Dobutamine Stress Testing as a Diagnostic Tool for Evaluation of Myocardial Contractile Reserve in Asymptomatic or Mildly Symptomatic Patients With Dilated Cardiomyopathy

Objectives: We performed dobutamine stress testing for evaluation of myocardial contractile reserve in asymptomatic or mildly symptomatic patients with dilated cardiomyopathy (DCM). Background: 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. Methods: The maximal first derivative of left ventricular pressure (LV dP/dt_max) was determined during infusion of dobutamine (10 μg kg^-1 min^-1) 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. Results: Patients were classified into 3 groups based on the percentage increase in LV dP/dt_max induced by dobutamine (ΔLV dP/dt_max) and on LV ejection fraction (LVEF) at baseline: group I (n = 18): ΔLV dP/dt_max >100% and LVEF >25%; group IIa (n = 17): ΔLV dP/dt_max ≤100% and LVEF > 25%; and group IIb (n = 11): ΔLV dP/dt_max ≤100% and LVEF ≤25%. 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. Conclusions: 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.