Relation of circulating cardiac myosin light chain 1 isoform in stable severe congestive heart failure to survival and treatment with flosequinan

Mark S. Hansen, Eric B. Stanton, Yehia Gawad, Milton Packer, Bertram Pitt, Karl Swedberg, Jean L. Rouleau

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)969-973
Number of pages5
JournalAmerican Journal of Cardiology
Volume90
Issue number9
DOIs
StatePublished - Nov 1 2002

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flosequinan
Cardiac Myosins
Myosin Light Chains
Protein Isoforms
Heart Failure
Survival
Therapeutics
Mortality
Logistic Models
Placebos
Contractile Proteins
Kaplan-Meier Estimate

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Relation of circulating cardiac myosin light chain 1 isoform in stable severe congestive heart failure to survival and treatment with flosequinan. / Hansen, Mark S.; Stanton, Eric B.; Gawad, Yehia; Packer, Milton; Pitt, Bertram; Swedberg, Karl; Rouleau, Jean L.

In: American Journal of Cardiology, Vol. 90, No. 9, 01.11.2002, p. 969-973.

Research output: Contribution to journalArticle

Hansen, Mark S. ; Stanton, Eric B. ; Gawad, Yehia ; Packer, Milton ; Pitt, Bertram ; Swedberg, Karl ; Rouleau, Jean L. / Relation of circulating cardiac myosin light chain 1 isoform in stable severe congestive heart failure to survival and treatment with flosequinan. In: American Journal of Cardiology. 2002 ; Vol. 90, No. 9. pp. 969-973.
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