization and intermolecular interactions, and heterozygous substitutions activating cryptic splice sites. These variants lead to different disorders, such as dilated cardiomyopathy and Hutchinson-Gilford progeria (HGP). Among these, the phenotypic terms for -associated cardiocutaneous progeria syndrome (LCPS), which does not alter lamin A processing and has an older age of onset, have been described. Here, we present the workup of an variant of uncertain significance, NM_170707.2 c. 4G>A, p.(Glu2Lys), in a 36-year-old female with severe calcific aortic stenosis, a calcified mitral valve, premature aging, and a family history of similar symptoms. Due to the uncertainty of in silico predictions for this variant, an assessment of nuclear morphology was performed using the immunocytochemistry of stable cell lines to indicate whether the p.(Glu2Lys) had a similar pathogenic mechanism as a previously described pathogenic variant associated with LCPS, p.Asp300Gly. Indirect immunofluorescence analysis of nuclei from stable cell lines showed abnormal morphology, including lobulation and occasional ringed nuclei. Relative to the controls, p.Glu2Lys and p.Asp300Gly nuclei had significantly ( < 0.001) smaller average nuclear areas than controls (mean = 0.10 units, SD = 0.06 for p.Glu2Lys; and mean = 0.09 units, SD = 0.05 for p.Asp300Gly versus mean = 0.12, SD = 0.05 for WT). After functional studies and segregation studies, this variant was upgraded to likely pathogenic. In summary, our findings suggest that p.Glu2Lys impacts nuclear morphology in a manner comparable to what was observed in p.Asp300Gly cells, indicating that the variant is the likely cause of the LCPS segregating within this family.
Topics: Female; Humans; Adult; Progeria; Lamin Type A; Cardiomyopathies; Cardiomyopathy, Dilated; Cell Line; Intermediate Filament Proteins
PubMed: 38255001
DOI: 10.3390/genes15010112 -
Pediatric Cardiology Jan 2024Despite their anatomical differences, congenitally corrected (ccTGA) and complete transposition of the great arteries (d-TGA) post-atrial switch are frequently studied...
Despite their anatomical differences, congenitally corrected (ccTGA) and complete transposition of the great arteries (d-TGA) post-atrial switch are frequently studied together and managed similarly from a medical standpoint due to the shared systemic right ventricle (sRV). The aim was to assess differences in their underlying hemodynamics. The study is a retrospective review of 138 adults with ccTGA or d-TGA post-atrial switch undergoing cardiac catheterization at Mayo Clinic, MN between 2000 and 2021. ccTGA was categorized into isolated or complex ccTGA depending on concomitant ventricular septal defect and/or left ventricular outflow obstruction. There were 53 patients with d-TGA (91% post-Mustard procedure), 51 with complex and 34 with isolated ccTGA. Isolated ccTGA patients were older (51.8 ± 13.1 years) than those with d-TGA (37.5 ± 8.3 years) or complex ccTGA (40.8 ± 13.4 years). There were no differences in sRV or left ventricular size and function across groups. The ccTGA group more commonly had ≥ moderate tricuspid regurgitation than those with d-TGA; ≥ moderate mitral and ≥ moderate pulmonary regurgitation were most prevalent in complex ccTGA. There were no differences in sRV end-diastolic pressure (sRVEDP) or PAWP between groups. However, the ratio of PAWP:sRVEDP was higher in those with d-TGA compared to those with ccTGA. Cardiac index was higher in the d-TGA group than both groups of ccTGA patients with the latter showing higher indices of ventricular afterload. In conclusion, despite sharing a sRV, adults with d-TGA and ccTGA have substantial differences in hemodynamics and structural/valvular abnormalities. Further investigation regarding disease-specific responses to heart failure therapy in those with d-TGA and ccTGA is warranted.
PubMed: 38231238
DOI: 10.1007/s00246-023-03381-w -
Annals of Medicine and Surgery (2012) Jan 2024Edward syndrome is a severe chromosomal defect that occurs as a result of non-disjunction through meiosis. It presents with cardiac septal defects, horseshoe kidneys,...
INTRODUCTION AND IMPORTANCE
Edward syndrome is a severe chromosomal defect that occurs as a result of non-disjunction through meiosis. It presents with cardiac septal defects, horseshoe kidneys, patent ductus arteriosus, central nervous system dysgenesis, distinctive craniofacial deformities, and overriding or overlapping fingers. Klinefelter syndrome (47, XXY) is found in 1 in 660 newborn males. It is considered to be one of the most common genetic causes of infertility. It manifests with small firm testes, androgen insufficiency, and azoospermia.
CASE PRESENTATION
A 2-month-old male infant with a history of weakness in feeding, frequent convulsions, and an increase in cyanosis two days ago. There were multiple skeletal deformities and a tendency to spasm in the extremities, left ventricular atrophy, mitral atresia, atrial septal defect, ventricular septal defect with dilated right cavities, tricuspid valve regurgitation, pulmonary valve stenosis; and the aorta exits in the right ventricle. There is a widening of the subdural space, which was observed in the left frontal-parietal side with cortical atrophy in that area and a widening of the Sylvian fissure. A karyotype test confirmed the presence of Edward and Klinefelter syndromes.
CLINICAL DISCUSSION
Aneuploidy is a chromosomal issue characterized by an abnormal number of a chromosome copies. The coexistence of two aneuploidies is called "double aneuploidy" which is a rare occurrence. Herein, we report a case of a 2-month-old male with Edward syndrome and Klinefelter syndrome.
CONCLUSION
This publication aims to highlight the challenges in diagnosing and treating a complicated genetic disease.
PubMed: 38222680
DOI: 10.1097/MS9.0000000000001468 -
Journal of Clinical Medicine Dec 2023Left ventricular (LV) non-compaction (LVNC) is a rare genetic cardiomyopathy due to abnormal intra-uterine arrest of compaction of the myocardial fibers during... (Review)
Review
Left ventricular (LV) non-compaction (LVNC) is a rare genetic cardiomyopathy due to abnormal intra-uterine arrest of compaction of the myocardial fibers during endomyocardial embryogenesis. Due to the partial or complete absence of LV compaction, the structure of the LV wall shows characteristic abnormalities, including a thin compacted epicardium and a thick non-compacted endocardium with prominent trabeculations and deep intertrabecular recesses. LVNC is frequently associated with chronic heart failure, life-threatening ventricular arrhythmias, and systemic embolic events. According to recent findings, in the presence of LVNC, dysfunctional LV proved to be associated with left atrial volumetric and functional abnormalities and consequential dilated and functionally impaired mitral annulus, partly explaining the higher prevalence of regurgitation. Although the non-compaction process morphologically affects only the LV, signs of remodeling of the right heart were also detected. Moreover, dilation and stiffening of the aorta were present. The aim of the present detailed review was to summarize findings regarding changes in cardiac mechanics, valvular abnormalities, and vascular remodeling detected in patients with LVNC.
PubMed: 38202085
DOI: 10.3390/jcm13010078 -
Developmental Cell Feb 2024Congenital heart malformations include mitral valve defects, which remain largely unexplained. During embryogenesis, a restricted population of endocardial cells within...
Congenital heart malformations include mitral valve defects, which remain largely unexplained. During embryogenesis, a restricted population of endocardial cells within the atrioventricular canal undergoes an endothelial-to-mesenchymal transition to give rise to mitral valvular cells. However, the identity and fate decisions of these progenitors as well as the behavior and distribution of their derivatives in valve leaflets remain unknown. We used single-cell RNA sequencing (scRNA-seq) of genetically labeled endocardial cells and microdissected mouse embryonic and postnatal mitral valves to characterize the developmental road. We defined the metabolic processes underlying the specification of the progenitors and their contributions to subtypes of valvular cells. Using retrospective multicolor clonal analysis, we describe specific modes of growth and behavior of endocardial cell-derived clones, which build up, in a proper manner, functional valve leaflets. Our data identify how both genetic and metabolic mechanisms specifically drive the fate of a subset of endocardial cells toward their distinct clonal contribution to the formation of the valve.
Topics: Animals; Mice; Mitral Valve; Retrospective Studies; Cell Differentiation; Embryonic Development
PubMed: 38198889
DOI: 10.1016/j.devcel.2023.12.006