Sudden Cardiac Death in Systemic Sclerosis: Diagnostics to Assess Risk and Inform Management

Ross, Laura; Paratz, E.; Baron, Murray; Gerche, André La; Nikpour, Mandana

doi:10.3390/diagnostics11101781

Cited by 5 publications

(3 citation statements)

References 89 publications

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“…In our study, we found that male gender is associated with a severe course of SSc with cardiac involvement, which is consistent with previous studies [11]. We also found that a risk factor for heart involvement is extensive skin sclerosis expressed as high values of mRSS.…”

Section: Risk Factors Of Cardiac Involvement In Systemic Sclerosissupporting

confidence: 93%

Heart disease in the course of systemic sclerosis – an observational study

et al. 2022

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Introduction: Cardiac involvement is one of the major mortality factors in systemic sclerosis (SSc). This observational study aimed to compare patients with and without heart involvement in the course of SSc. Material and methods: Electronic medical records of patients treated between January 2021 and August 2022 in the Department of Rheumatology were searched for the diagnosis of SSc (ICD-10 code M47). The clinical characteristics of patients with and without heart involvement in the course of SSc were compared. Results: Out of 36 patients with SSc, 7 patients were diagnosed with heart disease in the course of SSc. The major type of cardiac involvement was myocarditis (71%). The majority of patients with heart involvement had elevated troponin (86%) and NT-proBNP (71%) concentrations. The most common finding observed in echocardiography was diastolic failure (71%). The most frequent abnormality found in 24-hour Holter ECG was isolated supraventricular extrasystoles (100%). Risk factors for developing heart disease in the course of SSc were male gender (p = 0.018), diffuse type of SSc (p = 0.03), higher values of modified Rodnan skin score (p < 0.001), gastrointestinal tract involvement (p = 0.027) and myositis (p = 0.018). Conclusions: Optimal screening for heart disease is needed in this group of patients.

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Section: Risk Factors Of Cardiac Involvement In Systemic Sclerosissupporting

confidence: 93%

Heart disease in the course of systemic sclerosis – an observational study

et al. 2022

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“…In 50% of cases, cardiac arrest is the first manifestation of SCD [ 3 ], and the survival rate is very low. Only 10% of patients with cardiac arrest can survive to discharge [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiac involved and autopsy in two patients with systemic sclerosis: Two cases report

Yu¹,

Wen²,

Zhang³

et al. 2023

Heliyon

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“…Arrhythmias and conduction abnormalities worsen the overall prognosis of SSc. These abnormalities may apparently be mild but can lead to a fatal outcome like sudden cardiac death in SSc ( Ross et al, 2021 ). Although myocardial damage and fibrosis are clearly important factors leading to conduction abnormalities, the underlying arrhythmogenic mechanisms observed in SSc are not well understood, and the activity of cardiac ion channels responsible for the cardiac myocyte action potential have not been investigated in the context of SSc with cardiac involvement.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Vascular Hemeoxygenase-1 Leads to Vasculopathy in Systemic Sclerosis

et al. 2022

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Systemic sclerosis (SSc) is a terminal disease characterized by vasculopathy, tissue fibrosis, and autoimmunity. Although the exact etiology of SSc remains unknown, endothelial dysfunction, oxidative stress, and calcium handling dysregulation have been associated with a large number of SSc-related complications such as neointima formation, vasculogenesis, pulmonary arterial hypertension, impaired angiogenesis, and cardiac arrhythmias. Hemeoxygenase-1 (HO-1) is an antioxidant enzyme involved in multiple biological actions in the cardiovascular system including vascular tone, angiogenesis, cellular proliferation, apoptosis, and oxidative stress. The aim of this work was to investigate the physiological role of HO-1 and its relevance in the cardiovascular complications occurring in SSc. We found that, in early phases of SSc, the expression of HO-1 in dermal fibroblast is lower compared to those isolated from healthy control individuals. This is particularly relevant as reduction of the HO-1/CO signaling pathway is associated with endothelial dysfunction and vasculopathy. We show evidence of the role of HO-1/carbon monoxide (CO) signaling pathway in calcium handling. Using an in vitro model of pulmonary arterial hypertension (PAH) we investigated the role of HO-1 in Ca2+ mobilization from intracellular stores. Our results indicate that HO-1 regulates calcium release from intracellular stores of human pulmonary arterial endothelial cells. We interrogated the activity of HO-1 in angiogenesis using an organotypic co-culture of fibroblast-endothelial cell. Inhibition of HO-1 significantly reduced the ability of endothelial cells to form tubules. We further investigated if this could be associated with cell motility or migration of endothelial cells into the extracellular matrix synthesized by fibroblasts. By mean of holographic imaging, we studied the morphological and functional features of endothelial cells in the presence of an HO-1 activator and selective inhibitors. Our results demonstrate that inhibition of HO-1 significantly reduces cell proliferation and cell motility (migration) of cultured endothelial cells, whilst activation of HO-1 does not modify either morphology, proliferation or motility. In addition, we investigated the actions of CO on the Kv7.1 (KCQN1) channel current, an important component of the cardiac action potential repolarization. Using electrophysiology (whole-cell patch-clamp in a recombinant system overexpressing the KCQN1 channel), we assessed the regulation of KCQN1 by CO. CORM-2, a CO donor, significantly reduced the Kv7.1 current, suggesting that HO-1/CO signaling may play a role in the modulation of the cardiac action potential via regulation of this ion channel. In summary, our results indicate a clear link between: 1) downregulation of HO-1/CO signaling; and 2) pathophysiological processes occurring in early phases of SSc, such as calcium homeostasis dysregulation, impaired angiogenesis and cardiac arrhythmias. A better understanding of the canonical actions (mainly due to the biological actions of CO), and non-canonical actions of HO-1, as well as the interaction of HO-1/CO signaling with other gasotransmitters in SSc will contribute to the development of novel therapeutic approaches.

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Sudden Cardiac Death in Systemic Sclerosis: Diagnostics to Assess Risk and Inform Management

Cited by 5 publications

References 89 publications

Heart disease in the course of systemic sclerosis – an observational study

Heart disease in the course of systemic sclerosis – an observational study

Cardiac involved and autopsy in two patients with systemic sclerosis: Two cases report

Downregulation of Vascular Hemeoxygenase-1 Leads to Vasculopathy in Systemic Sclerosis

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