-
Scientific Reports Dec 2017There is an unmet need for treatments to reduce abdominal aortic aneurysm (AAA) progression. Vascular smooth muscle cell (VSMC) apoptosis precipitates AAA formation,...
There is an unmet need for treatments to reduce abdominal aortic aneurysm (AAA) progression. Vascular smooth muscle cell (VSMC) apoptosis precipitates AAA formation, whereas VSMC proliferation repairs the vessel wall. We previously demonstrated that over-expression of EC4-Fc (truncated N-cadherin), or deletion of matrix-metalloproteinase-7 (Mmp-7) reduced VSMC apoptosis in mouse atherosclerotic plaques. Additionally, MMP-7 promotes VSMC apoptosis by cleavage of N-cadherin. We investigated their combined effect on AAA formation. Increased apoptosis and proliferation were observed in human AAA (HAAA) sections compared to normal aortae (HA). This coincided with increased MMP-7 activity and reduced N-cadherin protein levels in HAAA sections compared to HA. Using a mouse model of aneurysm formation, we showed that the combination of Mmp-7 deletion and EC4-Fc overexpression significantly increased AAA severity. Medial apoptosis and proliferation were both significantly reduced in these mice compared to control mice. In vitro, MMP-7 inhibition and EC4-Fc administration significantly supressed human aortic VSMC apoptosis (via activation of PI-3 kinase/Akt signalling) and proliferation. In conclusion, combined Mmp-7 deletion and systemic over-expression of EC4-Fc reduced both proliferation and apoptosis. Reduced proliferation-mediated repair over-rides any benefit of reduced apoptosis, increasing aneurysm severity. Future studies should therefore focus on retarding VSMC apoptosis whilst promoting VSMC proliferation.
Topics: Angiotensin II; Animals; Aorta; Aortic Aneurysm, Abdominal; Apolipoproteins E; Apoptosis; Cadherins; Cell Proliferation; Disease Models, Animal; Humans; Male; Matrix Metalloproteinase 7; Mice; Mice, Inbred C57BL; Mice, Knockout; Severity of Illness Index; Signal Transduction
PubMed: 29229950
DOI: 10.1038/s41598-017-17700-8 -
European Heart Journal. Case Reports Sep 2019Tetralogy of Fallot is a congenital heart defect characterized by pulmonary valve stenosis, ventricular septal defect (VSD), overriding aorta, and right ventricular...
BACKGROUND
Tetralogy of Fallot is a congenital heart defect characterized by pulmonary valve stenosis, ventricular septal defect (VSD), overriding aorta, and right ventricular hypertrophy. In its' extreme form, the pulmonary valve orifice does not develop during organogenesis, resulting in pulmonary atresia. We report a case of catheter ablation of symptomatic atrial fibrillation (AF) in a 37-year-old patient with congenital pulmonary atresia.
CASE SUMMARY
The young man described paroxysmal tachycardia correlating to AF episodes in the previously implanted event recorder. Computed tomography scan described the complex anatomy with congenital pulmonary atresia, VSD, and major aortopulmonary collateral arteries. Electroanatomical mapping revealed typical pulmonary vein electrograms in a hypotrophic left atrium. Modified pulmonary vein isolation was successfully performed and non-excitability of the ablation line was reached. The patient recovered uneventfully and event recorder interrogation showed no AF recurrence after 3 months.
DISCUSSION
Incidence of pulmonary atresia is low. Untreated survival rate is 50% after 1 year and 8% after 10 years. Tachycardia is a major cause of increased morbidity and mortality in patients with cyanotic congenital heart defects and pulmonary vein foci are described as driver for AF. Considerations preceding catheter ablation included pathophysiological mechanism, complex anatomy, atypical left atrium access, and reduced pulmonary perfusion resulting in a hypotrophic left atrium. Pulmonary veins showed typical electrograms, and isolation of pulmonary veins was feasible without adverse events.
PubMed: 31660488
DOI: 10.1093/ehjcr/ytz115 -
Cardiology Journal 2011The aim of this study was to investigate the incidence, origins and courses of coronary artery anomalies using a combination of angiographic and surgical methods in...
BACKGROUND
The aim of this study was to investigate the incidence, origins and courses of coronary artery anomalies using a combination of angiographic and surgical methods in Turkish children with tetralogy of Fallot (ToF).
METHODS
Seventy-seven patients in whom coronary artery anomalies had been identified by angiography and/or at operation out of 549 ToF and 58 Fallot-type double outlet right ventricle (total 607) patients, were enrolled in the study.
RESULTS
Coronary artery anomalies were identified in 12.7% of the patients. The incidence was 12.2% (67/549) in patients with aortic overriding 50%, and 17.2% (10/58) with aortic overriding 〉 50% (p 〉 0.05). The incidence of anomalous coronary arteries crossing the right ventricular outflow tract (RVOT) was 7.91%. The commonest anomaly was the left anterior descending artery (LAD) or accessory LAD arising from the right coronary artery (RCA; n = 25). Other frequent anomalies were single coronary ostium (n = 21) and enlarged conal branch of RCA (n = 18). In 62.3% (48/77) of the patients with a coronary anomaly, the anomalous vessels were crossing the RVOT. The ratio of crossing the RVOT was 92.0% for LAD arising from the RCA, 66.7% for conal branch, and 42.9% for single coronary ostium.
CONCLUSIONS
Two thirds of the anomalous coronary arteries were crossing the RVOT, and had surgical importance. The most frequent coronary artery anomaly that crossed the RVOT was the LAD or the accessory LAD arising from the RCA. Also, an enlarged conus artery should be considered as an anomaly because of its surgical importance, given its high rate of crossing the RVOT.
Topics: Adolescent; Cardiac Surgical Procedures; Chi-Square Distribution; Child; Child, Preschool; Coronary Angiography; Coronary Vessel Anomalies; Female; Humans; Incidence; Infant; Male; Predictive Value of Tests; Sinus of Valsalva; Tetralogy of Fallot; Turkey
PubMed: 21947991
DOI: 10.5603/cj.2011.0011 -
Journal of Investigative Medicine High... 2020Tetralogy of Fallot is the most common cyanotic congenital heart defect consisting of an overriding aorta, right ventricular outflow obstruction, ventricular septal...
Tetralogy of Fallot is the most common cyanotic congenital heart defect consisting of an overriding aorta, right ventricular outflow obstruction, ventricular septal defect, and right ventricular hypertrophy. Without surgical management, approximately only 3% of patients survive past the age of 40 years. Cases of unoperated patients reaching adulthood have been reported; however, few studies describe treatment guidelines for surgical or therapeutic management. In this article, we report the case of a 59-year-old Hispanic male with unoperated tetralogy of Fallot presenting to our cardiology clinic for initial workup and management.
Topics: Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Disease Management; Eisenmenger Complex; Electrocardiography; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Middle Aged; Radiography, Thoracic; Survivors; Tetralogy of Fallot
PubMed: 32462941
DOI: 10.1177/2324709620926908 -
BMJ Case Reports May 2014A 17-year-old male patient presented with cyanosis, repeated squatting since childhood and haemoptysis since the past 1 month. He had central cyanosis with clubbing....
A 17-year-old male patient presented with cyanosis, repeated squatting since childhood and haemoptysis since the past 1 month. He had central cyanosis with clubbing. Cardiovasular examination revealed ejection systolic murmur in the pulmonary area with single S2. ECG showed right ventricular hypertrophy (RVH) with right atrial enlargement and first-degree heart block. Two-dimensional echo showed ventricular septal defect, overriding aorta, RVH, right ventricular enlargement (RVE) and right atrial enlargement with infundibular and valvular pulmonary stenosis and 1.9 cm ostium secondum atrial septal defect. There was no evidence of atrioventricular canal defect. The patient was diagnosed with pentology of Fallots. Follow-up ECG showed complete heart block (CHB) that again reverted to first-degree heart block. A diagnosis of pentology of Fallot with intermittent CHB was made with an awake heart rate of 50/min. This case report shows association of CHB with tetralogy of Fallot.
Topics: Abnormalities, Multiple; Adolescent; Atrioventricular Block; Cyanosis; Diagnosis, Differential; Echocardiography, Doppler, Color; Echocardiography, Three-Dimensional; Electrocardiography; Emergency Service, Hospital; Heart Defects, Congenital; Heart Murmurs; Heart Rate; Heart Septal Defects, Ventricular; Humans; Hypertrophy, Right Ventricular; Male; Monitoring, Physiologic; Prognosis; Radiography, Thoracic; Tetralogy of Fallot; Treatment Refusal; Trilogy of Fallot
PubMed: 24832712
DOI: 10.1136/bcr-2014-204140 -
The Medical Journal of Malaysia Mar 1994A 7-year old female child was admitted for recurrent bronchopulmonary since one week of life. She was diagnosed to have ventricular septal defect and was treated...
A 7-year old female child was admitted for recurrent bronchopulmonary since one week of life. She was diagnosed to have ventricular septal defect and was treated conservatively. At seven years of life, repeat echocardiogram revealed a large perimembranous ventricular septal defect, absent pulmonary valve with overriding of aorta, narrow pulmonary artery annulus, and dilated main pulmonary artery and its branches. She was treated conservatively, discharged and follow-up at the National Heart Institute Kuala Lumpur, for corrective surgery.
Topics: Child; Cough; Echocardiography; Failure to Thrive; Female; Follow-Up Studies; Humans; Pulmonary Valve; Respiratory Sounds; Tetralogy of Fallot
PubMed: 8057999
DOI: No ID Found -
Circulation Research Sep 2008Congenital heart diseases are traditionally considered to be multifactorial in pathogenesis resulting from environmental and genetic interactions that determine...
Congenital heart diseases are traditionally considered to be multifactorial in pathogenesis resulting from environmental and genetic interactions that determine penetrance and expressivity within a genetically predisposed family. Recent evidence suggests that genetic contributions have been significantly underestimated. However, single gene defects occur only in a minority of cases, and multigenetic causes of congenital heart diseases have not been fully demonstrated. Here, we show that interactions between alleles of 3 Pbx genes, which encode homeodomain transcription factors, are sufficient to determine the phenotypic presentation of congenital heart diseases in mice. A major role is served by Pbx1, whose inactivation results in persistent truncus arteriosus. Reduction or absence of Pbx2 or Pbx3 leads to Pbx1 haploinsufficiency and specific malformations that resemble tetralogy of Fallot, overriding aorta with ventricular septal defect, and bicuspid aortic valves. Disruption of Meis1, which encodes a Pbx DNA-binding partner, results in cardiac anomalies that resemble those caused by Pbx mutations. Each of the observed cardiac defects represents developmental abnormalities affecting distinct stages of cardiac outflow tract development and corresponds to specific types of human congenital heart disease. Thus, varied deficiencies in the Pbx gene family produce a full spectrum of cardiac defects involving the outflow tract, providing a framework for determining multigenetic causes of congenital heart anomalies.
Topics: Alleles; Animals; Heart Defects, Congenital; Homeodomain Proteins; Humans; Mice; Mice, Knockout; Myeloid Ecotropic Viral Integration Site 1 Protein; Neoplasm Proteins; Pre-B-Cell Leukemia Transcription Factor 1; Proto-Oncogene Proteins; Transcription Factors
PubMed: 18723445
DOI: 10.1161/CIRCRESAHA.108.175489 -
Case Reports in Radiology 2024Tetralogy of Fallot (TOF) is a significant cause of cyanotic congenital heart disease (CHD) encountered in childhood with few cases manifesting in adulthood. It has four...
Tetralogy of Fallot (TOF) is a significant cause of cyanotic congenital heart disease (CHD) encountered in childhood with few cases manifesting in adulthood. It has four classical features (ventricular septal defect, overriding of aorta, hypertrophy of right ventricular hypertrophy, and right ventricular outflow tract obstruction), but the clinical presentation and course can be variable. Due to various anatomical variations and complex anatomy, presurgical planning and postoperative follow-up by pulmonary computed tomographic angiography (CTA) have a very important role. With continued technological advances and the availability of 128-slice computed tomographic (CT) scans, they now play an important role in TOF preoperative evaluation and workup, assisting by minimizing routine invasive digital subtraction catheter angiography. The fast scan of a 128-slice CTA with very sensitive detectors is a very useful modality for studying the complex anatomy and variations as well as its utilization for postoperative management. In this article, we report four cases of TOF where we used a 128-slice scan for performing pulmonary angiography (Optima 660, GE 128, 2180 Premier Row, Orlando, FL 32809, U.S.A.) for preoperative diagnosis and management of three cases and work up for revision surgery for an already operated case with a nonfunctional modified Blalock-Taussig shunt with additional lung parenchymal findings simultaneously. This study will explain the advantageous role of the 128-slice CT scanner over the lesser-slice CT scanners with the ability of pulmonary CTA to facilitate accurate diagnosis and postoperative management.
PubMed: 38756334
DOI: 10.1155/2024/3543906 -
Journal of Medical Case Reports Mar 2024Tetralogy of Fallot is a congenital heart disease mostly diagnosed and treated in early childhood. However, there are some adult cases receiving treatment.
BACKGROUND
Tetralogy of Fallot is a congenital heart disease mostly diagnosed and treated in early childhood. However, there are some adult cases receiving treatment.
CASE PRESENTATION
We describe a 78-year-old Japanese woman who presented with severely hypertrophic right ventricle, ventricular septum defect, overriding aorta, and severe infundibular stenosis in the right ventricular outflow tract. As hypoxemia was mild and daily exertion was sufficiently possible, home oxygen therapy was introduced. After 1 month, she was referred because of a positive blood culture. The blood culture test was positive four times, therefore, the antibacterial drug was administered according to active infective endocarditis. SpO repeatedly decreased during hospitalization, thus oxygen was needed. As there were infective endocarditis onset and progressive hypoxemia, we planned a surgical correction.
CONCLUSION
Tetralogy of Fallot was diagnosed and successfully treated with complete surgical correction, and the development of infective endocarditis was the definitive indication for surgery at this late age.
Topics: Child, Preschool; Adult; Female; Humans; Aged; Tetralogy of Fallot; Endocarditis; Endocarditis, Bacterial; Oxygen; Hypoxia
PubMed: 38439111
DOI: 10.1186/s13256-024-04414-5 -
International Journal of Surgery Case... Sep 2023Pentaloy of fallot (POF) is a congenital cardiac anomaly that includes ventricular septal defect (VSD), pulmonary stenosis (PS), overriding of the aorta, and right...
A 20-year follow-up of successful surgical management for a complex case of pentalogy of fallot and dextrocardia with systemic and pulmonary venous anomalies: A rare case report.
INTRODUCTION AND IMPORTANCE
Pentaloy of fallot (POF) is a congenital cardiac anomaly that includes ventricular septal defect (VSD), pulmonary stenosis (PS), overriding of the aorta, and right ventricular hypertrophy. Dextrocardia, on the other hand, is a congenital condition in which the heart is right-sided. Rarely, both of these conditions can coexist. In this case, we report the 20-year follow-up results for the successful management of POF coexisting with Dextrocardia and other anomalies, which is the first described case in the literature.
CASE PRESENTATION
A 3.5-year-old boy was admitted to the hospital with the main complaint of cyanosis and dyspnea. He was diagnosed with POF. Intraoperative inspection further revealed a Double outlet right ventricle (DORV), and other cardiac anomalies. Total repair surgery was successfully performed. Follow-up results showed a normal postoperative status with no abnormalities. Mild exertional dyspnea was noted after 20 years, but the patient is currently in good health.
CLINICAL DISCUSSION
The coexistence of multiple congenital cardiac anomalies can make it challenging to be completely diagnosed, and for this purpose, different preoperative studies are recommended, like Echocardiography, cardiac catheterization, and Transabdominal echography. For the treatment of POF, pulmonary valve-sparing techniques have shown better long-term results, making them the preferred choice over other techniques.
CONCLUSION
Very few cases reported the occurrence of Dextrocardia with POF and additional cardiac anomalies. Echocardiography and Transabdominal echography play a very important role in the preoperative diagnosis of such complex cases. Surgery is the standard treatment for these congenital malformations.
PubMed: 37598487
DOI: 10.1016/j.ijscr.2023.108672