Suppressed enhancement of the force-frequency relation to adrenergic stimulation is an indicator of poor prognosis in patients with dilated cardiomyopathy

Abstract

Objectives: To investigate the relation between the response of force-frequency relation (FFR) to adrenergic stimulation, and gene expression of Ca 2+-handlin proteins in patients with dilated cardiomyopathy (DCM). Methods and Results: We measured the maximum first derivative of left ventricular (LV) pressure (LV dP/dt max) during pacing and dobutamine infusion in 10 patients with mild DCM (NYHA I-II). Endomyocardial biopsy was performed, and mRNA levels of SR Ca 2+-ATPase(SERCA2a), ryanodine receptor-2, phospholamban (PLB), calsequestrin, and Na +/ Ca2 + exchanger were quantified by a real-time quantitative reverse transcription-polymerase chain reaction method. In 6 patients (group A), the increase in LV dP/dt max during dobutamine infusion was greater than pacing alone, whereas in 4 patients (group B), the increase in LV dP/dt max during dobutamine infusion was significantly attenuated compaired with group A. The ratio of SERCA2a to PLB mRNA expression was significantly higher in group B than group A. In group B, one patient has died, and two has hospitalized for congestive heart failure during follow-up period (25 ± 18months). Conversely, there were no death and hospitalization in group A. Conclusions: In this study, the LV contractile reserve to adrenergic stimulation was impaired in some patients with mild DCM, and those showed poor prognosis, although the ratio of SERCA2a to PLB mRNA expression was in normal range.