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In symptomatic women with suspected microvascular coronary dysfunction, the risks of invasive coronary reactivity testing (CRT) are relatively low and outweigh the value of diagnosing the condition, linked with increased rates of major adverse events, according to a study published in the June issue of JACC: Cardiovascular Interventions.

Between 30% and 50% of women with stable angina who undergo angiography show no signs of obstructive CAD, yet about half of this group have microvascular coronary dysfunction. CRT can be used to definitively diagnose the condition, but the safety of the procedure has not been well studied.

To help address this need, investigators led by C. Noel Bairey Merz, MD, of Cedars-Sinai Medical Center (Los Angeles, CA), evaluated 293 women with ischemia and no obstructive CAD who underwent CRT at 3 experienced centers participating in the Women’s Ischemia Syndrome Evaluation (WISE) study. The testing was done with a Doppler wire and left coronary artery injections of the vasodilators adenosine, acetylcholine, and nitroglycerin.

There were no CRT-related deaths. Two women suffered serious adverse events associated with the testing, including 1 STEMI due to coronary artery spasm and 1 coronary artery dissection. Two others experienced a CRT-related event deemed not serious: 1 transient air microembolism to the right coronary artery, causing chest pain, and 1 deep venous thrombosis on the side of the groin access site more than 30 days after testing.

CRT results showed abnormalities in a substantial proportion of the women:

• Abnormal nonendothelial microvascular function (47%)
• Abnormal endothelial microvascular function (51%)
• Abnormal endothelial macrovascular function (58%)
• Abnormal smooth muscle function (60%)
• Coronary vasospasm, > 50% reduction in diameter to high-dose acetylcholine vs. baseline (5%)
• Coronary vasospasm, > 70% reduction in diameter to high-dose acetylcholine vs. baseline (2.3%)

Over a follow-up of 5.4 years, 32 events were observed in 24 women (table 1).

Table 1. Long-term Outcomes

Safer Than Not Testing

The authors note that the combined CRT-related adverse event rate of 1.4% was substantially lower than the long-term MACE rate of 8.2%, suggesting that the value of diagnosing microvascular coronary dysfunction in this population outweighs the risks associated with CRT.

In fact, use of the test is routine in many other countries, including Japan, the United Kingdom, and Italy, Dr. Bairey Merz told TCTMD in an e-mail communication.

A firmer evidence base for using CRT, though, will come from studies looking at whether the information yielded by the testing can be used to improve outcomes, the authors observe. “To date in the United States, intermediate-outcome trials suggest benefit,” Dr. Bairey Merz said. “But larger major adverse cardiac event trials are being planned and hopefully funded to more definitively test this issue.”

In an accompanying editorial, Alison L. Bailey, MD, and Susan S. Smyth, MD, PhD, both of the University of Kentucky (Lexington, Kentucky), agreed that the results of CRT should change patient management enough to justify the small but real risk involved with testing. For instance, the use of angiotensin-converting enzyme inhibition to improve coronary flow velocity reserve—an indicator of microvascular function—may be an option based on CRT findings. Statins may also provide benefit, though Drs. Bailey and Smyth say that this remains theoretical at present.

The editorial questions whether other, less invasive procedures could substitute for CRT to establish the diagnosis of microvascular dysfunction. Standard measures of lipid and hormone levels, blood pressure, and left ventricular function do not appear correlated with coronary function, they note. And although digital reactive hyperemia peripheral arterial tonometry does serve as a surrogate marker for microvascular function, it cannot provide the same level of detail as CRT.

“Eventually, imaging modalities such as cardiac magnetic resonance imaging with pharmacological stress and gadolinium as a flow tracer might replace invasive testing, but at present invasive coronary reactivity remains the gold standard,” Drs. Bailey and Smyth conclude.

Study Details

The mean age was 54 years and 84% of the women were white. In addition, 48% had a history of smoking, 10% were diabetic, 35% were hypertensive, and 32% had dyslipidemia.

Sources:

1. Wei J, Mehta PK, Johnson BD, et al. Safety of coronary reactivity testing in women with no obstructive coronary artery disease: Results from the NHLBI-sponsored WISE (Women’s Ischemia Syndrome Evaluation) study. J Am Coll Cardiol Intv. 2012;5:646-653.
2. Bailey AL, Smyth SS. Invasive coronary vasoreactivity testing to diagnose microvascular dysfunction in women. J Am Coll cardiol Intv. 2012;5:654-655.

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