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Abstract

Background

despite therapeutic improvement, pulmonary arterial hypertension (PAH) is still a chronic, incurable, high mortality disease. Several clinical, laboratory, hemodynamic and instrumental prognostic factors have been already established in PAH patients. However, no electrocardiographic prognostic factors have been identified so far in a systematic multivariate analysis together with clinical, exercise and haemodynamic parameters.

Methods

patients with idiopathic/heritable/drug-induced PAH (I/H/D-PAH) referred to a single centre were included from 1993 to 2021. All patients underwent baseline clinical, 12-lead ECG, hemodynamic with vasoreactivity test, 6 minutes walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), WHO functional class evaluation and risk stratification (according to a recently validated simplified version of 2015 ESC/ERS guidelines’ risk table). All cause mortality has been considered to identify the predictors of mortality using univariate and multivariate Cox regression analysis.

Results

570 PAH patients were included: 448 idiopathic (79%), 105 heritable (18%) and 17 drug-induced (3.0%). 20 patients were on atrial flutter/fibrillation at baseline. Considering only electrocardiographic parameters the variables independently associated with prognosis are shown in the table below:

n = 550HR (95% CI)p-value
Heart rate, bpm1.015 (1.006-1.024)0.001
PR interval, ms1.010 (1.005-1.014)<0.001
Right bundle branch block (complete/incomplete/no)1.252 (1.025-1.527)0.027
QTc, ms1.006 (1.001-1.010)0.009
n = 550HR (95% CI)p-value
Heart rate, bpm1.015 (1.006-1.024)0.001
PR interval, ms1.010 (1.005-1.014)<0.001
Right bundle branch block (complete/incomplete/no)1.252 (1.025-1.527)0.027
QTc, ms1.006 (1.001-1.010)0.009
n = 550HR (95% CI)p-value
Heart rate, bpm1.015 (1.006-1.024)0.001
PR interval, ms1.010 (1.005-1.014)<0.001
Right bundle branch block (complete/incomplete/no)1.252 (1.025-1.527)0.027
QTc, ms1.006 (1.001-1.010)0.009
n = 550HR (95% CI)p-value
Heart rate, bpm1.015 (1.006-1.024)0.001
PR interval, ms1.010 (1.005-1.014)<0.001
Right bundle branch block (complete/incomplete/no)1.252 (1.025-1.527)0.027
QTc, ms1.006 (1.001-1.010)0.009

Taking into account also the risk stratification the independent prognostic variables are:

n = 550HR (95% CI)p-value
Baseline risk (low/interm/high)2.220 (1.786-2.759)<0.001
Heart rate, bpm1.009 (1.000-1.018)0.041
PR interval, ms1.008 (1.003-1.012)0.001
QTc, ms1.012 (1.006- 1.018)<0.001
n = 550HR (95% CI)p-value
Baseline risk (low/interm/high)2.220 (1.786-2.759)<0.001
Heart rate, bpm1.009 (1.000-1.018)0.041
PR interval, ms1.008 (1.003-1.012)0.001
QTc, ms1.012 (1.006- 1.018)<0.001
n = 550HR (95% CI)p-value
Baseline risk (low/interm/high)2.220 (1.786-2.759)<0.001
Heart rate, bpm1.009 (1.000-1.018)0.041
PR interval, ms1.008 (1.003-1.012)0.001
QTc, ms1.012 (1.006- 1.018)<0.001
n = 550HR (95% CI)p-value
Baseline risk (low/interm/high)2.220 (1.786-2.759)<0.001
Heart rate, bpm1.009 (1.000-1.018)0.041
PR interval, ms1.008 (1.003-1.012)0.001
QTc, ms1.012 (1.006- 1.018)<0.001

Considering also clinical, exercise and haemodynamic variables the independent prognostic variables are:

n = 570HR (95% CI)p-value
Age at baseline (y)1.026 (1.018-1.034)<0.001
Male gender2.448 (1.897-3.159)<0.001
Long-term calcium channel blocker responder0.485 (0.270-0.873)0.016
6MWD, m0.995 (0.994-0.996)<0.001
Heart rate, bpm1.012 (1.002-1.021)0.015
n = 570HR (95% CI)p-value
Age at baseline (y)1.026 (1.018-1.034)<0.001
Male gender2.448 (1.897-3.159)<0.001
Long-term calcium channel blocker responder0.485 (0.270-0.873)0.016
6MWD, m0.995 (0.994-0.996)<0.001
Heart rate, bpm1.012 (1.002-1.021)0.015
n = 570HR (95% CI)p-value
Age at baseline (y)1.026 (1.018-1.034)<0.001
Male gender2.448 (1.897-3.159)<0.001
Long-term calcium channel blocker responder0.485 (0.270-0.873)0.016
6MWD, m0.995 (0.994-0.996)<0.001
Heart rate, bpm1.012 (1.002-1.021)0.015
n = 570HR (95% CI)p-value
Age at baseline (y)1.026 (1.018-1.034)<0.001
Male gender2.448 (1.897-3.159)<0.001
Long-term calcium channel blocker responder0.485 (0.270-0.873)0.016
6MWD, m0.995 (0.994-0.996)<0.001
Heart rate, bpm1.012 (1.002-1.021)0.015
Conclusions

in patients with I/H/D-PAH heart rate is a prognostic factor independently from other electrocardiographic, clinical, exercise and haemodynamic parameters as reflects the attempt to preserve the cardiac output in patients with an increased right ventricular afterload causing a reduced stroke volume; both PR interval prolongation, marker of right atrial overload, and QTc prolongation, marker of right ventricle's electrical remodeling, are prognostic variables independently from baseline patient's risk level; right bundle branch block, expression of right ventricular electrical remodeling, has proved to be an independent predictor of mortality merely if we consider only the electrocardiographic parameters.

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Published by Oxford University Press on behalf of European Society of Cardiology 2022.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
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Abstracts > Congenital Heart Disease and Diseases of the Pulmonary Circulation
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