Stress testing links heart failure to altered molecular markers

Twitter icon
Facebook icon
LinkedIn icon
e-mail icon
Google icon
In patients with severe left ventricular dysfunction, dobutamine stress testing is a useful diagnostic tool to evaluate decreased myocardial contractile reserve, according to a study in the November issue of the Journal of the American College of Cardiology: Cardiovascular Imaging.

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, according to background information in the article.

Using dobutamine stress testing (10 µg kg/min) Masakazu Kobayashi, MD, of Nagoya University Graduate School of Medicine in Nagoya, Japan, and colleagues studied 46 dilated cardiomyopathy patients with a N.Y. Heart Association functional class of I or II to identify individuals with a reduced adrenergic myocardial contractile reserve, reflected by altered myocardial molecular biology. The expression of proteins 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.

The investigators found that there was a reduced adrenergic myocardial contractile reserve in all patients with severe left ventricular systolic dysfunction (left ventricular ejection fraction less than or equal to 25 percent). The mRNA expression of beta1-adrenergic receptor, sarcoplasmic reticulum Calcium2+ ( Ca2+)-adenosine triphosphatase, and phospholamban mRNA were similarly decreased in these patients, even in patients without symptoms or only mild symptoms of dilated cardiomyopathy.

Kobayashi and colleagues determined that 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.

"The fact that these changes were observed in relatively early stages of heart failure, and were more marked in those patients with reduced myocardial contractile reserve, would suggest that changes observed at the molecular level may actually be the cause of at least some of the impairment in left ventricular function," wrote Gary S. Francis, MD, and Milind Y. Desai, MD, of Cleveland Clinic Heart and Vascular Institute, in an accompanying editorial.