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ADMIRE HF: 123I-mIBG myocardial scintigraphy can assess sympathetic heart nerves in HF
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A radioactive tracer that helps physicians evaluate sympathetic nerves in the heart can evaluate the integrity of nerves in patients with HF, study results suggested.
Researchers for the trial sought to evaluate the prognostic utility of nuclear imaging with 123I meta-iodobenzylguanidine (123I-mIBG; AdreView, GE Healthcare) in patients with NYHA Class II and III HF and LVEF≤35%. The researchers enrolled 964 patients with NYHA Class II and III HF and followed them for up to two years.
According to the study results, 238 (25%) patients had major adverse cardiac events during a median 17-month follow-up (163 patients with HF progression, 51 with an arrhythmic event, and 24 cardiac deaths); 52 of these patients had a second event after HF progression or arrhythmic events. Two-year event-free survival was 85% in patients with heart:mediastinum ratio 1.60 compared with 63% for patients with a heart:mediastinum ratio ≤1.60 (P≤.0001). The negative predictive value of heart:mediastinum ratio 1.60 for cardiac death at 2 years was 98.2%.
“The ADMIRE-HF trial achieved its primary efficacy objective, which was to demonstrate a significantly different prognosis between patients with baseline images showing heart:mediastinum ratio of ≤1.6 or 1.6 in this NYHA Class II and III population with moderate to severe reduced ejection fraction,” Arnold F. Jacobson, MD, PhD, head of the Cardiac Center of Excellence at GE Healthcare, said in a presentation at the American College of Cardiology 58th Annual Scientific Sessions in Orlando, Fla. “In addition, the prognostic value of 123I-mIBG imaging was demonstrated for all three categories of outcome events: HF progression, arrhythmic events and cardiac death.” – by Eric Raible
For more information:
- Jacobson AF. #416. Presented at: American College of Cardiology 58th Annual Scientific Session; March 29-31, 2009; Orlando, Fla.
Despite significant advances in the management of HF during the past two decades, the efficacy of our current pharmacologic and device strategies in HF is variable and often unpredictable. Accordingly, there has been growing interest in using molecular imaging to personalize treatment of patients with HF. It is therefore of considerable interest that the first large clinical trial of the molecular imaging in HF, ADMIRE-HF, was presented at the 2009 Scientific Sessions of American College of Cardiology. The ADMIRE-HF study was conducted to examine the cardiac uptake of a radioactive tracer, 123I-mIBG, which is a physiologic analog of norepinephrine that is taken up into sympathetic nerves. Whereas the normal heart usually extracts norepinephrine from the arterial blood, in patients with moderate HF the coronary sinus norepinephrine concentration exceeds the arterial concentration, indicating increased adrenergic stimulation of the heart. However, as HF progresses, there is a significant decrease in the myocardial concentration of norepinephrine. The mechanism responsible for cardiac norepinephrine depletion in advanced HF is not clear and may relate to an “exhaustion” phenomenon resulting from the prolonged adrenergic activation of the cardiac adrenergic nerves in HF. In addition, there is decreased activity of myocardial tyrosine hydroxylase, which is the rate-limiting enzyme in the synthesis of norepinephrine. In patients with cardiomyopathy, 123I-mIBG is not taken up normally, suggesting that norepinephrine reuptake is impaired in HF.
In the ADMIRE-HF trial, 964 patients with NYHA Class II and III HF were assigned to 123I-mIBG by IV injection and then underwent nuclear imaging. Clinical follow-up was every six weeks for up to two years. Quantification of cardiac uptake of the tracer was expressed as the ratio of counts between the heart and the upper mediastinum. For the purposes of this study, a cutoff value of 1.6 was used, with values higher than this denoting high uptake and values below this denoting low uptake. Results showed that the primary endpoint, which was a composite of the first occurrence of NYHA HF class progression, potentially life-threatening arrhythmic event or cardiac death as determined by a panel of independent adjudicators, occurred significantly more frequently in patients who had low uptake of the tracer <1.6. The two-year event-free survival was 85% in patients with a heart:mediastinum ratio >1.6. The researchers also noted that patient with the lowest heart:mediastinum ratios (<1.2) tended to die more of HF progression, whereas arrhythmic events tended to occur in patients with heart:mediastinum ratios in the 1.2 to 1.6 range.
The most obvious implication of the findings of ADMIRE-HF is that quantification or radioactive tracer uptake might be used to optimize the selection of patients with HF for implantable cardiac defibrillators. Current practice guidelines recommend that all patients with NYHA Class II to III HF have an ICD placed to prevent sudden cardiac death, despite the knowledge that not all patients who have implanted ICDs will benefit from these devices. Apart from the practical implications of ADMIRE-HF, this study may also allow investigators to better understand the contribution of the adrenergic nervous system to the development and progression of HF in patients with asymptomatic HF (Class B) or in patients with a high likelihood of developing HF (Class A). This in turn might lead to earlier and broader use of beta-adrenergic blocking agents to prevent symptomatic HF from developing. Thus, the use of 123I-mIBG appears promising as a way to monitor the development and progression of HF. With that said, the use of molecular imaging to guide therapy will require additional prospective testing in a separate cohort of patients to determine the feasibility and utility of using a preset cutoff value for uptake of 123I-mIBG by the heart. Indeed, it will be critical for patients and physicians to better understand the predictive accuracy of negative and positive 123I-mIBG uptake before this promising imaging technique can be used to guide HF therapy beyond what has been established in current practice guidelines.
– Douglas Mann, MD
Cardiology Today Editorial Board member