, new results show.
Further analysis in the small study suggested that mental stress–induced myocardial ischemia (MSIMI) was not statistically related to coronary microvascular dysfunction (CMD).
“Since the findings do not support a correlation between MSIMI and CMD, which has been a widely accepted mechanistic explanation of ANOCA, routine mental stress testing in patients with ANOCA seems necessary,” researchers led by Qingshan Geng, MD, PhD, of Shenzhen People’s Hospital, Guangdong, China, conclude in a report published online in the Journal of the American College of Cardiology.
Dr. Geng said in an interview that the use of virtual reality devices to administer mental stress tests “ensures standardized experimental procedures, with each participant receiving an objectively equivalent level of stress load.
“The immersive experience provided by VR lowers the environmental requirements for the test,” he noted. “Furthermore, the application of VR reduces the workload of personnel responsible for inducing mental stress, simplifying the experimental process.”
The team also developed a mobile app that enables remote monitoring of participants’ visual experiences during PET/CT scans and facilitates communication, he added.
Mental stress testing and meds?
Both ANOCA and MSIMI in patients with coronary artery disease disproportionately affect women and are associated with poor cardiovascular prognosis, the researchers write.
“However, the role of MSIMI and the exact influence of mental stress in ANOCA have not previously been studied,” they point out.
For this investigation, 84 women with ANOCA and 42 age-matched controls underwent three mental stress challenges delivered via VR.
Tests included mental arithmetic, making a public speech describing a recent emotionally upsetting event, and a task-modified Stroop test, in which participants were asked to say the color in which the word appears, not the color that the word names. For example, if the word “yellow” appears in blue type, blue would be the correct answer.
An adenosine stress test was given 5-8 minutes after the mental stress challenges started, and cardiac PET/CT was used to examine myocardial blood flow and perfusion.
The investigators report that women with ANOCA had a much higher rate of MSIMI (42.9%), compared with control participants (one patient; 2.4%). They also had a higher proportion of coronary microvascular dysfunction (CMD; 24.6% vs. 8.6%), but the occurrence of MSIMI and CMD was not related, the authors note.
Consistent with previous studies, “we observed that CMD is more prevalent in ANOCA women than the age-matched healthy individuals. MSIMI rate, however, was notably higher than the rate of CMD in our female ANOCA population,” they write. “The lack of a significant association between MSIMI and CMD indicates the mechanisms of MSIMI cannot be well explained by the adenosine-induced CMD.”
Dr. Geng suggested that ANOCA patients may benefit from treatment with escitalopram.
“Compelling evidence” from the REMIT randomized, placebo-controlled trial validates the efficacy of the drug as an MSIMI treatment, he said.
Sample size too small?
Asked for comment on the findings, Viola Vaccarino, MD, PhD, Wilton Looney Distinguished Professor of Cardiovascular Research at Emory University’s Rollins School of Public Health and a professor in the university’s School of Medicine, Atlanta, said she disagreed with several aspects of this study and the investigators’ conclusions.
Although the study suggests that MSIMI is prevalent among women with ANOCA, “the sample size was too small to make any definite conclusions,” she said in an interview.
“In fact,” she said, “I do not agree with the authors’ conclusions that MSIMI and CMD were not related, based on the data presented, even though the P value was not significant.”
In addition, more research is needed before screening can be recommended, she said. “The effectiveness of this testing modality in this population should be demonstrated first.”
Furthermore, she added, “an established treatment for MSIMI has yet to be tested in large, controlled trials, which limits the potential clinical benefit that may result from this [screening] test.”
For now, to ameliorate potential MSIMI in women with ANOCA, Dr. Vaccarino recommends behavioral modalities or stress-reduction management techniques, including biofeedback, meditation, breathing exercises, and “just plain regular physical activity,” rather than the use of psychotropic medications.
Dr. Vaccarino’s team has a study underway that builds on earlier work involving more than 900 participants, which showed that MSIMI was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction (hazard ratio, 2.5).
The ongoing study, which investigates the link between emotional stress and heart disease in men and women, should be completed in about 3 years, she said.
Microvascular disease or spasm?
Leslie Cho, MD, chair of the American College of Cardiology’s Cardiovascular Disease in Women Committee, director of the Cleveland Clinic’s Women’s Cardiovascular Center, and professor of medicine at Cleveland Clinic Lerner School of Medicine and Case Western Reserve Medical School, commented on the mental stress–heart connection and mental stress testing for this article.
A “very big flaw” of the JACC study, she said, is that although PET testing can detect microvascular disease, it cannot detect microvascular spasm.
PET can show the coronary flow reserve, “which is a nice way to assess microvascular dysfunction,” she acknowledged, “but it really can’t tell microvascular spasm, because adenosine works in a different pathway than acetylcholine – and I think it’s important for people to have the right diagnosis.
“We do physiologic testing to distinguish the two conditions,” she noted. “We do the gold standard, which is the cath lab.”
“The problem with women with chest pain for years is that they get a stress test, they get a cath, and everything’s normal. Then they get blown off as anxious or whatever.”
Clinicians should conduct the gold standard workup – provocative physiologic testing – for these women who continue to have chest pain when results of other tests are negative, she said. “The test used to be very cumbersome, but today, we have systems that make it super easy to use and to distinguish microvascular disease and microvascular spasm.”
Importantly, she added, physiologic testing should be performed when women are off therapy – something that doesn’t always happen in the clinic.
Regarding treatment, she added, “if you’re having emotional stress, the answer is not another medicine. The answer is cognitive-behavioral therapy or another behavioral intervention to overcome anxiety.”
Tune in and advocate
What can clinicians do for women with ANOCA after testing reveals no significant coronary artery disease or microvascular spasms?
“Very often, it’s a matter of the doctor listening and responding to the patient,” Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital, New York, said in an intereview.
In her practice, Dr. Contreras sees highly stressed women on a daily basis. Many of her patients are women from diverse racial/ethnic groups, often of lower socioeconomic status, who are heads of households, work more than one job, and experience other major stressors.
“My message to clinicians is: don’t give up on a woman just because you looked at the arteries and couldn’t find anything specific. If she keeps coming back with the same symptom, it’s important to address it,” she said. “Maybe it isn’t the symptom. Maybe she needs to talk about her situation, about the physiological and psychosocial factors contributing to the symptom that a test alone won’t reveal.”
Regarding cardiovascular spasms that are identified through physiologic testing, she said, “I don’t know that medications such as SSRIs [selective serotonin reuptake inhibitors] are going to change anything. But many things can be changed by listening or helping the patient to stop and think about her mental health.”
Following up with a referral to a therapist can help, she said; “Take away the mental health stigma by telling the patient that the referral is simply to help her cope.”
Dr. Contreras urges clinicians to be advocates for such patients. If an insurance company says it will cover only three therapy sessions, “tell them that three appointments are not enough” to address multiple issues.
“If we invest money in helping patients identify and cope with these issues, we are likely to get better long-term outcomes, rather than having that woman come into the emergency department with chest pain over and over and doing 20,000 tests that are going to show exactly the same thing,” Dr. Contreras concluded.
Dr. Geng’s study was supported by the High-Level Hospital Construction Project of Guangdong Provincial People’s Hospital, by a grant from Guangdong Provincial Bureau of Traditional Chinese Medicine, and by a grant from Guangdong Medical Science and Technology Research Foundation. The authors, Dr. Vaccarino, Dr. Contreras, and Dr. Cho report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.