The ninth annual Mario S. Verani memorial lecture: Testing our tests: The evidence bar is rising. Regulatory considerations in the development of cardiac imaging agents

Abstract

It is indeed an enormous honor and a privilege to have been invited to present the ninth annual Mario S. Verani memorial lecture. It has been almost 10 years since Mario left us, and it is likely that many here with us today at the American Society of Nuclear Cardiology Annual meeting are not very aware of the major contributions he made to our field. As one of the purposes of this annual lectureship is to honor that body of work, and carry on its legacy, I thought it would be fitting to start with a reminiscence of the mark he made on the field of Nuclear Cardiology. In the contemporary era, many of us are very highly specialized in our clinical and investigative work, even within a subspecialty such as Nuclear Cardiology. In contrast, because Dr. Verani was among those at the forefront of the field of Nuclear Cardiology at its inception, his research touched on an amazingly broad swath of cardiovascular disease, and how the imaging techniques in this nascent modality could potentially benefit our patients. He was interested not only in the development of the techniques themselves, but also in how the imaging modalities within the field could illuminate pathophysiology in a manner that could not have been done before. I learned many lessons from his work. In the area of the ability of perfusion imaging to detect angiographic coronary artery disease (CAD), his were among the first papers to critically evaluate this new technique, examining the performance of planar thallium-201 scintigrams to detect CAD in native vessels, and also the role of this modality in assessing disease in coronary bypass grafts. He published the seminal paper on the role of pharmacologic stress testing with adenosine to detect CAD in patients who were unable to exercise, in 1990. Ten years later, he continued to advance the field of pharmacologic stress testing with very early work on more selective agonism of adenosine A2a receptors to cause coronary arteriolar vasodilatation, recognizing that other adenosine receptor subtypes were predominantly responsible for the common side effects seen during adenosine testing. This work led to continuing development of this class of agents, culminating in the recent approval of regadenoson. As noted above, one of the features of his work that I most admire was how he used these new imaging techniques to study pathophysiology in a way that could not have been done noninvasively before they were developed. In a 1981 paper, he reported on the effect of exercise training on left ventricular function and stress myocardial perfusion, in a tour de force study for the time, using rest and exercise radionuclide angiography and exercise thallium-201 scintigraphy, as well as cardiopulmonary exercise testing, before and after 12 weeks of exercise training. This type of work was well ahead of its time. In the area of assessment of myocardial viability, his work also had important impact. His 1996 paper on the validation of Tc99m-sestamibi for viability involved intraoperative myocardial biopsies of patients with ischemic cardiomyopathy undergoing heart transplantation who had been injected with the tracer on the way in to the operating room. The analysis correlated the histologic findings in the explanted heart with quantitative analysis of tracer uptake from slices of the explanted heart that had been imaged on a gamma camera. The results of this very clever study design validated the use of Tc99m-sestamibi for this purpose, at a time when many were skeptical of that use. Even prior to the approval of the Tc99m-based agents that had minimal redistribution, Dr. Verani took advantage of that property and published a paper that had enormous subsequent impact, on the use of Tc99mhexakis 2-MIBI (now known as sestamibi) for the From the The Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Boston, MA. Reprint requests: James E. Udelson, MD, The Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Box 70, 800 Washington St., Boston, MA 02111; JUdelson@tuftsmedicalcenter. org. J Nucl Cardiol 2011;18:547–60. 1071-3581/$34.00 Copyright 2011 American Society of Nuclear Cardiology. doi:10.1007/s12350-011-9404-x