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Background: The 2022 European Society of Cardiology/European Respiratory Society pulmonary hypertension (PH) guidelines incorporate cardiac magnetic resonance (CMR) imaging metrics in the risk stratification of patients with pulmonary arterial hypertension (PAH). Thresholds to identify patients at estimated 1-year mortality risks of < 5%, 5% to 20%, and > 20% are introduced. However, these cutoff values are mostly single center-based and require external validation., Research Question: What are the discriminative prognostic properties of the current CMR risk thresholds stratifying patients with PAH?, Study Design and Methods: We analyzed data from incident, treatment-naïve patients with PAH from the Amsterdam University Medical Centres, Vrije Universiteit, The Netherlands. The discriminative properties of the proposed CMR three risk strata were tested at baseline and first reassessment, using the following PH guideline variables: right ventricular ejection fraction, indexed right ventricular end-systolic volume, and indexed left ventricular stroke volume., Results: A total of 258 patients with PAH diagnosed between 2001 and 2022 fulfilled the study criteria and were included in this study. Of these, 172 had follow-up CMR imaging after 3 months to 1.5 years. According to the CMR three risk strata, most patients were classified at intermediate risk (n = 115 [45%]) upon diagnosis. Only 29 (11%) of patients with PAH were classified at low risk, and 114 (44%) were classified at high risk. Poor survival discrimination was seen between risk groups. Appropriate survival discrimination was seen at first reassessment., Interpretation: Risk stratifying patients with PAH with the recent proposed CMR cutoffs from the European Society of Cardiology/European Respiratory Society 2022 PH guidelines requires adjustment because post-processing consensus is lacking and general applicability is limited. Risk assessment at follow-up yielded better survival discrimination, emphasizing the importance of the individual treatment response., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: H. J. B. and A. V. N. were supported by research grants from Actelion, GSK, and Ferrer (Therabel). None declared (L. R. C., J. N. W., J. T. M., L. J. M., F. S. d. M.)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The right ventricle plays a pivotal role in patients with pulmonary hypertension (PH). Its adaptation to pressure overload determines a patient's functional status as well as survival. In a healthy situation, the right ventricle is part of a low pressure, high compliance system. It is built to accommodate changes in preload, but not very well suited for dealing with pressure overload. In PH, right ventricular (RV) contractility must increase to maintain cardiac output. In other words, the balance between the degree of RV contractility and afterload determines stroke volume. Hypertrophy is one of the major hallmarks of RV adaptation, but it may cause stiffening of the ventricle in addition to intrinsic changes to the RV myocardium. Ventricular filling becomes more difficult for which the right atrium tries to compensate through increased stroke work. Interaction of RV diastolic stiffness and right atrial (RA) function determines RV filling, but also causes vena cava backflow. Assessment of RV and RA function is critical in the evaluation of patient status. In recent guidelines, this is acknowledged by incorporating additional RV parameters in the risk stratification in PH. Several conventional parameters of RV and RA function have been part of risk stratification for many years. Understanding the pathophysiology of RV failure and the interactions with the pulmonary circulation and right atrium requires consideration of the unique RV anatomy. This review will therefore describe normal RV structure and function and changes that occur during adaptation to increased afterload. Consequences of a failing right ventricle and its implications for RA function will be discussed. Subsequently, we will describe RV and RA assessment in clinical practice., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: A 45% threshold of right ventricular ejection fraction (RVEF) is proposed clinically relevant in patients with pulmonary arterial hypertension (PAH). We aim to determine treatment response, long-term right ventricular (RV) functional stability and prognosis of patients with PAH reaching or maintaining the RVEF 45% threshold., Methods: Incident, treatment-naive, adult PAH patients with cardiac magnetic resonance imaging at baseline and first follow-up were included (total N=127) and followed until date of censoring or death/lung transplantation. Patients were categorised into two groups based on 45% RVEF. Baseline predictors, treatment response and prognosis were assessed with logistic regression analyses, two-way analysis of variance and log-rank tests., Results: Patients were 50±17 years old, 73% female, of which N=75 reached or maintained the 45% RVEF threshold at follow-up (RVEF≥45%@FU), while N=52 patients did not (RVEF<45%@FU). RV end-diastolic volume and N-terminal pro-B-type natriuretic peptide at baseline were multivariable predictors of an RVEF ≥45% at follow-up. A 40% pulmonary vascular resistance (PVR) reduction resulted in greater improvement in RV function (ΔRVEF 17±11 vs. 5±8; p interaction <0.001) compared to a PVR reduction <40%, but did not guarantee an RVEF ≥45%. Finally, the 45% RVEF threshold was associated with stable RV function during long-term follow-up and better survival (HR: 1.91 (95% CI: 1.11 to 3.27)). Patients failing to reach or maintain the 45% RVEF threshold at first follow-up mostly stayed below this threshold over the next consecutive visits., Conclusion: After treatment initiation, 60% of patients with PAH reach or maintain the 45% RVEF threshold, which is associated with a long-term stable RV function and favourable prognosis., Competing Interests: Competing interests: HJB and AVN were supported by research grants from Actelion, GSK and Ferrer (Therabel). The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Surgical removal of thromboembolic material by pulmonary endarterectomy (PEA) leads within months to the improvement of right ventricular (RV) function in the majority of patients with chronic thromboembolic pulmonary hypertension. However, RV mass does not always normalize. It is unknown whether incomplete reversal of RV remodeling results from extracellular matrix expansion (diffuse interstitial fibrosis) or cellular hypertrophy, and whether residual RV remodeling relates to altered diastolic function., Methods: We prospectively included 25 patients with chronic thromboembolic pulmonary hypertension treated with PEA. Structured follow-up measurements were performed before, and 6 and 18 months after PEA. With single beat pressure-volume loop analyses, we determined RV end-systolic elastance (Ees), arterial elastance (Ea), RV-arterial coupling (Ees/Ea), and RV end-diastolic elastance (stiffness, Eed). The extracellular volume fraction of the RV free wall was measured by cardiac magnetic resonance imaging and used to separate the myocardium into cellular and matrix volume. Circulating collagen biomarkers were analyzed to determine the contribution of collagen metabolism., Results: RV mass significantly decreased from 43±15 to 27±11g/m 2 (-15.9 g/m 2 [95% CI, -21.4 to -10.5]; P <0.0001) 6 months after PEA but did not normalize (28±9 versus 22±6 g/m 2 in healthy controls [95% CI, 2.1 to 9.8]; P <0.01). On the contrary, Eed normalized after PEA. Extracellular volume fraction in the right ventricular free wall increased after PEA from 31.0±3.8 to 33.6±3.5% (3.6% [95% CI, 1.2-6.1]; P =0.013) as a result of a larger reduction in cellular volume than in matrix volume ( P interaction =0.0013). Levels of MMP-1 (matrix metalloproteinase-1), TIMP-1 (tissue inhibitor of metalloproteinase-1), and TGF-β (transforming growth factor-β) were elevated at baseline and remained elevated post-PEA., Conclusions: Although cellular hypertrophy regresses and diastolic stiffness normalizes after PEA, a relative increase in extracellular volume remains. Incomplete regression of diffuse RV interstitial fibrosis after PEA is accompanied by elevated levels of circulating collagen biomarkers, suggestive of active collagen turnover., Competing Interests: Disclosures All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this article.

Background: Pulmonary arterial hypertension (PAH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. This study assessed the impact of RV diastolic stiffness on RA-RV interaction., Methods: PAH patients with low or high end-diastolic elastance (E ed ) (n=94) were compared with controls (n=31). Treatment response was evaluated in 62 patients. RV and RA longitudinal strain, RA emptying and RV filling were determined and diastole was divided into a passive and active phase. Vena cava backflow was calculated as RA active emptying-RV active filling and RA stroke work as RA active emptying×RV end-diastolic pressure., Results: With increased E ed , RA and RV passive strain were reduced while active strain was preserved. In comparison to controls, patients had lower RV passive filling but higher RA active emptying and RA stroke work. RV active filling was lower in patients with high E ed , resulting in higher vena cava backflow. Upon treatment, E ed was reduced in ~50% of the patients with high E ed , which coincided with larger reductions in afterload, RV mass and vena cava backflow and greater improvements in RV active filling and stroke volume in comparison with patients in whom E ed remained high., Conclusions: In PAH, RA function is associated with changes in RV function. Despite increased RA stroke work, severe RV diastolic stiffness is associated with reduced RV active filling and increased vena cava backflow. In 50% of patients with high baseline E ed , diastolic stiffness remained high, despite treatment. A reduction in E ed coincided with a large reduction in afterload, increased RV active filling and decreased vena cava backflow., Competing Interests: Conflict of interest: J.N. Wessels has nothing to disclose. Conflict of interest: S.A. Mouratoglou has nothing to disclose. Conflict of interest: J. van Wezenbeek has nothing to disclose. Conflict of interest: M.L. Handoko has nothing to disclose. Conflict of interest: J.T. Marcus has nothing to disclose. Conflict of interest: L.J. Meijboom has nothing to disclose. Conflict of interest: B.E. Westerhof has nothing to disclose. Conflict of interest: H.J. Bogaard was supported by research grants from Actelion, GSK and Ferrer (Therabel). Conflict of interest: G.J. Strijkers has nothing to disclose. Conflict of interest: A. Vonk Noordegraaf was supported by research grants from Actelion, GSK and Ferrer (Therabel). Conflict of interest: F.S. de Man has nothing to disclose., (Copyright ©The authors 2022.)