Myocardial perfusion, function, and dyssynchrony in patients with heart failure: baseline results from the single-photon emission computed tomography imaging ancillary study of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) Trial

Abstract

Background: There are currently limited data on the relationships between resting perfusion abnormalities, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, and exercise capacity as defined by peak VO(2) and 6-minute walk test in patients with heart failure (HF) and reduced LVEF. Furthermore, the association between resting perfusion abnormalities and left ventricular dyssynchrony is currently unknown. This article addresses the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) gated SPECT imaging (gSPECT) substudy baseline results.

Methods: HF-ACTION was a multicenter, randomized controlled trial of aerobic exercise training versus usual care in 2,331 stable patients with LVEF of < or = 35% and NYHA class II to IV HF symptoms treated with optimal medical therapy. Subjects enrolled in the HF-ACTION substudy underwent resting Tc-99m tetrofosmin gSPECT at baseline (n = 240). Images were evaluated for extent and severity of perfusion abnormalities using a 17-segment and a 5-degree gradation severity score (summed rest score [SRS]). Left ventricular function and dyssynchrony were assessed using validated available commercial software.

Results: The average age of patients enrolled was 59, 69% were male, 63% were white, and 33% were African American. Of the 240 participants, 129 (54%) were ischemic and 111 (46%) were nonischemic in etiology. The median LVEF by gSPECT for the entire cohort was 26%. Among the nuclear variables, there was a modest correlation between LVEF and SRS (r = -0.31, P < .0001) and there were stronger correlations between phase SD and SRS (r = 0.66, P < .0001) as well as phase SD and LVEF (r = -0.50, P < .0001). Patients with NYHA class III symptoms had more severe and significant degrees of dyssynchrony (median phase SD 54 degrees ) than those with NYHA class II symptoms (median phase SD 39 degrees, P = .001). Patients with an ischemic etiology had a higher SRS (P < .0001) and significantly more dyssynchrony (P < .0001) than those who were nonischemic. However, there was no difference in LVEF or objective measures of exercise capacity between these groups. With respect to peak VO(2), there was a weak correlation with LVEF (r = 0.18, P = .006) and no correlation with SRS (r = -0.04, P = 0.59) or with dyssynchrony (r = -0.13, P = .09). A weak but statistically significant correlation between SRS and 6-minute walk was observed (r = -0.15, P = .047).

Conclusions: Gated SPECT imaging can provide important information in patients with HF due to severe LV dysfunction including quantitative measures of global systolic function, perfusion, and dyssynchrony. These measurements are modestly but significantly related to symptom severity and objective measures of exercise capacity.

Trial registration: ClinicalTrials.gov NCT00047437.

Figure 1

240 patients from the overall HF-ACTION trial were enrolled in the nuclear substudy. 238 studies were included for the SRS analysis (2 studies not interpretable). LVEF and volumes were unavailable in 6 studies. There were 29 non-gated studies (i.e. multigated acquisition, MUGA) where LVEF and ventricular volumes were reported, but dyssynchrony analysis could not be performed. An additional 37 patients with bi-ventricular pacemakers were excluded from the dyssynchrony analysis.

Figure 2

Representative phase histograms. A) Normal phase histogram: The X-axis represents the timing of one cardiac cycle (R-R interval) normalized in degrees. The Y-axis represents the percent of myocardium demonstrating the onset of mechanical contraction during any particular phase of the cardiac cycle. The color maps have 256 levels with the minimum level corresponding to black and the maximum level corresponding to white. B) Abnormal phase histogram showing a wide bandwidth indicating a delayed onset of myocardial contraction representing significant left ventricular mechanical dyssynchrony.

Figure 3

SPECT Dyssynchrony Phase SD versus Sum Rest Score

Figure 4

SPECT Dyssynchrony Phase SD versus EF by SPECT

Figure 5

Peak VO₂ versus SPECT Dyssynchrony Phase SD

Figure 6

Perfusion tomographs from the HF-ACTION nuclear substudy demonstrating A) a patient with nonischemic cardiomyopathy and a LVEF of 30%. Note that there is only mild decreased tracer activity in the basal inferior segment secondary to attenuation artifact and B) a patient with an ischemic cardiomyopathy and a LVEF of 28%. Note the severe perfusion defects and infarct in the anterolateral, inferolateral, inferior, and inferoapical segments.