Evaluation of heart rate variability and behavior of electrocardiographic parameters in dogs affected by chronic Monocytic Ehrlichiosis

Abstract

Canine Monocytic Ehrlichiosis (CME) is a systemic disease prevalent in the entire world caused by the obligate intracellular bacteria Ehrlichia canis . The occurrence of myocarditis with a high prevalence of arrhythmias in dogs affected by this disease in the cytopenic phase has already been proven. This study aims to evaluate the concentrations of CK MB, cTnI and NT-proBNP in dogs affected by Ehrlichia canis in the chronic phase since the intense stimulation of the immune system can lead to myocarditis; to evaluate if the condition can lead to arrhythmic events and, if so, define their frequency and classification through conventional and ambulatory electrocardiogram tests (Holter method) for a period of 24 hours; to analyze heart rate variability in the time domain and whether the condition can lead to autonomic imbalance; and to determine the survival rate of affected dogs, identifying possible risk factors for mortality at this stage of the disease. For this purposes, we evaluated clinical, hematological and biochemical data, as well as the concentrations of cardiac biomarkers Creatine Kinase-MB (CK MB), Cardiac Troponin I (cTnI) and N-terminal pro-peptide natriuretic type B (NT-proBNP). We also analyzed conventional and ambulatory electrocardiography (24-hour Holter) and heart rate variability (HRV) in 20 dogs afflicted by cytopenic CME in the chronic phase of the disease (G1) and compared the results with a control group comprised of ten healthy dogs (G2). G1 was monitored during the treatment for 28 days, during which eight (8) of the 20 infected dogs died (40%). Anorexia, vomiting, fatigue, hypoalbuminemia, heart murmurs and increased concentrations of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were common clinical signs. The mean concentrations of cTnI and CKMB were significant (0.24 ng / mL ± 0.5, 229 ± 205 IU / mL) in comparison to the control group (0.042 ± 0.07 ng / mL, 126 ± 46.12 IU / mL). No significant differences were observed between NT-proBNP concentrations in G1 (135.46 ± 29.7) and G2 (138.28 ± 19.77). Nine of the twenty dogs (45%) presented a high frequency of arrhythmias during 24-hour recording, ranging from first and second-degree atrioventricular block, ventricular and supraventricular ectopic events and sinus tachycardia. No sinus pause was observed. One dog had 120 episodes of unsustained ventricular tachycardia and two episodes of sustained ventricular tachycardia. The short-term and long-term HRV data, represented by SDNN (ms), SDANN (ms) and pnn50 (%) were also significant lower (83 ± 65, 56.05 ± 37.3 and 14.56 ± 20, respectively) in comparison to the healthy animals (268 ± 74.6, 168.3 ± 39.14 and 55.87 ± 12.8, respectively). These results suggest that cytopenic CME is characterized by an arrhythmogenic component and intense stimulation of the sympathetic autonomic nervous system in the heart, reflecting an imbalance in the activity of the ANS.

Heart rate variability for small animal veterinarians - A concise debate

“…Therefore, this index calculates HRV due to cycles shorter than 5 min (Task Force of the European Society of Cardiology, 1996; Shaffer & Ginsberg, 2017). Since it is normalized by the length of the raw recording, its value is less variable than, for example, SDNN; for a 3 h recording, Bogucki & Noszczyk-Nowak (2017 ) found the value to be 190.75?76.12 ms, while Pirintr et al (2017 ) observed 128.7?9.4 ms for a 14 h recording, and Gianfranchesco Gianfranchesco Filippi et al (2019 ) obtained 216.9?74.28 ms in a 24 hours-long recording. Bogucki & Noszczyk-Nowak (2017) also observed that clinically normal dogs exhibited lower SDNNidx values (190.75?76.12 ms) when compared to dogs presenting SSS (341.4?56.69 ms), but higher than those presenting CMVD (117.21?70.5 ms).…”

“…For instance, Alfonso et al (2020 ) and Baisan et al (2020 ) performed SDNN analysis in dogs using 5 min recordings, and found similar results. On the other hand, Bogucki & Noszczyk-Nowak (2017 ) used three-hour ECG recordings, while Pirintr et al (2017 ) recorded for 14 hours, Hezzell et al (2018 ) used 30 min, and Gianfranchesco Filippi et al (2019 ) performed Holter recordings of 24 h, and all these studies came across very different results. These differences may not only be ascribed to different time recordings, but also to other factors such as time of the day, animal stress during recordings, and animal size.…”

“…As observed for SDNN, SDANN is also an index of global HRV; hence, its values may be affected by the length of the ECG recording and by the longest and shortest R-R intervals. SDANN may also vary depending on the duration of data acquisition ( Bogucki & Noszczyk-Nowak, 2017 ; Pirintr et al, 2017 ; Gianfranchesco Filippi et al, 2019 ). Bogucki & Noszczyk-Nowak (2017) observed that healthy dogs presented lower SDANN values than animals with SSS, but higher than dogs presenting CMVD.…”

“… Study Species Recording length Healthy Pathophysiological conditions Hezzell et al (2018 ) Canine 30 min 269.9 ms (median); 153.6 - 437.5 ms (range). ART: 332.1 ms (median), 140.7 - 375.0 ms (range); NEO: 242.2 ms (median), 175.8 - 384.8 ms (range) Gianfranchesco Filippi et al (2019 ) Canine 24 hours 267.37?113.38 ms CME: 648.88?238.97 ms ART, arthritis; NEO, neoplasia; CME, chronic monocytic ehrlichiosis; ms, milliseconds. Data are presented as mean ?…”

Correlation between canine biochemical analytes and TRP36 ELISA seropositivity for Ehrlichia canis in Brazil

“…The measurement of this enzyme helps detect heart damage in the chronic phase of CME. [14][15][16] In this context, the proteins TRP19 and TRP36 were used as antigens for indirect ELISAs to detect anti-E. canis antibodies in naturally infected dogs from an endemic area of Brazil. Possible associations between different variables that represent biochemical alterations were evaluated by canonical correlation tests, which can highlight the most important data occurring when specific antigens are used.…”