FDA’s Breakthrough Designation: What This Means for Your Patients & Why It Matters

Published on
May 3, 2023
Contributors
Rhea Malhotra
VP of Product
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Statistically, there’s really no debate. Chest pain is by far the most common sign of a heart attack in both men and women.

But hidden behind this statement is a simple fact: the collection of symptoms we refer to as “anginal equivalents” – symptoms that include shortness of breath, cold sweats, fatigue, and jaw or back pain – should also be considered common. The literature increasingly recognizes how anginal equivalents disproportionately affect women more than men, and regrettably, they are oftentimes “deadlier” in the sense that patients and physicians alike typically take longer to arrive at a conclusive diagnosis because of the understated nature of these equivalent symptoms.

Unfortunately, this trend goes beyond just acute cardiac events and holds for more stable and persistent forms of heart disease as well.

Consider the case of a patient presenting with symptoms that persist for anywhere from one to ten years. Imagine that, despite a strong belief and fear that their symptoms are indicative of an issue with their heart, this patient consults with 3 or more different cardiologists just to hear that their “symptoms are not cardiac in nature.” Worse still, consider that this patient is likely to be referred to another specialty and, in many cases, receives a prescription for antidepressants.

✓ 50.2% Saw three or more cardiologists for appropriate treatment1.

✓ 77.8% Told their symptoms were non-cardiac1.

✓ 66.4% Told they would not die or suffer a heart attack1.

✓ 53.9% Told their symptoms were due to gastroesophageal reflux disease1.

This exact scenario described above outlines a typical day-to-day (and sometimes year-to-year) scenario for the majority of patients who are found to have ischemia with non-obstructive coronary arteries (INOCA).

While there’s a pervasive belief that this delay in care is inconvenient more than it is deadly, the data demonstrates the exact opposite to be true. Coronary microvascular dysfunction (CMD), which describes the most common subgroup of INOCA patients, is increasingly recognized as an independent predictor of mortality with a 4-fold increase in mortality risk.

Annually, INOCA is estimated to affect over 4 million men and women in the United States alone.

INOCA occurs when the tiny blood vessels supplying oxygen and nutrients to the heart are damaged, diseased, or otherwise dysfunctional, leading to symptoms that look almost identical to those used to identify patients experiencing a heart attack. This overlap in symptoms is one of the biggest reasons that making a successful diagnosis can be so challenging. The other major contributor to this stark reality is the fact that the current standard of care – mainly the tests we choose to use and how we choose to use them – focuses far too heavily on interrogating suspected disease for an expected anatomy, virtually ignoring the microvasculature of the heart.

That begs the question then, what do we do for patients whose disease exists within the microvasculature of the heart? Are we really appreciating the importance of the microvasculature, where 75-95% of the heart’s function occurs, when it’s practically “invisible” to anatomical testing?

Because interrogating function in the microcirculation of the heart requires such extreme sensitivity, almost all tests (including both non-invasive tests and invasive angiography both) we use to diagnose coronary artery disease are virtually useless in the diagnosis of CMD. In fact, it’s the use of these subpar tests which oftentimes lead cardiologists to believe that their patient’s symptomology is non-cardiac in nature. Patients studied during our recently concluded MICRO trial (NCT05150054) frequently stated they had undergone multiple stress tests and/or invasive coronary angiographies that were either “negative” or otherwise led to no further diagnosis being made.

Currently, there are only two validated ways to attempt a confirmatory diagnosis of CMD: invasive functional angiography with specific functional measurements or PET imaging. It goes without saying that both modalities have clear drawbacks from both a patient and physician perspective. Both are costly, sometimes prohibitively so. Both require specialized staff to be on-site. And both expose the patient to procedure-related risk or radiation.

This is where our recent Breakthrough Device Designation from the FDA comes in, and it represents a significant step towards resolving this gap in care.

CardioFlux MCG is a completely non-invasive test that takes less than 5 minutes to perform without requiring the use of radiation, stress agents, or injections. While these are all welcome benefits from the patient’s perspective, the FDA’s recent announcement here takes it a step further by recognizing the significant impact of CMD on overall public health and CardioFlux’s potential as a solution that may be able to address this unmet clinical need. More on the technical details of this designation can be found in Dr. Takla’s post here.

This milestone offers a glimpse of the standard of care we are trying to build towards at Genetesis, one that provides a full interrogation of cardiac function non-invasively. Under this new standard of care, a patient would undergo a single CardioFlux scan to receive a diagnosis of myocardial ischemia due to CMD. Said patient could then immediately start guideline-directed medical therapy, and over time, they could receive subsequent scans to monitor the progress of their treatment. Due to the obvious limitations described previously, diagnostic monitoring of CMD patients is effectively absent within the current standard of care.

In this case, the promise of CardioFlux is the potential ability to test for CMD non-invasively, without the risk of an inconclusive result, and to then further monitor the effectiveness of patient treatments. Serial CardioFlux scans could measure a normalization of function that would signal treatment efficacy, where a stagnant or worsening scan would alternatively indicate the need for more aggressive disease management or additional diagnostic testing.

There’s still plenty of work to be done, but the FDA’s Breakthrough Device Designation for CardioFlux is another sign that MCG sits at the frontline of medical innovation with its potential to be a first line diagnostic for patient care.

If you’re a physician interested in our research to date and you would like to play a role in actively defining this new standard of care, feel free to reach out to me directly at rhea@genetesis.com.

1 Gulati, M., Khan, N., George, M., Berry, C., Chieffo, A., Camici, P. G., Crea, F., Kaski, J.-C., Marzilli, M., &; Merz, C. N. (2022). Ischemia with no obstructive coronary artery disease (INOCA): A patient self-report quality of life survey from INOCA international. International Journal of Cardiology, 371, 28–39. https://doi.org/10.1016/j.ijcard.2022.09.047