Endogenous Ouabain: An Old Cardiotonic Steroid as a New Biomarker of Heart Failure and a Predictor of Mortality after Cardiac Surgery

Abstract

Cardiovascular diseases remain the main cause of mortality and morbidity worldwide; primary prevention is a priority for physicians. Biomarkers are useful tools able to identify high-risk individuals, guide treatments, and determine prognosis. Our aim is to investigate Endogenous Ouabain (EO), an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. In a population of 845 patients undergoing elective cardiac surgery, we have investigated the relationships between EO and echocardiography parameters/plasmatic biomarker of cardiac function. EO was found to be correlated negatively with left ventricular EF (p = 0.001), positively with Cardiac End-Diastolic Diameter (p = 0.047), and positively with plasmatic NT-proBNP level (p = 0.02). Moreover, a different plasmatic EO level (both preoperative and postoperative) was found according to NYHA class (p = 0.013). All these results have been replicated on an independent cohort of patients (147 subjects from US). Finally, a higher EO level in the immediate postoperative time was indicative of a more severe cardiological condition and it was associated with increased perioperative mortality risk (p = 0.023 for 30-day morality). Our data suggest that preoperative and postoperative plasmatic EO level identifies patients with a more severe cardiovascular presentation at baseline. These patients have a higher risk of morbidity and mortality after cardiac surgery.

Lanosterol Synthase Genetic Variants, Endogenous Ouabain, and Both Acute and Chronic Kidney Injury

“…Although it was not feasible to biopsy kidney tissue from patients with AKI in this study, other recent studies involving multiple centers have shown that preoperative circulating EO level is a predictive biomarker for postoperative AKI and also is indicative of risk for postoperative mortality. 10,22,23 As part of the present study, we confirmed a significant association between high preoperative circulating EO levels and the development of AKI. Taken together, results indicate that LSS and EO are significant determinants of the renal response to acute ischemia.…”

“…Logistic regression was used for multivariable analysis for postoperative AKI outcomes and accelerated eGFR decline. Associations between postoperative AKI and LSS rs2254524 genotype were corrected for clinical variables, in particular the clinical risk model 22,23 (a composite risk model including age, sex, preoperative ejection fraction, baseline eGFR, surgery type [ie, complicated surgery or not], history of hypertension and history of diabetes, and redo-intervention) and the European System for Cardiac Operative Risk Evaluation 24,25 (EuroSCORE: age, sex, chronic pulmonary disease, extracardiac arteriopathy, neurologic dysfunction disease, previous cardiac surgery, baseline eGFR, active endocarditis, critical preoperative state, unstable angina, left ventricular dysfunction, recent myocardial infarct, pulmonary hypertension, emergency, major cardiac procedure other than or in addition to isolated coronary artery bypass grafting, and surgery on thoracic aorta and postinfarct septal rupture).…”

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“…In one study, elevated preoperative EO levels were associated with a higher incidence of postoperative AKI and ICU stay in a second study [36]. Finally, post-operative EO levels were also associated with a higher mortality rate after cardiac surgery [37].…”

Reducing Cardiac Fibrosis: Na/K-ATPase Signaling Complex as a Novel Target

“…It was found that ouabain and Marinobufagenin (MBG) exist in human blood with the same structure as plant-derived and toad gland-derived digitalis compounds, respectively [110–114]. The elevation of circulating levels of these endogenous compounds was reported in heart failure patients and was correlated with the severity of heart dysfunction [111,115–117]. Other diseases such as renal failure [118], preeclampsia [119], myocardial ischemia/infarction [120,121], and diabetes mellitus [122,123] were also observed in association with elevated levels of endogenous compounds in human plasma samples.…”