Plasma Levels of SERCA2a as a Noninvasive Biomarker of Primary Graft Dysfunction After Heart Transplantation.

BACKGROUND: Noninvasive detection of primary graft dysfunction (PGD) remains a major challenge. SERCA2a plays an important role in cardiac homeostasis and its dysregulation has been associated with ventricular dysfunction and rejection. This study aimed to determine the potential utility of plasma levels of SERCA2a as a biomarker of PGD. METHODS: One hundred thirty-five plasma samples were collected from adult recipients 2-6 hours before heart transplantation (HT). Plasma concentrations of SERCA2a were determined using a specific sandwich ELISA. Variables related to the recipient, the donor, and the periprocedural were collected to determine a multivariate predictive model of PGD. RESULTS: Levels of SERCA2a were decreased in patients who developed PGD (median 0.430 ng/mL [interquartile range, 0.260-0.945] versus 0.830 ng/mL [interquartile range, 0.582-1.052]; P = 0.001). Receiver operating characteristic curve analysis revealed that SERCA2a discriminated between patients with and without PGD (AUC = 0.682; P = 0.001), and a cutoff point ≥ 0.60 ng/mL was a protective independent predictor of PGD (odds ratio 0.215 [P = 0.004]). Three independent predictors of PGD in this study were reduced levels of pre-HT SERCA2a, increased bilirubin levels, and short-term mechanical circulatory support bridge to transplantation. The analysis of the receiver operating characteristic curve of the model obtained a significant AUC 0.788, P = 0.0001. CONCLUSIONS: Our findings suggest that assessment of SERCA2a plasma levels may improve risk prediction for the occurrence of PGD and could be considered as a novel noninvasive biomarker in patients undergoing HT.

Impact of intravenous ferric carboxymaltose on heart failure with preserved and reduced ejection fraction.

AIMS: Heart failure (HF) is a proinflammatory disease often associated with the onset of iron deficiency (ID). ID alters mitochondrial function, reducing the generation of cellular energy in skeletal muscle and cardiomyocytes. This study aimed to analyse the response of patients with HF to intravenous iron administration according to the type of HF: preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). METHODS AND RESULTS: We conducted a retrospective, single-centre study of 565 consecutive outpatients diagnosed with HF, recruited over 5 years, who were given intravenous ferric carboxymaltose (FCM) for the treatment of ID [defined as ferritin < 100 µg/L or ferritin 100-300 µg/L with transferrin saturation (TSAT) < 20%]. Clinical, laboratory, and echocardiographic parameters were analysed before and after administration. After FCM administration, overall ferritin, TSAT, and haemoglobin levels increased up to 5-fold, 1.6-fold, and 1.1-fold, respectively, relative to baseline values in HF patients with reduced and preserved ejection fraction (P < 0.0001), with a greater increase in ferritin and TSAT in HFpEF patients. The left ventricular ejection fraction of the overall series improved by 8 percentage points in both types of HF (from 40% to 48%, P < 0.0001). The percentage of patients with normalization of right ventricular function increased by 6.9 points (from 74.1% to 81%) in HFpEF patients and by 6.4 points (from 53% to 59.4%) in the HFrEF subgroup (P < 0.0001). New York Heart Association functional status slightly improved, from a median of 2.4 (interquartile range, IQR: 2-2.7) to 1.9 (IQR: 1.5-2.5; P < 0.0001) after FCM in both types of HF. No changes were noted in plasma levels of liver enzymes, creatinine, or natriuretic peptide (P > 0.05). CONCLUSIONS: Intravenous iron administration appeared to improve ejection fraction and cardiac functional status in outpatients with ID and HF with both preserved and reduced ejection fraction.

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

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.

Usefulness of Immunoglobulin A in Patients With Decompensated Heart Failure: Is It a Future Marker of Congestion? Preliminary Experience.

BACKGROUND: The purpose of this study was to analyze whether the level of IgA is related to right ventricular function and systemic congestion in patients with decompensated heart failure (HF) and reduced ejection fraction (EF). METHODS: This was a consecutive prospective and observational study of hospitalized patients diagnosed with decompensated HF with reduced EF. The recruitment period lasted 2 months. In the first 24 hours after admission, clinical assessment, general laboratory tests, determination of HF biomarkers, IgA and echocardiographic study were performed. Patients were classified into 2 groups according to whether the plasma IgA level was lower (n = 11) or higher than 300 mg/dL (n = 12). RESULTS: Significant differences in IgA levels were found in the peripheral congestion variables (no congestion: 232, interquartile range [IQR], 125-310 mg/dL vs congestion: 429, IQR, 308-520 mg/dL; P = .03). There were also differences in echocardiographic parameters of right ventricular function, with a greater deterioration of right ventricular function in the group with higher IgA levels (P < .05). There was a highly significant correlation between tricuspid annulus systolic excursion values and IgA levels (P = .004). CONCLUSIONS: In decompensated HF, patients with greater clinical congestion and echocardiographic parameters of right ventricular dysfunction have higher plasma IgA levels. This study is a preliminary experience that will help to establish the basis of the cardiointestinal syndrome as a clinical picture of systemic congestion in HF.