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Incremental Prognostic Implications of Brain Natriuretic Peptide, Cardiac Sympathetic Nerve Innervation, and Noncardiac Disorders in Patients with Heart Failure

¹ Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
² Sapporo Cardiovascular Clinic, Sapporo, Japan
³ Division of Cardiovascular Medicine, Hakodate Goryokaku Hospital, Hakodate, Japan

Plasma brain natriuretic peptide (BNP) level and cardiac autonomic function are closely related to prognosis in patients with heart failure. However, their correlation and incremental prognostic values in human heart failure are unclear. We sought to evaluate the correlation between BNP level and cardiac sympathetic innervation assessed by ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) and the prognostic value of combined assessment of risk factors for mortality in patients with heart failure. Methods: After conventional examinations and measurements of plasma BNP level and heart-to-mediastinum ratio (HMR) of cardiac ¹²³I-MIBG activity, 158 patients with heart failure were prospectively followed with an endpoint of cardiac death for 16 mo. Results: Fifteen deaths due to pump failure and 2 sudden cardiac deaths were documented. Plasma BNP level correlated with HMR significantly but not so tightly (r = 0.330, P < 0.0001). Univariate analysis identified plasma BNP level, HMR, chronic renal dysfunction, diabetes mellitus, age, and use of nitrates as significant predictors of fatal pump failure, and multivariate Cox analysis showed that plasma BNP level was the most powerful predictor of cardiac death. Patients with both plasma BNP level of 172 pg/mL and late HMR of 1.74 had a greater annual rate of fatal pump failure than did those without (17.5%/y vs. 0%–3.9%/y, respectively). The hazard ratio of plasma BNP level (7.2) or cardiac ¹²³I-MIBG activity (10.1) increased to 34.4 when both variables were used, and prevalence of fatal pump failure significantly increased from 22% to 62.5% when diabetes mellitus and chronic renal dysfunction were present with a higher plasma BNP level and low cardiac ¹²³I-MIBG activity. Conclusion: Plasma BNP level is a stronger predictor than other risk factors for mortality in heart failure patients and is statistically significantly, but roughly, related to cardiac sympathetic nerve innervation. Impaired cardiac sympathetic nerve innervation and the presence of diabetes mellitus and chronic renal dysfunction, however, improve risk stratification of patients with heart failure and increased plasma BNP concentration.

Key Words: heart failure • natriuretic peptides • sympathetic nervous system • prognosis • diabetes mellitus • renal dysfunction

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