Market Size
In Europe today, there is a 3.1 million procedure annual addressable market. Assuming a $200 price, Imagify targets more than a $600 million opportunity in Europe today. CAD is the single most common cause of death in Europe. Growth opportunity in this market comes from the increasing incidence of CAD due to obesity and diabetes, two major risk factors for CAD, as well as an aging population. In addition, cardiac stress testing in Europe appears to be substantially underutilized compared to the U.S., where the population and prevalence of CAD is about the same as in Europe, but the number of cardiac stress imaging procedures is three times that of the Europe with a corresponding lower death rate from CAD in the U.S. In the United States, there is a 10.4 million procedure cardiac stress market. About three-quarters of these procedures are nuclear stress and one-quarter are stress ultrasound. At a $200 price per procedure, Imagify targets a potential $2 billion market in the U.S.
Current Market Solution
Cardiac stress tests are used in patients at intermediate risk of CAD to triage them for angiography. Coronary angiography allows direct visualization of the coronary artery lumen to determine if a blockage exists. However, it has many drawbacks relative to less invasive alternatives. Mortality is estimated at one per thousand patients and morbidity includes vascular injury from the arterial puncture and nephrotoxicity from the large dose of contrast agent. Exposure of the patient, and to a lesser extent the medical staff, to ionizing radiation is significant and is equivalent to the dose received in ~140 chest X-rays. The costs of angiography are significant, and depending on referral patterns, a significant proportion of patients referred for angiography prove to have no significant disease. Due to these limitations, in most countries attention has shifted to the use of non‑invasive imaging modalities for the preliminary diagnosis of CAD and for triaging to angiography.
Cardiac stress testing
Nuclear stress testing and cardiac stress ultrasound are the two most common stress imaging methods for determining the level of risk for patients with suspected CAD, with 1.8 million and 1.3 million procedures respectively each year in Europe. Nuclear stress testing evaluates myocardial perfusion, which is considered a more direct and sensitive indicator of CAD than heart wall motion information that ultrasound provides, and the primary reason for nuclear’s dominant market share.
Nuclear stress
Nuclear stress testing involves the intravenous injection of a radiopharmaceutical while the patient is at rest and again under stressed conditions, followed by scans of the heart using a special camera. Nuclear stress tests are supervised and read by radiologists or nuclear cardiologists usually after referral by a cardiologist. These tests typically take five hours to complete, are expensive, due to significant capital equipment costs and complex regulatory requirements associated with the use of radioactive material. Furthermore, they are not readily available in many hospital or physician office settings. The radiation dose for a single nuclear stress procedure is equivalent to 180 or 800 chest x-rays, depending on whether newer (sestamibi) or older (thallium) radiopharmaceuticals are used, and even radiation exposure associated with sestamibi results in a 1 in 1000 cancer death rate. Many patients have multiple procedures throughout their lifetime and the radiation dose effect is cumulative.
In Europe, radiation safety is a critical issue and legislation exists discouraging the use of radiation when non-radioactive alternatives are available. Additionally, the key nuclear stress agent raw material used in sestamibi has recently been in critically short supply, causing many studies to be canceled or postponed and causing an increased use of thallium, which leads to higher radiation exposure. These shortages could last for several more years.
Cardiac stress ultrasound
Cardiac stress ultrasound is a widely available, fast, radiation-free, and inexpensive method for detecting cardiac wall motion abnormalities (downstream consequences of inadequate perfusion). However, wall motion is considered to be a less sensitive marker of CAD than myocardial perfusion. As a result, cardiac stress ultrasound, in spite of all of its advantages, has competed less effectively with nuclear stress testing. Traditional stress ultrasound alone is incapable of assessing myocardial perfusion. Cardiac ultrasounds are supervised and read by non-invasive cardiologists, usually with special training in echocardiography.
Other imaging techniques
Clinicians have at their disposal a variety of non-invasive testing equipment to assist in their assessment of CAD. Although each of the methodologies listed below provides useful data to clinicians, each suffers from shortcomings in accuracy, safety, or convenience in detecting CAD. As a result, none of these techniques represents a significant share of the CAD detection market, each representing less than 150,000 procedures per year in the EU:
- CT Angiography (often referred to as a CAT scan) uses special X-ray equipment to produce cross-sectional views of internal organs, bones, soft tissue and blood vessels. It subjects the patient to high doses of radiation — the equivalent of 240 chest x-rays. The efficacy of this test for detecting disease in intermediate risk patients is still questionable, and so it is not routinely used in the stable chest pain patient population.
- MR (Magnetic Resonance) measures electromagnetic energy released when a patient is exposed to the strong magnetic field of the MRI machine. MRI can produce two- or three-dimensional images of organs and blood vessels, but is expensive, complex and requires capital equipment that is rarely available in cardiology departments or offices. It is therefore not suitable for the routine detection of CAD in chest pain patients.
- PET (Positron Emission Tomography), uses positrons which are tiny particles that are emitted from a radioactive substance that has been administered to a patient. PET suffers from very limited availability. Although it is slightly more accurate than nuclear stress testing, it shares the disadvantage of requiring a radioactive agent and is even more expensive.
Earlier generation ultrasound contrast agents
The performance limitations of older, approved ultrasound contrast agents make them unsatisfactory for myocardial perfusion assessment. Early ultrasound contrast agents that were developed in the early 1990’s were encapsulated microbubbles, with thin natural shells of human serum albumin or lipids, filled with air or nitrogen, and offered insufficient time for cardiac perfusion assessment. Next generation ultrasound contrast agents (e.g. Sonovue®, Bracco) are also microbubbles made with the same thin shells of natural materials but contain insoluble fluorinated gases, which extend the duration of enhancement, but like earlier generation agents, are still not robust enough for reliable cardiac perfusion assessment and so are not approved for this indication.
In Europe, only one ultrasound contrast agent, Sonovue, is currently commercially available and it has been approved by the EMA for indications other than myocardial perfusion assessment. A limitation of Sonovue is that its shells still break readily in the ultrasound beam, causing short half-life in blood. Its demonstrated effectiveness in cardiology is limited to left ventricular opacification, which only enables better wall motion analysis of the cardiac chamber. Two other ultrasound contrast agents have been approved by the EMA for indications other than myocardial perfusion assessment: Optison® (GE Healthcare) and Luminity® (Lantheus). These agents, however, have been withdrawn from the market. No ultrasound contrast agent is approved anywhere in the world for the large market in myocardial perfusion assessment.