Platts, David G.

Scalia, Gregory M.

Waldie, Anna M.

University of Queensland eSpace

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Incremental value of ePLAR – echocardiographic Pulmonary to Left Atrial
Ratio – in the diagnosis of chronic thromboembolic pulmonary hypertension
Anna M. Waldie, David G. Platts, Gregory M. Scalia
PII: S0167-5273(16)31340-7
DOI: doi: 10.1016/j.ijcard.2016.06.329
Reference: IJCA 22957
To appear in: International Journal of Cardiology
Received date: 19 May 2016
Accepted date: 29 June 2016
Please cite this article as: Waldie Anna M., Platts David G., Scalia Gregory M., In-
cremental value of ePLAR – echocardiographic Pulmonary to Left Atrial Ratio – in
the diagnosis of chronic thromboembolic pulmonary hypertension, International Journal
of Cardiology (2016), doi: 10.1016/j.ijcard.2016.06.329
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Letter to the Editor 
 
Incremental value of ePLAR – echocardiographic Pulmonary to Left 
Atrial Ratio – in the diagnosis of chronic thromboembolic pulmonary 
hypertension  
 
Anna M. Waldie a,  
David G Platts c d  
Gregory M. Scalia a b c d 
a The Wesley Hospital, Brisbane 4066, Australia 
b Heart Care Partners, Brisbane 4066, Australia 
c The University of Queensland, Brisbane 4072, Australia 
d The Prince Charles Hospital, Brisbane Australia 
Keywords: 
 Pulmonary hypertension 
 Echocardiography 
 Pulmonary Embolism 
Corresponding Author: 
Assoc Prof Gregory M Scalia 
30 Chasely St  
Auchenflower QLD AUSTRALIA 4066 
gmscalia@gmail.com 
 
All authors have no conflict of interest. 
  
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Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct 
pulmonary vascular disease characterised by the presence of numerous 
organised occlusive thrombi or emboli in the elastic pulmonary vascular tree 
after at least 3 months of effective anticoagulation [1-4]. CTEPH is 
distinguishable from pulmonary arterial hypertension (PAH) by the 
nonhomogeneous distribution of thrombus within various segments of the 
pulmonary vasculature (main, lobar, segmental, subsegmental) and its 
association with venous thromboembolism (VTE) [3, 5]. CTEPH is progressive 
and carries a poor prognosis when established pulmonary pressures are 
severely elevated, unless amenable to pulmonary thromboendarterectomy 
(PTE) [5, 6].  If left untreated, patients with CTEPH develop irreversible 
disease progression associated with a significant risk of death from right heart 
failure [3, 7]. It is often diagnosed late.  However, early diagnosis allows 
institution of long-term anticoagulant therapy and referral to an appropriate 
pulmonary hypertension centre to initiate timely therapeutic interventions [3]. 
This includes assessment for operability in severe cases of CTEPH by an 
experienced PTE surgeon [4].  
 
Given that CTEPH presents clinically with non-specific symptoms of exertional 
dyspnoea, fatigue, chest pain, and exercise induced syncope, which are 
ubiquitous with other common cardiopulmonary conditions, diagnosis is often 
delayed [8]. More frequently, common conditions are implicated as causal, 
such as left heart disease, which often culminates in post-capillary pulmonary 
hypertension (PHT). Patients with CTEPH have pre-capillary PHT. 
Hemodynamically, obstructed trans-pulmonary flow will yield elevated mean 
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pulmonary artery pressures (PAPmean >25 mmHg) in the setting of normal/low 
left atrial filling pressures (LAP <15 mmHg).  
 
There is therefore significant scope for the implementation of a more readily 
available, less invasive, cost effective test to predict the presence of pre-
capillary PHT, of which CTEPH is a life-threating cause.  The 
echocardiographic Pulmonary to Left Atrial Ratio (ePLAR), has been validated 
as a non-invasive surrogate of trans-pulmonary gradient, and is an effective 
differentiator of pre-capillary from post-capillary PHT [9, 10].  The ePLAR 
(m/s) is calculated from the maximum tricuspid regurgitation continuous-wave 
Doppler velocity (m/s) divided by the trans-mitral E-wave : septal mitral 
annular Doppler Tissue Imaging e’-wave ratio (ePLAR (m/s) = TRVmax (m/s) 
/ E/e’) [9, 10]. Higher ePLAR values reflect increasing trans-pulmonary 
gradient (TPG) consistent with pre-capillary PHT physiology.  Lower ePLAR 
values indicate elevated left heart pressures as the driver for post-capillary 
PHT (see figure 1A). An ePLAR cut-off value of 0.28 m/s has >80% sensitivity 
and specificity for distinguishing pre-capillary from post-capillary PHT [9]. 
 
Any patient with pre-capillary PHT should be evaluated for CTEPH [4]. 
Ventilation perfusion (V/Q) scintigraphy is the preferred screening test for 
chronic pulmonary thromboembolic disease, despite advances in computed 
tomography pulmonary angiography (CTPA) and magnetic resonance 
angiography (MRA) of the lungs [2, 6]. We report 2 cases of CTEPH where 
the diagnosis of pre-capillary PHT initially was initially considered clinically 
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unlikely. The cases demonstrate the incremental value of ePLAR in provoking 
diagnostic workup of pre-capillary causes for PHT, including CTEPH.  
 
Case 1 
A 71-year-old female experiencing progressive exertional dyspnoea 
demonstrated no significant abnormality on standard cardiorespiratory testing 
including spirometry, gas transfer, chest X-ray and high resolution CT. 
Echocardiography showed normal left ventricular size and systolic function 
(EF 60%) with no significant valvular disease and normal left heart filling 
(mitral E/e' 10).  Mild PHT was evident (TRVmax 3.1m/s, RVSP 43mmHg – see 
figure 1A). The ePLAR was elevated at 0.31m/s, consistent with pre-capillary 
PHT physiology.  Despite a normal D-dimer, a V/Q scintigram revealed 
multiple bilateral mismatched defects.  Anticoagulation was instigated and at 
six months, the patient was clinically improved, though all echocardiographic 
parameters were unchanged. CTEPH was diagnosed and long-term 
anticoagulation mandated. 
 
Case 2 
A 43-year-old male presented with decompensated restrictive 
cardiomyopathy. The initial clinical presentation with anasarca, 
breathlessness and anorexia was rapid in onset, possibly coincident with the 
onset of atrial fibrillation.  Urgent echocardiography showed severe global 
systolic left ventricular dysfunction (EF 20%) with severe concentric wall 
thickening.  Doppler displayed markedly elevated filling pressures, and mild 
PHT (TRVmax 3.1m/s, RVSP = 55mmHg).  The ePLAR was elevated at 
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0.44m/s consistent with pre-capillary PHT (see figure 1A).  Initial therapy with 
diuretics and ACE inhibitors, improved his clinical status, with 15kg of fluid 
weight loss.  The rapid resolution of congestive symptoms and signs with 
diuretics rendered obstructive pulmonary vascular symptoms unlikely at that 
time. Formal anticoagulation with rivaroxiban 20mg/d for atrial fibrillation was 
instituted. At 6 month follow up, with stable clinical status, echocardiography 
showed similar left ventricular thickening, systolic dysfunction and left heart 
filling parameters (E/e' 8.3).  Mild PHT persisted (TRVmax = 3.0m/s, RVSP = 
40-44mmHg) and ePLAR remained elevated at 0.36m/s, consistent with pre-
capillary PHT physiology. 
 
Clinical deterioration at 7 months, with progressive breathlessness in the 
absence of recurrent fluid retention, prompted repeat echocardiography. The 
patient remained fully anticoagulated.  Left heart systolic and diastolic function 
was unchanged with the ejection fraction moderately reduced at 36% and 
filling pressures not elevated with mitral E/e' 9. There was worsening of 
pulmonary hemodynamics (TRVmax 3.5m/s, RVSP 61mmHg).  The ePLAR 
remained elevated at 0.39m/s consistent with pre-capillary PHT physiology. 
Dilated main pulmonary arteries with no filling defects or obstruction were 
evident on CT pulmonary angiography. However, V/Q scintigraphy showed 
bilateral mismatched defects – despite compliance with novel anticoagulant 
therapy (see figure 1B).  Heparin and warfarin therapy was commenced. 
 
A small minority of patients with exertional dyspnoea will have pre-capillary 
PHT as their fundamental hemodynamic disturbance. Aetiologies within this 
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group include PAH, connective tissue disease, parenchymal lung disease and 
a very small subset will have CTEPH [9]. Patients with pre-capillary PHT will 
undergo a standardised testing sequence including V/Q scintigraphy, which if 
suggestive of CTEPH, will lead to lifelong anticoagulation with significant 
prognostic advantage and possibly PTE surgery [3, 7]. However, because of 
the subtlety of presenting symptoms and frequently, the absence of any 
discernible acute pulmonary embolic event, the diagnosis of CTEPH is easily 
overlooked. Echocardiography is commonly used in the clinical workup of 
exertional breathlessness. These cases demonstrate the incremental value of 
ePLAR in prompting clinical consideration of causes of pre-capillary 
pulmonary hypertension, such as CTEPH.  
 
 
 
 
 
References: 
[1] Lang I. Chronic thromboembolic pulmonary hypertension: a distinct disease 
entity. European Respiratory Review. 2015;24:246-52. 
[2] Tunariu N, Gibbs SJR, Win Z, Gin-Sing W, Graham A, Gishen P, et al. 
Ventilation-Perfusion Scintigraphy Is More Sensitive than Multidetector CTPA in 
Detecting Chronic Thromboembolic Pulmonary Disease as a Treatable Cause of 
Pulmonary Hypertension. The Journal of Nuclear Medicine. 2007;48:680-4. 
[3] Piazza G, Goldhaber SZ. Chronic Thromboembolic Pulmonary Hypertension. 
The New England Journal of Medicine. 2011;364:351-60. 
[4] Wilkens H, Lang I, Behr J, Berghaus T, Grohe C, Guth S, et al. Chronic 
thromboembolic pulmonary hypertension (CTEPH): updated Recommendations 
of the Cologne Consensus Conference 2011. International journal of cardiology. 
2011;154 Suppl 1:S54-S60. 
[5] Lang IM, Madani M. Update on Chronic Thromboembolic Pulmonary 
Hypertension. Circulation. 2014;130:508-18. 
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[6] Kim NH, Delcroix M, Jenkins DP, Channick R, Dartevelle P, Jansa P, et al. 
Chronic thromboembolic pulmonary hypertension. Journal of the American 
College of Cardiology. 2013;62:D92. 
[7] Ross MH, Pawlina W. Histology: a text and atlas : with correlated cell and 
molecular biology. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins 
Health; 2011. 
[8] Klok FA, Surie S, Kempf T, Eikenboom J, van Straalen JP, van Kralingen KW, et 
al. A simple non-invasive diagnostic algorithm for ruling out chronic 
thromboembolic pulmonary hypertension in patients after acute pulmonary 
embolism. Thrombosis Research. 2011;128:21-6. 
[9] Scalia GM, Scalia IG, Kierle R, Beaumont R, Cross DB, Feenstra J, et al. ePLAR - 
The echocardiographic pulmonary to left atrial ratio - a novel non-invasive 
parameter to differentiate pre-capillary and post-capillary pulmonary 
hypertension. International Journal of Cardiology.212:379-86. 
[10] Waldie AM, Eliadis PE, Fraser JF, Little SG, Scalia IG, Scalia GM. Acute life-
threatening reversible pulmonary vasoconstrictive reaction to bleomycin 
chemotherapy demonstrating the clinical application of ePLAR &#x2013; 
echocardiographic Pulmonary to Left Atrial Ratio. International Journal of 
Cardiology. 2016;215:438-40. 
 
 
 
Figure 1. A. Box and whisker display of distribution of ePLAR values for patients 
with pre-capillary PHT (0.44±0.22 m/s) and post-capillary PHT (0.20±0.11 m/s) 
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– boxes represent middle quartiles and whiskers represent range, LAP = left 
atrial pressure, TPG = trans-pulmonary gradient.  In that data, an optimal ePLAR 
cut-off value of 0.28 m/s yielded >80% sensitivity and specificity for 
differentiating pre-capillary from post-capillary PHT (modified and reproduced 
with permission [9]).  Case 1 and case 2 demonstrate ePLAR values of 0.31 m/s 
and 0.44 m/s respectively, both of which fall within the pre-capillary PHT range. 
ePLAR (m/s) = peak tricuspid regurgitation continuous-wave Doppler velocity 
(m/s) divided by the trans-mitral peak pulsed-wave Doppler E-wave (cm/s) : 
peak Doppler Tissue Imaging mitral septal annular e’-wave (cm/s). B. 
Ventilation/perfusion scintigraphy of case 2 demonstrating bilateral mismatch 
perfusion defects (arrows) after >3 months of anticoagulation consistent with 
multiple chronic pulmonary emboli – CTEPH.  


Incremental value of ePLAR – echocardiographic Pulmonary to Left Atrial Ratio – in the diagnosis of chronic thromboembolic pulmonary hypertension

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