An Unusual Cause of Right Heart Dysfunction and High Output Heart Failure in a Young Woman

Ordoñez, Nicolás Ariza; Marín, Antonia Pino; Crespo, Juan Sebastián Bonilla; Navajas, Alberto Navarro; Oliver, Gabriel Antonio; Medina, Héctor M.; Forero, Julián F.

doi:10.3390/jcdd9120418

Cited by 2 publications

(4 citation statements)

References 26 publications

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“…However, roles for genetic aberrations in immune cell specification and neutrophil activation cannot be ruled out. Additionally, severe right heart dysfunction and high output heart failure (HOHF) are rare complications of HHT [ 50 ]. Therapeutic options for these complications are limited because of insufficient information and clinical trial data.…”

Section: Discussionmentioning

confidence: 99%

Employment of diverse in vitro systems for analyzing multiple aspects of disease, hereditary hemorrhagic telangiectasia (HHT)

Koh,

Kang,

Mao

et al. 2024

Cell Biosci

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Background In vitro disease modeling enables translational research by providing insight into disease pathophysiology and molecular mechanisms, leading to the development of novel therapeutics. Nevertheless, in vitro systems have limitations for recapitulating the complexity of tissues, and a single model system is insufficient to gain a comprehensive understanding of a disease. Results Here we explored the potential of using several models in combination to provide mechanistic insight into hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder. Genome editing was performed to establish hPSCs (H9) with ENG haploinsufficiency and several in vitro models were used to recapitulate the functional aspects of the cells that constitute blood vessels. In a 2D culture system, endothelial cells showed early senescence, reduced viability, and heightened susceptibility to apoptotic insults, and smooth muscle cells (SMCs) exhibited similar behavior to their wild-type counterparts. Features of HHT were evident in 3D blood-vessel organoid systems, including thickening of capillary structures, decreased interaction between ECs and surrounding SMCs, and reduced cell viability. Features of ENG haploinsufficiency were observed in arterial and venous EC subtypes, with arterial ECs showing significant impairments. Molecular biological approaches confirmed the significant downregulation of Notch signaling in HHT-ECs. Conclusions Overall, we demonstrated refined research strategies to enhance our comprehension of HHT, providing valuable insights for pathogenic analysis and the exploration of innovative therapeutic interventions. Additionally, these results underscore the importance of employing diverse in vitro systems to assess multiple aspects of disease, which is challenging using a single in vitro system.

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Section: Discussionmentioning

confidence: 99%

Employment of diverse in vitro systems for analyzing multiple aspects of disease, hereditary hemorrhagic telangiectasia (HHT)

Koh,

Kang,

Mao

et al. 2024

Cell Biosci

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“…Of note, the volume of blood involved in arteriovenous shunting typically exceeds 20% of the CO to produce such hemodynamic disorders. 40 While the majority of hemodynamic profiles of patients with HHT and PH secondary to HOHF demonstrate isolated postcapillary PH, a considerable number of studies reports combined pre-and postcapillary PH. [41][42][43] This may be due to mild pulmonary arterial remodeling in the setting of chronic exposure to increased blood flow.…”

Section: Pathophysiology and Presentationmentioning

confidence: 99%

“…Chronic progression of left‐sided heart dysfunction and PH can contribute to the onset of atrial fibrillation as well as right heart failure. Of note, the volume of blood involved in arteriovenous shunting typically exceeds 20% of the CO to produce such hemodynamic disorders 40 …”

Section: High‐output Heart Failurementioning

confidence: 99%

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Pulmonary hypertension in hereditary hemorrhagic telangiectasia: A clinical review

Mathavan,

Reddy

et al. 2023

Pulm. circ.

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Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disorder characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectasias, and solid organ arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is an increasingly recognized complication in patients with HHT, most often precipitated by high‐output heart failure in the presence of hepatic AVMs as well as pulmonary arterial hypertension in the form of a proliferative vasculopathy. The presence of PH in patients with HHT is associated with significant elevations in rates of morbidity and mortality. Additionally, there is growing recognition of a thromboembolic propensity in this population that increases the risk of chronic thromboembolic PH, posing unique clinical considerations regarding the use of anticoagulation. Patients with HHT are also at risk of PH due to disorders commonly seen in the general population, including left‐sided heart and lung disease. The etiology of PH in HHT is multifaceted and complex; the diagnostic approach and treatment strategies must consider the underlying pathophysiology of HHT. This comprehensive review summarizes current knowledge of PH in HHT, detailing the pathogenesis of known etiologies, diagnostic evaluation, and suggested treatment modalities as well as emerging therapies that may be of future interest.

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An Unusual Cause of Right Heart Dysfunction and High Output Heart Failure in a Young Woman

Cited by 2 publications

References 26 publications

Employment of diverse in vitro systems for analyzing multiple aspects of disease, hereditary hemorrhagic telangiectasia (HHT)

Employment of diverse in vitro systems for analyzing multiple aspects of disease, hereditary hemorrhagic telangiectasia (HHT)

Pulmonary hypertension in hereditary hemorrhagic telangiectasia: A clinical review

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