Synergistic effect of myocardial injury and mid-regional proAdrenomedullin elevation in determining clinical outcomes of SARS-CoV-2 patients

Abstract

ObjectiveCoronavirus disease 2019 (COVID-19) is a systemic disease induced by SARS-CoV-2 causing myocardial injury. To date, there are few data on the correlation between mid-regional proAdrenomedullin (MR-proADM) and myocardial injury. The aim of this study was to evaluate whether the association of myocardial injury and elevated mid-regional proAdrenomedullin values could predict mortality of SARS-CoV-2 patients, to offer the best management to COVID-19 patients.Materials and methodsAll patients hospitalized for SARS-CoV-2 infection at the COVID-19 Center of the Campus Bio-Medico of Rome University were included between October 2020 and March 2021 and were retrospectively analyzed. Myocardial injury was defined as rising and/or fall of cardiac hs Troponin I values with at least one value above the 99th percentile of the upper reference limit (≥15.6 ng/L in women and ≥34.2 ng/L in men). The primary outcome was 30-day mortality. Secondary outcomes were the comparison of MR-proADM, CRP, ferritin, and PCT as diagnostic and prognostic biomarkers of myocardial injury. Additionally, we analyzed the development of ARDS, the need for ICU transfer, and length of stay (LOS).ResultsA total of 161 patients were included in this study. Of these, 58 (36.0%) presented myocardial injury at admission. An MR-proADM value ≥ 1.19 nmol/L was defined as the optimal cut-off to identify patients with myocardial injury (sensitivity 81.0% and specificity 73.5%). A total of 121 patients (75.2%) developed ARDS, which was significantly more frequent among patients with myocardial injury (86.2 vs. 68.9%, p = 0.015). The overall 30-day mortality was 21%. Patients with myocardial injury presented significantly higher mortality compared to those without the same (46.6 vs. 6.8%, p < 0.001). When dividing the entire study population into four groups, based on the presence of myocardial injury and MR-proADM values, those patients with both myocardial injury and MR-proADM ≥ 1.19 nmol/L presented the highest mortality (53.2%, p < 0.001). The combination of myocardial injury and MR-proADM values ≥ 1.19 nmol/L was an independent predictor of death (OR = 7.82, 95% CI = 2.87–21.30; p < 0.001).ConclusionThe study is focused on the correlation between myocardial injury and MR-proADM. Myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality.

Circulating mid-regional proadrenomedullin is a predictor of mortality in patients with COVID-19: a systematic review and meta-analysis

“…Recent studies have proposed that virus-induced endothelial dysfunction and damage, resulting in impaired vascular blood flow, coagulation and leakage, may partially explain the development of organ dysfunction [ 74 , 75 ]. Another study showed that myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality [ 76 ]. The assessment of MR-proADM may provide vital information to explain the pathophysiological mechanisms of vascular endothelial injury and subsequent organ dysfunction in patients with COVID-19.…”

A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections

“…It is due to hypoxia inducing a reduced oxygen supply to the heart, causing a modest or massive elevation in troponin concentration, which is not necessarily related to the deterioration of systolic left ventricular function in left ventricular overload secondary to parenchymal or vascular disease of the lung resulting in subendocardial damage of the right ventricular myocardium in 19% of cases and by cytokine-induced injury [ 177 , 178 , 182 , 183 , 184 , 185 , 186 ]. Myocardial injury can be caused through one of three mechanisms: myocyte stretching, myocardial damage, or oxidative stress [ 187 ]. The MR-proADM biomarker indicates cardiovascular stress [ 187 , 188 ].…”

Mid-Regional Pro-Adrenomedullin Can Predict Organ Failure and Prognosis in Sepsis?

“…ADM is a peptide of 52 amino acids, a member of the CT/CGRP superfamily whose gene is located on the 11 chromosome. It expresses the onset of organ damage, its severity, the degree of edema and prognosis [4][5][6][7][8][9][10][11][12][13][14].…”

“…The precursor peptide, mid-regional pro-adrenomedullin (MR-proADM), is more stable than ADM, released in 1:1 ratio to ADM. MR-proADM shows high predictiveness regarding prognosis during severe inflammation, such as in the case of sepsis, acute heart failure (AHF) or COVID-19 [8][9][10][11][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

“…MR-proADM has proven to be superior to NT-proBNP (the "gold standard" biomarker) in the case of tissue congestion, such as edema and lung congestion [12,13]. Furthermore, MR-proADM significantly correlates with myocardial injury, identifying patients at high risk of death who could benefit from adrecizumab therapy [5,10,14,[30][31][32].…”