Cardiac Mortality Assessment Improved by Evaluation of Cardiac Sympathetic Nerve Activity in Combination with Hemoglobin and Kidney Function in Chronic Heart Failure Patients

Abstract

We examined prognostic interactions among cardiac autonomic function assessed by 123 I-labeled metaiodobenzylguanidine ( 123 I-MIBG) activity, hemoglobin, and kidney function in chronic heart failure patients. Anemia, chronic kidney disease, and impairment of cardiac sympathetic function have been shown as determinants of prognosis in heart failure patients, but there has been little information on their synergistic correlations with cardiac mortality. Methods: After evaluations of hemoglobin and estimated glomerular filtration rate (GFR), 468 heart failure patients with left ventricular ejection fraction less than 50% underwent cardiac 123 I-MIBG imaging before discharge and were then followed up for a mean interval of 60.5 mo with a primary endpoint of cardiac death. Cardiac 123 I-MIBG activity was quantified using heart-to-mediastinum ratio (HMR) and washout rate. Results: For 89 fatal cardiac events documented (19.0%), besides New York Heart Association class, multivariate Cox analysis revealed HMR, hemoglobin, and estimated GFR as significant independent determinants, with hazard ratios of 0.215 (P 5 0.0129; 95% confidence interval [CI], 0.064-0.718), 0.821 (P 5 0.0062; 95% CI, 0.708-0.946), and 0.984 (P 5 0.0243; 95% CI, 0.970-0.998), respectively. Receiver-operating-characteristic analysis determined the thresholds for identifying patients at increased risk for cardiac death to be 1.57 for HMR, 11.9 g/dL for hemoglobin, and 46.4 mL/min/1.73 m 2 for estimated GFR. Combining the 4 independent predictors incrementally (P , 0.05) improved prognostic powers maximally up to a global x 2 value of 97.3 compared with sole or other combinations. Conclusion: Hemoglobin, kidney function, and alterations of cardiac sympathetic nerve activity are independently and synergistically associated with increased cardiac mortality in chronic heart failure patients, together with New York Heart Association functional class.

Synergistic prognostication of left ventricular hypertrophy and three‐dimensional mechanical dyssynchrony in heart failure

“…The precise mechanisms underlying cardiac mortality have not been determined. Together with the results of our previous studies, however, it has been shown that impairment of cardiac sympathetic nerve function may exacerbate LV hypertrophy and increase LVMD in association with cardio‐renal anaemia syndrome, leading to lethal cardiac events in HF patients.…”

“…Impaired kidney function or chronic kidney disease and anaemia are known to be closely correlated with cardiac outcomes in HF patients, independently of LV systolic function. 3,4,21,22 The precise mechanisms underlying cardiac mortality have not been determined. Together with the results of our previous studies, [21][22][23][24] however, it has been shown that impairment of cardiac sympathetic nerve function may exacerbate LV hypertrophy and increase LVMD in association with cardio-renal anaemia syndrome, 25 leading to lethal cardiac events in HF patients.…”

A Pooled Analysis of Multicenter Cohort Studies of 123I-mIBG Imaging of Sympathetic Innervation for Assessment of Long-Term Prognosis in Heart Failure

“…However, the present results cannot be used to indicate which mode of death will affect a particular high-risk patient. Sudden death per se is an outcome resulting from multifactorial pathologies and several triggers that could be modulated by interaction in various clinical conditions, including diabetic state, kidney function, and anemia (31). Hemodynamic instability enhances tachyarrhythmias via augmentations of afferent and efferent autonomic neuronal regulation and the renin-angiotensin-aldosterone system, leading to ischemia and myocyte injury, all of which in turn produce a vicious cycle resulting in pump failure and lethal arrhythmic events.…”

Cardiac 123I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

“…Several studies in the literature have demonstrated independent and incremental prognostic values of cardiac 123 I-MIBG imaging for patients with chronic HF in combination with clinical information, such as a history of myocardial infarction, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), plasma brain natriuretic peptide (BNP) level, and coexisting noncardiac conditions (such as diabetes mellitus, impaired kidney function, and anemia) (2,10,15,19,20,25,(34)(35)(36). The prognostic value has been shown irrespective of the etiologies (ischemic or nonischemic) of HF and LVEF (Fig.…”

“…A diabetic heart is also likely to have impaired 123 I-MIBG activity (low HMR and 123 I-MIBG defect) in association with disease progression (14). Table 1 summarizes major investigations that prospectively monitored patients with chronic HF for more than 2 y with an endpoint of cardiac death (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). (26).…”