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‘’I expect to see steady growth in the number of CT scanners in India’’

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How did cardiac CT begin? How do you see the technology evolving?

Dr Lawrence Boxt

Cardiac CT (CCTA) as we practice it now, really began after 1999-2000, with the commercial introduction of 64-detector scanners. In a dramatic advance over recent, kindred technology (i.e., 4-, 8-, 16-detector scanners), the 64-detector scanner produced isotropic voxels. That is, the imaging elements obtained from a scan are cubes; equal length on all sides. Thus, digital imagery of the epicardial coronary arteries reconstructed from these volume elements is of adequate spatial resolution to be artifact-free, and thus reliable for detection and quantitation of coronary artery calcium and the detection of significant coronary stenosis. Prior to 2001, the electron beam CT (EBCT) scanner developed at The University of California should have “revolutionised” cardiac imaging. It produced cine cardiac examinations of adequate quality for evaluation of myocardial wall thickening and valvular function. However, it was limited in spatial resolution, and thus unable to visualise the epicardial coronary arteries. Also, CCTA became commercially available in the early 1980’s, when magnetic resonance imaging was becoming commercially available. Radiology Department Chairmen were uncomfortable supporting two new and expensive technologies at the same time. EBCT was seen as a cardiac imaging device, and Radiology Chairmen didn’t want to fight with Chiefs of Cardiology. Radiology went headlong into MRI, and the EBCT virtually evaporated.

As to the future; the spread of multidetector CT technology, and the growth of 16- and 64-detector scanners, was associated with a dramatic increase in the number of CT scans, and the cumulative patient radiation exposure from multiple scanning. An uproar over patient radiation dose and risk of developing new cancer provided a moment of clarity for the CT and CCTA communities. In a remarkable change of industrial philosophy, there began another “revolution” in CT technology. Conscious attention to dose lowering methods and technologies have lowered the CCTA dose by nearly an order of magnitude. This is the first area of change we will see in the near and intermediate future. We will continue to see advances in tube and detector materials, and continued lowering of patient radiation exposure. The second area of change will come in the arena of computer-based image processing and image distribution algorithms and the network technology to connect scanners with workstations and physicians. We are already seeing “afterhour” exams in the US sent to India for review, and vice versa. Advanced display technology will allow us to visualise cardiac abnormalities rather than infer their presence. Furthermore, association of relevant databases will provide correlation with other tests, other clinical information, or other imaging studies. Association of particular characteristics of coronary arterial plaque with specific genetic loci on the individual’s genome will open new areas of clinical intervention based on the morphologic appearance of coronary plaque.

When is the prognostic value of CCTA best utilised?

CCTA is increasingly used as a clinical tool to visualise the coronary artery lumen and to identify coronary stenosis. That is, the foremost current use for CCTA is to exclude significant coronary artery disease, and avoid bringing the patient to the catheterisation laboratory for the performance of a diagnostic coronary catheterisation. The predictive power of coronary calcium quantitation, with regard to both future cardiovascular events and overall mortality has been well established. Given the significant contribution of underlying genetic mechanisms for the development of coronary atherosclerosis, and the high prevalence of asymptomatic individuals among those with coronary stenosis, the prognostic value of CCTA lies in the evaluation of asymptomatic or minimally symptomatic individuals with low or intermediate risk of coronary heart disease. These patients can be risk stratified, and directed toward aggressive risk lowering management in face of the presence of coronary calcium and mild-to-moderate arterial stenosis. The results of several prospective, multi-centre trials has demonstrated that hospital costs are lowered and patient length of stay shortened when CCTA is performed in low-to-intermediate risk, emergency department patients complaining of recent onset of chest pain, but without a known history of coronary heart disease. In these series, individuals in whom no significant coronary artery disease was demonstrated have a near zero cardiac event rate after emergency department discharge.

What are the benefits of cardiac CT? What are the risks involved?

The diagnostic benefits of CCTA are offset by the existing risks and potential risks of intravenous contrast administration for the opacification of the coronary arterial lumen, and the radiation exposure necessary to produce the tomographic imagery itself. Intravenous iodinated contrast administration always carries a potential risk of an adverse effect on the patient, and should only be used in circumstances where the benefit of its administration is greater than the risk of that administration in a particular patient. Although acute ‘allergic’ (anaphylactoid or idiosyncratic) contrast reaction is rare, it is the most frequent form of contrast reaction, and may, very rarely have severe, occasionally fatal complications. These reactions are five times more common in patients with asthma, four-to-six times more common in patients with a history of previous contrast reaction, and increasingly in patients with cardiovascular and renal disease, and those receiving beta-blockers. Non-anaphylactoid reactions may be associated with transient alteration of circulatory homeostasis. They are less commonly seen when non-ionic versus ionic contrast is administered, with low versus high iodine concentration, and in upon intravenous versus intra-arterial injection. Various pre-medication protocols may be utilised with varying degree of success.

The diagnostic benefit of CCTA is offset by the potentially increased risk of the radiation exposure of the exam itself, as well as the patient’s cumulative radiation burden that the exam contributes to. The theoretical risk posed to a patient by the examination lies in the random interaction between radiation and cellular molecules resulting in sufficient damage to result in development of a malignancy years after performance of the exam. Although any radiation exposure carries with it the potential risk of development of a malignancy, radiogenic health effects have been demonstrated in humans, through epidemiological studies, only at doses exceeding 5-10 rem delivered at high dose rates. Below this dose, estimation of adverse health effects remain speculative, and there is no consensus as to whether the effects observed in Japanese individuals (i.e., survivors of the Hiroshima and Nagasaki bombings) exposed to whole-body acute exposure to primarily high levels of radiation can be extrapolated to the partial-body exposures at much lower levels of radiation delivered to patients undergoing medical diagnostic procedures. A prudent approach to performing CCTA recognises the possibility that there is indeed no threshold below which radiation cannot cause malignancy, and that the risk of malignancy increases linearly with radiation dose. Therefore, examination planning and performance should revolve around limiting examination in patients at greatest risk, as well as limiting radiation exposure during examination in all patients.

How accurate is multislice CT angiography (CTA) as compared with standard angiography performed in the catheterisation lab?

Cardiac CTA does not provide the same degree of image quality or diagnostic accuracy as is achieved by conventional coronary arteriography. Nevertheless, sensitivity and specificity rates for stenosis detection are high when expert operators perform and interpret the examinations. Meta-analysis of comparisons made between CCTA and conventional coronary arteriography has demonstrated high sensitivity (96-99 per cent) and specificity (93-94 per cent) for the CCTA detection of individuals with at least one coronary stenosis. Large multicentre trials comparing CCTA with conventional coronary arteriography have demonstrated high sensitivity (75-95 per cent) and specificity (77-93 per cent) when evaluating per-vessel accuracy for detection of coronary stenosis. When per-patient accuracy is evaluated, higher sensitivity (85-99 per cent) but lower specificity (64-90 per cent) is found in CCTA examinations. However, in both meta-analyses and multicentre trials, the constant findings of moderate positive predictive value and very high negative predictive values are found. Thus, the true value of CCTA lies in its power to exclude significant coronary heart disease, rather than in its accuracy to quantitate per cent coronary artery stenosis determination. Most individuals with coronary heart disease exhibit coronary calcification. CCTA is exquisitely sensitive to the presence of such calcification, which is reflected in the high accuracy of CCTA to detect the presence of coronary heart disease. However, the physics and engineering of CT technology results in significant “blooming” artifact in the region of such calcified lesions, severely limiting the ability of cardiac CTA to actually quantitate the severity of such stenosis, an important attribute of conventional coronary arteriography.

What is its potential and its comparison vs conventional coronary angiography?

The potential value of CCTA, as compared with conventional coronary arteriography lies in both the accuracy of the CT technology and the evolving role of the catheterisation laboratory, the traditional location for the performance of conventional coronary arteriography. Thirty years ago, the paradigm for the management of patients with coronary heart disease was for an individual with chest pain to have a coronary arteriogram. If significant (>70 per cent) stenosis was identified, then the patient was sent for surgical revascularisation. In the vast majority of patients, revascularisation was associated with relief of pain. Individuals with normal coronary arteries, or those with less than significant stenosis were managed medically. With the development of percutaneous angioplasty, and subsequently intracoronary stent placement, revascularisation moved from the operating theatre to the catheterisation laboratory. Outcomes after percutaneous revascularisation were similar to those obtained surgically; pain was relieved. However, all individuals who underwent either surgical or percutaneous revascularisation all eventually died of their coronary heart disease. In other words, revascularisation improved symptoms, but (with the exception of left main coronary stenosis) had little effect on outcome. Revascularisation plays an important role in the management of individuals with coronary heart disease. However, it does not treat the underlying atherosclerotic process, and is thus a temporising methodology. With the increasing role for percutaneous revascularisation, we have created an increased demand for access to catheterisation laboratories, and strain on their utilisation. Here is where CCTA will make great inroads in patient management. CCTA is extraordinarily accurate as a tool for the exclusion of significant coronary artery stenosis. Thus, directing patients with low- or intermediate risk of coronary heart disease to the CT scanner (i.e., away from the catherisation laboratory) lowers the burden on the cath lab, shortening door-to-balloon time, and thus increasing clinical efficacy. Furthermore (and this will become much more important when we begin to understand and utilise the vast stores of genomic data we can now obtain from an individual patient), CCTA allows us to characterise the less than significant coronary stenosis, providing a means of identifying individuals with early, or less diffuse coronary heart disease. These individuals would benefit the most by early and aggressive medical intervention, and, as we have found in patients in whom their serum cholesterol levels have been lowered, have improved outcome.

Is there a patient selection criteria for this? Who are the patients that can best benefit from CCTA?

Currently, CCTA is proposed as a first line diagnostic tool in the context of low- and intermediate-risk individuals with chest pain but no documented history of coronary heart disease. In large institutions with very active cardiology services, catheterisation laboratory availability may be limited from time-to-time, thus bringing pressure to bear on lowering and loosening rigorous criteria for patient selection. As mentioned above, however, the strong association of coronary calcium with coronary stenosis limits the power of CCTA to characterise less-than-significant coronary lesions. Institutions with large CCTA services have garnered great experience, and may move selected patients waiting for a catheterisation appointment to the CT scanner.

The patient who benefits most from CCTA examination is a middle-aged man with chest pain, with some, but not many cardiac risk factors (low Framingham or TIMI score), and no documented history of coronary heart disease. The clinician taking care of this individual will send the patient for catheterisation if significant stenosis or an acute coronary syndrome is suspected. On the other hand, CCTA can exclude coronary heart disease in such a patient, giving both the patient and physician reassurance that no acute event is occurring. Furthermore, in these lower risk individuals, characterisation of individual coronary arterial plaque (which cannot be obtained by conventional coronary arteriography) may provide the basis for tailored medical management of their abnormal cholesterol metabolism.

What is the growth rate of this segment in India and what would be the estimated size of the market, five years from now?

Most CT scanners are installed in the United States, Europe, and Japan. The number of CT scanners at an institution, as well as the number of scans performed continues to increase (certainly in the US, and presumably in the other markets). Non-64 detector scanners continue to be sold in these markets because of the continued high CT utilisation, and their significant advantage over older (1-to-4-detector) scanners for non-cardiac use. However, nearly 40 per cent of CT scanners installed in the US in 2010 were 16-detector scanners.

India is a rapidly growing, emerging market for CT scanners; scanner sales and installations will follow an increasing population, domestic economic growth, and increasing healthcare spending, including new hospital construction. There is no reason to expect the demand for high technology to wane. Rapid expansion will be met with installation of conventional (<64-detector) and refurbished CT scanners, as well as the expansion of the 64-detector market. Approximately one-third of all new scanners in India are 64-detector devices; only about four per cent are “mega-scanners” (i.e., 128-256+ detectors). If I could predict the Indian market in 5-10 years, I would expect to see steady growth in the number of scanners and in their utilisation. I would also expect to see growth in the >128-detector market, as older scanners become out of service and are replaced.

Tell us about your association with CT Fest 2012? What will be your area of focus while speaking at the CT Fest 2012?

This is my first time to India, much less speaking at CT Fest 2012. Actually, Dr Sanjeev Mani contacted me two years ago, inviting me to speak at the 2011 meeting, but I had a previous engagement, and couldn’t come. I implored him to please remember me for the 2012 meeting, which he did. I intend to discuss the utility of CCTA to diagnose not only coronary, but other common, and less common forms of acquired valvular and myocardial heart disease. CCTA is a valuable diagnostic problem solver, and will continue to help elucidate normal and pathologic anatomy and function in patients with difficult to interpret echo-cardiograms and electrocardiograms, in a manner analogous to cardiac MRI. I will also point out the value of CCTA for the evaluation of adult patients with congenital heart disease. This growing population (there are now more adult patients than paediatric patients with congenital heart disease) is well-served by the speed, convenience, and accuracy of cardiac CTA. There is a great deal of cardiac CTA performed in India today, and the attendees at the meeting will reflect a broad spectrum of awareness, experience, and utilisation of the technology. I hope to teach a little, reinforce a lot, and learn from my audience.

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