A new pathophysiology in heart failure patients

Sciomer, Susanna; Rellini, Carlotta; Agostoni, Piergiuseppe; Moscucci, Federica

doi:10.1111/aor.13770

Cited by 5 publications

(3 citation statements)

References 19 publications

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“…In particular, we integrated information on the period of age (prenatal, childhood, adulthood), ventricle (left and right), diagnosis, LVAD implantation, and then performed a secondary screening. Data from LVAD patients were excluded due to the possible interference of LVAD with left ventricle mechanics and chronic LVAD-induced hemolysis, thus affecting iron balance [52]. Hence, 436 specimens from adult NF (n = 218) individuals and DCM (n = 218) patients were employed in the study (Figure 4A and Supplementary Table S3).…”

Section: Data Collectionmentioning

confidence: 99%

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Dysregulation of iron metabolism-linked genes at myocardial tissue and cell levels in dilated cardiomyopathy

Massaiu

Campodonico

Mapelli

et al. 2023

European Journal of Preventive Cardiology

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Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Fondazione Gigi & Pupa Ferrari ONLUS Italian Ministry of Health-Ricerca Corrente. Background Heart failure (HF) is defined as one of the main clinical and public health burdens with multifactorial symptoms and high worldwide prevalence. Dilated cardiomyopathy (DCM) is one of the leading causes of HF and is responsible for over half of all left ventricular assist device implantations and heart transplantations. DCM is regarded as a multiple disease entity linked to a number of genetic, nutritional, inflammatory, infective, metabolic, and environmental causes. Among the metabolic processes associated with HF, iron metabolism disorders, ranging from iron deficiency to iron overload, are gaining attention. However, the understanding of iron mechanisms, at cardiac level, involved in HF and particularly in DCM, remains elusive. Purpose We aim to evaluate the possible dysregulation of iron metabolism-linked genes in DCM, through a quantitative analysis of public myocardial gene expression data at tissue and cell levels. Methods Bulk RNA sequencing (RNA-seq) and single-nucleus RNA-seq (snRNA-seq) datasets, respectively of 436 and 38 left ventricle samples from adult non-failed (NF) and DCM subjects, were retrieved from public studies. We defined a list of 272 genes directly related to intramyocardial iron metabolism and performed the differential gene expression analysis both at whole cardiac tissue level and in cardiomyocytes, fibroblasts, myeloid, endocardial, and endothelial cells. Results In the overall myocardial tissue, we found 44 iron-linked genes differentially expressed between DCM and NF subjects. To better understand iron genes abnormalities in the myocardium of DCM patients we deepened the analysis from tissue to single-cell level. Among the five considered cell types (cardiomyocytes, fibroblasts, myeloid, endocardial, and endothelial cells) at least 9% of iron-linked expressed genes were significantly regulated in DCM when compared to NF. Specifically, the iron metabolism in DCM cardiomyocytes is altered at several levels (Figure 1), including: 1) imbalance of Fe3+ internalization (SCARA5 down-regulation) and reduction of internal conversion from Fe3+ to Fe2+ (STEAP3 down-regulation), 2) increase of iron consumption to produce hemoglobin (HBA1/2 up-regulation), 3) higher heme synthesis and externalization (ALAS2 and ABCG2 up-regulation), 4) lower cleavage of heme to Fe2+, biliverdin and carbon monoxide (HMOX2 down-regulation), and 5) positive regulation of hepcidin (BMP6 up-regulation). Conclusions In conclusion, the present study provides significant progress in knowledge of iron metabolism changes in DCM disease, which likely have a clinical meaning. Indeed, our data show that regulation of intracellular iron homeostasis is dysfunctional in DCM patients’ cardiac tissues, supporting, but not providing, the hypothesis of a direct effect of iron in the disease progression.

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Section: Data Collectionmentioning

confidence: 99%

“…thus affecting iron balance [52]. Hence, 436 specimens from adult NF (n = 218) individuals and DCM (n = 218) patients were employed in the study (Figure 4A and Supplementary Table S3).…”

Section: Data Collectionmentioning

confidence: 99%

Dysregulation of iron metabolism-linked genes at myocardial tissue and cell levels in dilated cardiomyopathy

Massaiu

Campodonico

Mapelli

et al. 2023

European Journal of Preventive Cardiology

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“…Considering that an increment in intraventricular pressure leads to adverse remodeling of LV myocardium, LVAD, with its unloading effect, may help recover native cardiac function. Recovery of physiological hemodynamic conditions in patients treated with long-term LVAD is still a complex matter of debate with an emerging working hypothesis ( 30 ).…”

Section: Percutaneous Mcs Support During Arrhythmia-related Cardiogen...mentioning

confidence: 99%

Mechanical circulatory support in ventricular arrhythmias

Tavazzi

Dammassa

Colombo

et al. 2022

Front. Cardiovasc. Med.

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In atrial and ventricular tachyarrhythmias, reduced time for ventricular filling and loss of atrial contribution lead to a significant reduction in cardiac output, resulting in cardiogenic shock. This may also occur during catheter ablation in 11% of overall procedures and is associated with increased mortality. Managing cardiogenic shock and (supra) ventricular arrhythmias is particularly challenging. Inotropic support may exacerbate tachyarrhythmias or accelerate heart rate; antiarrhythmic drugs often come with negative inotropic effects, and electrical reconversions may risk worsening circulatory failure or even cardiac arrest. The drop in native cardiac output during an arrhythmic storm can be partly covered by the insertion of percutaneous mechanical circulatory support (MCS) devices guaranteeing end-organ perfusion. This provides physicians a time window of stability to investigate the underlying cause of arrhythmia and allow proper therapeutic interventions (e.g., percutaneous coronary intervention and catheter ablation). Temporary MCS can be used in the case of overt hemodynamic decompensation or as a “preemptive strategy” to avoid circulatory instability during interventional cardiology procedures in high-risk patients. Despite the increasing use of MCS in cardiogenic shock and during catheter ablation procedures, the recommendation level is still low, considering the lack of large observational studies and randomized clinical trials. Therefore, the evidence on the timing and the kinds of MCS devices has also scarcely been investigated. In the current review, we discuss the available evidence in the literature and gaps in knowledge on the use of MCS devices in the setting of ventricular arrhythmias and arrhythmic storms, including a specific focus on pathophysiology and related therapies.

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Sex- and gender-related disparities in chest pain syndromes: the feminine mystique of chest pain

Angeli,

Ricci,

Moscucci

et al. 2024

Current Problems in Cardiology

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A new pathophysiology in heart failure patients

Abstract: In the treatment of patients with severe heart failure, left ventricle assist device (LVAD) plays an important role, especially as a destination therapy. Nevertheless, even in successful cases, patients' progressive weaning is rarely taken into

Cited by 5 publications

References 19 publications

Dysregulation of iron metabolism-linked genes at myocardial tissue and cell levels in dilated cardiomyopathy

Dysregulation of iron metabolism-linked genes at myocardial tissue and cell levels in dilated cardiomyopathy

Mechanical circulatory support in ventricular arrhythmias

Sex- and gender-related disparities in chest pain syndromes: the feminine mystique of chest pain

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