It is known that PH increases the probability for arrhythmias to occur by several methods such as the modulation of autonomic activity, delayed cardiac repolarization, and right ventricular myocardial ischemia (Rajdev et al., 2012). In this investigation, we studied the applicability of different ventricular repolarization markers such as QT, QRS, and TpTe intervals in dogs with PH.
A significant difference in average heart rates was observed between pre-PH, post-PH, and control groups (P < 0.001), showing a higher heart rate in post-PH patients with an average of 153 bpm; this is due to probably activation of autonomic activity. Post-PH is more common in dogs with congestive left heart failure with an increased LA pressure, leading to congestion of the pulmonary veins, increasing pulmonary pressure, and reducing cardiac output (CO) (Guazzi and Naeije, 2017).
In this study, regardless of the group analyzed, there was a variety in the polarity of the T wave, and the majority was negative, followed by positive and biphasic polarity. This characteristic was presented in the same proportion in each group, different from a study made with 129 and another with 15 healthy dogs where the positive polarity predominated followed by the negative and biphasic (Romito et al., 2022; Vila et al., 2021), agreeing with the biphasic minority in all studies including this one. Vila et al (2021) also observed a higher prevalence of negative T waves in patients with MMVD stages B2 and C.
On the other hand, QRSdisp is defined as the difference between the maximum and minimum QRS duration measured in the standard twelve lead ECG and it has been poorly studied in dogs. In people, it has been suggested that an increased QRSdisp is a marker of inhomogeneous ventricular depolarization and could be associated with a negative prognosis (Chávez-González et al., 2017). It was found that an increase in QRSdisp in humans after 48 hours of acute myocardial infarction could predict arrhythmias (Chávez-González et al., 2022). Turrini et al (2001) demonstrated that augmented QRSdisp was the strongest independent predictor of SCD in human patients with arrhythmogenic right ventricular cardiomyopathy. All these findings demonstrate the importance of the statistically significant difference of this variable (P = 0.0359) in dogs with PH compared with the control group and the shortest median survival time of dogs with QRSdisp > 16.5 observed in the present study.
Furthermore, a previous study in dogs with MMVD showed that TpTe/QT is a good marker for predicting ventricular arrhythmias and all-cause mortality (Vila et al., 2021). Although TpTe/QT in lead II should not be used as an isolated parameter for diagnosis of arrhythmogenic risk, it can be useful as a complementary tool as it was in this investigation because it was proved that dogs with a TpTe/QT in lead II > 0.2026 could have minor survival probabilities. The TpTe/QT in lead II in our study had a sensitivity of 80.0 % and specificity f 56.2% in identifying dogs with pulmonary hypertension. This result has potential applicability in a clinical setting because most electrocardiographic measurements in veterinary medicine are performed in lead II.
In this study, QT and QTc (all leads), failed to differentiate PH dogs and healthy dogs and showed no reasonable sensibility and specificity results for predicting augmented ventricular arrhythmogenesis. This is in agreement with the findings in dogs with MMVD, where no increase was found in the QT interval with the progression of the disease and the appearance of arrhythmias (Vila et al., 2021).
In people, there is a positive correlation between TpTe and mean pulmonary artery pressure calculated by right catheterization (Elitok et al., 2020). This study showed a statistical difference between TpTe values in lead III in dogs with and without PH. A poor correlation was found between TpTe in lead II and weight, which could be explained by the significant difference between the weights from the different groups, with larger breed dogs in the control group that could alter repolarization conditions.
No difference was found between the two methods of pre-cordial leads used to record the electrocardiogram in this study, even though in humans it has been established that the use of a 12-lead ECG is necessary to identify certain types of arrhythmias and variations in QRS duration (Chávez-González et al., 2017) However, it should be noted that only the durations of the repolarization indices were evaluated and future studies will be convenient to determine if there is a variation in the amplitude or duration of other parameters between both methods.
We used the Poincaré plot to describe QT instability and, we found higher values of QT instability (TI, STI, and LTI) in the post-PH group and high PH probability, with no statistical difference compared with pre-PH, control, and, low and intermediate PH probability groups agreeing with an investigation in dogs with MMVD in stage C, in which the authors showed longer STI and identified dogs with more probability of arrhythmias occurrence (Brüler et al., 2018).
The results of this study showed that dogs with high PH probability are 3 times more likely to die earlier than patients with low PH probability with a median survival time of 427 days. This median survival time was longer than that in dogs with pos-PH (368 days) (Udomkiattikul et al., 2022) and similar to 456 days in PH dogs secondary to MMVD stage B2 and C (Borgarelli et al., 2015). Factors such as actual medications for current diseases and owner care may have had an influence, making survival times not comparable between different studies.
Excellent repeatability and reliability were found in inter and intra-observer in QRSdisp interval in this study. Although good inter and intraobserver and excellent repeatability and reliability have been found in TpTe interval measurement in cats with hypertrophic cardiomyopathy (Bastos et al., 2022), this was not seen in this study, maybe due to the variable polarity of the T wave observed in the dogs included, this could limit the correct identification of the peak and the end of the T wave.
The reason why this study did not find risk indicators of arrhythmogenesis in pre-PH remains unclear, but we hypothesize that it may have an association with the fact that in the precapillary group, there were few dogs with a high probability of PH, thus there could be discrete remodeling in the RV that was insufficient to lead to increased or altered repolarization markers. The results found in the post-PH group could be due to the influence of left heart failure caused by MMVD in the majority of the dogs in post-PH group. Regardless of the origin, PH syndrome does not bring a real risk for developing arrhythmias, and the reason for it remains unclear. Further research is needed to elucidate the electrophysiological phenomena that underlie changes in various ECG parameters that reflect electrical changes in dogs with pre-PH.