Comorbidity and Multimorbidity in Adults With Congenital Heart Disease: Findings From a Multi-Site Population-Based Study.

Background: Survival of individuals with congenital heart disease (CHD) has improved, leading to a growing and aging population of adults living with these conditions. Over their lifetime, they often face an array of comorbidities that affect outcomes and complicate medical management. However, population-based information on such comorbidities is scarce, reducing opportunities for prevention.

Helix-fixed leadless pacemaker implantation through a valve-in-valve tricuspid prosthesis via the femoral approach.

Leadless pacemakers offer the opportunity to avoid transvenous hardware among patients with tricuspid valve prostheses. We present the first case of a helix-based fixation leadless pacemaker implanted through valve-in-valve tricuspid prostheses in a 43-year-old female with extensive prior cardiac history. At the time of presentation, epicardial pacing was no longer a viable option in the setting of pacemaker dependence.

De Novo Brain Vascular Malformations in Hereditary Hemorrhagic Telangiectasia.

Background: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT diagnosis in children but do not address rescreening.

Brain AVM compactness score in children with hereditary hemorrhagic telangiectasia.

Objective: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population.

Methods: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC.

Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice.

Background: PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans.

Reply to Eker et al. Comment on "Kilian et al. Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT. 2023, , 2704".

We are grateful to Eker et al. for their thoughtful analysis and response to our publication titled Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT [..

Frequency of epistaxis and telangiectasia in patients with hereditary hemorrhagic telangiectasia (HHT) in comparison with the general population: Curaçao diagnostic criteria revisited.

Purpose: The Curaçao criteria are well-established diagnostic criteria for hereditary hemorrhagic telangiectasia (HHT), but they lack details regarding a predictive presentation of epistaxis and telangiectasias. This study collects and compares data in HHT and population cohorts to inform the application of these criteria.

Methods: In-person interviews regarding epistaxis and targeted examination for telangiectases in a general population cohort (n = 204) and an HHT cohort (n = 432) were conducted.

Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterized by the development of vascular malformations (VMs) in organs such as the brain and lungs, as well as telangiectases on mucosal surfaces. Prophylactic treatment of organ VMs may prevent potential complications, such as hemorrhage. However, brain VM treatment-surgical resection, embolization, and/or radiosurgery-is not recommended for all patients due to the associated risks.

Choroidal melanoma with synchronous Fuchs' adenoma and novel ATRX mutation.

Background: To report a case of Fuchs' adenoma occurring in an eye with a large choroidal melanoma. We have reviewed the literature to describe the clinical presentation, ultrasound characteristics and pathological features of these entities.

Case Presentation: A 69-year-old Caucasian man presented with vision loss from a large choroidal melanoma.

Late-in-life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts.

Protein quality control mechanisms decline during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age-associated cardiac dysfunction. Macroautophagy is the process by which post-mitotic cells such as cardiomyocytes clear defective proteins and organelles.

Association between pregnancy and long-term cardiac outcomes in individuals with congenital heart disease.

Background: As early life interventions for congenital heart disease improve, more patients are living to adulthood and are considering pregnancy. Scoring and classification systems predict the maternal cardiovascular risk of pregnancy in the context of congenital heart disease, but these scoring systems do not assess the potential subsequent risks following pregnancy. Data on the long-term cardiac outcomes after pregnancy are unknown for most lesion types.

Cardiac-specific deletion of voltage dependent anion channel 2 leads to dilated cardiomyopathy by altering calcium homeostasis.

Voltage dependent anion channel 2 (VDAC2) is an outer mitochondrial membrane porin known to play a significant role in apoptosis and calcium signaling. Abnormalities in calcium homeostasis often leads to electrical and contractile dysfunction and can cause dilated cardiomyopathy and heart failure. However, the specific role of VDAC2 in intracellular calcium dynamics and cardiac function is not well understood.

Systemic and CNS manifestations of inherited cerebrovascular malformations.

Cerebrovascular malformations occur in both sporadic and inherited patterns. This paper reviews imaging and clinical features of cerebrovascular malformations with a genetic basis. Genetic diseases such as familial cerebral cavernous malformations and hereditary hemorrhagic telangiectasia often have manifestations in bone, skin, eyes, and visceral organs, which should be recognized.

Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia.

Description: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications.

Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation.

Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in , , or Disease onset is earlier and more severe in individuals with mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kinase kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation by lipopolysaccharide derived from the gut microbiome.

Biomarkers of cavernous angioma with symptomatic hemorrhage.

BACKGROUNDCerebral cavernous angiomas (CAs) with a symptomatic hemorrhage (CASH) have a high risk of recurrent hemorrhage and serious morbidity.METHODSEighteen plasma molecules with mechanistic roles in CA pathobiology were investigated in 114 patients and 12 healthy subjects. The diagnostic biomarker of a CASH in the prior year was derived as that minimizing the Akaike information criterion and validated using machine learning, and was compared with the prognostic CASH biomarker predicting bleeding in the subsequent year.

A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.

Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes. Midline cleft defects are present at birth. Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.

Localization and age distribution of telangiectases in children and adolescents with hereditary hemorrhagic telangiectasia: A retrospective cohort study.

Background: The location of telangiectases in hereditary hemorrhagic telangiectasia (HHT), as set forth in the consensus diagnostic (Curaçao) criteria, is based primarily on adults.

Objective: Document the locations and numbers of telangiectases in a cohort of pediatric patients with HHT.

Methods: A retrospective chart review using a standardized data collection form for site and number of telangiectases was performed for pediatric patients with HHT (age, 0-18 years) from 2005 to 2016.

Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial.

Background: More than a million Americans harbor a cerebral cavernous angioma (CA), and those who suffer a prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may confer a therapeutic benefit.

Objective: To evaluate whether atorvastatin produces a difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM) on magnetic resonance imaging in CAs that have demonstrated a symptomatic hemorrhage in the prior year.

Genome sequencing reveals a deep intronic splicing mutation hotspot in Hereditary Haemorrhagic Telangiectasia.

Introduction: Hereditary haemorrhagic telangiectasia (HHT) is a genetically heterogeneous disorder caused by mutations in the genes , , and Yet the genetic cause remains unknown for some families even after exhaustive exome analysis. We hypothesised that non-coding regions of the known HHT genes may harbour variants that disrupt splicing in these cases.

Methods: DNA from 35 individuals with clinical findings of HHT and 2 healthy controls from 13 families underwent whole genome sequencing.

The effects of nasal closure on quality of life in patients with hereditary hemorrhagic telangiectasia.

Introduction: Epistaxis is the most common symptom of hereditary hemorrhagic telangiectasia (HHT). Complete nasal closure is one of the treatment options for patients with severe, intractable epistaxis. In our experience, this surgery can be life changing in a positive sense; but many patients as well as their physicians understandably fear that such a procedure will diminish certain aspects of quality of life (QOL).

Plasma Biomarkers of Inflammation and Angiogenesis Predict Cerebral Cavernous Malformation Symptomatic Hemorrhage or Lesional Growth.

Rationale: The clinical course of cerebral cavernous malformations is highly unpredictable, with few cross-sectional studies correlating proinflammatory genotypes and plasma biomarkers with prior disease severity.

Objective: We hypothesize that a panel of 24 candidate plasma biomarkers, with a reported role in the physiopathology of cerebral cavernous malformations, may predict subsequent clinically relevant disease activity.

Methods And Results: Plasma biomarkers were assessed in nonfasting peripheral venous blood collected from consecutive cerebral cavernous malformation subjects followed for 1 year after initial sample collection.

Clinical presentation and treatment paradigms of brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectases, and multisystem arteriovenous malformations (AVMs). Brain AVMs typically present at birth and are identified in approximately 10-20% of patients with HHT. A retrospective review was undertaken of all HHT patients with known single or multiple brain AVMs treated at our institution.