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

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

Michifumi Kyuma, MD¹, Tomoaki Nakata, MD, PhD¹, Akiyoshi Hashimoto, MD, PhD¹, Kazuhiko Nagao, MD, PhD², Hisataka Sasao, MD, PhD³, Toru Takahashi, MD¹, Kazufumi Tsuchihashi, MD, PhD¹ and Kazuaki Shimamoto, MD, PhD¹

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

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FIGURE 1. (A) A late cardiac planar ¹²³I-MIBG image obtained from a 60-y-old female with congestive heart failure who had fatal pump failure. She had a persistently depressed LVEF (16%) and a highly increased plasma BNP level (1,070 pg/mL). Her late HMR (1.49) was markedly reduced. (B) A late cardiac planar ¹²³I-MIBG image obtained from a 66-y-old male with congestive heart failure who survived. In response to drug therapy, he has an LVEF of 62%, a plasma BNP level of 76 pg/mL, and a normally preserved late HMR (2.14) at discharge. The box and oval indicate regions of interest on the upper mediastinal and cardiac areas, respectively, for calculation of the HMR of ¹²³I-MIBG activity.

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FIGURE 2. Correlations of the plasma BNP level with the cardiac ¹²³I-MIBG activity quantified as late HMR (A) and LVEF (B). The inverse correlations between them are statistically significant but weak.

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FIGURE 3. Kaplan–Meier event (fatal pump failure)-free curves when patients were stratified into 2 groups using the thresholds of a plasma BNP level of 172 pg/mL and an ¹²³I-MIBG HMR of 1.74. The group of patients with plasma BNP levels of <172 pg/mL (left) or HMRs of >1.74 (right) had a significantly lower event rate than did each counterpart not only when all 158 patients were considered (A) but also when 127 patients who had an LVEF of <50% were considered for this analysis (B).

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FIGURE 4. Comparison of prevalence (left) and annual rate of fatal pump failure (right) when patients were classified into 4 groups using the thresholds of a plasma BNP level of 172 pg/mL and an HMR of 1.74. The group of patients who had both a plasma BNP level of $>=$ 172 pg/mL and an HMR of $<=$ 1.74 had significantly greater event rates than those of the other 3 groups not only when all 158 patients were considered (A) but also when 127 patients who had an LVEF of <50% were considered for this analysis (B). *P < 0.05 vs. the other 3 groups.

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FIGURE 5. Incremental prognostic values of combined assessment of the plasma BNP level, the cardiac ¹²³I-MIBG activity, diabetes mellitus (DM), or chronic renal dysfunction (CRD), all of which are significant predictors of fatal pump failure in univariate analysis (Table 2). Hazard ratios ( ${square}$ ) for fatal pump failure increased to 34.413 when both the plasma BNP level and the cardiac ¹²³I-MIBG activity were used, but no further improvement was achieved in any other combination. On the other hand, the greatest prevalence (62.5%) of fatal pump failure ( ${blacksquare}$ ) was observed when all of these variables were used.