Author + information
- Bertram Pitt, MD* ()
- ↵*Reprint requests and correspondence:
Dr. Bertram Pitt, Department of Cardiology, University of Michigan School of Medicine, Cardiovascular Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0366
Myocardial meta-iodobenzylguanidine iodine-123 (123I-mIBG) imaging has been shown to provide prognostic information on patients with chronic heart failure (HF) and a reduced left ventricular ejection fraction (HFREF), in patients with HF and a normal left ventricular ejection fraction (HFNEF), in patients post-myocardial infarction, and in patients with diabetes mellitus. A recent multicenter study of 123I-mIBG in approximately 1,000 patients with New York Heart Association functional class II to III HFREF found the heart /mediastinum (H/M) ratio of 123I-mIBG to provide information on the risk of death independent of that provided by left ventricular ejection fraction or determination of B-type natriuretic peptide (1). A decrease in 123I-mIBG H/M independently predicted death due to both progressive HF and sudden cardiac death. 123I-mIBG has also been shown to be of value in evaluating the effectiveness of various therapeutic interventions in patients with HF, such as aldosterone blockade, improving cardiac norepinephrine uptake and therefore predicting an improvement in long-term cardiac outcomes.
In this issue of iJACC, Martins et al. (2) explore the utility of myocardial 123I-mIBG imaging to detect asymptomatic family members of patients with familial dilated cardiomyopathy (FDCM). They evaluated 45 members of 23 families with FDCM with both the H/M and the myocardial washout rate (WR) of 123I-mIBG as well as 2-dimensional echocardiography, electrocardiography, B-type natriuretic peptide, and, in 40 of 45 individuals, cardiac magnetic resonance. Of interest was their finding of an abnormally high 123I-mIBG WR in 11 (69%) of the subset of 16 family members with normal left ventricular function. These 11 patients with an abnormal myocardial 123I-mIBG WR included 5 with reverse remodeling, 4 of 5 identified carriers of the familial trait, and 2 relatives with normal echocardiograms and unknown carrier state. In this subset of individuals with normal left ventricular function at risk of the development of FDCM, they did not find any correlation between 123I-mIBG H/M or WR and left ventricular function or mass. However, there was a significant correlation with parameters of heart rate variability relating to increased sympathetic nervous system activity, suggesting an increased long-term cardiovascular risk. The small number of patients and the relatively short follow-up precluded an evaluation of the prognostic value of the finding of an abnormal myocardial WR with myocardial 123I-mIBG imaging in asymptomatic individuals with normal left ventricular function at risk of the development of FDCM. The promise of the early detection of asymptomatic individuals with normal left ventricular function at risk of the development of FDCM holds the promise for the early application of therapy to prevent its development and or consequences, such as sudden cardiac death or progressive HF. A far larger number of patients will, however, need to be studied to determine the prognostic value of the finding of an abnormal 123I-mIBG WR in these asymptomatic individuals with normal left ventricular function and further information on the time course from detection of an abnormal WR to the development of HF will be needed as well. However, even if future studies demonstrate that an abnormal 123I-mIBG WR predicts the subsequent development of HF, the application of this technique into clinical practice remains uncertain. 123I-mIBG requires cyclotron production, and therefore myocardial imaging with this agent will likely be relatively expensive. To justify its clinical application in the coming era of increased cost containment of health care resources, myocardial 123I-mIBG will not only need to be shown to detect early disease, but the net effect of the myocardial imaging and the therapeutic approach elicited by the finding of an abnormal WR will also need to be cost-effective.
Similarly, the finding that myocardial 123I-mIBG imaging provides independent prognostic information in patients with HF, in post-myocardial infarction, and in diabetes mellitus, although of interest, is unlikely in and of itself to be sufficient to justify its adoption into clinical practice unless the information that it provides results in a change in clinical outcomes and that the net cost of the 123I-mIBG myocardial imaging and the strategy evoked by the information that it provides can be shown to be cost-effective. Although the finding of a decreased 123I-mIBG H/M in a patient with HFREF suggesting an increased risk of cardiac death might prompt optimization of medical therapy such as an increase in the dose of an angiotensin-converting enzyme inhibitor or a beta-adrenergic blocking agent, it might not be cost-effective in the long run because one might argue that all patients with HF should be treated with target or maximally tolerated doses of guideline-recommended therapy such as angiotensin-converting enzyme inhibitors and angiotensin receptor blocking agents, beta-adrenergic blocking agents, and aldosterone blocking agents. One might, however, envision that the use of the information provided by a normal or abnormal 123I-mIBG myocardial image could be of value in deciding on the use of high-risk/high-cost strategies such as an implantable cardiac defibrillator, cardiac resynchronization therapy, and stem cell and/or gene therapy. For example, the finding of a normal H/M and myocardial WR in a patient with HFREF and an indication for an implantable cardiac defibrillator might avoid implantation of this device, which, although effective in reducing death, is often not required and therefore often not used in the most cost-efficient manner. Conversely, the finding of an abnormal 123I-mIBG H/M and or myocardial WR in a patient with HFNEF suggesting an increased risk of cardiac death might prompt consideration of implantation an implantable cardiac defibrillator, cardiac resynchronization therapy, or both. It would, however, be necessary to more clearly understand the confidence limits of the false-negative and false-positive implications of these findings before deciding to withhold potentially life-saving therapy on the basis of a normal 123I-mIBG myocardial image or to use a high-cost/high-risk strategy due to an abnormal image suggesting an increased risk of cardiac death in a patient in whom it is not otherwise indicated. Clearly, relatively high-cost techniques such as 123I-mIBG imaging, although holding great promise to improve the early detection of cardiovascular disease and allowing the selection of low- and high-risk subsets to more appropriately apply high-risk/high-cost therapeutic strategies, face new challenges in the coming era of cost containment in health care resources.
Dr. Pitt is a consultant for GE HealthCare, Pfizer, Novartis, Merck, Takeda, AstraZeneca, Boehringer Ingelheim, Forrest Laboratories, and Bayer; has stock options in Relypsa, BG-Medicine, and Aurasence; and has received grants from Medtronic, Novartis, Bayer, and Abbott.
↵* Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
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