Regional Myocardial Sympathetic Denervation is Associated with Systolic Dysfunction Independently of Myocardial Scar in Heart Failure

Objectives: Although myocardial sympathetic innervation is generally altered in accordance with myocardial systolic dysfunction or infarcted myocardium in heart failure, their regional relationship has not been well investigated. This study aimed to assess the interrelationship between regional sympathetic innervation, systolic function, and scar extent in patients with heart failure.

Methods: We studied 34 patients (mean age, 63 ± 15 years; 23 male) with ischemic cardiomyopathy (ICM, n = 10) and non-ischemic cardiomyopathy (NICM, n = 24). Cardiac magnetic resonance imaging (CMR) was performed to evaluate left ventricular (LV) size, ejection fraction (EF), wall thickness, and systolic wall thickening (%WT). The extent of late gadolinium enhancement (LGE) on CMR images was quantified as a percent area of myocardium with CMR signal intensity 蠅 5 standard deviations above the mean signal intensity in the remote myocardium. ¹¹C-hydroxyephedrine (HED) positron emission tomography was performed to assess myocardial sympathetic innervation. ¹¹C-HED retention index (RI [% /min]) as an indicator of myocardial sympathetic innervation was calculated as the mean LV myocardial activity in the last frame (30 to 40 min) divided by the integral of the arterial blood time-activity curve. Regional analyses of CMR and ¹¹C-HED imaging were performed using the 16 segments (excluding the apex) of the American Heart Association 17-segment model. To identify predictors of regional ¹¹C-HED RI, we proposed a multivariate mixed-effect model for repeated measures over segments.

Results: The median EF was 50% (interquartile range, 40%-58%). The global LGE extent of ICM patients (median, 10.6%; IQR, 3.4%-13.5%) and NICM patients (median, 5.1%; IQR, 7.9%-23.3%) were not significantly different (P = 0.65). Similarly, the global ¹¹C-HED RI of ICM patients (8.6% ± 1.4% /min) and NICM patients (8.1% ± 2.5% /min) were not significantly different (P = 0.57). Global ¹¹C-HED RI was significantly correlated with EF (r = 0.39, P = 0.02) and LGE extent (r = −0.37, P = 0.03). Furthermore, regional ¹¹C-HED RI was significantly correlated with wall thickness, %WT (r = 0.33, P < 0.001) and regional LGE extent (r = −0.37, P < 0.001). Multivariate analysis demonstrated that LV wall thickness, %WT, and LGE extent were independent predictors of regional ¹¹C-HED RI in both ICM and NICM patients (Table).

Conclusion: Regional myocardial sympathetic denervation was associated with systolic dysfunction independently of myocardial scar in patients with heart failure. Regional sympathetic innervation may reflect a broad spectrum of myocardial damage. Research Support:

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