Defining quality standards of care in CTD-PAH and management best practices: a Delphi panel consensus

Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation.

The term pulmonary arterial hypertension (PAH) identifies a heterogeneous group of diseases characterized by a progressive increase in pulmonary arterial resistance (PVR), which causes a significant burden in terms of quality of life, right heart failure and premature death. The pathogenesis of PAH is not completely clear: the remodeling of the small pulmonary vessels is crucial, causing an increase in the resistance of the pulmonary circle. Its diagnosis is based on cardiac catheterization of the right heart. According to the present hemodynamic definition of pulmonary hypertension (PH) proposed by the Guidelines of the European Society of Cardiology/European Respiratory Society (ESC-ERS), the mean pulmonary arterial pressure (mPAP) values are ≥25 mmHg. In case of PAH, apart from an mPAP value ≥25 mmHg, patients must have a >3 Wood units increase in PVR and normal pressure values of the left heart. PH is a pathophysiological condition observed in more than 40 different diseases, while PAH is a primary disease of the pulmonary bloodstream potentially treatable with specific drugs. PAH is a severe complication of systemic sclerosis (SSc) affecting about 10% of the patients. Due to the devastating nature of SSc-PAH, there is a clear need to systematically adopt appropriate screening programs. In fact, despite awareness of the negative impact of SSc-PAH on quality of life and survival, as well as on the severity of lung function, at the moment standardized and shared guidelines and/or screening programs for the diagnosis and the subsequent early treatment of PAH in SSc are not available. The aim of the present paper is to highlight the lights and shadows of SSc-PAH, unraveling the unmet clinical needs on this topic with a proposal of clinical-diagnostic and therapeutic guidelines.

57 - Childhood Pulmonary Arterial Hypertension

Background Doppler echocardiography is the most widespread and well-recognized technique for the screening of patients with pulmonary hypertension (PH). When tricuspid regurgitation peak velocity (TRPV) ≥3.4 m/s, right heart catheterization is requested to confirm mean pulmonary artery pressure >25 mm Hg. In the proceedings from the 6th world symposium on pulmonary arterial hypertension recently released, the new definition of PH has been lowered to mean pulmonary artery pressure > 20 mm Hg. Purpose The purpose of our work was twofold : i) to determine a new cut-off value for TRPV to accommodate the new hemodynamic definition of PH, ii) to investigate the impact on the demand of right heart catheterization (RHC) from our echo CORE lab. Methods We extracted and analyzed both the haemodynamic and echocardiographic records of 130 patients who underwent investigations the same day. Tricuspid regurgitation peak velocity was measured in apical-4 chamber view using continuous-wave doppler modality and compared to mean pulmonary artery pressure recorded from fluid-filled catheter. Results Tricuspid regurgitation peak velocity has a weak correlation with mean pulmonary pressure (y = 9.2x-2.2, r² = 0.22, p < 0.01). Targeting a mean pulmonary pressure on right heart catheterization of 20 mm Hg for the definition of PH, receiver operating characteristic curve analysis demonstrated a good association between TRPV and PH diagnosis (area under the curve, 0.78 ; p < 0.001). The cut-off value obtained for TRPV was 3.0 m/s (Se = 0.78, Sp = 0.37). From 01/01/18 to 31/12/18, 2539 out of 6215 had TRPV recorded from which 283 had TRPV ≥ 3.0 m/s (24,1%) and 615 had TRPV ≥ 3.4 m/s (11,1%). When applied to a community population the new TRPV cutoff > 3m/s used as surrogate for mean pulmonary artery pressure > 20 mm Hg may produce a 111% increase of right heart catheterization demand. Conclusions The new definition of pulmonary hypertension (invasive mean pulmonary artery pressure > 20mm Hg) necessitates revisiting tricuspid regurgitation peak velocity > 3 m/s as a screening test leading to more than twice RHC demand.

Rebuttal From Drs Johnson and Maron

Objectives: In the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, the hemodynamic definition of pulmonary hypertension (PH) was revised to mean pulmonary arterial pressure (mPAP)>20 mmHg (1 mmHg=0.133 kPa) at rest. This study aimed to evaluate the impact of the revised hemodynamic definition on the diagnosis of PH. Methods: Patients with dyspnea or highly suspected PH who underwent right heart catheterization (RHC) in Beijing Anzhen hospital affiliated to Capital Medical University from September 2021 to October 2022 were enrolled retrospectively. According to resting hemodynamics, the patients were divided into 3 groups: no-PH (mPAP≤20 mmHg) group, low-pressure PH (20 mmHg<mPAP<25 mmHg) group and high-pressure PH (mPAP≥25 mmHg) group. The diagnosis and classification of PH and the hemodynamic parameters in different groups were compared before and after the revision of diagnostic criteria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of maximum of mPAP (mPAPmax) and mPAP/cardiac output (CO) slope of multi-point in PH. Results: A total of 117 patients were included for analysis, the age was (53.7±17.5) years, 37 (31.6%) patients were male. According to the 2022 ESC/ERS definition, 99 patients were diagnosed as PH, including 8 patients (6.8%) in the low-pressure PH group and 91 patients (77.8%) in the high-pressure PH group. There were 18 patients (15.4%) in the non-PH group. Comparing to the 2015 ESC/ERS definition, 8 patients were newly diagnosed as PH. Echocardiography indexes pulmonary systolic pressure (sPAP) [(57.6±7.3) vs (38.5±13.6) mmHg], max tricuspid regurgitation velocity (TRVmax) [(360.4±28.9) vs (271.4±52.2) cm/s] and RHC index mPAP [(22.2±1.3) vs (16.1±2.6) mmHg] in low-pressure PH group were higher than those in no-PH group (all P<0.05). However, further analysis of hemodynamics during exercise showed mPAPmax [(42.1±5.6) vs (35.6±4.7) mmHg, P=0.006] and mPAP/CO slope of multi-point [(4.9±1.3) vs (3.6±1.1) mmHg·L-1·min-1,P=0.024] in low-pressure PH group were higher than those in no-PH group. The ROC curve cut-off value of mPAPmax for the diagnosis of PH was 39 mmHg, with a sensitivity of 75.0%, a specificity of 76.5%, and the area under the curve (AUC) and 95%CI is 0.816 (0.638-0.994). The ROC curve cut-off value of mPAP/CO slope of multi-point for the diagnosis of PH was 4.44 mmHg·L-1·min-1,with a sensitivity of 75.0%, a specificity of 76.5%, and an AUC (95%CI) of 0.794 (0.606-0.983). Conclusion: After the revision of the hemodynamic definition of PH in the 2022 ESC/ERS guidelines, more PH patients with pulmonary vascular disease are detected, thereby facilitating early diagnosis and treatment.

Introduction: Pulmonary hypertension (PH) in Idiopathic Pulmonary Fibrosis (IPF) is associated with poor outcomes. The hemodynamic definition of PH was revised from a mean pulmonary artery pressure (mPAP) ≥25 mmHg to &gt;20 mmHg. We sought to explore the implications of these criteria in patients with IPF with a focus on outcomes in those with an elevated mPAP not meeting criteria for Pre- or Post-capillary PH, herein termed Borderline PH. Methods: We identified patients with IPF who underwent chest CT, transthoracic echocardiography (TTE), and right heart catheterization (RHC) using the Mass General Brigham Research Patient Data Repository. Medical records were reviewed to confirm the diagnosis of IPF. Established hemodynamic criteria categorized patients by PH status. Patients with elevated mPAP &gt;20 mmHg not meeting the definition of Pre-capillary PH (PVR ≥3 Wood Units) or Post-capillary PH (PCWP ≥15 mmHg) were defined as Borderline PH. Categorical variables were assessed using Chi-squared, Continuous variables using Wilcoxon Rank-Sum, and transplant-free survival using Kaplan-Meier analysis and Gehan-Breslow-Wilcoxon test. Results: 212 patients were identified: PH Present (n=92), Borderline PH (n=45), and PH Absent (n=75). One year from RHC, transplant-free survival was lower in patients with PH Present (n=37/92, 40%; p = 0.0002) or Borderline PH (n=20/45, 45%; p = 0.009) compared to those without PH (n=49/75, 65%) (Figure 1). Additionally, patients with Borderline PH had lower Pulmonary Artery Pulsatility Index (3.6 (3.0-6.0) vs 6.5 (4.2-10.5); p &lt; 0.001), Pulmonary Artery Compliance (3.9 (3.2-4.6) vs 4.5 (3.4-5.8) mL/mmHg; p = 0.012), and an elevated Right Ventricular Stroke Work Index (9.9 (8.5-11.6) vs 7.3 (5.7-8.7) mmHg*mL/m 2 ; p &lt; 0.001) versus those without PH. Conclusions: In this retrospective study of patients with IPF, those with Borderline PH had lower rates of transplant-free survival and worse derived hemodynamics compared to those without PH.

IntroductionThere is evidence that early screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. We compared the predictive accuracy of two recently published screening algorithms (DETECT 2013 and Australian Scleroderma Interest Group (ASIG) 2012) for SSc-associated PAH (SSc-PAH) with the commonly used European Society of Cardiology/European Respiratory Society (ESC/ERS 2009) guidelines.MethodsWe included 73 consecutive SSc patients with suspected PAH undergoing right heart catheterization (RHC). The three screening models were applied to each patient. For each model, contingency table analysis was used to determine sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for PAH. These properties were also evaluated in an ‘alternate scenario analysis’ in which the prevalence of PAH was set at 10%.ResultsRHC revealed PAH in 27 (36.9%) patients. DETECT and ASIG algorithms performed equally in predicting PAH with sensitivity and NPV of 100%. The ESC/ERS guidelines had sensitivity of 96.3% and NPV of only 91%, missing one case of PAH; these guidelines could not be applied to three patients who had absent tricuspid regurgitant (TR) jet. The ASIG algorithm had the highest specificity (54.5%). With PAH prevalence set at 10%, the NPV of the models was unchanged, but the PPV dropped to less than 20%.ConclusionsIn this cohort, the DETECT and ASIG algorithms out-perform the ESC/ERS guidelines, detecting all patients with PAH. The ESC/ERS guidelines have limitations in the absence of a TR jet. Ultimately, the choice of SSc-PAH screening algorithm will also depend on cost and ease of application.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0517-5) contains supplementary material, which is available to authorized users.

The first clinical classification and hemodynamic definition of pulmonary hypertension (PH) was introduced at a WHO meeting in Geneva in 1973. The diagnostic classification was updated at the world conference in Evian, 1998, introducing 5 clinical groups instead of the original groups of primary and secondary PH. Although changes have been made, the basic structure of this classification was adopted in the following world congresses in Venice 2003 and Dana Point 2008.Since 1973, PH was hemodynamically defined as mean pulmonary arterial pressure (PAP) >25 mmHg at rest or >30 mmHg during exercise. In 2008, the hemodynamic definition was discussed again. The analysis of the published data, based on invasive measurements in healthy individuals, suggested that resting PAP is 14.0±3.3 mmHg and independent of gender and is only mildly influenced by posture and age. During exercise, however, PAP is dependent on exercise level and age. Accordingly, the Dana Point statement defines the normal range of resting mean PAP between 8 and 20 mmHg and PH as resting mean PAP ≥25 mmHg. The exercise part of the old definition of PH was abandoned.

Clinicians should be cognizant of the symptoms and risk factors associated with pulmonary hypertension (PH). While known PH poses significant therapeutic challenges, occult PH carries the added potential for unanticipated complications when treating concurrent medical illnesses. PH may occur with underlying medical conditions and risk factors or may occur de novo as idiopathic pulmonary arterial hypertension (IPAH). Symptoms of PH are frequently attributed to more common conditions, and their nonspecific nature and insidious onset may lead to delay in presentation, evaluation, and diagnosis. Initial symptoms are dyspnea, fatigue, chest pain, and palpitations. Lower extremity edema, presyncope, and syncope are symptoms of more advanced disease. Thorough evaluation of symptoms and identification of patients with risk factors for PH are critical in making a timely diagnosis. History and physical examination can identify patients with suspected PH. Further testing is necessary for definitive diagnosis, classification, assessment of severity, and guiding therapeutic decisions.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials.

Sarcoidosis-associated pulmonary hypertension (SAPH) is a very severe complication of the disease, largely impacting its morbidity and being one of its strongest predictors of mortality. With the recent modifications of the hemodynamic definition of pulmonary hypertension (mean arterial pulmonary pressure >20 instead of <25 mmHg,) its prevalence is presently not precisely known, but it affects from 3 to 20% of sarcoid patients; mostly, although not exclusively, those with an advanced, fibrotic pulmonary disease. Its gold-standard diagnostic tool remains right heart catheterization (RHC). The decision to perform it relies on an expert decision after a non-invasive work-up, in which echocardiography remains the screening tool of choice. The mechanisms underlying SAPH, very often entangled, are crucial to define, as appropriate and personalized therapeutic strategies will aim at targeting the most significant ones. There are no recommendations so far as to the indications and modalities of the medical treatment of SAPH, which is based upon the opinion of a multidisciplinary team of sarcoidosis, pulmonary hypertension and sometimes lung transplant experts.

It is well established that patients with CTDs such as SSc carry a considerable risk of developing pulmonary arterial hypertension (PAH). Such SSc-PAH patients have an even worse prognosis than patients with only one of these two conditions. In view of the high incidence and prevalence of PAH in SSc, and the available treatment options that improve quality of life, exercise capacity and possibly survival, systematic screening has been recommended. The present article reviews current recommendations from PAH guidelines, focusing on studies that used Doppler echocardiography for screening, and describes limitations associated with the procedure. Furthermore, characteristics and parameters used to identify patients at high risk of developing PAH are summarized.

Background:Pulmonary arterial hypertension (PAH) can complicate systemic sclerosis (SSc), representing the leading cause of death in these patients. According to recent epidemiological evidence, about 10% of SSc patients may be...

The new haemodynamic definition of pulmonary hypertension: evidence prevails, finally!