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Unlabelled: 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 (123)I-metaiodobenzylguanidine ((123)I-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 (123)I-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 > or = 172 pg/mL and late HMR of < or =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 (123)I-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 (123)I-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.

We evaluated the diagnostic accuracy of a new method for quantitative analysis of myocardial perfusion at exercise using (99m)Tc-tetrofosmin tomographic imaging. (99m)Tc-tetrofosmin imaging of an exercise-rest sequence was performed in 30 patients with coronary artery disease (CAD) and eight age-matched control subjects. The exercise-induced myocardial count increase was calculated as the relative value (per cent increase ratio, %IR) to that at rest by correcting for physical decay for (99m)Tc and injected doses and by a subtraction technique. Exercise and rest (99m)Tc-tetrofosmin images were assessed visually and quantitatively using the per cent peak count and %IR of the myocardial count at exercise. Segments with significant coronary stenosis (diameter stenosis=75% or more) showed a significantly lower %IR than did those without significant coronary stenosis in the CAD patients (37+/-19% vs 63+/-21%, P<0.05). The diagnostic efficacy of visual analysis for detecting coronary stenosis was as follows: sensitivity, 58.1% and specificity, 81.4%. When %IR=37% was used for detecting significant coronary stenosis, sensitivity and specificity increased to 74.2% and 93.2%, respectively. Furthermore, the quantitative analysis significantly (P=0.04) improved the overall diagnostic accuracy from 73.3% to 86.7% compared to that of visual assessment. Thus, augmentation of myocardial (99m)Tc-tetrofosmin uptake at exercise is blunted in the myocardium with significant coronary stenosis. The calculation of myocardial count increase at exercise relative to that at rest can improve the diagnostic value of (99m)Tc-tetrofosmin SPECT imaging and may contribute to more accurate quantification of myocardial ischaemia and impaired tracer uptake in coronary artery disease.

Despite the diagnostic efficacy of stress myocardial perfusion imaging, the correlation between the actual perfusion tracer activity and diseased state of a coronary artery has not been studied in detail. We estimated exercise-related perfusion augmentation in relation to disease states of a coronary artery in diabetic and non-diabetic patients by a newly developed quantitative technetium (Tc)-99m-tetrofosmin myocardial imaging technique. Tc-99m-tetrofosmin tomographic imaging with an exercise-rest protocol was performed in 26 stable coronary patients and in 8 age-matched controls. Percent increase (%IR) in myocardial count during symptom-limited submaximal exercise-stress was calculated in 16 non-infarcted polar map segments and in each coronary territory by a subtraction technique with corrections for physical decay and injected tracer doses, and the results were compared with those of angiographically quantified coronary diameter stenosis (%DS). Percent IR and peak heart rate during exercise showed a positive linear correlation both in coronary territories with significant stenosis (%DS > or = 75%) and in control or nonstenotic (%DS < 75%) territories. The regression line in stenotic regions was, however. significantly (p < 0.01) shifted downward compared to that in non-stenotic regions. Percent IR in stenotic regions showed a significant inverse correlation with %DS. Coronary stenosis of 75% or more was identified by a %IR cutoff value of 40% with 77% sensitivity, 70% specificity, and an accuracy of 72%. In coronary territories with a %DS of less than 75%, %IR in diabetic patients was significantly lower (46+/-15%) than that in nondiabetic patients (61+/-25%). Thus, blunted exercise-related augmentation of myocardial uptake of Tc-99m-tetrofosmin correlates with the severity of coronary narrowing and diabetic state.

Background: Although cardiac sympathetic nerve dysfunction is related to poor clinical outcome, a critical sympathetic dysfunction level for predicting cardiac death is still unclear. The current study was designed to investigate which indices derived from metaiodobenzylguanidine (MIBG) imaging have prognostic value compared with clinical and cardiac function variables, and to determine the threshold of cardiac MIBG activity for identifying patients likely to suffer cardiac death in both failing and nonfailing hearts., Methods and Results: Myocardial I-123-MIBG activity was quantified as a heart-to-mediastinum ratio in 414 consecutive patients, 173 (42%) of whom had symptomatic heart failure. After cardiac function measurements, patients were followed up with an end-point of cardiac or noncardiac death. During a mean follow-up period of 22 months, 37 cardiac deaths occurred: 23 resulted from heart failure, 9 were sudden cardiac deaths, and 5 were fatal myocardial infarctions. Multivariate analysis using the Wald chi2 and the Cox proportional hazard model revealed that late heart-to-mediastinum ratio, the use of nitrates, early heart-to-mediastinum ratio, and left ventricular ejection fraction were independent predictors of cardiac death; late heart-to-mediastinum ratio, New York Heart Association (NYHA) class, the presence of previous myocardial infarction, and age were independent predictors of heart failure and sudden cardiac death. Late heart-to-mediastinum ratio was the most powerful predictor of overall cardiac death among the variables. The Kaplan-Meier analysis showed that a late heart-to-mediastinum ratio of 1.74 or less, age greater than 60 years, the presence of myocardial infarction, and NYHA functional class 3 or 4 strongly indicated poor clinical outcomes. Furthermore, the more powerful incremental prognostic values were obtained by using MIBG imaging in combination with conventional clinical variables., Conclusions: Impaired cardiac sympathetic innervation assessed by MIBG activity has the greatest potential for predicting cardiac death and may be useful for identifying a threshold level for selecting patients at risk for death by heart failure, sudden cardiac death, and fatal myocardial infarction.