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

Masakazu Kobayashi, MD^_*, Hideo Izawa, MD, PhD^_*, Xian Wu Cheng, MD, PhD, Hiroyuki Asano, MD^_*, Akihiro Hirashiki, MD, PhD^_*, Kazumasa Unno, MD^_*, Satoru Ohshima, MD^_*, Takashi Yamada, MD^_*, Yosuke Murase, MD, PhD^_*, Tomoko S. Kato, MD, PhD^_*, Koji Obata, PhD, Akiko Noda, PhD, Takao Nishizawa, MD, PhD^_*, Satoshi Isobe, MD, PhD^_*, Kohzo Nagata, MD, PhD^¶, Tatsuaki Matsubara, MD, PhD, Toyoaki Murohara, MD, PhD^_*, Mitsuhiro Yokota, MD, PhD, FACC^||,_*

^_* Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Cardiovascular Research Medicine, Nagoya University School of Medicine, Nagoya, Japan
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
^|| Department of Genome Science, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
^¶ Nagoya University School of Health Sciences, Nagoya, Japan

^_* Reprint requests and correspondence: Dr. Mitsuhiro Yokota, Department of Genome Science, School of Dentistry, Aichi-Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan (Email: myokota{at}dpc.aichi-gakuin.ac.jp).

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 (LV dP/dt_max) and on LV ejection fraction (LVEF) at baseline: group I (n = 18): LV dP/dt_max >100% and LVEF >25%; group IIa (n = 17): LV dP/dt_max 100% and LVEF > 25%; and group IIb (n = 11): LV 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.

Key Words: cardiomyopathy • contractility • heart failure • biopsy • dobutamine

Abbreviations and Acronyms   AR = adrenergic receptor   DCM = dilated cardiomyopathy   DST = dobutamine stress testing   GRK2 = G-protein–coupled receptor kinase 2   LV = left ventricular   LV dP/dtmax = maximal first derivative of left ventricular pressure   LVEF = left ventricular ejection fraction   MIBG = metaiodobenzylguanidine   mRNA = messenger ribonucleic acid   NYHA = New York Heart Association   SERCA2a = sarcoplasmic reticulum Ca2+-adenosine triphosphatase 2a

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