The role of nuclear imaging in the failing heart: myocardial blood flow, sympathetic innervation, and future applications

Abstract

Heart failure represents a common disease affecting approximately 5 million patients in the United States. Several conditions play an important role in the development and progression of heart failure, including abnormalities in myocardial blood flow and sympathetic innervation. Nuclear imaging represents the only imaging modality with sufficient sensitivity to assess myocardial blood flow and sympathetic innervation of the failing heart. Although nuclear imaging with single-photon emission computed tomography (SPECT) is most commonly used for the evaluation of myocardial perfusion, positron emission tomography (PET) allows absolute quantification of myocardial blood flow beyond the assessment of relative myocardial perfusion. Both techniques can be used for evaluation of diagnosis, treatment options, and prognosis in heart failure patients. Besides myocardial blood flow, cardiac sympathetic innervation represents another important parameter in patients with heart failure. Currently, sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine (123-I MIBG) is often used for the assessment of cardiac innervation. A large number of studies have shown that an abnormal myocardial sympathetic innervation, as assessed with 123-I MIBG imaging, is associated with increased mortality and morbidity rates in patients with heart failure. Also, cardiac 123-I MIBG imaging can be used to risk stratify patients for ventricular arrhythmias or sudden cardiac death. Furthermore, novel nuclear imaging techniques are being developed that may provide more detailed information for the detection of heart failure in an early phase as well as for monitoring the effects of new therapeutic interventions in patients with heart failure.

Fig. 1

Schematic display of flow quantification, static perfusion images, and functional assessment from list mode acquisition data by a positron emission tomography (PET) system. List mode acquisition can be started at the same time of tracer injection. Electrocardiographic and respiratory gating signals are sampled in addition to continuous acquisition of images (left upper panel). After acquisition, data are re-sampled and re-framed for each image analysis (left lower panel). For flow quantification, a small region of interest is positioned in the left ventricle (LV) and time–activity curves for LV input and myocardium are plotted (right upper panel). Subsequently, tracer kinetic modeling is applied to obtain flow maps under resting and hyperemic stress conditions (right lower panel)

Fig. 2

Cardiac sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine (123-I MIBG) can be used to assess global (panel A) and regional (panel B) sympathetic innervation in patients with heart failure. a Global reduction of 123-I MIBG uptake (sympathetic denervation) in a patient with advanced heart failure. The heart-to-mediastinum (H/M) ratio on late planar imaging was calculated by dividing the mean counts per pixel within the heart (H) by the mean counts per pixel within the upper mediastinum (M). In this example, the late H/M ratio was 1.31. b An example of regional abnormalities in sympathetic innervation is illustrated below (as indicated by regional defect in 123-I MIBG uptake, white arrow)

Fig. 3

Cumulative event rates for heart failure patients with heart-to-mediastinum (H/M) ratio < 1.60 and patients with H/M ratio ≥ 1.60 on late planar 123-iodine metaiodobenzylguanidine (123-I MIBG) imaging. The composite primary endpoint of heart failure progression, potential lethal arrhythmic events or cardiac death was significantly more documented in patients with late H/M ratio < 1.60 when compared to patients with late H/M ratio ≥ 1.60 at 2-year of follow-up (38 vs. 15%, P < 0.01). Reprinted with permission from reference 33

Fig. 4

Cardiac 123-iodine metaiodobenzylguanidine (123-I MIBG) imaging allows prediction of ventricular arrhythmias causing appropriate implantable cardioverter-defibrillator (ICD) therapy in heart failure patients. Patients with a large defect on late 123-I MIBG SPECT imaging (summed defect score > 26) showed significantly more ventricular arrhythmias when compared to patients with a small defect on late 123-I MIBG SPECT imaging (summed defect score ≤ 26) at 3-year of follow-up (52 vs. 5%, P < 0.01). Reprinted with permission from reference 47

Fig. 5

Cardiac 123-iodine metaiodobenzylguanidine (123-I MIBG) planar imaging in patients with (n = 18) and without (n = 88) sudden cardiac death. Myocardial washout rate was significantly higher in patients with sudden cardiac death when compared to patients without sudden cardiac death (39.9 ± 15.2% vs. 27.6 ± 14.2%, P = 0.0013) during a mean follow-up period of 65 ± 31 months. Data were based on reference 45

Fig. 6

Fused positron emission tomography (PET) images of 18F-fluorodeoxyglucose (¹⁸F-FDG)-labeled stem cells (solid arrows) and N-13 Ammonia (¹³NH₃) myocardial perfusion in rat infarction model. Radiolabeled stem cells were administrated intramyocardially into the infracted region. Subsequently, FDG images confirmed the orientation and survival of delivered cells (solid arrow) with the reference of ammonia perfusion image which showed a large defect in the anterior region (dotted arrows)