Circulating microRNAs and sudden cardiac arrest outcomes

Abstract

Aim MicroRNAs (miRNAs) have regulatory functions in organs critical in resuscitation from sudden cardiac arrest due to ventricular fibrillation (VF-SCA); therefore, circulating miRNAs may be markers of VF-SCA outcome. Methods We measured candidate miRNAs (N=45) in plasma using qRT-PCR among participants of a population-based VF-SCA study. Participants were randomly selected cases who died in the field (DF, n=15), died in hospital (DH, n=15), or survived to discharge (DC, n=15), and, age-, sex-, and race-matched controls (n=15). MiRNA levels were compared using ANOVA, t-tests, and fold-changes. Results Mean age of groups ranged from 66.9 to 69.7. Most participants were male (53%–67%) and white (67%). Comparing cases to controls, plasma levels of 17 miRNAs expressed in heart, brain, liver, and other tissues (including miR-29c, -34a, -122, -145, -200a, -210, -499-5p, and -663b) were higher and three non-specific miRNAs lower (miR-221, -330-3p, and -9-5p). Among DH or DC compared with DF cases, levels of two miRNAs (liver-specific miR-122 and non-specific miR-205) were higher and two heart-specific miRNAs (miR-208b and -499-5p) lower. Among DC vs. DF cases, levels of three miRNAs (miR-122, and non-specific miR-200a and -205) were higher and four heart-specific miRNAs (miR-133a, -133b, -208b, and -499-5p) lower. Among DC vs. DH cases, levels of two non-specific miRNAs (miR-135a and -9-3p) were lower. Conclusions Circulating miRNAs expressed in heart, brain, and other tissues differ between VF-SCA cases and controls and are related to resuscitation outcomes. Measurement of miRNAs may clarify mechanisms underlying resuscitation, improve prognostication, and guide development of therapies. Results require replication.

The association between plasma miR-122-5p release pattern at admission and all-cause mortality or shock after out-of-hospital cardiac arrest

“…After reaching the peak of admission, miR-122-5p levels decreased rapidly before plateauing at 48 h. miR-122-5p at admission correlated to lactate, bystander CPR and LVIDD, but was not associated with all-cause mortality at 180 days or shock at admission. The acutely increased levels of plasma miR-122-5p at admission harmonize with findings by Wander et al (2016), who reported an elevated plasma miR-122 already during resuscitation from ventricular fibrillation compared to controls. Plasma miR-122 during resuscitation was also higher among patients surviving to discharge compared to those who died in the field.…”

“…This was notable since previous studies have found high plasma levels of miR-122-5p during cardiogenic shock in patients and in pigs (Andersson et al 2012, Cortez-Dias et al 2016. Moreover, plasma levels of miR-122-5p during resuscitation for OHCA were higher among patients who died compared to survivors (Wander et al 2016). Plasma levels of miR-122-5p after OHCA seem to fall between 24 h and 72 h after OHCA but the timeframe between resuscitation and 24 h after OHCA has not been evaluated (Devaux et al 2017).…”

miR‐1, miR‐499 and miR‐208 are sensitive markers to diagnose sudden death due to early acute myocardial infarction

“…miR‐499‐5p was lower in both subjects died in hospital and those survived to discharge compared to subjects died in the field. Furthermore, miR‐133, miR‐208 and miR‐499 were lower in subjects survived to discharge compared to those who deceased in the field . In several studies, plasmatic concentrations of miR‐499 were increased in AMI compared to individuals without cardiovascular diseases .…”

MicroRNAs as Potential Prognosticators of Neurological Outcome in Out-Of-Hospital Cardiac Arrest Patients

“…• C. A study in 2016 included 45 participants of a population-based case control study looking at causes of cardiac arrest in OHCA patients (Cardiac Arrest Blood Study [46]) [47]. miRNAs were measured in the plasma of patients that died in the field (n = 15), patients who had sustained ROSC after OHCA due to ventricular fibrillation (n = 30 survived to hospital, 15 died during admission and 15 survived to discharge), as well as in a matched control cohort (n = 15).…”

“…Only one study measured miRNA levels at time of arrest [47]. Other studies measured circulating miRNAs 24-48 h post-ROSC [43][44][45]48].…”