Comparison between iodine 123 metaiodobenzylguanidine scintigraphy and heart rate variability for the assessment of cardiac sympathetic activity in mild to moderate heart failure

doi:10.1016/S0002-8703(97)70081-4

American Heart Journal

Volume 134, Issue 3, September 1997, Pages 456-458

https://doi.org/10.1016/S0002-8703(97)70081-4 Get rights and content

Abstract

This study demonstrates that in patients with mild to moderate heart failure, cardiac metaiodobenzylguanidine (MIBG) washout positively correlates with normalized low-frequency power in the heart rate variability spectrum. Alterations of the cardiac sympathetic nervous system could be detected with MIBG scintigraphy in patients with normal plasma norepinephrine levels. Therefore cardiac MIBG washout may be a valuable noninvasive technique to assess early alterations in cardiac sympathetic activity that may have potential clinical implications in patients with mild to moderate heart failure. (Am Heart J 1997;134:456-8.)

Section snippets

Methods

Patients were eligible for the study if they had stable chronic heart failure (New York Heart Association functional class II or III) for at least 2 months; sinus rhythm; radionuclide left ventricular nuclear ejection fraction <0.40%; and a fixed oral medication regimen, including angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Patients with diabetes mellitus were excluded. All studies were performed on the same day.

Plasma NE level was determined by high-performance liquid

Results

Table I, Table II show patient characteristics and neurohormonal data, respectively. Cardiac MIBG washout significantly correlated with normalized low-frequency power ( r = 0.70, p = 0.02, Fig. 1) .

. Relation between cardiac MIBG washout and normalized low-frequency power ( r = 0.70, p = 0.02). 95% confidence interval is indicated.

No correlation was found with any other HR variability parameter, ejection fraction, or plasma NE levels.

Plasma NE levels were within the normal range in all patients

Discussion

In this study cardiac MIBG washout was positively correlated with the normalized low-frequency power in the HR variability spectrum. This finding suggests that increased cardiac sympathetic neuronal activity can be detected in patients with heart failure and normal plasma NE levels. Therefore MIBG washout from the heart may be used to noninvasively assess early alterations of the cardiac sympathetic nervous system. Our findings are supported by data from Imamura et al., ⁶ who recently found a

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Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause
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β-adrenergic receptor antagonism with drugs like carvedilol slows the progression of heart failure by an undefined mechanism. ¹²³I-metaiodobenzylguanidine (MIBG) is an analog of norepinephrine used to study cardiac sympathetic function.
In this double-blind randomized, placebo-controlled study, we used MIBG imaging to evaluate the effect of carvedilol (n = 15) or placebo (n = 7) on neuronal norepinephrine reuptake in patients with heart failure due to idiopathic dilated cardiomyopathy, with LVEF less than 35% and functional class II or III. The drug was begun at 6.25 mg b.i.d. and titrated up to 25 mg t.i.d, as tolerated. Thorax planar scintigraphy images were obtained 15 min (Initial) and 4 h (Late) after MIBG injection at baseline (t₀) as well as 2 months (t₁) and 6 months (t₂) after drug initiation. The multifarious statistical technique of profile analysis was applied and p ≤ 0.05 was considered significant. The heart/mediastinum MIBG uptake (H/M ratio) was calculated from these images. On the Initial images, the H/M ratio was 1.64 ± 0.24 (t₀), 1.71 ± 0.21 (t₁), and 1.87 ± 0.34 (t₂) in the carvedilol group and 1.68 ± 0.42 (t₀), 1.81 ± 0.45 (t₁), and 1.69 ± 0.44 (t₂) in controls (p = 0.0455). On the Late images, the H/M ratio was 1.39 ± 0.24 (t₀), 1.53 ± 0.23 (t₁), and 1.64 ± 0.36 (t₂) in the carvedilol group, and 1.49 ± 0.45 (t₀), 1.53 ± 0.47 (t₁), and 1.47 ± 0.41 (t₂) in controls (p = 0.0513).
Compared with placebo, the addition of carvedilol to existing heart failure treatment incites the reverse remodeling of cardiac sympathetic nervous system function.
Prognostic value of iodine-123-metaiodobenzylguanidine myocardial uptake and heart rate variability in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy
2005, American Journal of Cardiology
Autonomic nervous system dysfunction is common in congestive heart failure (CHF) and is believed to predispose patients to an increased risk of death. This study aimed to assess the prognostic significance of heart rate variability (HRV) measurements in conjunction with scintigraphic imaging using metaiodobenzylguanidine (MIBG) labeled with iodine-123 (I-123-MIBG), which detects abnormalities in autonomic nervous activity, in patients with stable CHF during optimal medical treatment. The study population included 52 patients (56 ± 12 years of age) with a mean left ventricular ejection fraction of 31 ± 12%. All underwent I-123-MIBG scanning and 24-hour ambulatory electrocardiographic monitoring for the analysis of HRV on entrance into the study. The heart/mediastinum MIBG uptake ratio was calculated. HRV analysis included the assessment of time- and frequency-domain variables. During the 2-year follow-up, 14 patients (27%) died. MIBG uptake at 1 hour was less (1.39 ± 0.10) in nonsurvivors than in survivors (1.50 ± 0.16; p = 0.013). In univariate Cox regression analysis, MIBG uptake was a significant prognostic factor (p = 0.038, hazard ratio [HR] 0.017, 95% confidence interval [CI] 0.00 to 0.79). Time- and frequency-domain variables were similar in survivors and nonsurvivors. However, high-frequency power was associated with an increased risk for sudden death (HR 0.310, 95% CI 0.101 to 0.954, p = 0.041) but not with all-cause mortality. In conclusion, cardiac I-123-MIBG imaging identifies patients with CHF at high risk of dying and may be a more reliable predictor of overall mortality than HRV.
Comparison of the prognostic value of cardiac iodine-123 metaiodobenzylguanidine imaging and heart rate variability in patients with chronic heart failure: A prospective study
2003, Journal of the American College of Cardiology
We sought to prospectively compare the prognostic value of cardiac iodine-123 (I-123) metaiodobenzylguanidine (MIBG) imaging with that of heart rate variability (HRV) in patients with mild-to-moderate chronic heart failure (HF).
Cardiac I-123 MIBG imaging, which reflects cardiac adrenergic nerve activity, provides prognostic information on chronic HF patients. Reduced HRV, indicating derangement in cardiac autonomic control, was also reported to be associated with a poor prognosis in chronic HF patients.
At study entry, I-123 MIBG imaging and 24-h Holter monitoring were performed in 65 chronic HF outpatients with a radionuclide left ventricular ejection fraction <40%. The cardiac MIBG heart to mediastinum ratio (H/M) and washout rate (WR) were obtained from MIBG imaging. The time and frequency domain parameters of HRV were calculated from 24-h Holter recordings.
At a mean follow-up of 34 ± 19 months, WR (p < 0.0001), H/M on the delayed image (p = 0.01), and normalized very-low-frequency power (n-VLFP) (p = 0.047) showed a significant association with the cardiac events (sudden death in 3 and hospitalization for worsening chronic HF in 10 patients) on univariate analysis. Multivariate analysis revealed that WR was the only independent predictor of cardiac events, although the predictive accuracy for the combination of abnormal WR and n-VLFP significantly increased, compared with that for abnormal WR (82% vs. 66%, p < 0.05).
Cardiac MIBG WR has a higher prognostic value than HRV parameters in patients with chronic HF. The combination of abnormal WR and n-VLFP would be useful to identify chronic HF patients at a higher risk of cardiac events.
Cardiac sympathetic activity as measured by myocardial 123-I- metaiodobenzylguanidine uptake and heart rate variability in idiopathic dilated cardiomyopathy
1999, American Journal of Cardiology
In patients with idiopathic dilated cardiomyopathy (IDC) the increased sympathetic activity owing to chronic congestive heart failure leads to an imbalance of cardiac autonomic tone, as reflected by decreased heart rate variability (HRV). Iodine-123-metaiodobenzylguanidine (123-I-MIBG), which has the same affinity for sympathetic nerve endings as norepinephrine, can be used to assess the integrity and function of the cardiac sympathetic nervous system. The aim of the present study was to measure cardiac sympathetic activity by assessing 123-I-MIBG uptake compared with HRV in patients with IDC. In 12 patients with IDC and mild to moderate heart failure, myocardial MIBG uptake was calculated from the myocardial (M) to left ventricular cavity (C) voxel values density ratio and the 123-I activity in a blood sample as a reference (= M/C ratio) using a double radionuclide study with 123-I-MIBG and technetium-99m-MIBI. To investigate the relation between myocardial MIBG uptake and HRV in time domain, the linear regression between the M/C ratio, a new scintigraphic parameter, and the mean RR interval or the HRV triangular index, respectively, was determined. A significant correlation between the M/C ratio and mean RR interval (r = 0.52; p = 0.016) or M/C ratio and HRV triangular index (r = 0.76; p = 0.003), respectively, was found. Thus, the significant correlation between the M/C ratio and HRV indicate that they are both suitable noninvasive methods for evaluating cardiac sympathetic activity in patients with IDC and, furthermore, favor the view that there is evidence of a relation between HRV and the disorder of the cardiac presynaptic sympathetic nerve endings as demonstrated by a reduced M/C ratio.
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Comparison between iodine 123 metaiodobenzylguanidine scintigraphy and heart rate variability for the assessment of cardiac sympathetic activity in mild to moderate heart failure☆,☆☆