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An innovative technique for the evaluation of coronary artery disease has been proven clinically useful, according to a study conducted by the Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine of the University of Hong Kong (HKUMed). This new technique could provide a reliable way of identifying coronary artery disease patients who require stenting of the arteries. The findings of the study are now published in the Journal of Cardiovascular Translational Research [link to publication].

Research background and findings
Coronary artery disease is one of the leading causes of morbidity and mortality, with an estimated global burden of 240 million people living with the disease in 2020.¹ In our locality, heart disease is the third commonest cause of death with 60% of them being coronary artery disease.² With such a high prevalence rate, it is extremely pertinent that patients with coronary artery disease receive suitable treatment. Medical treatment of coronary artery disease focuses on lowering the workload of the heart and controlling other cardiovascular risk factors. Apart from medical treatment, percutaneous coronary intervention (PCI) is another invasive treatment modality for such patients. There were approximately 350-500 elective PCI operations done in Hong Kong per year. PCI is a procedure to expand the lumen of coronary arteries that had been narrowed due to fat plaques, ensuring that blood supply to the heart muscle is maintained. Modern PCI often involves the placement of a stent, which maintains the patency of the expanded artery lumen.

In stable patients presenting with chest pain, traditionally, a more stenotic artery lumen is thought to cause more obstruction to the blood supply thus PCI is needed to augment the blood flow across coronary arteries. However, studies have shown that the blood flow across certain coronary artery stenoses can be maintained, and PCI may not be required. In such cases, cardiologists can use an adjunctive technique known as fractional flow reserve (FFR) to assess the true extent of blood flow obstruction thereby the need for PCI. PCI only provides clinical benefit if FFR shows significant blood flow obstruction across the stenotic segment (‘ischemic’), while PCI does not improve outcome or even does harm if FFR suggests the coronary artery stenosis does not significantly affect the blood flow (‘non-ischemic’). International guidelines have recommended the use of FFR to guide PCI treatment in stable coronary artery disease patients. Despite its clinical utility, the use of FFR involves insertion of extra guidewires and adenosine injection, which causes chest discomfort for the patient. Due to the extra costs, procedural risks, and patient discomfort, the utilisation rate of FFR is low in real-world practice, for example, in 2017, with FFR only being used in 18.5% of USA patients who had intermediate coronary lesions (40-69% stenosis) shown on angiogram.³ As a result, a new wire-free technique known as coronary angiography-derived FFR (caFFR) has recently emerged to overcome the above obstacles. caFFR employs a computational model to estimate the true FFR from coronary angiography images without the need of extra guidewire or adenosine injection, and it has been shown to have high accuracy compared to FFR.⁴ Thereby increasing the utilisation rate of caFFR to benefit patients with suitable treatment.

With the advantages of caFFR, this study aimed to evaluate whether patients in Hong Kong could benefit from the use of caFFR. A total of 1,308 patients from a public hospital were included, and their coronary angiogram images were analysed. caFFR was used to quantify the severity of their coronary artery stenoses. Over three years of follow-up, PCI reduced cardiovascular mortality and the rate of new myocardial infarction in patients with ‘ischemic’ disease but did not significantly benefit patients with ‘non-ischemic’ disease. This suggests that those with ‘ischemic’ disease as indicated by caFFR should undergo PCI to prevent future myocardial infarction and death, and PCI is not necessary if caFFR suggests ‘non-ischemic’ disease. More importantly, suitable treatment by PCI based on caFFR evaluation reduced the risk of adverse outcomes by 30%.

Research significance
Many patients with stable coronary artery disease undergo coronary angiography evaluation in public hospitals, and a portion of those patients receive treatment by PCI to improve blood supply to heart muscles. However, PCI itself carries risks including bleeding, infection, and stent-related complications such as restenosis and stent thrombosis etc. Moreover, PCI is an expensive procedure and patients will be prescribed anti-platelet regimen that lasts up to one year after PCI. With the implementation of caFFR, patients can be more effectively triaged according to disease severity, and patients who have less severe diseases can avoid unnecessary stent placement. As such, patients can avoid the procedural risks and high financial costs of PCI. Public health expenditures can also be lowered as a result of reduced post-PCI medication prescriptions and follow-up appointments.

‘FFR is the gold standard adopted by international guidelines to guide PCI treatment in coronary artery disease patients, yet its utilisation rate is not as high as expected. caFFR provides an alternative which eliminates the need of extra wire and medication injection, which could be more widely accepted and used in Hong Kong. With the use of caFFR, we wish to provide the best treatment to coronary artery disease patients,’ noted by Professor Yiu Kai-hang, Clinical Professor, Department of Medicine, School of Clinical Medicine, HKUMed, who led the research team in conducting this study.

About the research team
The study is led by Professor Yiu Kai-hang, Clinical Professor, Department of Medicine, School of Clinical Medicine, HKUMed. Other collaborators include Professor Tse Hung-fat, William MW Mong Professor in Cardiology and Chair of Cardiovascular Medicine, Department of Medicine, School of Clinical Medicine, HKUMed; Dr Fung Yundi, PKU-HKUST Shenzhen-Hongkong Institution; Dr Calvin Leung Ka-lam and Dr Li Hang-long, Department of Medicine, School of Clinical Medicine, HKUMed; Dr Cao Gaozhen, Dr Wu Min and Dr Wang Run, The University of Hong Kong-Shenzhen Hospital; PhD candidates Wu Meizhen, Ren Qingwen, former research nurse Yu Shuk-yin, medical student researchers Jane Lam Lok-yee, Li Kwan-yu, Yu Si-yeung and Stephanie Tse Yi-kei, Department of Medicine, School of Clinical Medicine, HKUMed.

Media enquiries
Please contact LKS Faculty of Medicine of The University of Hong Kong by email (medmedia@hku.hk).

¹ Tsao CW, Aday AW, Almarzooq ZI et. al; on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2022 update: a report from the American Heart Association [published online ahead of print Wednesday, January 26, 2022]. Circulation.

² Centre for Health Protection, Department of Health - Heart Diseases. Centre for Health Protection. (2023). https://www.chp.gov.hk/en/healthtopics/content/25/57.html

³ Parikh, R. V., Liu, G., Plomondon, M. E., Sehested, T. S. G., Hlatky, M. A., Waldo, S. W., & Fearon, W. F. (2020). Utilization and outcomes of measuring fractional flow reserve in patients with stable ischemic heart disease. Journal of the American College of Cardiology, 75(4), 409–419.

⁴ Li J, Gong Y, Wang W, Yang Q, Liu B, Lu Y, et al. Accuracy of computational pressure-fluid dynamics applied to coronary angiography to derive fractional flow reserve: FLASH FFR. Cardiovasc Res. 2020;116:1349–56.