On 26 August 2012, HeartFlow announced that data from the company’s landmark prospective, international DeFACTO (Determination of fractional flow reserve by anatomic computed tomographic angiography) study were presented by principal investigator James K Min, director of Cardiac Imaging Research at the Department of Medicine, Imaging and Biomedical Sciences at Cedars-Sinai Medical Center in Los Angeles, USA, in a hotline session at the European Society of Cardiology (ESC) meeting in Munich, Germany, and simultaneously published in The Journal of the American Medical Association.
The study results demonstrate that, when compared to standard coronary CT angiography alone, HeartFlow’s computed fractional flow reserve (FFRCT) coupled with coronary CT angiography provides a more accurate determination of which patients’ arterial blockages require invasive evaluation.
The study assessed the ability of FFRCT to identify flow-restricting lesions versus CT alone, by comparing the results to invasive fractional flow reserve (FFR), which is recognised by the European Society of Cardiology as the gold standard for determining which arterial blockages require treatment.
FFRCT provided a nearly 20% improvement in the ability to identify flow-restricting arterial blockages over the use of CT alone using an area under the curve (AUC or Receiver Operating Characteristics) analysis (AUC 0.81 vs. 0.68, p=0.0002). AUC is a robust measure of diagnostic test reliability and accuracy. The per-patient sensitivity and specificity of FFRCT were also higher than CT alone.
The improvement in diagnostic performance was even greater in arterial blockages of intermediate severity. In this set of patients, there was more than a two-fold increase in test sensitivity, from 37 to 82%, with no loss of specificity. In these patients, the AUC improved from 0.53 for CT alone to 0.80 for FFRCT (p=0.0002).
“One of the central challenges in taking care of patients with coronary artery disease is knowing which patients need further invasive evaluation for determining the need for coronary revascularisation. The results of the DeFACTO trial clearly demonstrate that when added to coronary CT angiographic findings, FFRCT provides essential physiologic information as to which specific arterial blockages truly restrict blood flow to the heart and heighten patient risk. This is an exciting step forward for cardiology that could significantly improve how we guide patients towards the most effective and efficient care,” said Min. “Further, our findings suggest that FFRCT could be particularly useful for evaluating patients with arterial blockages of an intermediate severity, which often are the most difficult to assess non-invasively. This is a large group of patients that is unfortunately often prone to frequent misdiagnosis.”
“We are very pleased with the results of DeFACTO, which suggest that FFRCT coupled with CT could be poised to become the new standard for non-invasive cardiac testing. It offers the promise of a single standardised test to determine whether patients have coronary artery disease that needs further evaluation or therapy,” said John H Stevens, chairman and CEO of HeartFlow. “This technology holds the potential to substantially improve the ability of physicians to accurately determine which patients need and do not need coronary angiography and intervention, resulting in better patient outcomes and reduced costs.”
DeFACTO enrolled 252 stable patients with suspected coronary artery disease at 17 centres in five countries. All patients underwent CT, invasive coronary angiography (ICA), invasive FFR and subsequent FFRCT analysis. This study evaluated the first-generation of HeartFlow’s software technology and there will likely be continued improvement in accuracy in the future. These results also expand upon the findings of the DISCOVER-FLOW study published in the Journal of the American College of Cardiology in November 2011.
Recent analysis of the potential positive impact of FFRCT on healthcare costs and patient outcomes was presented by Mark A Hlatky, professor of Health Policy and Research at Stanford University, USA, at the Society for Cardiovascular Computed Tomography (SCCT) meeting in Baltimore, USA. In his presentation, Hlatky noted that a strategy of using CCTA with FFRCT to guide selection of patients for invasive evaluation and percutaneous coronary intervention “might reduce costs and improve clinical outcomes compared to current treatment pathways.” The simulation model presented at SCCT showed per-patient savings of more than US$3,000 when compared to the conventional angiography based treatment strategy.
HeartFlow technology is designed to provide physicians non-invasively computed FFR (FFRCT) values at every point along the coronary tree. Until now, FFR measurements could only be measured invasively during coronary angiography with a pressure-sensing guidewire.
Studies have shown that treatment guided by invasively measured FFR has better clinical outcomes, including a 34% reduced risk of death or major cardiac event, and significantly lower healthcare costs. Other currently available non-invasive diagnostic tests, such as CT, provide anatomic information but do not provide lesion-specific data, and therefore have marginal diagnostic accuracy compared to the invasive FFR gold standard.