Identifying inflammation is at the heart of the matter

CaRi-Heart technology can uncover deadly coronary inflammation and atherosclerosis and generate individualized cardiac risk.

Think heart attack, and you probably lay the blame at the door of the build-up of plaque that causes a dangerous narrowing of the arteries. However, over half of heart attacks and strokes occur in patients without these problems – and the primary culprit is inflammation. There is currently no way to identify the coronary inflammation that causes most of these heart attacks because inflammation is invisible on cardiac CT scans, which is the primary means of identifying the cause of recurring chest pain.

Longevity.Technology: While short-term inflammation serves as a vital shield against pathogens and injuries, its prolonged presence, characteristic of aging, is a considerable danger to the heart. Heart disease is the world’s biggest killer and chronic inflammation, contributes pivotally to both cardiovascular and cerebrovascular disease. Chronic, low-grade inflammation can be something of a silent killer, playing a role not only in CVD, but in cancer and type 2 diabetes, and driving aging itself, a process often called inflammaging. Oh, and systemic inflammation increases with age as well.

Now Oxford-based Caristo Diagnostics has developed an AI solution that can detect and quantify coronary inflammation, a primary driver of coronary artery disease. CaRi-Heart® can detect previously invisible coronary inflammation in routine CCTA scans meaning anti-inflammatory therapeutics can be administered.

We sat down with Frank Cheng, CEO of Caristo Diagnostics, to find out more about this world-first technology which is already in use in multiple NHS trusts and private hospitals in the UK, Europe and Australia and in the process of securing FDA approval for use in the US.

Heart attacks happen as a result of atherosclerosis (plaque) build-up and rupture in patients’ coronary arteries, and Cheng explains that cardiologists have known for many years that atherosclerosis is an inflammatory disease, as inflammation in the wall of coronary arteries drives the gradual build-up of plaque inside coronary arteries and also drives the eventual plaque rupture prior to heart attacks.

Cheng says that despite the importance of detecting and monitoring coronary inflammation, a majority of routine tests that clinical cardiologists currently rely on are only trying to detect arteries that are narrowed and thus causing a restriction of the blood supply to the heart muscle.

“Specifically, a coronary computed tomography angiography (CCTA or cardiac CT scan), which is the first-line test recommended to diagnose coronary artery disease, measures coronary narrowings (stenosis) in the arteries caused by plaque,” he explains. “While plaque detection is important, it is only useful in the late stages of underlying cardiovascular disease.

“By contrast, information on coronary inflammation can provide crucial early warning signs of a cardiac event. Yet traditional diagnostic methods of measuring inflammation are not specific for cardiovascular diseases. Inflammation is invisible to CT scans, for instance. And biomarkers such as hsCRP (High-sensitivity C-reactive Protein) measure systemic inflammation, rather than cardiovascular inflammation, so the test may show up high in the case of inflammation driven by non-heart organs. 

CaRi-Heart leverages AI tech to detect and quantify coronary inflammation, giving it an edge over traditional diagnostic methods. Cheng explains that while it is important to find patients who already have significantly narrowed coronary arteries, and obviously need immediate treatment, cardiologists often end up archiving many cases of patients with no visible signs of disease but who potentially have high coronary inflammation. This inflammation, driven by cholesterol, or smoking, or diabetes and other risk factors, ultimately causes the wall of the artery to become thickened and narrowed.

“Caristo’s CaRi-Heart technology is a non-invasive cloud-based solution that utilizes AI to analyse CT scans, overcoming the limitations of traditional diagnostic methods, offering a more sensitive and specific approach to detecting and quantifying coronary inflammation,” says Cheng. “CaRi-Heart is the only commercially available technology that can detect and measure coronary inflammation on routine cardiac CT scans, and it has been cleared for clinical use in the UK, EU and Australia.”

Frank Cheng is CEO of Caristo Diagnostics

CaRi-Heart’s AI tech enables the uncovering of coronary inflammation in the perivascular fat surrounding arteries on routine cardiac CT scans. The platform measures coronary inflammation, generating a proprietary biomarker called a FAI-Score™, which, says Cheng, is a strong predictor of cardiovascular risk. 

“In a real-world NHS trial using CaRi-Heart technology, almost half of patients without coronary narrowings were reclassified for cardiovascular risk when coronary inflammation, rather than only plaque alone, was taken into account,” Cheng explains.

“This has major significance in detecting the disease earlier, understanding how the disease is progressing, and ultimately managing the patient’s cardiovascular risk with personalised treatments.”

Caristo’s tech could be a gamechanger – millions of adults present with chest pain every year; many undergo a CT scan to diagnose coronary artery disease, but, says Cheng, three quarters of these patients display no clear sign of significant narrowing or plaque and are seen as low risk of having a heart attack.

“There are twice as many deaths or cardiac events in these ‘low risk’ patients than in those identified as high-risk,” he says. “A primary cause of these events is coronary inflammation.”

Cheng and his colleagues recently presented new research findings from the ORFAN study at the 2023 American Heart Association’s (AHA) Late Breaking Science session.

“Our research results have shown that among patients who had no plaque and zero calcium at the time of CCTA, those with the highest level of coronary inflammation experienced an 11-fold higher risk for cardiac mortality and a 5-fold higher risk for major adverse cardiac events (MACEs) than those who had minimal coronary inflammation,” he says. “This illustrates the significant role coronary inflammation plays in heart attacks.”

The path to pioneering a new way of looking at heart disease had a couple of minor bumps in the road. Caristo needed to acquire sufficient patient data to train the AI model, so the company partnered with major academic research organizations in the US, UK and the rest of Europe to access large cohorts of patient data for model training and validation. Using data from studies it conducted, Caristo achieved regulatory clearance in the UK, the EU and Australia for CaRi-Heart’s clinical use, and the company is currently in the process of seeking regulatory clearance in the US as well.

”We also needed to validate CaRi-Heart’s performance in real-world patient care, and we have published studies proving its performance in real-world clinical tests in more than 10 peer-reviewed scientific journals around the world,” says Cheng.

Now CaRi-Heart is in use in multiple healthcare settings globally, Cheng hopes it will catalyse a transformation in cardiovascular disease management, moving it from reactive to proactive and preventative.

“CaRi-Heart technology is shifting how we address this critical health issue on a global scale,” he explains. “What’s extremely exciting about Caristo’s Cari-Heart technology is its simplicity in operation. It is a non-invasive cloud-based solution that can be applied to almost any routine cardiac CT scan without requiring new scans or any other physical equipment or tests.“

In addition, CaRi-Heart offers retrospective analysis, allowing clinicians to gain insights into disease activity and treatment response from past CT scans, which could enable missed inflammation to be detected. 

“The dynamic nature of the CaRi-Heart FAI-Score, which measures coronary inflammation, provides a valuable tool for tracking the efficacy of medical treatments and lifestyle interventions,” Cheng explains. ”This not only enables clinicians to monitor drug compliance but also facilitates personalised treatment strategies based on individualised risk scores.”

Now that CaRi-Heart is being used to predict and hopefully prevent heart attacks, Caristo has its eye on two other big diseases – stroke and diabetes – and will be evaluating the potential of its AI tech to predict and prevent them. 

Cheng explains that the company expects to see CaRi-Heart used by more pharmaceutical and biotech companies to assist with clinical trials. 

“CaRi-Heart has already been used in this way to accomplish three things that are critical to the success of testing new medications: first, identifying patients who have cardiac inflammation who qualify for enrolment in the clinical trial; second, monitoring the effect of cardiovascular treatments on inflammation; and third, monitoring the effect of non-cardiovascular medications on inflammation as an unintended side-effect.” 

Photographs courtesy of Caristo Diagnostics