The Oracle of the Auricle?

FOR RELATED ARTICLE, SEE PAGE 669Echocardiography is an important tool in the diagnosis of pulmonary hypertension and the assessment of right heart morphologic condition and function.1Raymond R.J. Hinderliter A.L. Willis P.W. et al.Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension.J Am Coll Cardiol. 2002; 39: 1214-1219Crossref PubMed Scopus (664) Google Scholar, 2Wright L. Dwyer N. Wahi S. Marwick T.H. Relative importance of baseline and longitudinal evaluation in the follow-up of vasodilator therapy in pulmonary arterial hypertension.JACC Cardiovasc Imaging. 2019; 12: 2103-2111Crossref PubMed Scopus (13) Google Scholar, 3Shelburne N.J. Parikh K.S. Chiswell K. et al.Echocardiographic assessment of right ventricular function and response to therapy in pulmonary arterial hypertension.Am J Cardiol. 2019; 124: 1298-1304Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar However, the incorporation of echocardiographic parameters in pulmonary arterial hypertension (PAH) risk stratification tools that were developed with the use of large multicenter registries has been limited by the absence of sufficient echocardiographic data. The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) tool incorporates only the presence or absence of pericardial effusion; the European Society of Cardiology/European Respiratory Society guidelines incorporate right atrial size and the presence or absence of a pericardial effusion.4Galiè N. Humbert M. Vachiery J.L. et al.2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46: 903-975Crossref PubMed Scopus (2175) Google Scholar,5Benza R.L. Gomberg-Maitland M. Elliott C.G. et al.Predicting survival in patients with pulmonary arterial hypertension: the REVEAL risk score calculator 2.0 and comparison with ESC/ERS-based risk assessment strategies.Chest. 2019; 156: 323-337Abstract Full Text Full Text PDF PubMed Scopus (329) Google Scholar In this issue of CHEST, Shah et al6Shah T. Manthena P. Patel C. et al.Prognostic value of echocardiographic variables prior to and following initiation of parenteral prostacyclin therapy: an observational study.Chest. 2022; 162: 669-683Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar used predominantly nonquantitative data from echocardiograms that were performed before and after the initiation of prostacyclin therapy to identify parameters most closely associated with survival both at baseline and at follow up. Predictors that were associated with survival from the initiation of parenteral therapy included walk distance, N-terminal B-type natriuretic peptide, mixed venous oxygen saturation, pericardial effusion, and trends for qualitative right atrial (RA) size and right ventricular (RV) function. It is noteworthy that the strongest predictors of survival were those measured at first follow up, underscoring the critical nature of meticulous reassessment of risk. Factors most strongly associated with outcome from first follow up included qualitative RA size, RV dimension, tricuspid regurgitant severity, and inferior vena cava assessment. It is interesting that qualitative RA size performed somewhat better than RV size and qualitative measures of RV function at predicting outcome from first follow-up. It is also interesting that there was no significant change in qualitative RA size across the entire cohort, with as many subjects showing increase in RA size as those showing decrease. This suggests that RA size may be well-positioned to monitor response to parenteral prostacyclin therapy and that persistently severe or worsening RA dilation should prompt careful consideration of overall patient compensation. The present study did not address the relationship of RA size to other parameters, which could contribute to remodeling of the RA (such as RA pressure or degree of tricuspid regurgitation), which previously has been associated with both RA dilation and clinical outcomes,7Chen L. Larsen C.M. Le R.J. et al.The prognostic significance of tricuspid valve regurgitation in pulmonary arterial hypertension.Clin Respir J. 2018; 12: 1572-1580Crossref PubMed Scopus (27) Google Scholar or could identify other variables that may mediate the interaction between RA size and survival (such as the presence of atrial arrythmias).8Smith B. Genuardi M.V. Koczo A. et al.Atrial arrhythmias are associated with increased mortality in pulmonary arterial hypertension.Pulm Circ. 2018; 82045894018790316Crossref PubMed Scopus (18) Google Scholar FOR RELATED ARTICLE, SEE PAGE 669 A major limitation of the present study is that it includes only qualitative measures of RA size and RV function. This precludes analysis of which quantitative measures of RA and RV size and function, widely used in current practice, are associated most strongly with outcomes. Current echocardiography guidelines recommend quantitative measurement of RA and RV size and RV function such as fractional area change, tricuspid annular plane systolic excursion (TAPSE) and RV strain as well as assessments of tricuspid regurgitation, RV systolic pressure, and RA pressure.9Rudski L.G. Lai W.W. Afilalo J. et al.Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography.J Am Soc Echocardiogr. 2010; 23: 685-713Abstract Full Text Full Text PDF PubMed Scopus (5113) Google Scholar,10Mitchell C. Rahko P.S. Blauwet L.A. et al.Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: recommendations from the American Society of Echocardiography.J Am Soc Echocardiogr. 2019; 32: 1-64Abstract Full Text Full Text PDF PubMed Scopus (865) Google Scholar As well-summarized in eTable 1 of the article, multiple studies have advanced the field of PAH risk stratification by more extensively characterizing right heart morphologic condition and function. Prior work that included serial quantitative measures of RA size and RV size and function demonstrated that follow-up TAPSE ≥ 2 cm strongly predicted survival; this was accompanied by a significant reduction in RA dimension (4.8 to 4.3 cm), although there was no change in those results with TAPSE < 2 cm at follow up.11Mazurek J. Vaidya A. Mathai S.C. et al.Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension.Pulm Circ. 2017; 7: 361-371Crossref PubMed Scopus (44) Google Scholar Those individuals who achieved TAPSE > 2 cm had slight numeric improvement in RA area index compared with those individuals who did not achieve TAPSE > 2 cm. When quantitative measures of RV function are available, RA dimension is not usually an independent predictor of outcome. RA function as measured by longitudinal strain has also been examined.12Hasselberg N. Kagiyama N. Soyama Y. et al.The prognostic value of right atrial strain imaging in patients with precapillary pulmonary hypertension.J Am Soc Echo. 2021; 34: 851-861Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar There was a modest association between RA size and RA strain, which demonstrated that patients with severe RA enlargement tend to have severely impaired RA strain. RV global strain, RA area, RA strain, and pericardial effusion were associated with a 5-year mortality rate; on multivariate analysis only, RA strain remained associated independently with a 5-year mortality rate. Changes in RV free wall strain have also been shown to predict outcome in PAH. It is likely that incorporation of these quantitative measures of RA and RV function in the current study would have impacted variable selection for the models presented. Similarly, it is not possible, based on the current study, to determine whether subjective assessment of size or quantitative metrics of RA diameter, area, or volume is the optimal way to describe changes in RA size. However, quantitative measures should be superior for generalizability and tracking change over time. It also seems more intuitive to react to impairment or changes in RV function than to parameters of RA size; however, ultimately, it is performance in predicting outcome that counts. It is also to be noted that serial measures of multiple metrics of right heart morphologic condition and function seems optimal to provide a more complete picture than reliance on directional change in single parameters. Despite these limitations, the present study is an important reminder that the concern in PAH is not only the right ventricle, but the right heart as a unit. The association of RA size at follow up to patient death supports the notion that the RA is an upstream indicator that is related to several important physiologic measures such as RA and RV systolic and diastolic function, tricuspid valve regurgitation, and central venous pressure. For patients with PAH, the right heart is a critical marker of disease severity and predictor of clinical outcomes. As demonstrated by the present study, there is significant variability in the response of the right heart to PAH treatment that contributes significantly to observed variability in outcomes. There remains a need for the identification of patient-specific factors that would allow a more personalized approach to therapy with the goal of increasing the number of patients who respond to initial treatment strategy and allow earlier referral for advanced therapies, such as transplantation, for those individuals who are unlikely to respond to maximal combination therapy. As we continue to optimize clinical assessment of patients with PAH, the results of the current study support being mindful of the right atrium as we consider the overall state of the right heart and its responsiveness to treatment. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. J. S. reports research funding from Bayer; R. P. F. reports consulting, advisory board, and steering committee relationships with Altavant Sciences, Bayer, Gossamer Bio, Janssen, Tenax, ShouTi, Liquidia, United Therapeutics and UptoDate. Prognostic Value of Echocardiographic Variables Prior to and Following Initiation of Parenteral Prostacyclin Therapy: An Observational StudyCHESTVol. 162Issue 3PreviewEchocardiographic variables improved following IV/SC therapy, and multiple echocardiographic measures associated significantly with survival, particularly when reassessed after at least 90 days of therapy. RA size in particular may be useful in prognostication in follow-up of patients with PAH on IV/SC therapy. Full-Text PDF