Abstract
Background: Heart failure (HF) alters the nucleo-cytoplasmic transport of cardiomyocytes and reduces SERCA2a levels, essential for intracellular calcium homeostasis. We consider in this study whether the molecules involved in these processes can differentiate those patients with advanced HF and the need for mechanical circulatory support (MCS) as a bridge to recovery or urgent heart transplantation from those who are clinically stable and who are transplanted in an elective code. Material and method: Blood samples from 29 patients with advanced HF were analysed by ELISA, and the plasma levels of Importin5, Nucleoporin153 kDa, RanGTPase-Activating Protein 1 and sarcoplasmic reticulum Ca2+ ATPase were compared between patients requiring MCS and those patients without a MCS need prior to heart transplantation. Results: SERCA2a showed significantly lower levels in patients who had MCS compared to those who did not require it (0.501 ± 0.530 ng/mL vs. 1.123 ± 0.661 ng/mL; p = 0.01). A SERCA2a cut-off point of 0.84 ng/mL (AUC 0.812 ± 0.085, 95% CI: 0.646–0.979; p = 0.004) provided a 92% sensitivity, 62% specificity, 91% negative predictive value and 67% positive predictive value. Conclusions: In this cohort, patients with advanced HF and a need for MCS have shown significantly lower levels of SERCA2a as compared to stable patients without a need for MCS prior to heart transplantation. This is a small study with preliminary findings, and larger-powered dedicated studies are required to confirm and validate these results.
Highlights
Introduction and ObjectiveHeart transplantation (HT) is currently considered the gold standard for the treatment of patients with advanced heart failure (HF) because it improves survival, functional status, and quality of life [1] the number of heart donors is naturally very low, and the waiting times for recipients can be very long
Heart failure (HF) has been associated with changes at the molecular level in the mitochondria, cytoskeleton, and nuclei of cardiomyocytes [2,3,4], and identifying these changes has helped in understanding the ventricular remodelling process and its pathophysiology [5]
The aim of this study was to evaluate whether changes in certain molecules involved in nucleocytoplasmic transport [Importin5 (IPO5), Nucleoporin153 kDa (NUP153), RanGTPase-Activating Protein 1 (RanGAP1)] and intramyocardial calcium homeostasis (SERCA2a) could be used to differentiate patients with advanced HF and mechanical circulatory support (MCS) carriers from those with a greater clinical stability in whom elective transplantation could be performed without prior MCS intervention
Summary
Introduction and ObjectiveHeart transplantation (HT) is currently considered the gold standard for the treatment of patients with advanced heart failure (HF) because it improves survival, functional status, and quality of life [1] the number of heart donors is naturally very low, and the waiting times for recipients can be very long. This, added to the growing number of unstable patients, has fostered the development of mechanical circulatory support (MCS). Systems which can act as a bridge to recovery, transplantation or decision. These decisions are based on clinical and hemodynamic criteria, with little evidence supporting the use of conventional biomarkers in decision-making. There is an urgent clinical need to develop a more robust risk stratification and patient selection tool to aid in MCS-mediated intervention planning and strategy. Heart failure (HF) alters the nucleo-cytoplasmic transport of cardiomyocytes and reduces SERCA2a levels, essential for intracellular calcium homeostasis. HF and the need for mechanical circulatory support (MCS) as a bridge to recovery or urgent heart transplantation from those who are clinically stable and who are transplanted in an elective code
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