Dynamic 123I-BMIPP single-photon emission computed tomography in patients with congestive heart failure: effect of angiotensin II type-1 receptor blockade.

BACKGROUND: Heart failure is a major and growing public health problem with a high mortality rate. Although recent studies have demonstrated that a variety of metabolic and/or neurohumoral factors are involved in the progression of this syndrome, the precise mechanisms responsible for this complex condition are poorly understood. HYPOTHESIS: To examine 123I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) kinetics in the early phase soon after tracer injection in patients with congestive heart failure (CHF), we performed dynamic single-photon emission computed tomography (SPECT). METHODS: Twenty-six patients with CHF and eight control subjects were examined. The consecutive 15 images of 2-min dynamic SPECT were acquired for 30 min after injection. In the early phase after injection (0-4 min), a significant amount of radioactivity existed in the blood pool. After 6 min, the myocardial 123I-BMIPP image was clear and thus the washout rate of 123I-BMIPP from 6 to 30 min was calculated. RESULTS: The washout rate of 123I-BMIPP from the myocardium was faster in patients with CHF than in the controls (8 +/- 4 vs. -5 +/- 3%, p < 0.01). The washout rate of 123I-BMIPP demonstrated positive correlation with left ventricular (LV) end-diastolic volume index (R = 0.54, p < 0.02) and inverse correlation with LV ejection fraction (R = 0.53, p <0.02). Patients were given the angiotensin II type-1 receptor antagonist candesartan for 6 months, and dynamic SPECT was repeated. The enhanced washout rate of 123I-BMIPP in CHF was reduced after treatment with candesartan (p < 0.05). CONCLUSION: These data suggest that (1) enhanced washout of 123I-BMIPP was observed soon after injection in patients with CHF, (2) the activation of angiotensin II signaling pathway is involved as an intracellular mechanism for enhanced 123I-BMIPP washout in heart failure, and (3) improvement in fatty acid metabolism may represent a new mechanism for beneficial effects of angiotensin II receptor blockade on cardiac function and survival in patients with heart failure. 123I-BMIPP washout in the early phase obtained from dynamic SPECT may be a new marker for evaluating the severity of heart failure and the effects of medical treatment.

Severity in myocardial dysfunction contributed to long-term fluctuation of heart rate, rather than short-term fluctuations.

BACKGROUND: It is known that heart rate shows complex behavior, long-term fluctuation of heart rate, and short-term fluctuations in heart failure. Analyzing these properties and examining the relationship to the disease, severity may increase the understanding of the background of heart rate variability (HRV). METHODS: In 61 patients (mean age 65 +/- 9 years, 32 ischemic heart disease, 29 cardiomyopathy), with myocardial dysfunction, 24-hour ambulatory electrocardiography was performed. After the construction of the time series of R-R intervals, 15 HRV parameters were measured, including mean heart rate, standard deviation of N-N intervals (SDNN), ratio of low frequency/high frequency power (LF/HF), HRV triangular index (TI), and ratio of length/width at the 90% level of all scattered points. RESULTS: By using the multiple regression analysis, we tested which HRV parameter (HR, SDNN, LF/HF, TI, or length/width) independently correlated with left ventricular ejection fraction (EF) or left ventricular diastolic dimension (EDD). The results demonstrated that TI and SDNN independently correlated with EF (multiple R = 0.59). Moreover, TI and SDNN independently correlated with EDD (multiple R = 0.45). CONCLUSION: TI and SDNN were indicators of the disease severity in myocardial dysfunction, while LF/HF, indicators of autonomic tone, did not have such an ability. It was of interest that the disease severity contributed to long-term fluctuations (TI, SDNN) of heart rate, rather than short-term fluctuations (LF/HF).

Regional prolongation of ARI and altered restitution properties cause ventricular arrhythmia in heart failure.

The mechanism of arrhythmogenicity in heart failure remains poorly understood. We examined the relationship between electrical abnormalities and ventricular arrhythmia by using experimental heart failure models. Sixty unipolar electrograms were recorded from the entire cardiac surface in control dogs (n = 13) and pacing-induced heart failure dogs (n = 16). In failing hearts, activation time (AT) was delayed at the apex, and AT dispersion increased in failing hearts. Activation-recovery intervals (ARI) were prolonged mainly at the apex and ARI dispersion was significantly augmented. The slope of the ARI restitution curve, interaction of diastolic interval, and ARI in failing hearts was significantly steeper than in control hearts. Ventricular fibrillation (VF) was easily induced by programmed stimulation in failing hearts, whereas no arrhythmia occurred in control hearts. Computer simulation studies could reproduce the experimental results. Altering the ARI restitution to the steep slope causes VF in a model heart. It is suggested that electrical remodeling, especially steepness of electrical restitution, may play a role in arrhythmogenicity in failing hearts.