title: Relation of circulating cardiac myosin light chain 1 isoform in stable severe congestive heart failure to survival and treatment with flosequinan.
abstract: The myocardial contractile protein myosin light chain 1 isoform (MLC-1) is released into the circulation during myocyte necrosis and could thus be a marker of low-grade myocardial damage and of poor prognosis in patients with heart failure. Two hundred eighteen patients with stable heart failure (ejection fraction [EF] <35%) and in New York Heart Association (NYHA) class III to IV had MLC-1 measured at baseline and 1 month after being randomized to the direct vasodilator flosequinan or placebo. Patients were followed a mean of 302 +/- 142 days. The prognostic value of an increase in MLC-1 above the 98th percentile of normal controls was compared with that of conventional prognostic variables in heart failure. MLC-1 was increased in over half of patients at baseline and 1 month, and this was associated with increased age, NYHA class IV, and renal insufficiency. By Kaplan-Meier survival analysis, patients with a baseline increase in MLC-1 had a greater mortality (26%) than those without an increase (15%) (p = 0.043). A significant interaction among MLC-1, survival, and treatment was found (p = 0.043). In the placebo group, MLC-1 was associated with increased mortality (29% vs 12%, p = 0.025), whereas there was no significant difference among patients receiving flosequinan. In a multivariate logistic regression model including age, treatment, and left ventricular (LV) ejection fraction, the MLC-1 chain was most predictive of mortality (p = 0.049). Thus, circulating MLC-1 is elevated in over half of patients with stable severe heart failure, and this increase is associated with a poor prognosis. Flosequinan treatment eliminates this association, highlighting the complexity of the relation between cardiac myocyte damage, drug treatment, and mortality.
authors.affiliation: Division of Cardiology of the University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hansen
authors.forename: Eric B
authors.initials: EB
authors.lastname: Stanton
authors.forename: Yehia
authors.initials: Y
authors.lastname: Gawad
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018994:Myosin Light Chains / Q000097:blood* / Q000187:drug effects*; D009656:North America; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011804:Quinolines / Q000627:therapeutic use*; D012537:Scandinavian and Nordic Countries; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D018994:Myosin Light Chains; D011804:Quinolines; D014665:Vasodilator Agents; C047316:flosequinan