Sympathetic denervation is associated with microvascular dysfunction in non-infarcted myocardium in patients with cardiomyopathy

AIMS: Sympathetic denervation typically occurs in the infarcted myocardium and is associated with sudden cardiac death. Impaired innervation was also demonstrated in non-infarcted myocardium in ischaemic and dilated cardiomyopathy (ICMP and DCMP). Factors affecting sympathetic nerve integrity in remote myocardium are unknown. Perfusion abnormalities, even in the absence of epicardial coronary artery disease, may relate to sympathetic dysfunction. This study was aimed to assess the interrelations of myocardial blood flow (MBF), contractile function, and sympathetic innervation in non-infarcted remote myocardium. METHODS AND RESULTS: Seventy patients with ICMP or DCMP and LVEF ≤35% were included. [(15)O]H2O- and [(11)C]hydroxyephedrine (HED) PET was performed to quantify resting MBF, hyperaemic MBF, and sympathetic innervation. Cardiovascular magnetic resonance (CMR) imaging was performed to assess left ventricular function, mass, wall thickening, and scar size. Wall thickening, [(11)C]HED retention index (RI), and MBF were assessed in remote segments without scar, selected on CMR. [(11)C]HED RI was correlated with resting MBF (r = 0.41, P < 0.001) and hyperaemic MBF (r = 0.55, P < 0.001) in remote myocardium in both ICMP and DCMP. In addition, LV volumes (r = -0.40, P = 0.001), LV mass (r = -0.31, P = 0.008), and wall thickening (r = 0.45, P < 0.001) correlated with remote [(11)C]HED RI. Multivariable analysis revealed that hyperaemic MBF (B = 0.79, P < 0.001), wall thickening (B = 0.01, P = 0.03), and LVEDV (B = -0.03, P = 0.02) were independent predictors for remote [(11)C]HED RI. CONCLUSION: Hyperaemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperaemic MBF is the primary cause of this relation remains unclear.