History Of Ventricular Septal Defect Research Articles

6912 Nail Fold Capillary Findings In Patients With Somatic EPAS1 Pathogenic Variants

Abstract Disclosure: H. Alkaissi: None. B. Turturice: None. J.S. Rosenblum: None. A.S. Alzahrani: None. S. Talvacchio: None. A. Derkyi: None. M. Nazari: None. H. Wang: None. I. Pinal Fernandez: None. Z. Zhuang: None. K. Pacak: None. We recently discovered a new syndrome characterized by a triad of pheochromocytoma/paraganglioma, polycythemia, and somatostatinoma (so called Pacak-Zhuang syndrome) caused by somatic gain-of-function pathogenic variants in the EPAS1 gene, encoding hypoxia-inducible factor 2α (HIF-2α). Recently, we have described additional features of this syndrome, including systemic developmental vascular malformations in patients and the mouse model [1]. Here we evaluated vascular changes in the nailfold capillaries by using video capillaroscopy in four patients, three of whom were female and carried the same pathogenic somatic EPAS1 variant allele (EPAS1A530V). The first patient is an 18-year-old female with a history of ventricular septal defect since birth, acrocyanosis, abdominal paraganglioma, left adrenal pheochromocytoma, and polycythemia. The second patient is a 64-year-old female who presented with paraganglioma without polycythemia, in whom we found the EPAS1A530V variant from hair sample, and an additional variant (EPAS1P53[1]A) in a resected paraganglioma, confirming the diagnosis. The third patient is a 33-year-old female had polycythemia, right adrenal pheochromocytoma, abdominal paragangliomas and duodenal somatostatinoma. The fourth patient is a 25-year-old male with PZS bearing a somatic EPAS1M535V pathogenic variant and an additional D536_L542 deletion, with hypoplastic left ventricle and metastatic paraganglioma who never developed polycythemia due to concomitant sickle cell-thalassemia traits. Despite the notable differences in genotype between the first three patients compared to the fourth patient, whose genotype is more complex, nailfold video capillaroscopy of all these patients showed similar phenotype—abnormal capillary structure marked by widespread dilations, megacapillaries, sporadic capillary hemorrhages, and regions with diminished capillary density. While polycythemia has been implicated in megacapillaries phenotype, two of our patients did not have polycythemia at the time of evaluation, further supporting the role of HIF-2a in angiogenesis. In conclusion, we describe nailfold capillary changes on video capillaroscopy as a non-invasive clinical sign in patients with EPAS1 pathogenic variants. Whether this finding is due to circulating angiogenic factors secreted by the tissues harboring HIF-2α mutation, or a direct effect of HIF-2α on angiogenesis remains to be determined.

SAT078 A Case Of MODY Due To A Rare Activating Variant In The ABCC8 Gene

Abstract Disclosure: J. Milosavljevic: None. J.M. Greally: None. S. Milman: None. Background: ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene encodes the sulfonylurea receptor 1 (SUR1) regulatory subunit of the beta cell ATP-sensitive K+ channel (KATP). Activating mutations in the ABCC8 cause both neonatal and maturity-onset diabetes of the young (MODY). The majority of patients (85%) with diabetes due to ABCC8 gene mutations could be successfully treated with oral sulfonylureas. A substitution c.2473C>T in the ABCC8 gene results in R825W change in the nucleotide-binding domain 1 of SUR1 and in activation of the KATP channel. We report a case of MODY with an activating mutation of ABCC8 gene (R825W). Clinical Case: A 23-year old woman with a history of ventricular septal defect was diagnosed with diabetes mellitus after she presented with a 2-month history of polyuria and polydipsia. At the time of diagnosis, random serum glucose level was 242 mg/dL, Hemoglobin A1c 7.6%, and BMI was 18 kg/m2. There was absence of acanthosis nigricans on exam or a family history of diabetes, although paternal medical history was unknown. A history of low birth weight was reported, but no developmental delays, neonatal diabetes or history of hypoglycemia. A history of seizure during childhood was also noted but was not associated with hypoglycemia. Additional work-up revealed absence of glutamic acid decarboxylase, islet cell, and insulin autoantibodies. C-peptide level was 2.0 ng/mL with blood glucose 113 mg/dL. The patient did not experience microvascular complications of diabetes. Genetic testing was negative for known mutations in HNF1A, HNF1B, HNF4A, GCK, and PPX1 genes. The patient was initially treated with metformin, but never achieved adequate glycemic control and experienced side effects. She was subsequently treated with sitagliptin and ertugliflozin, however, glycemic control remained inadequate (HbA1C 8.1%). At the age of 33 she was referred for clinical exome sequencing. This detected heterozygous ABCC8 variant c.2473 C>T; p.(R825W). Glucose control improved once therapy was switched to glipizide, resulting in the most recent HbA1C of 6.0%. Conclusion: Activating mutations of ABCC8 gene are infrequent genetic causes of diabetes in adults. Sequencing of the ABCC8 gene should be considered in select adult patients, as diagnosis can guide management decisions. Presentation: Saturday, June 17, 2023

Diagnosis, surgical management, and long-term outcomes of double chambered right ventricle: a rare and challenging disease in the adult population

BackgroundDouble Chambered right ventricle is a rare disease in adults and can be a late and incidental presentation in patients with history of ventricular septal defect. ObjectivesTo describe our institution's experience with late presentation of double chambered right ventricle. MethodsWe performed a review of demographic and clinical data and review of echocardiographic studies of patients with diagnosis of double chambered right ventricle. We examined pre-operative assessment, surgical outcomes, and clinical status at latest follow up. ResultsSix adults with mean age of 40 years were identified to have and underwent surgical repair of double chambered right ventricle in our institution in the last decade. Two patients were older than 60 years of age. In all the patients, the pre-operative gradient from right ventricular inflow to outflow chamber was greater than 70 mm Hg. All patients underwent successful repair without significant residual gradient. Arrhythmia was present in three of our patients in the postoperative period. ConclusionDouble chambered right ventricle is a rare disease but may be diagnosed in patients well into later adulthood who have a prior history of ventricular septal defect. The diagnosis requires a high index of suspicion in this patient population, but surgical repair can be done safely with satisfactory post-operative results.

What to look for in patient with continuous murmur and history of ventricular septal defect?

During diagnostic process it is very important to conduct scrupulous interview and thorough physical examination. Properly interpreted auscultation phenomena allow for appropriate planning of further imaging studies.

MULTIMODALITY APPROACH IN THE DIAGNOSIS OF DOUBLE-CHAMBERED RIGHT VENTRICLE IN AN ADULT

Double-chambered right ventricle (DCRV) seldom presents in adulthood. Diagnosis of this condition can be challenging, and requires a multimodality approach. A 38 year old woman with a history of ventricular septal defect (VSD) presented with exertional chest pain and dyspnea. A harsh systolic

Cardiac Function in Types II and III Spinal Muscular Atrophy: Should We Change Standards of Care?

In the last years, there has been increasing evidence of cardiac involvement in spinal muscular atrophy (SMA). Autonomic dysfunction has been reported in animal models and in several patients with types I and III SMA, these findings raising the question whether heart rate should be routinely investigated in all SMA patients. The aim of our study was to detect possible signs of autonomic dysfunction and, more generally, of cardiac involvement in types II and III SMA. We retrospectively reviewed 24-hour electrocardiography (ECG) in 157 types II and III SMA patients (age range, 2-74 years). Of them, 82 also had echocardiography. None of the patients had signs of bradycardia, atrial fibrillation, or the other previously reported rhythm disturbances regardless of the age at examination or the type of SMA. Echocardiography was also normal. There were no signs of congenital cardiac defects with the exception of one patient with a history of ventricular septal defects. Our results suggest that cardiac abnormalities are not common in type II and type III SMA. These findings provide no evidence to support a more accurate cardiac surveillance or changes in the existing standards of care.

Eccentric activation of the coronary sinus during typical atrial flutter: What is the mechanism?

A 79-year-old man with a history of ventricular septal defect underwent catheter ablation of drug refractory paroxysmal atrial flutter (AFL). The 12-lead electrocardiogram during tachycardia showed a biphasic, predominantly positive flutter wave with an initial negative component in leads II, III, and aVF, and positive flutter waves in leads V1 through V6 (Fig. 1, A), consistent with typical counterclockwise (CCW) AFL [1]. A decapolar catheter was advanced with its ♯17 and ♯18 poles in the proximal coronary sinus (CS), and a deflectable duodecapolar Halo catheter was placed parallel to the tricuspid annulus (TA), across the inferior vena cava (IVC)-TA isthmus, with its tip at the CS ostium (Fig. 1, B and C). Although we did not perform contrast CS venography to confirm the location of the CS ostium, we believe that the CS ostium is located near the 5 o'clock position of the mitral annulus as estimated by the shape of the CS catheter projected in the left anterior oblique fluoroscopic view, consistent with the location of the ♯17 and ♯18 poles of the CS catheter. The atrial activation sequence along the TA during ongoing tachycardia, combined with entrainment pacing at the IVC-TA isthmus, and 10 o'clock and 2 o'clock positions of the TA with a pacing cycle length of 220 ms confirmed the diagnosis of typical CCW AFL. We did not perform entrainment pacing from the CS. During entrainment pacing from any site along the TA, all atrial deflections in CS recordings immediately after the last pacing stimulus were captured with the activation sequence similar to that during the AFL and a spikeatrial interval shorter than AFL cycle length, consistent with an orthodromic capture. A line of radiofrequency energy delivery blocked conduction across the IVC-TA isthmus, terminated AFL, and restored sinus rhythm. Differential pacing from the low septal and lateral right atrial (RA) region confirmed the successful creation of bidirectional isthmus block. It is noteworthy that, during ongoing AFL before ablation, (1) a latency of low RA conduction, consistent with conduction across the septal isthmus, was observed along the distal Halo catheter (Fig. 1, D), and (2) recording of atrial activation along the CS, instead of being proximal to distal, was centrifugal from CS poles 9 to 10 (Fig. 1, D). What is the underlying electrophysiological mechanism of atypical atrial activation during typical CCW AFL?

The occasional finding of a ventricular septal defect

Certain congenital cardiac defects may go undetected for several years due to lack of symptoms and signs. Ventricular septal defects can occur as an isolate finding or as part of more congenital cardiac malformations [1–9]. The natural history of ventricular septal defects depends on the size of the defect and on the pulmonary resistance. Surgical closure, transcatheter occlusion and spontaneous closure have been reported [10–17]. We present the occasional finding of a ventricular septal defect in a 55-year-old Italian man reporting a recent history of dyspnea. He also reported a history of cancer with a successful lung lobectomy 8 years previously [18–21]. ECG (Fig. 1) has shown amild right bundle branch block [22–24] that was not seen previously. Echocardiographic evaluation revealed a ventricular septal defect a systolic shunt and with a mild right ventricular enlargement (Fig. 2 Panels A, B and C). Also this case focuses attention on the finding of a ventricular septal defect.

A New Mutation in the TBX5 Gene in Holt-Oram Syndrome: Two Cases in the Same Family and Prenatal Diagnosis

Holt-Oram Syndrome (HOS) is a rare autosomal dominant condition characterized by anomalies of the upper extremity and cardiac malformations. Mutations in the TBX5 gene are what cause HOS. The proband is an 8-year-old male who presented with upper-extremity abnormalities and a chest deformity. He was born to a nonconsanguineous marriage at full term. He has a history of ventricular septal defect. His mother presented with deformation in both hands and forearms, and was 9 weeks' pregnant. Mutation analysis for TBX5 gene revealed heterozygous p.L65Qfs*10 in both the patient and his mother. Molecular analysis of the fetus was normal for TBX5 gene in the 13th week of pregnancy. In conclusion, our case supports the fact that the HOS presents differently, case by case, even within the same family. The novel mutation reported here and phenotypic findings in the affected members may contribute to the phenotype-genotype correlation.

50 Years Ago in The Journal of Pediatrics: Natural History of Ventricular Septal Defects in Childhood Lesions with Predominant Arteriovenous Shunts

50 Years Ago in The Journal of Pediatrics: Natural History of Ventricular Septal Defects in Childhood Lesions with Predominant Arteriovenous Shunts

Contained Rupture of the Sinus of Valsalva Associated With Infective Endocarditis and Untreated Congenital Ventricular Septal Defect

Isolated sinus of Valsalva (SV) aneurysm is a rare condition that may arise in patients with congenital ventricular septal defects (VSD). Small VSDs are often left untreated because of high rate of spontaneous closure. However, complications such as aortic regurgitation and infective endocarditis may occur as complications of small VSDs. We present the case of a 19-year-old man with a history of VSD, who presented with Staphylococcus aureus endocarditis and a contained rupture of the SV into the right ventricle, which was successfully treated. In the light of this case, we believe that even small VSDs should be assessed regularly and treated before such drastic complications occur.

Natural history of ventricular septal defects in Nigerian children

Introduction. Ventricular septal defect (VSD) is a common congenital heart disease (CHD). Spontaneous closure of the VSD may occur, depending on the type and size of defects. This study was conducted to determine the natural history of VSD in a group of Nigerian children. Subjects and methods. Sixty-one children diagnosed with VSD were prospectively studied at a tertiary centre in Nigeria until they were 2 years old. They had regular two-dimensional (2D) and Doppler echocardiography evaluations for the VSD size and closure. Results. Most (35 – 57.4%) of the patients were female, their mean age at presentation was 11.2±5.2 months, and the most common type of VSD was the perimembranous (39 – 63.9%). Almost half (28 – 45.9%) of the patients had spontaneous closure. The spontaneous closure rate was highest in muscular VSD (82.4%) and in small defects (95.0%). Incidental presence of a murmur, absence of heart failure and bronchopneumonia were good clinical predictors of closure. Only 3 (4.9%) patients had surgery abroad. There were 2 (3.3%) deaths from bronchopneumonia and bacterial endocarditis. Conclusion. Spontaneous closure readily occurs in small-sized defects and muscular VSDs. However, most patients with moderate to large VSDs are confined to long-term medical management, highlighting the need for indigenous surgical capacity in Nigeria.

The chance finding of a ventricular septal defect in a 2-day-old newborn infant

Certain congenital cardiac defects may go undetected for several years due to lack of symptoms and signs.Ventricular septal defects can occur as part of more congenital cardiac malformations or as an isolate finding. The natural history of ventricular septal defects depends on the size of the defect and on the pulmonary resistance. We present a case of the chance finding of a ventricular septal defect in a 2-day-old newborn infant with an interatrial septal aneurysm.

Revelation of an asymptomatic ventricular septal defect in elderly patient before a surgical intervention

Certain congenital cardiac defects may go undetected for several years due to lack of symptoms and signs. The natural history of ventricular septal defects depends on the size of the defect and on the pulmonary resistance. In adults congenital heart disease, ventricular septal defects represent about 10% of the cases. However, the finding of a ventricular septal defect in an elderly individual > 80 years of age is extremely uncommon and only two cases have been reported in a living patient, as an accidental finding. We describe a case of an asymptomatic ventricular septal defect associated with interventricular septal hypertrophy, aortic regurgitation, mitral stenosis and regurgitation in an 83-year-old Italian man before a surgical treatment for inguinal hernia repair. To our knowledge, this is the third report of a ventricular septal defect in a living elderly individual > 80 years of age.

The natural history of ventricular septal defects in the south-western region of Saudi Arabia

To determine the natural history and spontaneous closure (SpC) of ventricular septal defect (VSD) in a cohort of patients. Using echocardiography, 86 patients with VSD were followed up for 1-168 mths (mean 66.3, SD 46.0). Mean age at diagnosis was 14 mths, 26 patients were diagnosed at < or = 1 mth (group 1) and 60 later (group 2). Types of VSD were: peri-membranous (PM-VSD) 67.4%, muscular (MU-VSD) 19.8%, inlet 7% and subpulmonary/subarterial 5.8%. SpC occurred in 16.3% of the whole group, 34.6% of group 1 and 8.3% of group 2 (p = 0.002). SpC occurred only in PM-VSDs (19%) and in MU-VSDs (17.6%). It occurred in 26.5% of the small VSDs and in none of the large VSDs. One patient (1.2%) developed endocarditis and another pulmonary vascular disease. PM-VSD was the most common type of VSD. SpC is age-dependent, occurring mainly in PM and MU-VSDs. SpC of a large VSD is unusual.

Estenose subaórtica associada a comunicação interventricular perimembranosa: acompanhamento clínico de 36 pacientes

To study the clinical pattern of subaortic stenosis associated with perimembranous ventricular septal defect. From January 1979 to June 2000, 36 children with perimembranous ventricular septal defect and fixed subaortic stenosis were followed-up regarding anatomic characteristics, evolvement, and clinical events. Age at diagnosis of subaortic stenosis ranged from 6 months to 170 months, and it was less than 1 year in only 2 children. Regarding sex, the distribution was 2:1 with a greater predominance of males. Ventricular septal defect was small in 61.0% of cases, medium in 30.56%, and large in 8.40%; the size of the septal defect decreased during follow-up in 30.56% (11 cases). In all patients, subaortic stenosis was membranous and fixed. During follow-up, 23 patients experienced evolvement of the stenosis. Surgical treatment was performed in 21 cases, and one patient underwent surgery for restenosis. Infectious endocarditis occurred in 2 patients; one of the patients died. Subaortic stenosis occurs in the natural history of ventricular septal defect usually after the first year of life, and it is progressive and requires surgery in most cases.

Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2.

Ventricular septal defects are common in human infants, but the genetic programs that control ventricular septation are poorly understood. Here we report that mice with a targeted disruption of the cardiovascular basic helix-loop-helix factor (CHF)1Hey2 gene show isolated ventricular septal defects. These defects result primarily in failure to thrive. Mice often succumbed within the first 3 wk after birth and showed pulmonary and liver congestion. The penetrance of this phenotype varied, depending on genetic background, suggesting the presence of modifier genes. Expression patterns of other cardiac-specific genes were not affected. Of the few animals on a mixed genetic background that survived to adulthood, most developed a cardiomyopathy but did not have ventricular septal defects. Our results indicate that CHF1 plays an important role in regulation of ventricular septation in mammalian heart development and is important for normal myocardial contractility. These mice provide a useful model for the study of the ontogeny and natural history of ventricular septal defects and cardiomyopathy.

Reoperation for dilatation of the pulmonary autograft after the Ross procedure

Reoperation for dilatation of the pulmonary autograft after the Ross procedure

Double-chambered right ventricle presenting in adulthood

Background. Double-chambered right ventricle is a form of right ventricular outflow tract obstruction that develops over time, often in patients with an abnormally short distance between the moderator band and pulmonary valve. This lesion typically presents in childhood or adolescence and is often accompanied by a ventricular septal defect. Only a handful of previous cases have been described in which double-chambered right ventricle occurred in adulthood. Methods. Since 1992, three patients more than 30 years old (38, 43, and 66 years of age) have presented at our institution with unusual symptoms or a previous incorrect diagnosis. We reviewed the clinical data in these patients. Results. Presenting symptoms included syncope, angina, and severe dyspnea resembling pulmonary hypertension. In 1 patient, disease was categorized as New York Heart Association class IV, and in the other 2 as class III. Coexisting anomalies included a patent foramen ovale or secundum atrial septal defect in 2 patients, a small ventricular septal defect in 1 (with a probable history of ventricular septal defect in another), and mild aortic regurgitation in 1. All patients required urgent or emergent operations, with peak pressures in the proximal right ventricular chamber of 135 to 180 mm Hg and severely depressed left ventricular function in 1 patient. Resection of the anomalous right venticular muscle bundles was achieved through a right atrial approach in all patients. All patients were alive with improved functional status at follow-up, which was between 15 and 40 months. Conclusions. Right ventricular outflow tract obstruction resulting from a double-chambered right ventricle is rare in adults, but when it does occur it can present with unusual symptoms. When evaluating the patient with signs or symptoms of primary right heart failure, cardiologists should make an effort to image the entire right heart complex. Subcostal echocardiography can facilitate adequate visualization of the right ventricle when it is difficult to distinguish the subpulmonary outflow tract from the parasternal and apical windows.

The natural history of ventricular septal defects

AIMSTo correlate the size and position of isolated ventricular septal defects with closure rate in a cohort of children with mean follow up of more than six years.DESIGNA birth cohort...