Valve Anomalies Research Articles

Prevalence of beta thalassemia, heart failure and valvular abnormalities in children at tertiary care hospital

Objective: to evaluate, stratified by age and educational attainment, the distribution of pediatric beta-thalassemia, heart failure, and valve anomalies in order to find any appreciable variations in the prevalence rates. Methods: A study using a cross-sectional design was carried out on 115 youngsters. There were two age categories of participants: 43.5 percent were between the ages of 2 and 9 and 56.5% were those over 10. Children's educational status was divided into two categories: those who attend school (8.7%) and those who do not (91.3%). Medical records were used to gather information on the prevalence of valvular anomalies, heart failure, and beta-thalassemia. P-values and other statistical analyses were used to assess the significance of variations in prevalence rates among different age and educational groups. Result: 17.4% of participants in the research had beta-thalassemia; there were no significant variations in this condition between age groups (p=0.101) or educational attainment (p=0.820). Children who attended school had a higher prevalence of heart failure (69.6%) than children who did not attend school (34.4%), however this difference was not statistically significant (p=0.625). Children who did not attend school (38.2%) had considerably higher rates of valve anomalies than children who attended school (8.6%); a p-value of less than 0.001 indicated a highly significant difference. Conclusion: The study finds no significant changes in the prevalence of beta-thalassemia or heart failure across age and educational status, but it does show a substantial difference in the prevalence of valvular anomalies between children who attend school and those who do not. These results highlight how crucial it is to address socio-economic and educational gaps in order to improve health outcomes for communities that are already at risk.

Exploring chest wall deformities in childhood and adolescence: insights from a case-control study

BackgroundChest wall deformities, though relatively uncommon in childhood and adolescence, significantly affect aesthetic perception and can impact cardiac and respiratory function. This study aims to compare individuals with pectus deformities to a healthy control group, shedding light on the condition’s etiology and prognosis.MethodConducted as a case-control study between 2020 and 2022, the research included a case group of 71 patients with pectus excavatum or pectus carinatum who were followed up at the Pediatric Cardiology outpatient clinic. The control group consisted of 80 children without chronic diseases. Researchers retrospectively reviewed patient files, recording demographic data, echocardiography findings, and serum levels of calcium, phosphate, vitamin D, and alkaline phosphatase.ResultsPatients with chest wall deformities exhibited significantly lower serum levels of vitamin D, calcium, and phosphorus compared to those without deformities. Males constituted 77% of the case group, with 15.5% exhibiting abnormal echocardiogram results, with mitral valve anomalies being most prevalent.ConclusionWhile pectus deformities may lead to cardiac or respiratory issues, patient concerns often center around aesthetics. Unlike typical studies focused on surgical techniques and postoperative patients, our study focused on all diagnosed patients. Findings emphasize the importance of monitoring calcium, phosphorus, and vitamin D levels in pectus patients to manage surgical risks and facilitate recovery.

Anatomical variations and embryological basis of arch of aorta and aortic valve.

Variations in the arch of the aorta and aortic valves among fetal, cadaveric, and post-mortem specimens present a spectrum of anatomical configurations, posing challenges in establishing a standard norm. While some variations hold surgical significance, many bear little functional consequence but provide insights into embryological origins. The aortic arch exhibits diverse branching patterns, including common trunks and different orders, relevant for endovascular surgeries. Meanwhile, malformations in the aortic valve, affecting the aorta, may lead to ischemia and cerebral infarction, warranting understanding of coexisting arch and valve anomalies to predict complications like aortic dissection. Studies in the Indian population mirror global variations, underscoring the need to explore embryological, clinical, and surgical implications for safer vascular surgeries involving the aortic arch and valves. The study's objectives included examining branching patterns, diameters, and distances between arch branches and exploring aortic valve variations. Employing a cross-sectional design, the study was conducted across Anatomy, Forensic Medicine, and Obstetrics and Gynecology departments. A sample of 100, comprising cadavers, fetuses, and postmortem specimens, were gathered. Specimens ranged from 14weeks of intrauterine life to 85years, with intact thoracic cages as inclusion criteria. Methodology involved dissection, specimen fixation, and macroscopic examination for variations and morphological parameters. Results showed aortic diameter increase with age, with significant gender differences. A statistically significant association between arch variations and anomalous valves was observed, suggesting mutual predictability. Individuals with valve anomalies should undergo comprehensive cardiology evaluation to avert complications like aortic dissection during endovascular surgeries. While atheromatous plaques were prevalent in younger groups, their frequency rose with age, necessitating vigilant vascular monitoring. Careful handling during surgeries is paramount, given potential adverse outcomes resulting from variations. Overall, the study underscores the importance of comprehensive anatomical understanding in clinical contexts, guiding effective management strategies and ensuring patient safety in vascular surgeries.

Congenital Heart Defects in Patients with Molecularly Confirmed Sotos Syndrome.

Sotos syndrome is an autosomal dominant condition characterized by overgrowth with advanced bone age, macrodolicocephaly, motor developmental delays and learning difficulties, and characteristic facial features caused by heterozygous pathogenetic variants in the NSD1 gene located on chromosome 5q35. The prevalence of heart defects (HDs) in individuals with Sotos syndrome is estimated to be around 15-40%. Septal defects and patent ductus arteriosus are the most commonly diagnosed malformations, but complex defects have also been reported. The aim of our study was to analyze the prevalence of HD, the anatomic types, and the genetic characteristics of 45 patients with Sotos syndrome carrying pathogenetic variants of NSD1 or a 5q35 deletion encompassing NSD1, who were followed at Bambino Gesù Children's Hospital in Rome. Thirty-nine of the forty-five patients (86.7%) had a mutation in NSD1, while six of the forty-five (13.3%) had a deletion. Most of the patients (62.2%, 28/45) were male, with a mean age of 14 ± 7 years (range 0.2-37 years). A total of 27/45 (60.0%) of the patients had heart defects, isolated or combined with other defects, including septal defects (12 patients), aortic anomalies (9 patients), mitral valve and/or tricuspid valve dysplasia/insufficiency (1 patient), patent ductus arteriosus (3 patients), left ventricular non-compaction/hypertrabeculated left ventricle (LV) (4 patients), aortic coarctation (1 patient), aortopulmonary window (1 patient), and pulmonary valve anomalies (3 patients). The prevalences of HD in the two subgroups (deletion versus intragenic mutation) were similar (66.7% (4/6) in the deletion group versus 58.91% (23/39) in the intragenic variant group). Our results showed a higher prevalence of HD in patients with Sotos syndrome in comparison to that described in the literature, with similar distributions of patients with mutated and deleted genes. An accurate and detailed echocardiogram should be performed in patients with Sotos syndrome at diagnosis, and a specific cardiological follow-up program is needed.

Clinical Presentation and Therapy of Semilunar Valve and Aortic Arch Anomalies.

The following semilunar valve defects and aortic arch anomalies are called simple defects because there is a single problem that can be well described. Based on the degree of malformation and hemodynamic consequence, these simple lesions can however be life threatening immediately after birth. They all affect either the left or right outflow tract or the aortic arch.

Human Genetics of Semilunar Valve and Aortic Arch Anomalies.

Lesions of the semilunar valve and the aortic arch can occur either in isolation or as part of well-described clinical syndromes. The polygenic cause of calcific aortic valve disease will be discussed including the key role of NOTCH1 mutations. In addition, the complex trait of bicuspid aortic valve disease will be outlined, both in sporadic/familial cases and in the context of associated syndromes, such as Alagille, Williams, and Kabuki syndromes. Aortic arch abnormalities particularly coarctation of the aorta and interrupted aortic arch, including their association with syndromes such as Turner and 22q11 deletion, respectively, are also discussed. Finally, the genetic basis of congenital pulmonary valve stenosis is summarized, with particular note to Ras-/mitogen-activated protein kinase (Ras/MAPK) pathway syndromes and other less common associations, such as Holt-Oram syndrome.

Molecular Pathways and Animal Models of Semilunar Valve and Aortic Arch Anomalies.

The great arteries of the vertebrate carry blood from the heart to the systemic circulation and are derived from the pharyngeal arch arteries. In higher vertebrates, the pharyngeal arch arteries are a symmetrical series of blood vessels that rapidly remodel during development to become the asymmetric aortic arch arteries carrying oxygenated blood from the left ventricle via the outflow tract. At the base of the aorta, as well as the pulmonary trunk, are the semilunar valves. These valves each have three leaflets and prevent the backflow of blood into the heart. During development, the process of aortic arch and valve formation may go wrong, resulting in cardiovascular defects, and these may, at least in part, be caused by genetic mutations. In this chapter, we will review models harboring genetic mutations that result in cardiovascular defects affecting the great arteries and the semilunar valves.

CASE-FA-03 - An Unusual Case of Congenitally Corrected Transposition of the Great Arteries with Situs Inversus, Levocardia, and Pulmonary Stenosis Due to Mitral Valve Anomalies

CASE-FA-03 - An Unusual Case of Congenitally Corrected Transposition of the Great Arteries with Situs Inversus, Levocardia, and Pulmonary Stenosis Due to Mitral Valve Anomalies

Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation.

A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family members have been reported to be able to modulate cardiovascular development and diseases. The present study aimed to further investigate the roles of ADAMTS family members in aortic valve development and BAV formation. Morpholino-based ADAMTS family gene-targeted screening for zebrafish heart outflow tract phenotypes combined with DNA sequencing in a 304 cohort BAV patient registry study was initially carried out to identify potentially related genes. Both ADAMTS gene-specific fluorescence in situ hybridization assay and genetic tracing experiments were performed to evaluate the expression pattern in the aortic valve. Accordingly, related genetic mouse models (both knockout and knockin) were generated using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) method to further study the roles of ADAMTS family genes. The lineage-tracing technique was used again to evaluate how the cellular activity of specific progenitor cells was regulated by ADAMTS genes. Bulk RNA sequencing was used to investigate the signaling pathways involved. Inducible pluripotent stem cells derived from both BAV patients and genetic mouse tissue were used to study the molecular mechanism of ADAMTS. Immunohistochemistry was performed to examine the phenotype of cardiac valve anomalies, especially in the extracellular matrix components. ADAMTS genes targeting and phenotype screening in zebrafish and targeted DNA sequencing on a cohort of patients with BAV identified ADAMTS16 (a disintegrin and metalloproteinase with thrombospondin motifs 16) as a BAV-causing gene and found the ADAMTS16 p. H357Q variant in an inherited BAV family. Both in situ hybridization and genetic tracing studies described a unique spatiotemporal pattern of ADAMTS16 expression during aortic valve development. Adamts16+/- and Adamts16+/H355Q mouse models both exhibited a right coronary cusp-noncoronary cusp fusion-type BAV phenotype, with progressive aortic valve thickening associated with raphe formation (fusion of the commissure). Further, ADAMTS16 deficiency in Tie2 lineage cells recapitulated the BAV phenotype. This was confirmed in lineage-tracing mouse models in which Adamts16 deficiency affected endothelial and second heart field cells, not the neural crest cells. Accordingly, the changes were mainly detected in the noncoronary and right coronary leaflets. Bulk RNA sequencing using inducible pluripotent stem cells-derived endothelial cells and genetic mouse embryonic heart tissue unveiled enhanced FAK (focal adhesion kinase) signaling, which was accompanied by elevated fibronectin levels. Both in vitro inducible pluripotent stem cells-derived endothelial cells culture and ex vivo embryonic outflow tract explant studies validated the altered FAK signaling. Our present study identified a novel BAV-causing ADAMTS16 p. H357Q variant. ADAMTS16 deficiency led to BAV formation.

Abstract EC.09: Single Nuclei RNA Sequencing Analysis Of Mybpc-3- Associated HCM To Identify Common Pathological Mechanisms In Human, Feline, And Murine Hearts

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease characterized by unexplained hypertrophy, often associated with left ventricular outflow tract (LVOT) obstruction, ventricular tachyarrhythmias, diastolic heart failure, and sudden cardiac death. Mutations in mybpc3 are the most common genetic mutations associated with human and feline HCM. To understand how mutations in mybc3 causing sarcomere dysfunction result in the development of non-myocyte phenotypes such as fibrosis, mitral valve anomalies, and microvascular occlusion across species, we generated single nuclei RNA-sequencing datasets from feline, human and murine heart tissue carrying mybpc3 variants. We analyzed these datasets for differential gene expression by genotype for each cell type and assessed changes in cell-cell communication by ligand-receptor analysis. Gene Ontology (GO) enrichment analysis of differentially expressed genes (DEGs) in feline cardiomyocytes revealed alteration in regulation of calcium ion transmembrane transporter activity, regulation of cation channel activity, and extracellular matrix structure and organization, consistent with known phenotypic aspects of HCM such as calcium dyshomeostasis and fibrosis. DEGs in cardiomyocytes of human tissues revealed novel obstruction of cGMP-mediated signaling, protein O-linked glycosylation and negative regulation of cAMP-mediated signaling. DEGs in murine cardiomyocytes affected cardiac muscle thin filament assembly, CDP-diacylglycerol biosynthesis and cell adhesion molecule production. Analysis of intercellular communication in feline and murine hearts revealed an overall loss of ligands broadcast from all cell types, with notable losses from fibroblast cells and cardiomyocytes. These findings are consistent with recent studies implicating altered intercellular communication between cardiomyocytes and non-myocyte cell types as a potential disease mechanism in human HCM. We will further identify common and species-specific disease-promoting pathways in HCM tissue that will allow identification of conserved disease mechanisms that may be targeted in both human and feline disease and will facilitate an understanding of the relevance of mouse models.

P86 WHEN THE HEMATOLOGIST HAS THE SOLUTION – A RARE CASE OF HEART FAILURE

Abstract Introduction Cardiologists are confident with heart failure due to cardiac etiology, but sometimes this may be due to other organs‘ dysfunction (e.g. endocrine problems); in this case we report a very rare cause of anasarca due to hematologic disease. Case report A 33 year old man with a known complete left bundle branch block and without other pathologies is admitted to the ED for sickness and abdominal pain. Low platelet count, splenomegaly and an anterior mediastinal mass (53x54mm) are found. A Positron Emission Tomography (PET) reveals multiple lymphnodes captation above and under the diaphragm and at mediastinal level. Bone marrow biopsy is consistent with myelofibrosis. During the hospitalization the patient experiences an important weight gain (14 kg) with edema and worsening renal function suspected for heart failure; echocardiogram shows a globally hypokinetic left ventricle with moderately reduced ejection fraction (EF 37%), mild pericardial effusion, no relevant valve anomalies; cardiac MRI confirmed moderately depressed EF with global hypokinesia and no LGE anomalies of the myocardial wall; a clinical benefit is noted with high dose i.v. diuretics, and echocardiogram findings rapidly improve with therapy, EF 49% after decongestion; a discrepancy is noted between the severity of anasarca and echocardiographic data; ultimately, lymph node biopsy is performed, which is consistent with Castleman disease, HHV 8 negative. TAFRO (Thrombocytopenia, Anasarca, Fever, Reticulin myelofibrosis/Renal dysfunction, Organomegaly) syndrome is therefore diagnosed. Therapy with siltuximab (anti IL–6) is started with good clinical response on lymph nodes enlargement and on anasarca, and the patient is currently followed–up by the hematologists of our institution. Discussion TAFRO syndrome is a very rare hematologic disease that can manifest with severe anasarca; usually it presents with non–cardiac features, but cardiologists should be aware of this disease as they could be involved in the management of this condition, especially in the fist stages when the diagnosis has not yet been made.

Quadricuspid Pulmonary Valve with Pulmonary Artery Aneurysm.

HomeRadiologyRecently Published PreviousNext Reviews and CommentaryFree AccessImages in RadiologyQuadricuspid Pulmonary Valve with Pulmonary Artery AneurysmAyşe Füsun Bekirçavuşoğlu , Süleyman BekirçavuşoğluAyşe Füsun Bekirçavuşoğlu , Süleyman BekirçavuşoğluAuthor AffiliationsFrom the Bursa City Hospital, Doğanköy mah, 16110 Nilüfer, Bursa, Turkey.Address correspondence to A.F.B. (email: [email protected]).Ayşe Füsun Bekirçavuşoğlu Süleyman BekirçavuşoğluPublished Online:May 16 2023MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 70-year-old female patient had repeatedly sought medical attention, and a subsequent chest radiograph showed enlargement in the pulmonary artery. Coronary CT angiography (CCTA) was performed, showing a quadricuspid pulmonary valve and aneurysmal enlargement of the pulmonary artery (diameter of 57 mm) (Figure). This was conservatively managed, and the patient is doing well.Images in a 70-year-old woman with multiple symptoms. (A) Chest radiograph shows an enlarged pulmonary artery (arrows). (B) Multiplanar reformatted coronary CT angiography (CCTA) scan shows a quadricuspid pulmonary valve (leaflets are numbered as 1, 2, 3, 4 [arrow]), with one smaller cusp (leaflet number 4). (C) Volume-rendered CCTA scan demonstrates aneurysmal dilatation of the pulmonary trunk and its main branches. Ao = aorta, LA = left atrium.Download as PowerPointOpen in Image Viewer The quadricuspid pulmonary valve is a rare congenital anomaly with a prevalence reported from one in 400 to one in 1000 in postmortem specimens (1). Although usually isolated, it may be associated with patent ductus arteriosus, atrial or ventricular septal defects, and aortic valve anomalies (2,3). Aneurysms of the pulmonary arteries are also rare, with a prevalence of 1:14000 in autopsy series (4). There are a limited number of cases associated with quadricuspid pulmonary valve (3–5). CCTA is a useful tool in the evaluation of rare anomalies that are difficult to evaluate with echocardiography.Disclosures of conflicts of interest: A.F.B. No relevant relationships. S.B. No relevant relationships.Data sharing: No data were generated or analyzed during the study.

Congenital aortic valve stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics.

Congenital aortic valve stenosis (AVS) is one of the most common valve anomalies and accounts for 3%-6% of cardiac malformations. As congenital AVS is often progressive, many patients, both children and adults, require transcatheter or surgical intervention throughout their lives. While the mechanisms of degenerative aortic valve disease in the adult population are partially described, the pathophysiology of adult AVS is different from congenital AVS in children as epigenetic and environmental risk factors play a significant role in manifestations of aortic valve disease in adults. Despite increased understanding of genetic basis of congenital aortic valve disease such as bicuspid aortic valve, the etiology and underlying mechanisms of congenital AVS in infants and children remain unknown. Herein, we review the pathophysiology of congenitally stenotic aortic valves and their natural history and disease course along with current management strategies. With the rapid expansion of knowledge of genetic origins of congenital heart defects, we also summarize the literature on the genetic contributors to congenital AVS. Further, this increased molecular understanding has led to the expansion of animal models with congenital aortic valve anomalies. Finally, we discuss the potential to develop novel therapeutics for congenital AVS that expand on integration of these molecular and genetic advances.

The association of congenital heart defects with prenatal exposure to air pollutants: An umbrella review

Background and aim: For idiopathic congenital heart defects (CHD), air pollution during fetal development is a potential risk factor. However, findings of previous epidemiological studies and consequently of systematic reviews, have been mixed. We aimed to synthesize and evaluate the extant evidence on associations between gestational exposure to air pollutants and CHD subtypes, using a systematic review of reviews approach ("umbrella review”). Methods: We systematically searched PubMed, Embase, and Epistemonikos for published and unpublished systematic reviews. The search was supplemented by the use of internet search engines and hand-searching of reference lists. The Risk of Bias in Systematic Reviews ("ROBIS”) tool was used to evaluate included systematic reviews. Results: We identified ten systematic reviews, including eight meta-analyses. Moderately strong evidence for an increased risk of coarctation of the aorta following prenatal exposure to NO2 was provided by five reviews, which reported statistically homogeneous pooled odds ratios of 1.10 to 1.20 (95% confidence interval range: 0.99 to 1.41). Also, there was limited evidence for positive associations between SO2 and coarctation of the aorta, PM10 and atrial septal defects, NO2 and pulmonary artery and valve anomalies, and for both, PM2.5 and NO2 and Tetralogy of Fallot. Findings for other pollutant-CHD associations were inconsistent. Based on the ROBIS tool, a high or unclear risk of bias rating was assigned to eight out of ten reviews. Conclusion: Beyond the increased risk of coarctation of the aorta following exposure to NO2, a clear pollutant-outcome pattern was not identified. These incoherent findings may partly be explained by differences in methods used across the reviews (e.g., inclusion criteria) as well as between individual studies (e.g., exposure and outcome assessment methods). Further establishment of and adherence to systematic review methods for environmental exposures and children’s health may improve the validity and consistency of future systematic review findings.

Mitral valve anomalies in transposition of the great arteries: Anatomical features, surgical management and outcomes

Mitral valve (MV) anomalies can be associated with transposition of the great arteries (TGA), but their influence on the choice of the surgical technique and the outcomes after anatomical repair, mainly mitral regurgitation (MR) and LVOT obstruction, have rarely been addressed. Our study objectives are to describe the MV anomalies found in patients with TGA, the different surgical procedures performed and the fate of the anomalous MV. From 1990 to 2020, 52 patients out of 1590 (3.3%) were identified. Main MV anomalies were a mitral cleft (88%) and anomalies of the subvalvular apparatus (60%) such as abnormal chordae attachments (16/52, 30.8%), straddling (6/52, 11.5%), accessory tissue (7/52, 13.5%) or an abnormal papillary muscle (4/52, 7.7%). The mitral cleft was described as anterior (ejection/outflow tract) in 40 and as AVSD-type in 6. A ventricular septal defect (VSD) was associated in 88.5% (58% outlet) ( Fig. 1 ). Main surgical procedure performed at repair was the arterial switch operation (ASO) ( n = 47, 90.4%). Two patients (3.8%) underwent a Bex-Nikaidoh procedure, 2 (3.8%) a half turned truncal rotation and 1 (1.9%) a “reparation à l’étage ventriculaire” (REV) procedure. Overall survival was 90% at 1 year and 88% at 10 and 20 years during a mean follow-up period of 9.5 years. Ten patients (19.2%) had a concomitant mitral procedure at repair (cleft closure in 7, procedure on the subvalvular apparatus in 6), of which 4 had a preoperative grade ≥ 2 MR. Five patients required reoperation for MR and/or for left ventricle outflow tract obstruction (LVOTO), none of them had previously undergone a mitral procedure at repair. All five underwent cleft closure, with LVOTO relief in 3. Freedom from MV reoperation was 96% at 1 year, 93% at 5 years, and 84.5% at 20 years. Main MV anomalies in TGA are the presence of an anterior cleft and abnormalities of the subvalvular apparatus, frequently associated with an outlet VSD. Mortality and reoperation rates are higher than in the other subtypes of TGA. Mitral repair at initial surgery should be considered only in cases of MR or LVOTO. Reoperation involves cleft closure and LVOTO relief. No MV replacement was required.

P393 MULTIMODALITY IMAGING IN ACROMEGALIC CARDIOMIOPATHY: A CASE REPORT

Abstract Background Acromegaly is a disease caused by an excessive production of GH. Cardiac involvement, called acromegalic cardiomyopathy, is present in 90% of cases. Clinical Presentation A 56–year–old woman with acromegaly from pituitary adenoma, hypertension and obesity undewent angioCT showing thoracic aortic aneurysm (Figure 1). She was referred to a cardiological visit to evaluate the possible presence of acromegalic heart disease. The EKG showed signs of left ventricular hypertrophy (LVH) and so transthoracic echocardiogram (TTE) was prescribed: it showed slightly dilated, very hypertrophic left ventricle with ejection fraction of about 50% and signs of diastolic dysfunction. The exam also highlighted moderate to severe aortic valve regurgitation (Figure 2). In order to better characterize the cardiomyopathy a Cardiac magnetic resonance with contrast media (CMR) was performed: cine images confirmed severe left ventricular hypertrophy associated with mild dilatation, global biventricular hypertrophy and hypokinesia. After contrast media administration, a diffuse mild–enhancement pattern was found, a possible expression of diffuse interstitial fibrosis (Figure 3). In consideration of the dilatation of the ascending aorta and the contextual valve insufficiency, the patient was referred for cardiac surgery outpatient visit. Discussion The most frequent manifestations of acromegalic cardiomyopathy are bi–ventricular hypertrophy, the presence of diastolic and systolic dysfunction and the presence of valve regurgitation. Concentric hypertrophy is due to the increase in cardiomyocytes secondary to the GH stimulus and it is often bi–ventricular. Another characteristic finding is diffuse interstitial fibrosis with consequent systo–diastolic dysfunction and heart rhythm abnormalities. Aortic valve anomalies are linked to matrix abnormalities and myxoid degeneration. Conclusions this case can be considered an example of acromegalic heart disease. Multimodality imaging plays a key role in the early diagnosis of cardiac involvement and therefore it allows an early start of therapeutic strategy. Additionally, it is useful for the risk stratification of acromegalic patient.

Altered intercellular communication and extracellular matrix signaling as a potential disease mechanism in human hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is considered a primary disorder of the sarcomere resulting in unexplained left ventricular hypertrophy but the paradoxical association of nonmyocyte phenotypes such as fibrosis, mitral valve anomalies and microvascular occlusion is unexplained. To understand the interplay between cardiomyocyte and nonmyocyte cell types in human HCM, single nuclei RNA-sequencing was performed on myectomy specimens from HCM patients with left ventricular outflow tract obstruction and control samples from donor hearts free of cardiovascular disease. Clustering analysis based on gene expression patterns identified a total of 34 distinct cell populations, which were classified into 10 different cell types based on marker gene expression. Differential gene expression analysis comparing HCM to Normal datasets revealed differences in sarcomere and extracellular matrix gene expression. Analysis of expressed ligand-receptor pairs across multiple cell types indicated profound alteration in HCM intercellular communication, particularly between cardiomyocytes and fibroblasts, fibroblasts and lymphocytes and involving integrin β1 and its multiple extracellular matrix (ECM) cognate ligands. These findings provide a paradigm for how sarcomere dysfunction is associated with reduced cardiomyocyte secretion of ECM ligands, altered fibroblast ligand-receptor interactions with other cell types and increased fibroblast to lymphocyte signaling, which can further alter the ECM composition and promote nonmyocyte phenotypes.

Congenital Heart Disease in Adults with Autosomal Dominant Polycystic Kidney Disease

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is caused mainly by pathogenic variants in PKD1 or PKD2 encoding the polycystin-1 and -2 proteins. Polycystins have shown to have an essential role in cardiac development and function in animal models. In the current study, we describe the clinical association between ADPKD and congenital heart disease (CHD). Methods: Medical records from Mayo Clinic were queried for all patients with confirmed ADPKD and CHD between 1993 and 2020. CHD was categorized into left-to-right shunt, obstructive, and complex lesions. Patent foramen ovale, mitral valve prolapse, and bicuspid aortic valve anomalies were excluded. Results: Twenty-five out of 1,359 (1.84%) ADPKD patients were identified to have CHD. Of these, 84% were Caucasians and 44% were males. The median (Q1–Q3) age (years) at CHD diagnosis was 12.0 (2.0–43.5). Fourteen patients (56%) had left-to-right shunt lesions, 6 (24%) had obstructive lesions and 5 (20%) complex lesions. Seventeen patients (68%) had their defects surgically corrected at a median age (Q1–Q3) of 5.5 (2.0–24.7). Among 13 patients with available genetic testing, 12 (92.3%) had PKD1 pathogenic variants, and none had PKD2. The median (Q1–Q3) age at last follow-up visit was 47.0 (32.0–62.0) and median (Q1–Q3) eGFR was 35.8 (11.4–79.0) mL/min/1.73 m². Three patients (12%) died; all of them had left-to-right shunt lesions. Discussion/Conclusion: We observed a higher CHD frequency in ADPKD than the general population (1.84 vs. 0.4%). While only PKD1 pathogenic variants were identified in this cohort, further studies are needed to confirm this novel finding and understand the role of polycystins in the development of the heart and vessels.

Possible Association of Pulmonary Atresia with In-Utero Coxsackievirus B Exposure

Gestational viral infection has been associated with congenital heart disease (CHD). Few studies, however, have studied the potential role of gestational Coxsackievirus B (CVB) exposure in the pathogenesis of CHD. We prospectively enrolled women with pregnancies affected by CHD to explore possible associations with in utero CVB exposure. Serum samples were obtained from 122 women referred for fetal echocardiography between 2006 and 2018. We quantified CVB IgG and IgM levels, with titers ≥ 15.0 U/mL considered positive and measured neutralizing antibodies for three CVB serotypes: CVB1, CVB3, and CVB4. Using data from the national enterovirus surveillance system, we compared the annual exposure rates for each serotype in our cohort to infections reported across the United States. 98 pregnancies with no genetic defects were included. Overall, 29.6% (29/98) had positive IgG and 4.1% (4/98) of women had positive CVB IgM titers. To explore first-trimester CVB exposure, we focused exclusively on the 26 women with positive IgG and negative IgM titers. 61.5% (16/26) had neutralizing antibodies against a single serotype and 38.5% (10/26) against multiple CVB serotypes. CVB4 neutralizing antibodies were the most common (65.4%, 17/26), followed by CVB3 (53.9%, 14/26) and CVB1 (30.8%, 8/26). Among these, 30.8% of babies presented pulmonary valve anomalies: 19.2% (5/26) pulmonary atresia, and 11.5% (3/26) pulmonary stenosis. 23.1% (6/26) of babies had coronary sinusoids. CVB exposure in our cohort mirrored that of reported infections in the United States. Our results suggest a possible association between gestational CVB exposure and specific CHD, particularly pulmonary valve anomalies and coronary sinusoids.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00246-021-02805-9.

Is There a Functional Role of Mitochondrial Dysfunction in the Pathogenesis of ARPKD?

Polycystic kidney diseases (PKD) form a group of severe genetic kidney diseases that are characterized by fibrocystic changes of the kidneys and the liver. The main forms of PKD are autosomal dominant and autosomal recessive polycystic kidney disease (ADPKD, ARPKD). In general, cystic kidney diseases are the most common genetic cause of chronic kidney failure in both children and adults (1). ARPKD is a disorder that typically is diagnosed very early in life or even prenatally. Typically, the kidneys show bilateral massive enlargement although they keep their reniform shape. Kidney disease results in a need for kidney replacement therapy (KRT) in around 50% of patients in the first two decades of life (2, 3). Liver involvement is obligatory in ARPKD, typically presenting with congenital hepatic fibrosis and portal hypertension or with dilated bile ducts. Both are considered to be a consequence of a defect during development of the bile ducts (“ductal plate malformation”) (4). Adult patients with ARPKD have been described with variable disease manifestations. Hepatic disease may be the leading clinical issue in adults with ARPKD (5). In ADPKD renal cystogenesis starts early in life or even before birth but does not present with obvious clinical symptoms until adulthood in most patients (1, 6, 7). Liver involvement is typically characterized by liver cysts. Additional extrarenal symptoms in ADPKD include for example intracranial aneurysms, cardiac valve anomalies like mitral prolapse or abdominal wall diverticula in a subset of patients (1, 7). Extrarenal manifestations may be very helpful for clinical differential diagnosis and to distinguish ADPKD from ARPKD. ADPKD is mainly caused by variants in the genes PKD1 and PKD2 with the large majority of patients carrying PKD1 variants (1). Variants in other genes e.g., with atypical forms of ADPKD have been identified (7). Variants in PKHD1 are the main cause of ARPKD with phenotypical overlay e.g., of kidney disease in patients with other underlying genetic changes (1, 8), including biallelic hypomorphic PKD1 variants. Genotype-phenotype correlations in ADPKD show more rapid progression of kidney disease in patients with PKD1 variants and especially in those patients carrying variants resulting in protein truncation (7, 9). For ARPKD it was shown by various groups that biallelic truncating variants are associated with severe phenotypes. A recent study extended the findings and revealed that for missense variants the affected region in PKHD1 also seems to be important (10). In a study on 304 children with the clinical diagnosis of ARPKD and detected PKHD1 variants it was found that patients with either two missense variants affecting the amino acids 709–1837 or a null variant and a missense variant in this region less frequently showed progression to chronic kidney failure when being compared during their follow-up when compared to patients with variants affecting other regions of PKHD1. On the other hand patients with variants affecting the amino acids 2625–4074 showed less favorable hepatic outcome (10). The underlying molecular mechanisms of these associations remain to be explored.