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Imaging for the diagnosis of Coronary Artery Disease (CAD) – what is new?

Professor Danilo Neglia was educated at the Università di Pisa where he studied medicine and specialized in cardiology. He obtained his PhD in 1984 at the Scuola Superiore ‘Sant’ Anna’ and specialized in Nuclear Medicine in 1987. He is Senior Cardiologist at Fondazione Toscana G. Monasterio, Associate Researcher at CNR Institute of Clinical Physiology and Affiliate Professor at Scuola Superiore Sant’Anna in Pisa, Italy.



Cardiovascular imaging (CVI) is evolving rapidly, placing new demands on the cardiologists’ profession and on health-care systems. Functional and anatomical CVI is more and more an essential component in the management of patients with cardiovascular conditions. It is thus likely that the need for CVI will continue to increase over the coming years due to the changes in CV     diseases epidemiology and ageing of the population. In addition, CVI techniques are evolving rapidly in terms of performance and diversity. The availability of more advanced imaging technology combined with an expanded target population would thus require new professional skills for properly indicate, acquire, interpret and use imaging information in the diagnostic and therapeutic decision making process of the single patient. Whether this would be better achieved by integration of different specialists (clinical cardiologists, cardiac imaging experts, interventional cardiologists) in ‘heart teams’ or by expanding the competences of single professionals is an opened discussion.

Approaches for CAD

Among CV diseases, coronary artery disease (CAD) is the single most common cause of health-related death in the EU, accounting for at least 681,000 deaths each year and costing the EU economy almost 38 billion Euro a year. Early diagnosis, invasive coronary procedures and effective medical treatments led to a significant decrease in mortality due to acute coronary syndromes. In   patients with stable CAD, however, the effectiveness of diagnostic and therapeutic management of patients on outcome is more questionable. There is increasing awareness that invasive coronary angiography (ICA) is used too frequently as an early   diagnostic testing in these patients, providing negative findings in up to 40% of exams and often driving inappropriate revascularization procedures without clear effects on symptoms and prognosis. Significant improvements in non-invasive imaging have driven increased interest to use these procedures more routinely in the diagnostic algorithm for         patients with suspected CAD to reduce costs and risks and to better address personalized management.

Choices to be made

In the current clinical setting, however, there is no clear guide on which non-invasive imaging approach is most effective in the specific patient so that the choice is mostly conditioned by availability, costs, local preferences and expertise. Non-     invasive testing provides different, and often not superimposable, information. Cardiac computed tomography angiography (CCTA) is used for non-invasively assessing the presence and the severity of ‘anatomical’ CAD. The functional relevance of the disease can be assessed by stress imaging evaluating myocardial perfusion (SPECT, PET, CMR), myocardial/coronary flow reserve (SPECT/PET/DopplerECHO) or wall motion (ECHO, CMR). According to current European Guidelines in Stable CAD, what would be required in each     patient is the definition of both the presence of an anatomical coronary disease and of its functional effects on the myocardium to indicate revascularization. Nevertheless, non-     invasive anatomical and functional evaluation is rarely used in the same patient delegating to the invasive study the final assessment.

Comparative studies

A few studies have compared different non-invasive imaging strategies for their ability to recognize patients with functionally significant CAD and to correctly address treatment in real world practice. Of note EVINCI is the most recent European multicenter study in which both anatomical     imaging by CCTA and functional   imaging (chosen among all available stress imaging modalities) were performed in the same patient with suspected CAD before ICA. The study demonstrated a higher accuracy of CCTA as compared with stress imaging in recognizing patients with significant disease demonstrated at invasive assessment. It also showed that the prevalence of significant CAD was lower than expected (29%) in a current European population clinically selected for diagnostic screening. Moreover, it evidenced that stress imaging is often performed using suboptimal protocols. These could be relevant factors explaining the better performance of CCTA in this population. The clinical follow-up of the EVINCI population was completed in September 2015 and results on the impact on outcome of different non-invasive imaging strategies are expected soon. In fact, this would be the most clinically valuable end-point of comparative effectiveness studies on imaging in CAD.

The PROMISE study is the most recent trial which was designed to compare the clinical effectiveness of initial functional testing to a strategy of initial anatomic imaging with CCTA in symptomatic patients with suspected CAD. It failed to demonstrate prognostic benefits of either of the two strategies. This trial confirmed that not only the prevalence of disease but also the long term clinical risk is lower than expected in the population currently submitted to diagnostic screening for suspected CAD.

Costs play a role

All this considered, an important additional dimension to define the appropriate use of imaging in patients with suspected stable CAD would be the relationship between clinical benefits, procedural risks and costs.

An ideal comparative cost-effectiveness analysis should include the risks associated with radiation exposure, magnetic fields, stress protocols, over-diagnosis or missed diagnosis, related direct and indirect costs with outcome as an end-point.

Despite some relevant available studies such as the CE-MARC which addressed the cost-effectiveness of combined strategies including CMR, such a comprehensive health economic assessment of multi-modality imaging in CAD is still lacking.

Future perspectives

New developments in cardiovascular imaging applied to the diagnosis of CAD are very promising. One possibility to get integrated information on coronary anatomy and function is allowed by fusion or hybrid imaging obtained by CCTA and SPECT/PET (with possible absolute quantification of flow), with an ultralow radiation exposure. Developments in CMR would allow a similar approach with a single modality. Use of stress ECHO for combined assessment of wall motion and coronary flow reserve already demonstrated improved performance. Great interest has been recently rised by perfusion and FFR measurements by CT and we will wait for the results of the large on-going PROSPECT and CREDENCE studies.

A new frontier would be to better select patients even before non-invasive imaging. Increasing evidence suggests that the accepted clinical definition of pre-test probability of CAD before imaging is overestimated in the actual European population. Based on the EVINCI study data it was recently demonstrated that simple predictive models including clinical variables and a few biomarkers could be able to reclassify pre-test probability from intermediate to low in 56% of patients with suspected CAD thus potentially avoiding useless and costly diagnostic tests. While waiting for new comparative research studies and for the implementation of technical developments in clinical practice, the assessment of the current status of the use of CV imaging in Europe has become a priority for the Imaging Taskforce of European Association of Cardiovascular Imaging (EACVI) and the European Society of Cardiology (ESC). A recent report highlighted the lack of national and international CV imaging registries, which could highlight the current use, effectiveness, costs and impact on outcome of non invasive imaging in patients with stable CAD in Europe.