Value of SERCA2a as a Biomarker for the Identification of Patients with Heart Failure Requiring Circulatory Support

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.

Serum SERCA2a levels in heart failure patients are associated with adverse events after discharge

“…As shown in Table 1: the mean values of left ventricular ejection fraction and E/A were higher in the group of patients with low serum SERCA2a heart failure than in the group with high serum SERCA2a levels, but none of them were statistically different, which we speculate is related to the small sample size of this study. Patients requiring mechanical circulatory support before heart transplantation have been found to have lower serum SERCA2a levels than clinically stable patients, [11] and low serum SERCA2a levels have also been associated with a higher incidence of rejection after heart transplantation. [6,7] This differs from our study suggesting that it is the female population of heart failure patients with high serum levels of SERCA2a that is more likely to cause the occurrence of prognostic adverse events, probably because the previous study population was mainly patients with advanced heart failure, whereas the population included in our present study was admitted with acute heart failure attack or acute exacerbation of chronic heart failure, with New York Heart Association classification of I and II in 46.4% (33).…”

Serum SERCA2a Levels in Heart Failure Patients Are Associated with Adverse Events After Discharge

“…As shown in Table I: the mean values of LVEF and E/A were higher in the group of patients with low serum SERCA2a heart failure than in the group with high serum SERCA2a levels, but none of them were statistically different, which we speculate is related to the small sample size of this study. Patients requiring mechanical circulatory support before heart transplantation have been found to have lower serum SERCA2a levels than clinically stable patients [11], and low serum SERCA2a levels have also been associated with a higher incidence of rejection after heart transplantation [6,7]. This differs from our study suggesting that it is the female population of heart failure patients with high serum levels of SERCA2a that is more likely to cause the occurrence of prognostic adverse events, probably because the previous study population was mainly patients with advanced heart failure, whereas the population included in our present study was admitted with acute heart failure attack or acute exacerbation of chronic heart failure, with NYHA classi cation of I and II in 46.4% (33 ).…”

Role of Posttranslational Modifications of Proteins in Cardiovascular Disease

“…The SUMOylation of SERCA2a also plays an important role in HF. SERCA2a levels decrease in HF and regulate intracellular calcium homeostasis, which has potential clinical application value [ 95 ]. Therefore, SERCA2a is SUMOylation at Lys 480 and 585 and regulates myocardial contractility in heart failure [ 96 ].…”