The spectrum and prevalence of arrhythmia in different clinical pulmonary hypertension groups in Chinese population

Arrhythmia is not uncommon among pulmonary hypertension (PH) population, and may be associated with disease severity.


| Study protocol and procedure
Every patient's ECGs and Holter (if applicable) during hospitalization or provided by them were collected. All ECGs and Holter electrocardiograms were carefully reviewed and all arrhythmias were adjudicated by an experienced cardiologist. All detected arrhythmias (except for arrhythmias within 72 h after RHC procedure) of the participants before the end of enrollment were taken into account.
Arrhythmias indicated by diagnoses of patients' medical records were also taken into account.
We subcategorized different arrhythmias into sinus node dysfunction (SND), sinus tachycardia, AF, AFL, other types of atrial tachycardia (AT) (consisting of atrial ectopic tachycardia, atrioventricular reentry tachycardia, and atrioventricular nodal reentry tachycardia), atrioventricular block (AVB), ventricular tachycardia (VT) (including non-sustained VT, NSVT) and ventricular fibrillation/flutter (VF). In our study, supraventricular arrhythmia (SVA) consisted of AF, AFL, and other AT. The prevalence of different types of arrhythmias in PH patients were calculated.
Baseline demographic and clinical parameters, including gender, age, body mass index, comorbidities, World Health Organization functional class (WHO-FC), six-minute walk distance (6MWD), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, parameters of echocardiography, hemodynamic parameters and medications, were recorded and compared.

| Statistical analysis
Statistical analyses were conducted using the SPSS system software, version 20.0.0. Continuous variables were presented as mean with standard deviation or median with interquartile ranges after testing for normality, and were compared using the Student t-test or the

| Characteristics of PAH patients with SND/ AVB versus PAH patients without SND/AVB
Besides SVA, the baseline characteristics of PAH patients with bradyarrhythmia (consisting of SND and AVB in our study) versus PAH patients without bradyarrhythmia were also analyzed (Table S1). Logistic regression analysis was also conducted to determine the predictors of SND/ AVB in PAH patients (Table S2)

| Previous studies focused on Chinese population
In 2014, Wen et al. 10

| Prevalence of arrhythmias
AF was seen in 8.1% patients in our overall PH population (6.6% for PAH patients), which is markedly higher than the prevalence of AF The prevalence of SVA (18.5%) in our overall PH population was lower than that of two recent studies (29%). 14, 15 Havranek et al. 14 analyzed the prevalence of AF/AT in CTEPH patients treated with pulmonary endarterectomy (PEA). In their study, early post-PEA arrhythmia was also taken into account, which might be the reason of high prevalence of AF/AT. The prevalence of AF/AT before PEA was 20% in their study, and was close to our result (18.5%). In the study of Fingrova et al., 15

| Risk factors of arrhythmias
Logistic regression analyses of our study indicated that: older age and larger RV were independently related with higher probability of SVA in patients with PAH; Complicating with CAD, larger RV and increased LVEDD were independently correlated with higher probability of SND/AVB in patients with PAH.
Wen et al. 10 also identified age and increased RV diameter as risk factors for developing SVA in patients with IPAH, which is in accordance with our result. The mechanism by which enlargement and dysfunction of the right heart might lead to and trigger brady-and tachy-arrhythmia was discussed above. Increased LVEDD could be the result of worse cardiac function, which might explain its relationship with the increased risk of arrhythmia.
After adjusting potential confounders (including β-blocker intake), complicating with CAD was still a strong independent risk factor for SND/AVB in PAH patients. SND/AVB is common in acute myocardial infarction, 26 but the relationship between SND/AVB with stable CAD is not well investigated yet. Chronic myocardial ischemia resulted by long-standing CAD might play a role.

| CONCLUSION
The prevalence of arrhythmia is 44.4% in our participants. The spectrum and prevalence of arrhythmia differ by different clinical PH groups. The most common seen arrhythmias were SVA (consisted of AF, AFL, and other AT), sinus tachycardia, and SND. The prevalence of AF in PH patients was markedly higher than that in general Chinese population. Older age and larger RV were independently related to higher probability of SVA in PAH patients. Complicating with CAD, larger RV and increased LVEDD were independently correlated with higher probability of SND/AVB in PAH patients.