Implication of the new definition of pulmonary hypertension in patients evaluated for heart transplantation

https://doi.org/10.1016/j.ijcard.2023.04.048Get rights and content

Higlights

  • In 2018 6th WSPH changed the definition of pulmonary hypertension to mPAP >20 mmHg instead of 25 mmHg.

  • Using this new definition in 693 patients with chronic heart failure evaluated for heart transplantation, 12.7%, 77.5% and 9.8% were classified as mPAP2025mmHg, mPAP≥ 25mmHg and mPAP20 mmHg, respectively.

  • Patients with a mPAP between 20 and 25 mmHg had significant co-morbidities, and a higher risk of mortality compared with patients with mPAP below 20 mmHg.

  • The new PH definition using mPAP >20 mmHg is associated with a significant risk of mortality.

Abstract

Background

The 2018 World Symposium on Pulmonary Hypertension (WSPH) changed the definition of pulmonary hypertension (PH) with a new threshold of mean pulmonary artery pressure (mPAP) above 20 mmHg.

Objective

To evaluate the profile and prognosis of patients with chronic heart failure (HF) considered for heart transplantation with the new definition of PH.

Methods

Patients with chronic HF considered for heart transplantation were classified as mPAP≤20mmHg, mPAP 2025 mmHg, and mPAP≥25mmHg. Using a multivariate Cox model, we compared the mortality of patients with mPAP2025mmHg, and mPAP≥25mmHg versus those with mPAP≤20mmHg.

Results

Of 693 patients with chronic HF considered for heart transplantation, 12.7%, 77.5% and 9.8% were classified as mPAP2025mmHg, mPAP≥ 25mmHg and mPAP≤20mmHg. Patients of mPAP ≥ 25mmHg and mPAP 2025 mmHg categories were older than mPAP ≤ 20 mmHg (56 versus 55 and 52 year-old, p = 0.02) with more frequent co-morbidities. Within 2.8 years, the mPAP2025mmHg category displayed a higher risk of mortality compared with those of the mPAP≤20mmHg category (aHR 2.75, 95% CI 1.27–5.97, p = 0.01). Overall, the new PH definition using a threshold of mPAP >20 mmHg was associated with a higher risk of death (adj HR 2.71, 95% CI 1.26–5.80) than the previous definition (mPAP >25 mmHg, aHR: 1.35 95% CI 1.00–1.83, p = 0.05).

Conclusions

One out of 8 patients with severe HF are reclassified as having PH following the 2018 WSPH. Patients with mPAP2025 evaluated for heart transplantation displayed significant co-morbidities and high mortality rates.

Graphical abstract

The new definition of pulmonary hypertension in patients with chronic heart failure evaluated for cardiac transplantation.

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Introduction

It is estimated that around 65% of patients with chronic heart failure (HF) develop pulmonary hypertension (PH) [1,2]. Pulmonary hypertension in the setting of chronic HF results from several complex mechanisms, including increased pressure in the left atrium transmitted to the pulmonary circulation, vascular remodeling, arteriolar intimal thickening, and microvascular thrombosis. [3,4]. In the setting of chronic HF, PH has been associated with poor outcomes including increased mortality. As such, screening for pulmonary hypertension is paramount before considering heart transplantation or cardiac assistance [[5], [6], [7], [8]].

From 1973 to 2018, PH was defined by the World Symposium on Pulmonary Hypertension (WSPH) as a mean pulmonary arterial pressure (mPAP) equal or superior to 25 mmHg [9]. Following the study of US Veterans including all indications of right heart catheterization (RHC), the 2018 6th WSPH changed the definition of PH to mPAP >20 mmHg to include patients previously considered as having a borderline PH [10]. This new threshold was implemented by the 2022 guidelines by European Society of Cardiology and the European Respiratory Society guideline [11].

Nonetheless, little is known regarding the implication of this new criteria for PH in a population of severe HF potentially eligible for heart transplant. Our primary hypothesis is that patients with mPAP between 20 and 25 mmHg present a high-risk profile with a high risk of worst outcomes including mortality. Our secondary hypothesis is that the threshold of mPAP >20 mmHg is clinically meaningful in the specific population of patients with severe chronic heart failure evaluated for heart transplantation.

Section snippets

Study design and population

The data supporting the findings of the present study are available from the corresponding author upon reasonable request. The study population consisted of consecutive patients with chronic HF addressed for RHC evaluation for heart transplantation eligibility assessment at the Institut de Cardiologie of the Pitié-Salpêtrière Hospital between January 1ST, 2000 and June 30th, 2020. Patients undergoing RHC for other motives such as chronic constrictive pericarditis, post-heart transplantation

Baseline clinical characteristics

Between January 2000 and June 2020, 782 patients with chronic HF underwent RHC to assess eligibility for heart transplantation, of whom 89 were excluded because of missing data. Among the 693 patients analyzed, 77.5% (n = 537) had mPAP ≥ 25mmHg, 9.8% (n = 68) had mPAP ≤ 20 mmHg, and 12.7% (n = 88) had mPAP 2025 mmHg (flow chart in supplemental appendix). The distribution of mPAP is provided in Fig. 1.

Baseline characteristics according to each category are described in Table 1. Patients of

Discussion

In the present cohort study with a long-term follow-up of patients with severe heart failure assessed for eligibility for heart transplantation, individuals with mPAP between 20 and 25 mmHg have: 1/ frequent co-morbidities such as diabetes, atrial fibrillation, chronic kidney disease and older age; 2/ severe symptoms, high NT-pro BNP and a decreased cardiac output; 3/ frequent pre-capillary PH with elevated pulmonary vascular resistance 4/ have a higher risk of mortality compared with patients

Funding

ACTION study group.

Author contributions

MZ, GM, QM, JS drafted the project, collected the data and established the statistical methods. NP contributed to the methodological and statistical analysis. All the authors contributed to the drafting of the manuscript and the critical review.

Declaration of Competing Interest

Gilles Montalescot reports research grants, funding or consulting fees from Abbott, Amgen, AstraZeneca, Axis, Bayer, BMS, Boehringer-Ingelheim, Boston-Scientific, Cell Prothera, CSL Behring, Idorsia, Leo-Pharma, Lilly, Medtronic, Novartis, Pfizer, Quantum Genomics, Sanofi, Terumo; Michel Zeitouni reports research grants, funding or consulting fees from Fédération Française de Cardiologie, Institut Servier, BMS/Pfizer, AstraZeneca and Amgen; Johanne Silvain reports reports research grants,

Acknowledgements

None.

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