Magnetic resonance spectroscopy identifies women with chest pain at high risk

The test, called magnetic resonance spectroscopy (MRS), could identify women with chest pain at high risk for repeat hospitalization, cardiac catheterization, and other diagnostic procedures, said B. Delia Johnson, Ph.D., of the University of Pittsburgh, co-author of the study.

MRS detects changes in levels of chemicals that provide energy for heart muscle contraction:  phosphocreatine (PCr) and adenosine triphosphate (ATP).  Reductions in the ratio of PCr to ATP in heart muscle indicate abnormal energy metabolism or myocardial ischemia (reduced blood flow to the heart).

Women in the study who had an abnormal MRS but no significant obstruction in their coronary arteries had a coronary event rate similar to women with documented coronary artery disease. 

“Our results suggest that MRS will become an important test for evaluating patients who have anginal chest pain in the absence of coronary artery disease, as well as for other conditions,” said Gerald M. Pohost, M.D., director of the division of cardiovascular medicine at the University of Southern California and the senior author of the study. 

Chest pain without coronary artery disease (CAD) remains a mystery in the cardiology field, Pohost said.   Of the 534,000 women who had chest pain and coronary angiography in 2003, 300,000 do not have significant CAD.  That’s compared to fewer than 20 percent of men. 

The source of the chest pain remains unknown, although some scientists suspect it could be caused by an abnormality of the microvasculature – which in the heart consists of the smaller blood vessels including capillaries, arterioles and venules. 

Johnson and her colleagues from various institutions evaluated the impact of abnormal PCr/ATP ratio over three-years.  The study involved women who had been referred for coronary angiography because they were experiencing chest pain or had suspected myocardial ischemia.  They were part of the National Heart Lung and Blood Institute’s Women’s Ischemia Syndrome Evaluation (WISE).  The study population consisted of 74 women who had chest pain and no significant CAD and a reference group of 352 women with CAD.  Among the women without CAD, 60 had a normal MRS handgrip stress study and 14 had an abnormal PCr/ATP ratio.  The women were an average 56 years old.

During three years of follow-up, 87 percent of women without significant CAD and a normal MRS study had no clinical events related to their heart.  In contrast, only 57 percent of patients without significant CAD and with an abnormal MRS were event free.  For every 1 percent decrease in the PCr/ATP ratio, the risk of a heart-related event increased by 4 percent.  The higher clinical event rate was due primarily to hospitalization for unstable angina (chest pain that can occur even at rest).  This led to repeat cardiac catheterizations and thus to increased health care costs.

The results are consistent with the concept that chest pain without CAD is a disorder that primarily affects women, the investigators concluded.  Because MRS detects metabolic activity in cells, an abnormality in metabolism related to reduced blood flow in the small vessels in the heart muscle could underlie the disorder.  No standard approaches to therapy for this condition exist, Pohost said.  Most of the patients do not have conventional risk factors associated with coronary disease, such as high blood pressure or abnormal cholesterol levels.

Therapies that treat the condition have generally been ineffective in preventing or resolving chest pain.  In some women, even light physical activity can induce chest pain so debilitating that it requires hospitalization.  Many women affected by the condition have a very poor quality of life, in large part because they are so limited in what they can do for themselves.  Future studies will focus on trying to identify the underlying cause of the condition, which could lead to more effective treatment.

Co-authors are Leslee J. Shaw, Ph.D.; Steven D. Buchthal, Ph.D.; C. Noel Bairey Merz, M.D.; Hee-Won Kim, Ph.D.; Katherine N. Scott, Ph.D.; Mark Doyle, M.D.; Marian B. Olson, M.S.; Carl J. Pepine, M.D.; Jan den Hollander, M.D.; Barry Sharaf, M.D.; William J. Rogers, M.D.; Sunil Mankad, M.D.; John R. Forder, Ph.D.; and Sheryl F. Kelsey, Ph.D.

The National Heart, Lung, and Blood Institute partly funded the study.

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