Catecholamine sensitivity is reduced in failing hearts as a result of myocardial abnormalities in the beta-adrenergic receptor signaling pathway. However, little is known about adrenergic myocardial contractile reserve in asymptomatic or mildly symptomatic patients with DCM.
The maximal first derivative of left ventricular pressure (LV dP/dtmax) was determined during infusion of dobutamine (10 ¦Ìg kg? min?) in 46 asymptomatic or mildly symptomatic (New York Heart Association functional class I or II) patients with DCM. The expression of messenger ribonucleic acid (mRNA) for contractile regulatory proteins in endomyocardial biopsy specimens was quantified by reverse transcription and real-time polymerase chain reaction analysis. Plasma norepinephrine levels were measured in all patients and [123I]metaiodobenzylguanidine (MIBG) scintigraphy performed.
Patients were classified into 3 groups based on the percentage increase in LV dP/dtmax induced by dobutamine (¦¤LV dP/dtmax) and on LV ejection fraction (LVEF) at baseline: group I (n = 18): ¦¤LV dP/dtmax >100 % and LVEF >25 % ; group IIa (n = 17): ¦¤LV dP/dtmax ?00 % and LVEF > 25 % ; and group IIb (n = 11): ¦¤LV dP/dtmax ?00 % and LVEF ?5 % . The amounts of beta1-adrenergic receptor, sarcoplasmic reticulum Ca2+-adenosine triphosphatase, and phospholamban mRNA were significantly smaller in groups IIa and IIb than in group I. The plasma norepinephrine level was increased and the delayed heart/mediastinum count ratio in MIBG scintigraphy was decreased in both groups IIa and IIb.
Dobutamine stress testing is a useful diagnostic tool for identifying reduced adrenergic myocardial contractile reserve related to altered myocardial expression of beta1-adrenergic receptor, sarcoplasmic reticulum Ca2+-adenosine triphosphatase, and phospholamban genes even in asymptomatic or mildly symptomatic patients with DCM.