Elsevier

Journal of Nuclear Cardiology

Volume 29, Issue 6, December 2022, Pages 3166-3176
Journal of Nuclear Cardiology

Original Article
Regional myocardial sympathetic denervation precedes the development of left ventricular systolic dysfunction in chronic Chagas’ cardiomyopathy

https://doi.org/10.1007/s12350-021-02869-3Get rights and content

Abstract

Background

Regional myocardial sympathetic denervation is a conspicuous and early disorder in patients with chronic Chagas’ cardiomyopathy (CCC), potentially associated to the progression of myocardial dysfunction

Objective

To evaluate in a longitudinal study the association between the presence and the progression of regional myocardial sympathetic denervation with the deterioration of global and segmental left ventricular dysfunction in CCC.

Methods

18 patients with CCC were submitted at initial evaluation and after 5.5 years to rest myocardial scintigraphy with 123Iodo-metaiodobenzylguanidine and 99mTc-sestamibi and to two-dimensional echocardiography to assess myocardial sympathetic denervation, extent of fibrosis, and the left ventricular ejection fraction (LVEF) and wall motion abnormalities.

Results

In the follow-up evaluation, compared to the initial one, we observed a significant decrease in LVEF (56 ± 11 to 49% ± 12; P = .01) and increased summed defects scores in the myocardial innervation scintigraphy (15 ± 10 to 20 ± 9; P < .01). The presence of regional myocardial sympathetic denervation in ventricular regions of viable non-fibrotic myocardium presented an odds ratio of 4.25 for the development of new wall motion abnormalities (P = .001).

Conclusion

Regional and global myocardial sympathetic denervation is a progressive derangement in CCC. In addition, the regional denervation is topographically associated with areas of future development of regional systolic dysfunction in patients with CCC.

Introduction

Chagas’ disease (CD) is considered one of the most neglected diseases in the world and is a major cause of morbidity and mortality in Latin America.1 Recently, CD has gained importance with the recognition of cases in North America and Europe due to increasing migratory currents from endemic regions.2,3

One of the peculiar pathophysiological features of Chronic Chagas’ Cardiomyopathy (CCC) is the extensive cardiac autonomic impairment4, 5, 6 that may occur early in the course of the disease7 and has been postulated to participate in the mechanisms triggering complex ventricular arrhythmias and sudden death8,9

A previous study using 123I-MIBG scintigraphy in CCC patients presenting diverse severity of cardiac dysfunction showed areas of sympathetic denervation even in those subjects with normal segmental and global left ventricular systolic function.7 In addition, sympathetic denervation ensued in the same left ventricular myocardial regions where the segmental wall motion and fibrosis developed in patients with worse left ventricular systolic dysfunction. These findings raise the possibility that derangement of sympathetic innervation might precede and even predict the progression of left ventricular systolic dysfunction in patients with CCC.7

Despite this initial evidence, no longitudinal clinical study so far tested the relationship between myocardial sympathetic denervation and the progression of ventricular dysfunction in patients with CCC.

This study aimed at evaluating in a longitudinal cohort using 123I-MIBG imaging the association between the extent of regional myocardial sympathetic denervation and the progression of left ventricular dysfunction in patients with CCC.

Section snippets

Study population

The initial patient population consisted of 48 subjects with chronic Chagas’ disease being followed in outpatient clinic. We included patients between 18 and 75 years old of both genders, with 2 positive serologic tests for Chagas’ disease (indirect immunofluorescence reaction, enzyme-linked immunosorbent assay) and the transthoracic echocardiogram showing left ventricular ejection fraction ≥ 35 %. Patients underwent initial clinical evaluation, which included resting 12-lead electrocardiogram,

Study population

From the initial sample of 23 patients with a clinical follow-up longer than 4 years only 18 patients could be reassessed. The exclusion of 5 patients occurred because of death 1patient, loss of follow-up 1patient, diagnosis of coronary heart disease 1patient, and 2 patients refused to perform the re-evaluation. The mean time between initial and follow-up evaluation was 5.5 ± 1.0 years and the minimum and maximum intervals were 4 and 8 years, respectively.

Demographic and clinical

Discussion

The main results of this retrospective longitudinal study in CCC patients showed the progression of the extent and severity of the myocardial sympathetic denervation during a 5-year period that was concomitant with a significant deterioration of the LV regional and global systolic function. Most importantly, we observed that the presence of regional sympathetic denervation at baseline was topographically correlated with the ultimate worsening of LV regional systolic dysfunction.

Cardiac

Conclusion

Our results indicate that regional and global myocardial sympathetic denervation are progressive derangements in CCC patients. Furthermore, the regional myocardial denervation is topographically associated with the development of regional wall motion impairment and forthcoming deterioration of global LV systolic function.

These results suggest the potential use of 123I-MIBG scintigraphy for risk stratification of the disease progression in CCC patients.

Disclosures

The authors have indicated that they have no financial conflict of interest.

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