Arrhythmias in Patients With Pulmonary Hypertension ; A Narrative Review of the Current Literature

Copyright © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Background Pulmonary hypertension (PH) is defined as an increase in the mean pulmonary pressure (mPAP) >25 mm Hg at rest and capillary wedge pressure (PCWP) <15 mm Hg in precapillary (group 1, 3-5) or >15 mm Hg in postcapillary (group 2) forms.1 Proliferation of pulmonary artery smooth muscle and endothelial cells, endothelial dysfunction, inflammation and excessive vasoconstriction lead to arteriolar obstruction, elevated pulmonary arterial pressure, and increased pulmonary vascular resistance (PVR).2,3 Increased PVR causes elevated afterload of the right ventricle and cardiac remodelling.4 Elevated rightsided filling pressure and cardiac remodelling could provide the substrate or trigger for arrhythmias.5,6 Several studies have evaluated the incidence of supraventricular and ventricular arrhythmias and their prognostical relevance in patients with PH.7-15 It is already known that supraventricular arrhythmias are associated with clinical deterioration, but the incidence of sudden cardiac death was not elevated in these patients.8,10,12,14,15 The incidence and clinical/prognostical relevance of non-sustained ventricular tachycardia was analyzed in only three studies.16-18

tachycardia, atrial fibrillation, atrial flutter, prognostic relevance, electrophysiological studies, ep-studies, EPS, and ablation.Studies fulfilling the search criteria were reviewed for incidence of arrhythmia, diagnostic tools, kinds of arrhythmia, patient characteristics, correlation of echocardiographic results/hemodynamic parameters and arrhythmias, clinical relevance of arrhythmias, and prognostic relevance of arrhythmias.

Supraventricular Arrhythmias
Supraventricular arrhythmias in patients with PH were evaluated in nine studies (Table 1).
Folino and colleagues' study evaluated ventricular arrhythmias and autonomic profiles in patients (n = 9) with group 1 PH using 24 h Holter ECG monitoring. 18n all patients, LV-EF was >50% (mean 65.2 ± 6), values of RV-EF were between 44%-55% (mean 49.3 ± 5%), and right ventrIcular systolic pressure (RVSP) of 91.2 ± 25 mm Hg.Three patients had an anamnesis of syncope.Holter ECG showed premature ventricular complexes (PVC, >700/24 h) in 4 patients and couplets in 2 patients.SDNN and SDANN were reduced in comparison to a control group of twenty healthy subjects (age 39 ± 18 years) and in patients with PVC >700/24 h.Cardiopulmonary exercise tests revealed reduced workloads in all patients.Reasons for discontinuation were dyspnea and physical exhaustion; ventricular arrhythmias were recorded in none of the patients.Patients with the lowest SDNN (<90 ms) showed
In Olsson and colleagues' study, all patients had normal left atrial dimensions 12 ; in Rottlaender and colleagues' study, in patients without group 2 PH, elevated right atrial pressure and right atrial dilatation were associated with Afib 13 and seemed to be responsible for it.
9]12 Interestingly, in the studies of Wen and Olsson, survival in patients with transient episodes of arrhythmias was not statistically different from patients without arrhythmias. 10,12Most patients with arrhythmias suffered from symptoms [8][9][10]14 and improved after restoration of SR. 8,12 In Olsson and colleagues' study, restoration of SR was associated with improved 6-MWD and decreased NT-proBNP. 12Interestingly, in Ruiz-Cano and colleagues' study, 46.4% of the patients needed more specific treatment of PH despite the restoration of SR or control of ventricular rate.14 Few studies have evaluated the prognostic relevance of ECG parameters.P-wave duration was associated with shorter survival, but in multivariate analysis this association was only borderline significant when age was included as a covariate (P = 0.06). 7 QR-width 19 and duration of QTinterval 20,21 were assessed in patients with PH and showed correlations with mortality.The results of these studies were not reported in other studies.
Ventricular tachycardias in patients with PH were revealed during continuous monitoring with Holter-ECG. 16,17In accordance with the results of studies evaluating supraventricular arrhythmias, TAPSE was reduced in patients with nsVT 16,17 and cardiac index was reduced, whereas PVR, sPAP, and mPAP were elevated. 16,17he authors' study showed that extending Holter ECG monitoring to longer than 24 hours raised the detection rate of arrhythmias. 17The main result of the study was that the prognostical relevance of nsVT was missing.Because of the moderate sample size, the prognostic relevance and risk factors for nsVTs need to be obtained in larger series.
2][23][24][25][26][27] In Medi and colleagues' study, patients with right atria showing What Is Already Known?Supraventricular arrhythmias are common in patients with pulmonary hypertension and lead in most cases to clinical deterioration.If possible cardioversion should be obtained.Permanent arrhythmias are associated with a worse prognosis.

What This Study Adds?
This review highlights the frequency of (non-sustained) ventricular arrhythmias in patients with pulmonary hypertension and their prognostical relevance.Rhythm control should be sought in patients with supraventricular arrhythmias.Another important information is extending of Holter ECG monitoring (>24 hours) to raise the detection rate of arrhythmias.In patients with atrial flutter, focal atrial tachycardia and atrioventricular nodal reentrant tachycardia ablation is feasible and safe.
Review Highlights reduction of conduction velocity and an increase of areas of low voltage or electrical silence due to interstitial fibrosis were found. 24The authors discussed these findings as a reason for lower pharmacologic or catheter-based success to restore SR. 24

Conclusion
Supraventriuclar arrhythmias are common and, except transient forms, prognostically relevant in patients with PH.Most patients suffer from clinical symptoms.Restoration of SR should be targeted to improve patients' clinical presentation.Elevated RAP and right atrial diameters and reduced TAPSE are risk factors.The relevance of ECG parameters has to be evaluted in further studies.Nonsustained ventricular tachycardias showed no prognostical relevance in one study.Ablation of arrhythmias is feasible and safe.

Table 2 .
Studies Investigating Ventricular Arrhythmias in Patients With Pulmonary Hypertension