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CLINICAL RESEARCH: HEART FAILURE

Cardiac Sympathetic Dysfunction Correlates With Abnormal Myocardial Contractile Reserve in Dilated Cardiomyopathy Patients

Satoru Ohshima, MD^_*, Satoshi Isobe, MD, PhD^_*,_*, Hideo Izawa, MD, PhD^_*, Mamoru Nanasato, MD, PhD^_*, Akitada Ando, MD, PhD^_*, Akira Yamada, MD^_*, Kiyoyasu Yamada, MD, PhD^_*, Tomoko S. Kato, MD, PhD^_*, Koji Obata, PhD, Akiko Noda, PhD, Takao Nishizawa, MD, Katsuhiko Kato, MD, PhD, Kohzo Nagata, MD, PhD, Kenji Okumura, MD, PhD^_*, Toyoaki Murohara, MD, PhD^_* and Mitsuhiro Yokota, MD, PhD, FACC

^_* Department of Cardiology, Nagoya University School of Medicine, Nagoya, Japan
Department of Cardiovascular Genome Science, Nagoya University School of Medicine, Nagoya, Japan
Department of Medical Technology, Nagoya University School of Health Science, Nagoya, Japan
Department of Radiology, Nagoya University Hospital, Nagoya, Japan.

Manuscript received January 21, 2005; revised manuscript received June 30, 2005, accepted August 1, 2005.

^_* Reprint requests and correspondence: Dr. Satoshi Isobe, Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. (Email: sisobe{at}med.nagoya-u.ac.jp).

OBJECTIVES: We investigated the relationship between iodine-123-metaiodobenzylguanidine (¹²³I-MIBG) findings and myocardial contractile reserve in patients with mild to moderate dilated cardiomyopathy (DCM).

BACKGROUND: Little is known regarding the relationship between cardiac sympathetic nervous function and myocardial contractile reserve in DCM.

METHODS: Twenty-four DCM patients who showed sinus rhythm underwent echocardiography, biventricular catheterization, and myocardial ¹²³I-MIBG scintigraphy. Left ventricular (LV) pressures were measured using a micromanometer-tipped catheter. The myocardial contractile function (LV dP/dt_max) was determined at rest and during atrial pacing. The messenger ribonucleic acid (mRNA) expressions of intracellular Ca²⁺-regulatory proteins were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. Myocardial ¹²³I-MIBG accumulation was quantified as a heart-mediastinum ratio (HMR).

RESULTS: A significant correlation was observed between the delayed ¹²³I-MIBG HMR and the percentage change in LV dP/dt_max from the baseline to the peak or critical heart rate (r = 0.64; p < 0.001). The delayed ¹²³I-MIBG HMR was significantly lower in patients showing a worsening change in LV dP/dt_max than in those showing a favorable change (p < 0.005). The maximum LV dP/dt_max during pacing and the sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2) mRNA levels were significantly more reduced in patients with a delayed HMR 1.8 than in those with a delayed HMR >1.8 (p < 0.05, respectively).

CONCLUSIONS: Abnormal myocardial ¹²³I-MIBG accumulation is related to an impaired myocardial contractile reserve and down-regulation of SERCA2 mRNA in DCM. Myocardial ¹²³I-MIBG scintigraphy can be useful in noninvasively evaluating myocardial contractile reserve in patients with mild to moderate DCM.

Abbreviations and Acronyms   DCM = dilated cardiomyopathy   HMR = heart-mediastinum ratio   123I-MIBG = iodine-123-metaiodobenzylguanidine   LV = left ventricular   LV dP/dtmax = maximum first derivative of left ventricular pressure   LVEF = left ventricular ejection fraction   mRNA = messenger ribonucleic acid   NE = norepinephrine   SERCA2 = sarcoplasmic reticulum Ca2+-ATPase   T1/2 = pressure half-time

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