Elsevier

International Journal of Cardiology

Volume 312, 1 August 2020, Pages 129-135
International Journal of Cardiology

Left-ventricular innervation assessed by 123I-SPECT/CT is associated with cardiac events in inherited arrhythmia syndromes

https://doi.org/10.1016/j.ijcard.2020.03.013Get rights and content

Highlights

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    123I-MIBG SPECT/CT allows for chamber-specific sympathetic innervation assessment.

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    Impaired LV innervation associated with worse outcome in inherited arrhythmias.

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    Potential role of LV innervation assessment for risk stratification in iAS.

Abstract

Aims

Impaired myocardial sympathetic innervation assessed by 123Iodine-Metaiodobenzylguanidine (123I-MIBG) scintigraphy is associated with cardiac events. Since regional disparities of structural abnormalities are common in inherited arrhythmia syndromes (iAS), a chamber-specific innervation assessment of the right (RV) and left ventricle (LV) could provide important insights for a patient-individual therapy. Aim of this study was to evaluate chamber-specific patterns of autonomic innervation by Single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with iAS with respect to clinical outcome regarding cardiac events.

Methods and results

We assessed ventricular sympathetic innervation (LV, RV and planar heart/mediastinum-ratios, and washout-rates) by 123I-MIBG-SPECT/CT in 48 patients (arrhythmogenic right ventricular cardiomyopathy [ARVC], n = 26; laminopathy, n = 8; idiopathic ventricular fibrillation [iVF], n = 14) in relation to a composite clinical endpoint (ventricular arrhythmia; cardiac death; cardiac hospitalization). RV tracer uptake was lower in patients with ARVC than in laminopathy and iVF patients (1.7 ± 0.4 vs. 2.1 ± 0.7 and 2.1 ± 0.5, respectively). Over a median follow-up of 2.2 years, the combined endpoint was met in 18 patients (n = 12 ventricular tachyarrhythmias, n = 5 hospitalizations, n = 1 death). LV, but not RV H/M ratio was associated with the combined endpoint (hazard-ratio 2.82 [1.30–6.10], p < 0.01). After adjustment for LV and RV function, LV H/M-ratio still remained a significant predictor for cardiac events (hazard-ratio 2.79 [1.06–7.35], p = 0.04).

Conclusion

We demonstrated that chamber-specific 123MIBG-SPECT/CT imaging is feasible and that reduced LV sympathetic innervation was associated with worse outcome in iAS. These findings provide novel insights into the potential role of regional autonomic nervous system heterogeneity for the evolution of life-threatening cardiac events in iAS.

Introduction

Disturbed myocardial sympathetic innervation has been shown to be associated with increased risk for life-threatening ventricular arrhythmias in patients with cardiomyopathy [[1], [2], [3]]. Smaller studies suggest that the precise assessment of cardiac autonomic nervous system (ANS) function might help to improve risk prediction [[4], [5], [6]] in inherited arrhythmia syndromes (iAS) because the ANS is considered a critical determinant of arrhythmia induction and maintenance [4,5,7]. Since iAS vary remarkably with regard to their phenotypes and clinical presentation, current imaging techniques do not reliably visualize the precise localization of the specific structural alterations [1,2]. Therefore, a functional assessment of chamber-specific ANS function along with determination of structural changes might be of particular value to phenotype patients with iAS.

Section snippets

123Iodine-Metaiodobenzylguanidine for assessment of the ANS

Cardiac sympathetic fibers are located in the upper 0.25 to 0.50 mm of the sub-epicardium, along the coronary arteries in a basal-to-apical direction and innervate the endocardium by small branches going transmural [8]. This autonomic innervation is accessible to presynaptic 123Iodine-Metaiodobenzylguanidine (123I-MIBG) re-uptake imaging [6,9]. 123I-MIBG, an analogue of norepinephrine (NE), is metabolized like NE, therefore reflects the anatomical and physiological integrity of the sympathetic

Patient selection

Patients were recruited from the Department of Medicine I at the Ludwig-Maximilians-University (LMU) of Munich. Between 2011 and 2016 n = 48 consecutive patients were enrolled in this study, including 26 patients with diagnosis of ARVC, as defined by the modified McKenna criteria [21], and 8 patients with laminopathy based on LV dilation and/or reduced LV ejection fraction in combination with the pathognomic gene alteration (heterocygotic LMNA gen, p.Ala79Asp, exon 1). Patients with iVF

Results

Patient characteristics of the study population are listed in Table 1 and further detailed information including data on MRI results (presence of LGE and corresponding LV H/M ratios) in the supplement section (Table S1). Patients were followed for a median time of 2.2 [1.6] years after the scan. Thirty-two patients (67%) were male, with a mean age at study enrolment of 50 ± 16 years. Thirty-eight patients (79%) were provided with an ICD, thereof 27/48 patients (56%) for secondary prevention

Discussion

This study demonstrates that this novel technique of hybrid 123I-MIBG SPECT/CT imaging provides a feasible and reliable tool to assess chamber-specific sympathetic innervation. Our results indicated a strong trend of lower isolated RV H/M ratio in ARVC patients compared to individuals with iVF or laminopathy. While RV H/M ratio failed to show a significant association, isolated LV H/M ratio was identified to be significantly associated with clinical outcome in patients with iAS independent from

Conclusion

The separate assessment of RV and LV neuronal function with a novel hybrid SPECT/CT technique was feasible showing a strong trend of lower RV H/M ratio values in ARVC patients. LV H/M ratio but not RV H/M ratio showed a strong inverse correlation to the occurrence of clinical events in patients with iAS. Therefore, SPECT/CT derived assessment of ventricular H/M ratios seems to be a valuable tool to assess the risk for cardiac events in iAS. Further evaluation and confirmation in large

Sources of funding

Reza Wakili and Stefan Kääb was supported by the German Centre for Cardiovascular Research (DZHK) Partner site Munich. Reza Wakili and Tienush Rassaf were funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation – DO637/23-1; Projektnummer 394433254 to RW and RA969/12-1 to TR).

CRediT authorship contribution statement

Johannes Siebermair: Conceptualization, Methodology, Validation, Data curation, Writing - original draft, Writing - review & editing, Supervision. Sebastian Lehner: Formal analysis, Writing - original draft, Writing - review & editing, Supervision, Project administration. Stefan M. Sattler: Methodology, Investigation, Data curation, Writing - original draft, Writing - review & editing, Supervision. Konstantinos D. Rizas: Methodology, Validation, Data curation, Writing - review & editing,

Declaration of competing interest

None of the authors has a conflict of interest to declare associated with this manuscript.

Acknowledgments

A substantial part of this work originated from the doctoral theses of Julia Schiller and Corona Metz.

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