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Find a program specializing in Coronary Microvascular Dysfunction (CMD) and the diagnosis and management of chest pain with open coronary arteries.

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Vanderbilt (Nadia Sutton, interviewee; January 2023)

JK: Tell us a little about yourself.

NS: I am an interventional cardiologist currently practicing at Vanderbilt University Medical Center in Nashville, right down the street from you! My clinical interests include intravascular imaging and physiology, complex coronary artery disease treatment, and management of older patients in the cath lab. 

JK: Tell us about how you became interested in taking care of patients with microvascular dysfunction?

NS: During training and my first years practicing as an interventional cardiologist, I frequently took care of patients that had anginal symptoms and abnormal stress tests, but they were found to have normal or non-obstructive coronary artery disease. The more I learned about ischemia with non-obstructive coronary arteries (INOCA), the more I became aware that in our field as a whole, we were likely often mis-informing patients that their symptoms were non-cardiac. In fact, they were describing symptoms of angina from microvascular dysfunction. At that time, I was working at the University of Michigan and wanted to start offering invasive microvascular testing. Serendipitously, increasing availability of the Coroventis CoroFlow software, which allows Abbott’s PressureWire X to measure microvascular dysfunction indices, enabled me to begin offering this testing. I am now in the process of launching an invasive microvascular dysfunction program at Vanderbilt University Medical Center.

JK: Was it difficult to set up a program for invasive microvascular dysfunction testing?

NS: Not at all. I requested the equipment though our usual process at each institution. There is a lot of enthusiasm for women’s heart health, and women are more likely to have non-obstructive coronaries after an abnormal stress test than men are. This made it easy to pitch the need for having the testing available at my institution. However, microvascular dysfunction is also common in men, and testing should be offered to all patients with a clinical presentation where it is suspected. In addition, microvascular dysfunction testing received a Class IIa recommendation in the most recent Chest pain guidelines (1).

JK: Was it challenging to integrate microvascular dysfunction testing into your cath lab workflow?

NS: This was also not a challenge. Performing microvascular dysfunction testing involves delivery of a coronary physiology wire and administration of a vasodilator, such as adenosine. The process is very similar to performing a fractional flow reserve (FFR), which most labs offer and can perform without difficulty. Microvascular dysfunction testing with the PressureWire X simply adds performing thermodilutions to calculate an index of microvascular resistance, which is one of the indices that help rule in or rule out the diagnosis. Overall, the process takes only a couple minutes longer than an FFR. Most would agree that an FFR is a straightforward test.

JK: Do you see a lot of demand for invasive microvascular dysfunction testing?

NS: There have been some patients referred specifically for microvascular dysfunction testing. In my opinion, this testing should also be performed ad hoc when microvascular dysfunction is suspected. An added bonus is that an FFR and a resting full-cycle ratio (RFR) can be reported at the same time. So, if there is an intermediate severity stenosis, you can find out if it is hemodynamically significant and also determine if there is associated microvascular dysfunction. In my experience, the number of patients who are referred to the cath lab for an abnormal stress test who end up having non-obstructive coronary artery disease and undergo ad hoc microvascular dysfunction testing has been greater than the number of patients specifically referred for testing. If you only test patients specifically referred for testing, you will be missing the diagnosis in a lot of patients.

JK: Is it time-consuming to perform microvascular dysfunction testing?

NS: It is not time consuming. As mentioned above, it takes a couple minutes longer than FFR testing. It is ideal if patients hold medications such as beta-blockers and calcium channel blockers for 48 hours before testing. However, if the patient is already undergoing the invasive procedure but has not held these medications, I have still proceeded with testing to avoid them having to come back for a second procedure. The sensitivity of testing with and without holding vasodilators has not been rigorously studied. Also, many operators choose to avoid administering calcium channel blockers as part of their radial cocktail if radial access is chosen.

JK: How does performing invasive microvascular testing help patients?

NS: In my experience, patients are relieved to have microvascular dysfunction diagnosed or ruled out. If it is diagnosed, treatments can be tailored, and based off of the CorMicA (CORonary MICrovascular Angina) (2) trial, tailored therapy improves patients’ symptoms and quality of life. When microvascular dysfunction is ruled out, patients can pursue other possible etiologies for their symptoms and do not have to come back for unnecessary appointments or take unnecessary medications that could have associated side effects.

JK: How do you get the word out about having invasive microvascular dysfunction testing available in the cath lab you work in?

NS: Initially, when I would speak with referring physicians about patient results, I would let them know that microvascular dysfunction testing was being offered. In addition, I announced the availability of testing at institutional conferences, such as our Cardiovascular Medicine Grand Rounds, and also invited outside speakers with expertise in the area to present to our faculty. I made it known at local meetings, through women in cardiology groups, and at professional society meetings. I made myself available to assist my colleagues when they wanted to perform the testing initially; it takes very little time to become proficient with this technique.

JK: Do you find that patients are seeking out invasive microvascular dysfunction testing?

NS: Some patients are seeking this out after reading about it independently in the popular press. I have received patient messages and self-referrals specifically for microvascular dysfunction testing.

JK: How do you manage patient queries about why they were not previously offered invasive microvascular testing, either by you or a colleague or another program?

NS: We have to acknowledge that there is growing awareness of microvascular dysfunction, and not all programs have the capability to perform microvascular dysfunction testing at this time. My hope is that with increasing awareness, there will be less advice to patients that “it’s not their heart,” when they have an abnormal stress test and normal coronaries. Instead, it is advisable to let patients know that there is a possibility their symptoms represent microvascular dysfunction, and empirically treat them and refer them to a center which does offer invasive or non-invasive microvascular dysfunction testing. Ideally, patients would receive this information and advice from their cardiologist. It can be challenging when the testing is available, but one or more colleagues chooses not to offer or perform testing, when it could have been offered. In that case, some standardization or triage of patient care within a program may need to be addressed to avoid patient dissatisfaction.

JK: Do you find that microvascular dysfunction is a problem that primarily women are facing?

NS: Even though women are more likely to have angiographically non-obstructive coronary arteries after an abnormal stress test or myocardial infarction, microvascular dysfunction still occurs commonly in men. I have found testing very helpful for men with repeated admissions for angina and even those with prior percutaneous coronary interventions (PCI) with a repeated need for heart catheterizations. In retrospect, in some cases, their symptoms were probably from microvascular dysfunction, not from the stenosis that was treated with PCI.

JK: How often do you have requests for performing vasospasm testing? Is this integrated into the workflow similarly to microvascular dysfunction testing?

NS: Symptoms of vasospasm differ somewhat from angina due to microvascular dysfunction, which tends to be more consistent and less episodic. However, we do know from CorMicA 2 that approximately 20% of patients in whom these disease states are suspected have both microvascular dysfunction and coronary vasospasm. I perform vasospasm testing with acetylcholine only when the patient’s symptoms are concerning for it, and these patients are specifically consented for vasospasm testing. I do not perform vasospasm testing ad hoc, though I do perform microvascular dysfunction testing ad hoc.

JK: What are your key takeaways?

NS: Microvascular dysfunction testing is a coronary physiology test that every operator and every cath lab should be able to offer their patients, given how common microvascular dysfunction is and the impracticality of referring every suspected patient to another center or colleague. This testing is straightforward to learn, quick, and benefits patients.

References

1. Gulati M, Levy PD, Mukherjee D, Amsterdam E, Bhatt DL, Birtcher KK, Blankstein R, Boyd J, Bullock-Palmer RP, Conejo T, Diercks DB, Gentile F, Greenwood JP, Hess EP, Hollenberg SM, Jaber WA, Jneid H, Joglar JA, Morrow DA, O’Connor RE, Ross MA, Shaw LJ. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021 Nov 30;144(22):e368-e454. doi: 10.1161/CIR.0000000000001029. Epub 2021 Oct 28. Erratum in: Circulation. 2021 Nov 30;144(22):e455. PMID: 34709879.

2. Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25. PMID: 30266608.

Columbia University (Megha Prasad, Interviewee; May 2023)

NS: Megha, thanks for taking the time to introduce yourself and tell us about what’s happening with MVD at Columbia!

MP: Absolutely! My name is Megha Prasad. I am originally from California and did undergrad and medical school at the University of Southern California. I had an interest in cardiology early on and spent my 4th year at University of California San Francisco working in Yerem Yeghiazarians’ lab studying microvascular function, endothelial function, and the role of CD34+ cells in animal models of myocardial infarction. I then moved out to Rochester, MN and did my residency and fellowship at the Mayo Clinic, where I worked with Dr. Amir Lerman, also in the field of CMD. Together we worked on some memorable projects, including the CD34+ cell study for treatment of CMD. (1) This enabled me to get experience in working with the FDA to get approval for a cell therapy. From there, I pursued CHIP training at Columbia University. I was thrilled to be hired on staff at Columbia, where I have been able to continue my interests in CHIP interventions, as well my academic interest in microvascular dysfunction and cardiogenic shock. 

NS: Tell us about how you became interested in taking care of patients with microvascular dysfunction?

MP: I have a long-standing interest in studying the increased risk that Southeast Asians have for coronary artery disease, and during my training I recognized the links between risk factors and the development of CMD. I became dedicated to not only diagnosing microvascular dysfunction but also treating the high-risk lesions that result from this atherosclerotic process. I envisioned that perhaps one day there could be therapies to treat microvascular dysfunction that could be provided in the cath lab.  

NS: Was it challenging to integrate microvascular dysfunction testing into your cath lab workflow?

MP: I have been fortunate in having amazing support from hospital, pharmacy, and cath lab leadership at Columbia to integrate this into our cath lab. We have developed institution-specific protocols and begun to do this testing more routinely.

NS: Do you see a lot of demand for invasive microvascular dysfunction testing?

MP: It has been a work in progress. We are working with the cardiologists and the primary care physicians in the area to raise awareness through various educational conferences. People are recognizing the necessity of it. In my own practice, I take care of a lot of patients with kidney disease in my role as the Director of Cardiorenal Medicine and Interventions. I have been using invasive microvascular testing a lot in my patients with chronic kidney disease and those being evaluated for renal transplant who have a positive stress test. Also, there are patients that will present with chest pain on dialysis, and when we do microvascular circulation testing, these patients often have microvascular dysfunction, explaining their chest pain in the absence of obstructive disease. We are trying to better understand these relationships to clarify the role of the microcirculation in CKD, particularly as it relates to progression of CKD to needing dialysis and progression of the coronary artery disease in patients with CKD. 

NS: How does performing invasive microvascular testing help your patients?

MP: Having a diagnosis is comforting to patients.  When they leave the lab, I can tell patients, I know why you are having this pain. Also, it helps me tailor my therapy. If it’s vasospasm or isolated microvascular dysfunction, I change my recommendations accordingly. I have been prescribing L-arginine, which works well with limited side effects. There is limited data on this, and it needs to be explored further. (2) In addition, enrolling them into a program of diet and exercise and risk stratification does help knowing that patients with microvascular dysfunction have worse outcomes. 

NS: What are the key challenges for patients with microvascular dysfunction symptoms?

MP: The biggest challenge is the lack of awareness in the medical community. Many have the misconception that there’s no point in diagnosing it, or that it’s very risky, and often blindly treat it. In a field like cardiology that’s so data-driven, there needs to be more widespread acceptance and understanding by the cardiology community so patients with symptoms are not dismissed.

NS: What do you think are the key challenges for those providing care for those with microvascular dysfunction?

MP: One key challenge is the lack of resources that clinics have. Clinics taking care of patients with microvascular dysfunction require more time and resources than average. These patients require titration of medications and phone calls to review symptoms. This often goes beyond the average time that physicians have for seeing patients, and many physicians face the time pressures that result from working in a system that rewards volume.  

NS: What do you see as research priorities in this field?

MP: Research in this field is paramount. There are 2 big ideas we need to focus on. The first is standardizing definitions and the way we collect data. We are excited to be embarking on this. The second is the Achilles heel of CMD: the limited number of therapies. There is a lot of work to be done in this area. The CD34+ cells have shown some promise. The coronary sinus reducer is another interesting new device with respect to microvascular dysfunction. We need to start thinking about what potential therapies are and start to study them rigorously in a randomized fashion to distinguish what is a real effect vs. a placebo effect. We also need to refine protocols for diagnosis and develop treatment algorithms.

We are excited that Abbott and the MVN network will be supporting future research in the form of an international registry. We hope to study patients with non-obstructive coronary artery disease as well as those with post-PCI angina. We will be addressing questions that have not been addressed before. This will also be a resource to identify patients who could be candidates for future clinical studies. 

NS: What are your key takeaways?

MP: CMD is important to diagnose and treat. There are current treatments available, as have been described by the CoRMicA trial (3). Patients with CMD have significant quality of life impairments. As a field, we need to band together to raise awareness of this condition, encourage formal diagnosis, gather more data, and develop and trial therapies that will help to relieve symptoms and impact long-term prognosis.

References