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CLINICAL RESEARCH: HEART FAILURE

Prognostic Value of Pacing-Induced Mechanical Alternans in Patients With Mild-to-Moderate Idiopathic Dilated Cardiomyopathy in Sinus Rhythm

Akihiro Hirashiki, MD^_*,, Hideo Izawa, MD, PhD, Fuji Somura, MD, PhD, Koji Obata, PhD^_*, Tomoko Kato, MD, PhD, Takao Nishizawa, MD, PhD^_*, Akira Yamada, MD, Hiroyuki Asano, MD, Satoru Ohshima, MD, Akiko Noda, PhD, Shigeo Iino, MD, PhD, Kohzo Nagata, MD, PhD, Kenji Okumura, MD, PhD, Toyoaki Murohara, MD, PhD and Mitsuhiro Yokota, MD, PhD, FACC^_*,_*

^_* Department of Cardiovascular Genome Science, Nagoya University School of Medicine, Nagoya, Japan
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Nagoya Ekisaikai Hospital, Nagoya, Japan
Nagoya University School of Health Sciences, Nagoya, Japan

Manuscript received August 22, 2005; revised manuscript received September 29, 2005, accepted October 25, 2005.

^_* Reprint requests and correspondence: Dr. Mitsuhiro Yokota, Department of Cardiovascular Genome Science, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan (Email: myokota{at}med.nagoya-u.ac.jp).

OBJECTIVES: The relation between the occurrence of pacing-induced mechanical alternans and prognosis in patients with mild-to-moderate idiopathic dilated cardiomyopathy (IDCM) in sinus rhythm was investigated prospectively. The myocardial expression of genes for Ca²⁺-handling proteins in such patients was also examined.

BACKGROUND: Mechanical alternans occurs in some patients with severe heart failure, but the relation between the occurrence of mechanical alternans and prognosis in patients with IDCM has remained unknown.

METHODS: Left ventricular (LV) pressure was measured during atrial pacing, and LV endomyocardial biopsy specimens were collected in 36 IDCM patients and 8 controls. Idiopathic dilated cardiomyopathy patients were divided into two groups consisting of 22 individuals who did not develop mechanical alternans at heart rates up to 140 beats/min (group A) and of 14 individuals who did (group B). The patients were followed up for a mean of 3.7 years.

RESULTS: There was no significant difference in LV ejection fraction or the plasma concentration of brain natriuretic peptide between groups A and B. The myocardial abundance of ryanodine receptor 2 messenger ribonucleic acid (mRNA) was significantly lower in groups A and B than in controls, whereas that of sarcoplasmic reticulum Ca²⁺-ATPase mRNA was significantly lower in group B than in group A or controls. Stepwise multivariate analysis identified pacing-induced mechanical alternans as the strongest predictor of cardiac events. Event-free survival in group A was significantly greater than that in group B.

CONCLUSIONS: The occurrence of pacing-induced mechanical alternans is a potentially useful indicator of poor prognosis in patients with mild-to-moderate IDCM in sinus rhythm.

Abbreviations and Acronyms   BNP = brain natriuretic peptide   CHF = congestive heart failure   GAPDH = glyceraldehyde-3-phosphate dehydrogenase   IDCM = idiopathic dilated cardiomyopathy   LV = left ventricle or left ventricular   LVdP/dtmax = maximal first derivative of LV pressure   LVEF = left ventricular ejection fraction   mRNA = messenger ribonucleic acid   RT-PCR = reverse transcription-polymerase chain reaction   SERCA2 = sarcoplasmic reticulum Ca2+-ATPase   T1/2 = pressure half-time