Urinary 8-Hydroxy-2'-Deoxyguanosine as a Myocardial Oxidative Stress Marker Is Associated With Ventricular Tachycardia in Patients With Active Cardiac Sarcoidosis

Circ Cardiovasc Imaging. 2017 Dec;10(12):e006764. doi: 10.1161/CIRCIMAGING.117.006764.

Abstract

Background: Recently, we reported that urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), an oxidative stress marker, reflected inflammatory activity in cardiac sarcoidosis (CS). Here, we investigated whether U-8-OHdG levels were associated with ventricular tachycardia (VT) in patients with CS.

Methods and results: This prospective cohort study enrolled 62 consecutive patients with CS, of whom 36 were diagnosed as having active CS based on abnormal 18F-flurodeoxyglucose accumulation in the heart on positron-emission tomography/computed tomography. The 36 patients with active CS were subdivided as having CS with sustained VT (CS-VT group; n=18) or CS without sustained VT (CS-nVT group; n=18). Twenty-seven patients diagnosed with idiopathic dilated cardiomyopathy served as heart failure controls. U-8-OHdG, brain natriuretic peptide, cardiac function indices, and immunohistological data from subendomyocardial biopsy samples were compared across groups. Immunohistochemical examination of ventricle biopsy samples revealed that the anti-8-OHdG antibody-positive area of cardiac tissue was significantly greater in CS-VT than in CS-nVT or dilated cardiomyopathy and significantly correlated with U-8-OHdG levels (n=58; R=0.61; P<0.00001), which were significantly higher in CS-VT than in CS-nVT (24.6±7.1 versus 15.2±3.8 ng/mg·Cr; P<0.0001). Other baseline characteristics did not differ between the groups. Multivariate analysis indicated that U-8-OHdG was an independent determinant factor for VT. Receiver operating characteristic curve analysis to identify patients with VT resulted in a U-8-OHdG cutoff value of 17.5 ng/mg·Cr (sensitivity, 89%; specificity, 83%; area under the curve, 0.90).

Conclusions: U-8-OHdG levels are associated with VT in patients with active CS diagnosed by 18F-flurodeoxyglucose positron-emission tomography, providing additive and relevant information about the arrhythmia substrate.

Keywords: deoxyguanosine; heart failure; oxidative stress; sarcoidosis; tachycardia, ventricular.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aged
  • Biomarkers / urine*
  • Cardiomyopathies / diagnostic imaging*
  • Cardiomyopathies / physiopathology
  • Cardiomyopathies / urine*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / urine
  • Echocardiography
  • Electrocardiography
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Positron Emission Tomography Computed Tomography
  • Prospective Studies
  • Radiopharmaceuticals
  • Sarcoidosis / diagnostic imaging*
  • Sarcoidosis / physiopathology
  • Sarcoidosis / urine*
  • Tachycardia, Ventricular / diagnostic imaging*
  • Tachycardia, Ventricular / physiopathology
  • Tachycardia, Ventricular / urine*

Substances

  • Biomarkers
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine