Assessing Stroke Risk in Patients Undergoing Non-Surgical Aortic Valve Replacement

Lay Summary

Assessing stroke risk in patients undergoing non-surgical aortic valve replacement

This study will continue an assessment of whether the increased risk of stroke in older patients who undergo a catheter-based rather than surgical replacement of their aortic valve is associated with the technique or with their underlying vascular condition.

In 2012 the Directors awarded an initial grant to enable collaborating cardiologists and neurologists to explore why elderly patients who undergo a non-surgical catheter-based technique for replacing their aortic valve have an increased risk of stroke following the intervention. These patients are not candidates for surgical valve replacement due to their age and severity of underlying vascular disease. The question, therefore, is whether their underlying condition or the non-surgical technique is associated with the heightened risk of stroke.

The aorta is the main artery that carries blood from the heart’s left ventricle to all the branch arteries in the body except those in the lungs. The aortic valve lies between the left ventricle and the aorta. The valve has three “leaflets.” So, when the left ventricle contracts, these three leaflets open. Blood is ejected out and flows to blood vessels throughout the body. Thereafter, the leaflets close the valve and prevent blood from “refluxing” back into the heart. When the aortic valve becomes narrowed (called stenosis) as happens in about five percent of people 75 years or older, heart failure can ensue. When it does, it can be fatal within two years in about one-half of those affected.

These patients, because they have serious underlying heart disease and are elderly, are not good candidates for open heart surgery. Instead, many of them opt to undergo a recently developed non-surgical alternate procedure called transcatheter aortic valve replacement (TAVR). This procedure compares favorably to surgery in terms of the time needed for recovery (hours to days), and is as effective as surgery. Moreover, both surgery and TAVR are superior to medical therapy according to clinical study results. The caveat is that strokes occur about twice as often following TAVR than occurs following surgical or medical intervention. Are strokes and the occurrences of ischemic embolic events associated with the TAVR procedure? Or, are they associated with patients’ underlying risk factors which can include: age, hypertension, diabetes, history of previous stroke, and evidence of peripheral vascular disease?

The Hopkins University clinical investigators have been using a study design that had been successfully employed in a prior Dana-funded study. That prior research explored whether cognitive decline was associated with coronary artery by-pass graft (CABG) surgery that was undertaken with patients receiving oxygenated blood through a pump (“on-pump”) or with patients who did not receive the oxygenated blood (“off-pump”). That study was the first to include a control heart-healthy group as well as a medically treated group and the two CABG surgery groups (those on-pump and those off-pump). It also was the first study to utilize cognitive testing and MRI imaging prior to and following the surgical or medical intervention in patients and during similar time frames in the healthy volunteer participants. In that landmark study, the investigators found that the long-term cognitive decline in patients was associated with the patients’ underlying vascular disease rather than the medical or surgical interventions. While the investigators did not find a risk of cognitive decline, however, they did find that patients undergoing CABG surgery—whether on-pump or off-pump—had an increased risk of stroke following the surgery.

This finding led the researchers to develop a paradigm for calculating a patient’s risk of stroke based on factors known prior to surgery. This method for estimating risk now enables patients and their physicians and surgeons to make better informed decisions about which therapeutic options to choose, to modify the surgery if appropriate, and to more reliably predict outcomes from treatment.

The investigators have been employing this same clinical study design for the current study to assess the risk of stroke in patients undergoing surgical or non-surgical aortic valve replacement. The study includes heart healthy volunteers, and patients with aortic stenosis undergoing the non-surgical catheter-based replacement of the aortic valve (TAVR) and patients undergoing surgical valve replacement. Patients undergo cognitive testing and MRI imaging prior to the surgical or non-surgical treatment. The heart healthy volunteers undergo this same baseline cognitive testing and imaging. Patients are then tested and imaged following valve replacement and heart healthy volunteers similarly undergo these tests in the same timeframe. In the initial Dana-funded study of the risk of stroke in these patients, and in this planned continuation study, a total of 50 patients will be studied. Patients undergoing surgery or the TAVR procedure will be enrolled at Johns Hopkins but additional TAVR-group patients also may be enrolled at Harvard-Beth Israel Hospital in Boston. Through this on-going study, the investigators will determine: 1) the incidence of stroke by clinical evaluation prior to, and immediately and one month following TAVR or aortic valve replacement surgery; and 2) the presence of recent embolic ischemic events in the brain using Diffusion-Weighted MRI following the surgical or catheter-based TAVR procedure. The results are anticipated to lead to development of a predictive paradigm for stroke and embolic ischemic events following TAVR, consisting of the potential underlying disease risk factors that are identified.

Significance: Results will determine whether stroke and ischemic embolic events are associated with the non-surgical TAVR procedure for aortic valve replacement or with underlying vascular disease-related risk factors. The findings are anticipated to lead to improved methods for predicting treatment outcomes and minimizing risks of stroke by making informed choices among available options for treating this potentially fatal condition.