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(Circulation. 2001;104:658.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Reduced Myocardial Sarcoplasmic Reticulum Ca²⁺-ATPase mRNA Expression and Biphasic Force-Frequency Relations in Patients With Hypertrophic Cardiomyopathy

Fuji Somura, MD; Hideo Izawa, MD, PhD; Mitsunori Iwase, MD, PhD; Yasushi Takeichi, MD; Ryoji Ishiki, MD, PhD; Takao Nishizawa, MD; Akiko Noda, PhD; Kohzo Nagata, MD, PhD; Yoshiji Yamada, MD, PhD; Mitsuhiro Yokota, MD,PhD

From the Cardiovascular Division, Department of Clinical Pathophysiology (T.N., M.Y.), the First Department of Internal Medicine (F.S., H.I., Y.T., R.I., K.N.), Nagoya University, Graduate School of Medicine, and Nagoya University School of Health Sciences (M.I., A.N.), Nagoya; and Gifu International Institute of Biotechnology (Y.Y.), Mitake, Japan.

Correspondence to Mitsuhiro Yokota, MD, PhD, FACC, Department of Clinical Laboratory Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan. E-mail myokota{at}tsuru.med.nagoya-u.ac.jp

Background—— The relationship between left ventricular (LV) contractile functional reserve and gene expression of Ca²⁺-handling proteins in patients with hypertrophic cardiomyopathy (HCM) remains to be clarified.

Methods and Results—— We calculated the maximum first derivative of LV pressure (LV dP/dt_max) and the LV pressure half-time (T_1/2) during pacing in 14 patients with nonobstructive HCM (LV ejection fraction >55%) and 7 control subjects. Endomyocardial tissue was obtained, and mRNA levels of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2), ryanodine receptor-2, phospholamban, calsequestrin, and Na⁺/Ca²⁺ exchanger were quantified by use of a real-time quantitative reverse transcription—polymerase chain reaction method. Group A consisted of 7 HCM patients who showed a progressive rise in the LV dP/dt_max with increased heart rate. Group B consisted of 7 HCM patients in whom the heart rate—LV dP/dt_max relation was biphasic at physiological pacing rates. Both the mean maximal wall thickness and the LV hypertrophy score in group B were greater than in group A (20±5 versus 15±3 mm and 7±1 versus 5±2 points, respectively). SERCA2 mRNA levels were significantly lower in group B (SERCA2/GAPDH ratio 0.34±0.15) compared with group A (0.72±0.27) and control subjects (0.85±0.47), whereas the mRNA expression of ryanodine receptor-2, phospholamban, calsequestrin, and Na⁺/Ca²⁺ exchanger were similar in all groups.

Conclusions—— These results suggest that downregulation of SERCA2 mRNA, resulting in altered Ca²⁺ handling, may contribute to impaired LV contractile reserve in HCM patients with severe hypertrophy, even in the absence of detectable baseline systolic dysfunction.

Key Words: hypertrophy • cardiomyopathy • myocardial contraction • sarcoplasmic reticulum • biopsy

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