Managing Heart Failure Through Nuclear Imaging

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 - Nuclear Medicine Hypertension
A: Example of inferolateral wall supine and upright MPS artifact images from 49-year-old woman with typical chest pain and known hypertension, diabetes, hypercholesterolemia and family history of premature CAD. Electrocardiogram response to exercise was nonischemic for ST-segment depression.
Source: J Nucl Med 2010;51[11]: 1724-1736
Heart failure (HF) strikes an estimated 300,000 patients annually in the U.S. While treatment strategies for this patient population have gained traction in the recent years, configuring the optimum diagnosis and management strategies for the disease still needs work. Studies published in recent years have shown that nuclear imaging, using both PET and SPECT, may have the potential to provide clinically useful data to enable better stratification and most favorable treatments for HF patients.

Myocardium: Dead or alive?  

Practices have begun using FDG-PET to evaluate myocardial viability in patients with ischemic heart disease and impaired left ventricular (LV) function. The technique helps to identify patients at a heightened risk for developing cardiac events and can determine whether cardiac function can be improved with revascularization. This modality uniquely classifies heart tissue as either dead or viable.

"FDG-PET can detect cell integrity and is very sensitive for viability," Rob S.B. Beanlands, MD, chief of cardiac imaging and director of the National Cardiac PET Centre at the University of Ottawa Heart Institute in Canada. "This strategy helps define cell metabolism and hibernation."

To understand whether FDG-PET in HF can help inform decisions with ischemic cardiomyopathy, Beanlands and colleagues evaluated the benefits of PET-guided management in patients with LV dysfunction and coronary artery disease (CAD), (J Nucl Med 2010;51:567-574). In the Ottawa-FIVE trial, researchers randomized 111 patients who had reduced LV dysfunction from the PARR 2 study to  receive FDG-PET (56 patients) or standard care (55 patients). Cardiac events were significantly reduced for patients who underwent FDG-PET-assisted management, 19 percent versus 41 percent. The authors concluded that FDG-PET helped to point physicians toward revascularization or not. When followed, patients saw improved outcomes.

"We are confident that FDG-PET viability can be used to direct therapy," Beanlands notes. "If surgeons are on the fence about whether to perform revascularization in this sick HF population, PET can help decide which road to take."

Determining myocardial viability via FDG-PET can improve functional prediction and survival, says Andrew Van Tosh, MD, director of nuclear cardiology at St. Francis Hospital in Roslyn, N.Y.

Myocardial viability studies are performed by reviewing myocardial perfusion, and its relationship to cardiac glucose metabolism as measured with FDG-PET. In these cases, FDG-PET can help recognize whether myocardium, which would be classified as "dead" (or scarred) with other modalities, is actually in hibernation. If it is characterized as in hibernation, the blood flow can be restored and function will improve.

However, the results of the STICH substudy presented at ACC.11, were contradictory, finding that utilizing nuclear imaging modalities for myocardial viability may not be reliable. Bonow et al found that the presence of viable myocardium was associated with a greater chance of survival in CAD and LV dysfunction patients—but it was not statistically significant.

Yet, Beanlands attributes these negative findings to the fact that SPECT was used rather than PET; the definition of tissue viability may have overestimated the presence of myocardial viability; incorrect assignment of patients in the viability positive cohort; and selection bias was introduced in the non-randomized substudy (N Engl J Med 2011;364:1617-1625).

"Based on these results, some may think that viability imaging may not be useful but quite the opposite is true," says Beanlands. "In fact, viability assessment is particularly helpful in the sickest patients."

Improving HF management  

Nuclear imaging also is being assessed for other HF indications, such as a risk prediction tool and markers for treatment responses.

Marcelo F. Di Carli, MD, chief of nuclear medicine and molecular imaging and director of cardiovascular imaging at Brigham and Women's Hospital in Boston, and colleagues are currently evaluating the use of PET and SPECT for the following applications in HF patients:

  • To detect CAD in patients presenting with HF; and
  • PET detection and monitoring of treatment for cardiac sarcoidosis, an inflammatory disease of the heart muscle.  

"PET can separate patients who have HF symptoms with a marked ischemic component from those whose HF is predominantly due to resting myocardial fibrosis and irreversible dysfunction," Van Tosh offers.   

At this year's SNM meeting, Van Tosh at el presented a study evaluating 175 patients with suspected CAD (105 men, with an average age of 70) who underwent rest/regadenoson stress CT attenuation-corrected Rubidium-82 (Rb82) PET to measure LV dysfunction.  "The study showed a significant correlation between resting LV function and how it changed under pharmacological stress," he says.

Stress LV dysfunction, defined as a decrease of 5 percent in ejection fraction (EF) from rest to stress, was present in 17 patients. Both rest and stress were lower in the stress LV dysfunction patients (rest EF 41 vs. 51 percent; stress EF 33 vs. 56 percent). The presence of stress LV dysfunction had a good correlation between impairment in absolute stress myocardial blood flow and coronary flow reserve.

"We can now define certain predictors by looking at what happens to coronary blood flow, such as whether ejection fraction would get worse during a stress test compared with a rest test," he says. "These exams are a way of identifying patients whose symptoms are not only due to underlying degree of fibrosis, but an additional ischemic component with blocked arteries that needs to be addressed."

In the study, two patients had significantly diminished LV functions at rest (about 40 percent). When these patients exercised, their EFs dropped 10 to 12 percentage points. "The HF symptoms in these patients have a clear ischemic component," Van Tosh says. On the other hand, patients who augmented their LV function during stress (from 40 to 50 percent, for example) may have HF; however, these symptoms are more likely due to pure resting cardiac dysfunction.

This technique can help separate patients who have HF symptoms that have a marked ischemic component from those who have an ischemic component that is predominantly due to resting myocardium fibrosis and fixed dysfunction.

PET stress tests can explain a patient's symptom better by evaluating changes in EF and coronary blood flow.

"If you can address these types of issues, there is reasonable likelihood that symptoms will improve," Van Tosh concludes.

What's on the horizon?

New PET and SPECT isotopes may be on the way. Due to the comorbidities and age of HF patients, the majority cannot undergo drug-induced stress tests with PET, says Van Tosh. In addition, some isotopes have short half-lives, making it difficult for a patient to undergo an exercise test, inject him or her with the isotope and move him or her back to the camera before the radioactivity decays. Thus, new radiopharmaceuticals are needed.

Studied in multiple trials, Di Carli says Iobenguane I 123 injection (123I-mIBG, AdreView, GE Healthcare) may open up new avenues for the successful evaluation of cardiac neuronal function and help identify patients at high risk for sudden cardiac death.

In ADMIRE-HF, Jacobson et al enrolled 961 HF patients with LVEF less than 35 percent who underwent 123I-mIBG myocardial SPECT imaging (J Am Coll Cardiol 2010;55:2212-2221). Results showed that 237 patients experienced events during the median follow-up time of 17 months. Using a heart/mediastinum ratio (H/M) to assess the functionality of sympathetic nerves, they found the two-year event rate was 15 percent for H/M 1.60 and 37 percent for H/M less than 1.60.

"Although mIBG could be used as a risk marker, it does not necessarily guide physicians as to how they would use available interventional therapies for prevention of sudden cardiac death," Di Carli offers. "If we had agents that could help identify which patients will develop cardiac remodeling that could lead to HF, presumably we could intervene earlier and more aggressively to decrease the likelihood of disease development."