Dilation of the Aorta Ascendens Forms Part of the Clinical Spectrum of HCN4 Mutations

Vermeer, Alexa M.C.; Lodder, Elisabeth M.; Thomas, Dierk; Duijkers, Floor A.M.; Marcelis, Carlo; Gorselen, E.O.F. van; Fortner, Philipp; Buss, Sebastian J.; Mereles, Derliz; Katus, Hugo A.; Wilde, Arthur A.M.; Bezzina, Connie R.; Boekholdt, S. Matthijs; Schweizer, Patrick; Christiaans, Imke

doi:10.1016/j.jacc.2016.01.086

Cited by 29 publications

(24 citation statements)

References 5 publications

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“…She transmitted the HCN4 variant to her son, who at the age of 35 years also presented with sinus bradycardia 38 bpm, LVNC ( Figure 1D, 1E) and mild ascending aortic dilation of 42 mm ( Figure 1F). Our novel variant in the HCN4 gene (p.Arg483_Val487del) is directly adjacent ( Figure 1G, 1H) to the variants published by Vermeer et al [3] and Hanania et al [4], so this further confirms an existence of HCN4 mutation hot-spot site specific for the combined phenotype of sinus bradycardia/LVNC/TAA, as suggested previously [4].…”

supporting

confidence: 88%

“…In the meantime Vermeer et al [3] reported HCN4 variants (including p.Tyr481His and p.Gly482Arg) in families with sinus bradycardia and LVNC that co-segregated with TAA.…”

mentioning

confidence: 99%

“…A potential explanation for this complex of bradycardia with structural cardiac alterations is a developmental effect [3]. In addition to an established function of HCN4 in cardiac pacemaking, HCN4 was identified as a primary marker for cardiac progenitors of the first heart field in the early embryonic heart development, forming both the main parts of the cardiac muscle and the conduction system [1,5].…”

mentioning

confidence: 99%

“…In addition to an established function of HCN4 in cardiac pacemaking, HCN4 was identified as a primary marker for cardiac progenitors of the first heart field in the early embryonic heart development, forming both the main parts of the cardiac muscle and the conduction system [1,5]. A potential link with development of TAA may be based also on the studies in mice that demonstrated HCN4 expression in the endothelium of the aorta [3,5].…”

mentioning

confidence: 99%

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A novel <i>HCN4</i> variant related to familial sinus bradycardia, left ventricular noncompaction and thoracic aortic aneurysm

Ponińska¹,

Michalak²,

Śpiewak³

et al. 2020

Polish Archives of Internal Medicine

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supporting

confidence: 88%

“…In the meantime Vermeer et al [3] reported HCN4 variants (including p.Tyr481His and p.Gly482Arg) in families with sinus bradycardia and LVNC that co-segregated with TAA.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A novel <i>HCN4</i> variant related to familial sinus bradycardia, left ventricular noncompaction and thoracic aortic aneurysm

Ponińska¹,

Michalak²,

Śpiewak³

et al. 2020

Polish Archives of Internal Medicine

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“…5). Furthermore, Bloss-of-function^mutations in HCN4 were also associated with atrial fibrillation and dilation of the aorta ascending (Duhme et al 2013, Vermeer et al 2016, supporting the view that ion channel mutations often do not solely show arrhythmic symptoms but contribute to complex electrical and structural phenotypes (Akhirome and Jay, 2015).…”

Section: Ion Channels Cause Electrical and Structural Overlap Syndromesmentioning

confidence: 78%

Role of ion channels in heart failure and channelopathies

et al. 2018

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Heart failure (HF) is a complication of multiple cardiac diseases and is characterized by impaired contractile and electric function. Patients with HF are not only limited by reduced contractile function but are also prone to life-threatening ventricular arrhythmias. HF itself leads to remodeling of ion channels, gap junctions, and intracellular calcium handling abnormalities that in combination with structural remodeling, e.g., fibrosis, produce a substrate for an arrhythmogenic disorders. Not only ventricular life-threatening arrhythmias contribute to increased morbidity and mortality but also atrial arrhythmias, especially atrial fibrillation (AF), are common in HF patients and contribute to morbidity and mortality. The distinct ion channel remodeling processes in HF and in channelopathies associated with HF will be discussed. Further basic research and clinical studies are needed to identify underlying molecular pathways of HF pathophysiology to provide the basis for improved patient care and individualized therapy based on individualized ion channel composition and remodeling.

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Hereditary Cardiac Conduction Diseases

Tadros¹,

Cadrin‐Tourigny²

2020

Clinical Cardiogenetics

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Dilation of the Aorta Ascendens Forms Part of the Clinical Spectrum of HCN4 Mutations

Cited by 29 publications

References 5 publications

A novel <i>HCN4</i> variant related to familial sinus bradycardia, left ventricular noncompaction and thoracic aortic aneurysm

A novel <i>HCN4</i> variant related to familial sinus bradycardia, left ventricular noncompaction and thoracic aortic aneurysm

Role of ion channels in heart failure and channelopathies

Hereditary Cardiac Conduction Diseases

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