Getting to the Heart of Multivessel Disease Using Cardiac MRI

When a patient’s coronary artery disease symptoms appear to be coming from more than one source, physicians need the best picture possible to fully understand the root of the problems. Research suggests that new techniques in cardiac MRI may help narrow down which vessels are culprits even better than before.

The ability to image the heart is changing. While recent innovations aren’t global yet, cardiac magnetic resonance imaging techniques are taking understanding multivessel disease to a whole new level. Increased speed of MR image capture and coding  allows physicians the option to improve their view through either 3D or high-resolution technology (Circ Cardiovasc Imaging 2013;6[3]:339-348). While these techniques are still in their infancy, what they reveal holds significant promise. And many in the field are looking forward to even more changes to come. 

With speed comes innovation

With extra speed, a team of researchers were able to compare traditional and advanced cardiac MR techniques to get a better look inside coronary arteries. Sebastian Kozerke, PhD, a professor with the Institute for Biomedical Engineering at the University and ETH Zurich in Switzerland, Manish Motwani, PhD, a cardiologist formerly of University of Leeds in the U.K., lead the research teams.

“One of the problems with imaging multivessel disease or three-vessel disease is that sometimes the whole heart is ischemic,” says Motwani. “The whole heart doesn’t get a lot of blood and, therefore, it can be difficult to pick out normal areas from ischemic areas.” Improving cardiac MR’s resolution from 3 mm down to 1 mm, he notes, provides more detail into which vessels may specifically be part of the problem.

“MRI has high spatial resolution,” Motwani says, and by increasing that resolution further, “we found that technique was able to pick out areas of the heart with a low blood supply even better than standard cardiac MRI.”

While, as Kozerke states, the techniques are still being refined, these techniques and the increased speed could make a powerful tool even more so. Improved resolution, “helps a lot when looking at triple vessel disease because then you can see perfusion gradients across the myocardium which couldn’t be detected with coarser resolution,” he says. And when looking at the effected heart in three dimensions, it allows a physician to see perfusion defects in the apex, which can be missed with the standard three-slice 2D CMR. However, at present, “it’s a compromise between coverage and resolution.”

Both techniques were developed to overcome the limitations in using standard 2D CMR imaging to quantify ischemic burden and overall affected myocardial area. In particular, high resolution provides more minute detail, while 3D provides a greater area of coverage and better understanding of ischemic burden (Circ Cardiovasc Imaging. 2014 Jul;7[4]:647-654), allowing physicians to see more as recommended by current guidelines (Circ Cardiovasc Imaging 2015;8[5]).

With resolution down to 1 mm, physicians also have noticed fewer artifacts, like dark rim artifacts, which previously led to increased false positives. Other details that are clearer with improved resolution include the difference between primary stenosis and areas of the myocardium still receiving some blood flow through peripherals and subtle perfusion defects in the endocardium “that are very difficult when you have very course resolution. That’s what people are seeing now with the higher resolution techniques,” Kozerke says

At present, however, it’s important to note that cardiac MR imaging allows for either 3D, whole heart coverage or higher resolution imaging, but not both, barring further innovation.

Positive readings

Cardiac magnetic resonance imaging does have its advantages and limitations, however.

As Daniel S. Berman, MD, chief of cardiac imaging and nuclear cardiology and professor of imaging and cardiac medicine at Cedars Sinai Medical Center in Los Angeles, Calif., points out, the advantages already inherent in cardiac MR lie in the high resolution of the images and the ability to provide these images without exposing a patient to radiation. “It is the only technique to really accurately be able to do tissue characterization; to look at multiple different processes within in the myocardium or heart muscle, such as scaring or inflammation or edema that can occur in various cardiac diseases,” he says.

Berman argues that cardiac MR trumps SPECT and others, “providing a comprehensive assessment of the heart, possibly more comprehensive than any other modality.” With the additional definition provided by either a 3D or high resolution technique to an already strong modality, CMR “aids in the identification of multivessel disease and disease in individual coronary arteries.” Berman is excited by the progress suggested by the findings of the work of Motwani, who is now a fellow at Cedars-Sinai, and the European teams.

In particular, Berman sees higher-resolution MR having the potential to better distinguish findings confined to the subendocardium—the inner portion of the heart muscle, separate from the outer wall. “On a theoretical basis, there should be an improved ability to identify disease in individual coronary arteries.” He also suggests that high-resolution MR will be particularly advantageous in patients with small hearts. For example, he says “women tend to have smaller hearts than men. In smaller hearts, it becomes harder to distinguish inner and outer portions of the myocardial wall with [standard] MR. The higher the resolution, the more accurate it should be.”

Karolina M. Zareba, MD, from Ohio State University’s Wexner Medical Center in Columbus adds that a major strength of cardiac MR is the ability “to perform one comprehensive test which can evaluate heart structure, function, cardiac physiology in terms of perfusion, and the amount of scar and fibrosis burden. All of these components can help determine what is causing the patient’s symptoms, and can be cost saving versus doing an echo, nuclear stress test and then a cath.” She notes that many questions are answered by cardiac MR including “what area of the heart is not going to recover, what area may recover if it’s revascularized and what area may need to be treated more urgently because of the profusion defects”—all in one exam that takes 40 minutes to an hour.

Possible blockages, some perfusion

However, there are road blocks to full adoption over other imaging methods, even with the benefits for patients with multivessel disease. Some patients are not suited for cardiac MR, notably those with some pacemakers, defibrillators or other metallic implants, patients who are claustrophobic (Circ Cardiovasc Imaging 2015;8[5]) or those who may be hard to image or stress due to weight (JACC Cardiovasc Imaging 2014;7[5]:462-472). Patients who have compromised renal function are not appropriate for CMR, says Zareba.

Further, Zareba sees strengths in hospital-vendor collaboration in applying innovative sequences allows to patient care.  “When you have that research relationship and you have the ability to test new sequences, such as tissue characterization, 3D imaging, high resolution perfusion imaging, and you’re able to provide a more comprehensive service to the patient,” he says.

Along with collaboration, training is another key factor. Physicians require significant training to properly interpret the breadth of the pathology shown in a cardiac MRI, Zareba notes. Most cardiologists at top-notch cardiac MR centers have undergone an extensive 1 to 2 year fellowship focused solely on learning to interpret these complex images.

However, as the technology improves, so does ease of use. Berman speaks of “technical developments making it much easier for the technologist to acquire excellent images.” This includes new software that helps aid physicians in interpreting studies who aren’t yet subspecialized in this area.

Motwani has some concerns that the healthcare payment structure may affect how frequently stress cardiac MRI is used in the U.S. “The techniques we’re talking about, the high spatial resolution and the 3D whole heart techniques, they are another step above that,” he says. However, for the moment, both techniques, are both predominantly research techniques developed and used at two initial research centers in Europe.

Although the full price tag on these improved techniques still needs to be explored, there are those who feel cost isn’t a limiting factor. Both Zareba and Berman agree that cardiac MR is no more costly for patients with multivessel disease than other imaging modalities. In fact, as Zareba notes, in reducing the number of tests performed, reducing patients’ potential exposure, repeated hospital visits and so on, the improvements offered through the use of these new techniques can actually reduce costs.

Research presented at ACC.15 in March aimed at costs for new cardiac patients certainly suggests this. Utilizing a standard cardiac MR technique compared with 2D echo or myocardial perfusion imaging, the team found cardiac MR a cost saving technique. Those who were initially assessed with cardiac MR as opposed to 2D echo or myocardial perfusion imaging saved private insurance and Medicare close to four times the cost of the other two modalities in the first year alone (J Am Coll Cardiol 2015;65[10_S]).  The downstream cost savings are predicted to add up (J Cardiovasc Magn Reson. 2013;15:52). Since neither advanced cardiac MR technique requires purchasing new equipment, only upgrading existing software, costs would be less for established centers. Providing a clearer picture should improve diagnosis which in turn should save hospitals time, resources and money, passing those savings on to insurers and patients over the long term.

Brave new future

Physicians are excited about the new high resolution and 3D techniques. Improvements in visual field, either in terms of resolution down to 1 mm or whole heart coverage, mean greater accuracy in uncovering ischemia and understanding areas that may be starved for blood that were previously less visible with standard 2D methods.

“As powerful as MRI is already, it’s getting better all the time,” says Berman. “And there are multiple approaches in progress to improving resolution, improving coverage of how much of the myocardium is imaged and decreasing the artifacts sometimes seen. So we can look forward to having further development of MR over time.”

The Math of MVI vs. CVI

Whether to treat one or more vessels in patients with STEMI and multivessel disease is a subject of disagreement between clinicians and professional societies. Even so, evidence suggests that there may be benefit, if not equipoise in considering either treatment option on a case-by-case basis. The answer, researchers say, is in the numbers.

Research published by John A. Bittl, MD, a cardiologist at Monroe Regional Medical Center in Ocala, Fla., and colleagues looked at the hard data on interventions in multivessel disease. “Many studies compared multivessel against culprit vessel interventions for patients with STEMI and multivessel disease but the results were all over the map,” Bittl says. Using the Bayesian method, Bittl and his team looked at the available information by outcome and study type. “The bottom line was simply that we found that our results supported a position of equipoise; that the decision between multivessel intervention and culprit vessel intervention for a patient with multivessel disease must be individualized.”

These results include recently published data from the CvLPRIT (Complete versus Lesion-only Primary PCI trial) trial. This and other randomized control trials suggest that a multivessel approach is as safe and effective, and was in fact favored, in treating multivessel disease as a culprit-only approach. Bittl and colleagues noticed that studies favoring a culprit-only approach also were observational studies.

But observational studies have their limitations, Bittl notes. “Tending to be confounded because the sicker patients tend to get more intensive therapy than less sick patients and, therefore, the results of observational studies can be misleading.” Moreover, the nature of a randomized control trial is to be more rigorous and prospective. 

While CvLPRIT itself only accounts for less than 1 percent of the over 48,000 participants included in Bittl’s analysis—due to the weight of the rigor involved in a randomized control trial—it and other randomized controlled trials hold a stronger weight in the analysis.

Current guidelines are based on original observational data. These recommend strongly a culprit-only approach to the treatment of multivessel disease. However, globally, recommendations are being reconsidered by professional societies. “The European society has updated their guidelines liberalizing their use of MVI for patients with STEMI and multivessel disease,” Bittl says. Committees within the American College of Cardiology and American Heart Association are considering whether or not to follow suit.

“It’s interesting to note though that we’ve pretty much confined our practice to culprit vessel for STEMI and it hasn’t seemed to have hurt anyone.  It really seems to work pretty well as a primary strategy. But even if the guidelines are liberalized for the American physicians, maybe it should be legalized but no one should use it,” says Bittl. Stay tuned.