Dobutamine stress testing as a diagnostic tool for evaluation of myocardial contractile reserve in asymptomatic or mildly symptomatic patients with dilated cardiomyopathy.
OBJECTIVE
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 microg 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 [(123)I]metaiodobenzylguanidine (MIBG) scintigraphy performed.


RESULTS
Patients were classified into 3 groups based on the percentage increase in LV dP/dt(max) induced by dobutamine (DeltaLV dP/dt(max)) and on LV ejection fraction (LVEF) at baseline: group I (n = 18): DeltaLV dP/dt(max) >100% and LVEF >25%; group IIa (n = 17): DeltaLV dP/dt(max) <or=100% and LVEF > 25%; and group IIb (n = 11): DeltaLV dP/dt(max) <or=100% and LVEF <or=25%. The amounts of beta(1)-adrenergic receptor, sarcoplasmic reticulum Ca(2+)-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 beta(1)-adrenergic receptor, sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase, and phospholamban genes even in asymptomatic or mildly symptomatic patients with DCM.
Kobayashi
Masakazu
M
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Izawa
Hideo
H
Cheng
Xian Wu
XW
Asano
Hiroyuki
H
Hirashiki
Akihiro
A
Unno
Kazumasa
K
Ohshima
Satoru
S
Yamada
Takashi
T
Murase
Yosuke
Y
Kato
Tomoko S
TS
Obata
Koji
K
Noda
Akiko
A
Nishizawa
Takao
T
Isobe
Satoshi
S
Nagata
Kohzo
K
Matsubara
Tatsuaki
T
Murohara
Toyoaki
T
Yokota
Mitsuhiro
M
D019797:3-Iodobenzylguanidine; D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D004280:Dobutamine; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D055414:Myocardial Perfusion Imaging; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D019275:Radiopharmaceuticals; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D012720:Severity of Illness Index; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D000099211:Phospholamban
D019797:3-Iodobenzylguanidine; D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D002135:Calcium-Binding Proteins; D004280:Dobutamine; D009638:Norepinephrine; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D018342:Receptors, Adrenergic, beta-1; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C506946:ATP2A2 protein, human