Vasovagal tonus index (VVTI) as an indirect assessment of remission status in canine multicentric lymphoma undergoing multi-drug chemotherapy

Evi Pecceu,Hannah Hodgkiss-Geere,Yolanda Martinez Pereira,Brittainy Stebbing,Jessica Lawrence,Ian Handel,Geoff Culshaw

doi:10.1007/s11259-017-9695-8

Abstract

Vasovagal tonus index (VVTI) is an indirect measure of heart rate variability and may serve as a marker of disease severity. Higher heart rate variability has predicted lower tumour burden and improved survival in humans with various tumour types. The purpose of this pilot study was to evaluate VVTI as a biomarker of remission status in canine lymphoma. The primary hypothesis was that VVTI would be increased in dogs in remission compared to dogs out of remission. Twenty-seven dogs were prospectively enrolled if they had a diagnosis of intermediate to high-grade lymphoma and underwent multidrug chemotherapy. Serial electrocardiogram data were collected under standard conditions and relationships between VVTI, remission status and other clinical variables were evaluated. VVTI from dogs in remission (partial or complete) did not differ from dogs with fulminant lymphoma (naive or at time of relapse). Dogs in partial remission had higher VVTI than dogs in complete remission (p = 0.021). Higher baseline VVTI was associated with higher subsequent scores (p < 0.001). VVTI also correlated with anxiety level (p = 0.03). Based on this pilot study, VVTI did not hold any obvious promise as a useful clinical biomarker of remission status. Further investigation may better elucidate the clinical and prognostic utility of VVTI in dogs with lymphoma.

Highlights

Heart rate variability (HRV) is the physiologic variation in the beat-to-beat interval, or the R-R interval on an electrocardiogram (ECG) recording, which correlates with cardiac autonomic tone (Kuo et al 2005)
Of the 11 dogs lacking baseline VVTI data prior to initiation of chemotherapy, four dogs relapsed over time, providing a VVTI when OR at least once
It was expected that dogs in either clinical remission (CR) or partial remission (PR) would have increased VVTI compared to dogs that were OR

Summary

Introduction

Heart rate variability (HRV) is the physiologic variation in the beat-to-beat interval, or the R-R interval on an electrocardiogram (ECG) recording, which correlates with cardiac autonomic tone (Kuo et al 2005). Several studies have investigated HRV in healthy and unhealthy dogs, with diseases including myocarditis, myxomatous mitral valve disease and diabetes mellitus, suggesting a role for VVTI as a predictive or prognostic biomarker (Calvert and Wall 2002; Doxey and Boswood 2004; Pereira et al 2008; Manzo et al 2009; Oliveira et al 2012; Pirintr et al 2012; Vet Res Commun (2017) 41:249–256. Recent studies have investigated the prognostic value of HRV in human cancer patients. Higher HRV was associated with longer survival time, and predicted lower tumour burden and improved survival in patients with various solid tumours (Dekker et al 1997, Hoffmann et al 2001, Chiang et al 2010, Fadul et al 2009, Giese-Davis et al 2015, Guo et al 2015, Kim et al 2015). HRV has potential in oncology as a biomarker of response to chemotherapy and overall prognosis (De Couck and Gidron 2013; Giese-Davis et al 2015)

Results

Discussion

Conclusion