Long-term Survival and Quality of Life

Abstract

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) causes significant morbidity and mortality, but long-term outcomes from contemporary multicenter studies are lacking.Research QuestionHow are survival and health-related quality of life characterized in patients with CTEPH who are classified as inoperable, who are operable but have not undergone surgery, and who have undergone surgery including pulmonary thromboendarterectomy?Study Design and MethodsPatients with CTEPH recruited from 30 US sites from 2015 through 2018 completed the 36-item Short Form Health Survey (SF-36) and EmPHasis-10 survey at baseline and 6-month intervals. Mixed model repeated measures analysis was used to compare between-group differences in score up to 2 years vs baseline. Multivariable Cox proportional hazards models were used to analyze survival by CTEPH group.ResultsSeven hundred fifty patients with a median age of 59 years were enrolled; 566 patients, 88 patients, and 96 patients were in the operated, operable but no surgery, and inoperable groups, respectively. Survival at 1, 2, and 3 years was 93%, 91%, and 87%, respectively. Patients in the inoperable and the operable but no surgery groups showed higher mortality rates relative to the operated group (hazard ratios, 2.10 [95% CI, 1.17-3.77] and 2.19 [95% CI, 1.20-3.99], respectively). The EmPHasis-10 and both SF-36 scores improved during follow-up, with larger increases for the operated group (P < .05, unadjusted and adjusted vs inoperable and operable but no surgery groups at all time points up to 2 years for the SF-36 physical component score and EmPHasis-10 and at some time points for the SF-36 mental component score).InterpretationBetter survival and quality-of-life outcomes were observed in patients undergoing pulmonary thromboendarterectomy. Chronic thromboembolic pulmonary hypertension (CTEPH) causes significant morbidity and mortality, but long-term outcomes from contemporary multicenter studies are lacking. How are survival and health-related quality of life characterized in patients with CTEPH who are classified as inoperable, who are operable but have not undergone surgery, and who have undergone surgery including pulmonary thromboendarterectomy? Patients with CTEPH recruited from 30 US sites from 2015 through 2018 completed the 36-item Short Form Health Survey (SF-36) and EmPHasis-10 survey at baseline and 6-month intervals. Mixed model repeated measures analysis was used to compare between-group differences in score up to 2 years vs baseline. Multivariable Cox proportional hazards models were used to analyze survival by CTEPH group. Seven hundred fifty patients with a median age of 59 years were enrolled; 566 patients, 88 patients, and 96 patients were in the operated, operable but no surgery, and inoperable groups, respectively. Survival at 1, 2, and 3 years was 93%, 91%, and 87%, respectively. Patients in the inoperable and the operable but no surgery groups showed higher mortality rates relative to the operated group (hazard ratios, 2.10 [95% CI, 1.17-3.77] and 2.19 [95% CI, 1.20-3.99], respectively). The EmPHasis-10 and both SF-36 scores improved during follow-up, with larger increases for the operated group (P < .05, unadjusted and adjusted vs inoperable and operable but no surgery groups at all time points up to 2 years for the SF-36 physical component score and EmPHasis-10 and at some time points for the SF-36 mental component score). Better survival and quality-of-life outcomes were observed in patients undergoing pulmonary thromboendarterectomy. Take-home PointStudy Question: Do differences exist in long-term outcomes, including survival and quality of life, for patients with chronic thromboembolic pulmonary hypertension (CTEPH) classified as inoperable, operable but no surgery, and operated and underwent pulmonary thromboendarterectomy (PTE)?Results: Scores for the EmPHasis-10 and both 36-item Short Form Health Survey scores improved during follow-up, with larger increases for patients with CTEPH in the operated group vs the inoperable and operable but no surgery groups, whereas survival at up to 4 years of follow-up also was highest in patients with CTEPH undergoing PTE surgery.Interpretation: Better survival and quality-of-life outcomes were observed in patients undergoing PTE surgery relative to both patients classified as operable who did not undergo surgery and to those classified as inoperable. Study Question: Do differences exist in long-term outcomes, including survival and quality of life, for patients with chronic thromboembolic pulmonary hypertension (CTEPH) classified as inoperable, operable but no surgery, and operated and underwent pulmonary thromboendarterectomy (PTE)? Results: Scores for the EmPHasis-10 and both 36-item Short Form Health Survey scores improved during follow-up, with larger increases for patients with CTEPH in the operated group vs the inoperable and operable but no surgery groups, whereas survival at up to 4 years of follow-up also was highest in patients with CTEPH undergoing PTE surgery. Interpretation: Better survival and quality-of-life outcomes were observed in patients undergoing PTE surgery relative to both patients classified as operable who did not undergo surgery and to those classified as inoperable. Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when organized thromboemboli obstruct the pulmonary vascular bed, leading to dyspnea and fatigue and potentially to right heart failure and death. Current treatment of CTEPH includes pulmonary thromboendarterectomy (PTE), generally preferred when clot location and patient characteristics are favorable1Quadery S.R. Swift A.J. Billings C.G. et al.The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.Eur Respir J. 2018; 52Crossref PubMed Scopus (60) Google Scholar, 2Delcroix M. Lang I. Pepke-Zaba J. et al.Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry.Circulation. 2016; 133: 859-871Crossref PubMed Scopus (424) Google Scholar, 3Hobohm L. Keller K. Munzel T. Konstantinides S.V. Lankeit M. Time trends of pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension.Pulm Circ. 2021; 1120458940211008069Crossref Scopus (5) Google Scholar, 4Condliffe R. Kiely D.G. Gibbs J.S. et al.Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension.Am J Respir Crit Care Med. 2008; 177: 1122-1127Crossref PubMed Scopus (339) Google Scholar; balloon pulmonary angioplasty (BPA)5Mahmud E. Patel M.P. Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.Circ Cardiovasc Interv. 2018; 11e007462Crossref Scopus (0) Google Scholar; medical therapies6Ghofrani H.A. D’Armini A.M. Grimminger F. et al.Riociguat for the treatment of chronic thromboembolic pulmonary hypertension.N Engl J Med. 2013; 369: 319-329Crossref PubMed Scopus (985) Google Scholar; and long-term anticoagulation. Although improvements in outcomes of patients with CTEPH after PTE have been documented,3Hobohm L. Keller K. Munzel T. Konstantinides S.V. Lankeit M. Time trends of pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension.Pulm Circ. 2021; 1120458940211008069Crossref Scopus (5) Google Scholar,7Madani M.M. Auger W.R. Pretorius V. et al.Pulmonary endarterectomy: recent changes in a single institution’s experience of more than 2,700 patients.Ann Thorac Surg. 2012; 94 (discussion 103): 97-103Abstract Full Text Full Text PDF PubMed Scopus (414) Google Scholar,8Kerr K.M. Elliott C.G. Chin K. et al.Results from the United States Chronic Thromboembolic Pulmonary Hypertension Registry: enrollment characteristics and 1-year follow-up.Chest. 2021; 160: 1822-1831Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar contemporary multicenter outcome data from studies in the United States are not available. In addition, serial assessment of patient-reported symptoms and health-related quality of life is very limited, despite the importance of these end points as outcome measures of medical and surgical interventions for CTEPH.9McGoon M.D. Ferrari P. Armstrong I. et al.The importance of patient perspectives in pulmonary hypertension.Eur Respir J. 2019; 53Crossref Scopus (73) Google Scholar The United States Chronic Thromboembolic Pulmonary Hypertension Registry was organized to provide contemporary outcomes data for patients with CTEPH who received a diagnosis and were treated at 30 US pulmonary hypertension (PH) centers. The objective of the current analyses was to evaluate and compare long-term outcomes for symptoms, health-related quality of life, hospitalizations, and survival across three subgroups of patients with CTEPH: those who underwent PTE surgery during the study period (operated group), those were eligible for but had not undergone surgery (operable but no surgery group), and those who were not eligible for surgery (inoperable group). The United States Chronic Thromboembolic Pulmonary Hypertension Registry is a multicenter, prospective, longitudinal cohort study of patients with newly diagnosed CTEPH. The University of California, San Diego, is the sponsor and coordinating institution for the study, approved by the University of California, San Diego, Human Research Protection Program (Project no. 141379). Thirty US sites participated. Enrollment was from April 2015 through March 2018, with follow-up until March 2019. Consecutive patients with a diagnosis of CTEPH received within 6 months of consent and meeting the inclusion criteria were offered participation in the study. Patients had precapillary PH diagnosed by right heart catheterization (mean pulmonary arterial pressure [mPAP] of ≥ 25 mm Hg, pulmonary arterial wedge pressure of ≤ 15 mm Hg or > 15 mm Hg if justified by the investigator) and showed evidence of CTEPH on imaging that was reviewed for eligibility by an adjudication team. Patients were classified by the enrolling center as having operable or inoperable CTEPH, and if inoperable, the reasons for this classification. Details have been published previously.8Kerr K.M. Elliott C.G. Chin K. et al.Results from the United States Chronic Thromboembolic Pulmonary Hypertension Registry: enrollment characteristics and 1-year follow-up.Chest. 2021; 160: 1822-1831Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Patients were subdivided further into three groups: operated (patients undergoing PTE surgery during the study period), operable but no surgery (patients classified as operable who did not undergo surgery), and inoperable. Patients completed the Rand version of the 36-item Short-Form Health Survey (SF-36) and EmPHasis-10 at baseline and at 6-month intervals after enrolment. The SF-36 is a 36-item patient-reported survey of general health that has had good reliability and validity across many patient populations and settings.10Frendl D.M. Ware Jr., J.E. Patient-reported functional health and well-being outcomes with drug therapy: a systematic review of randomized trials using the SF-36 health survey.Med Care. 2014; 52: 439-445Crossref PubMed Scopus (78) Google Scholar, 11Mathai S.C. Suber T. Khair R.M. Kolb T.M. Damico R.L. Hassoun P.M. Health-related quality of life and survival in pulmonary arterial hypertension.Ann Am Thorac Soc. 2016; 13: 31-39Crossref PubMed Scopus (53) Google Scholar, 12Sanders J. Bowden T. Woolfe-Loftus N. Sekhon M. Aitken L.M. Predictors of health-related quality of life after cardiac surgery: a systematic review.Health Qual Life Outcomes. 2022; 20: 79Crossref Scopus (5) Google Scholar The EmPHasis-10 is a 10-item disease-specific questionnaire developed to assess symptoms of PH; it has good internal and test-test reliability and was developed and validated in patients with pulmonary arterial hypertension and CTEPH.13Yorke J. Corris P. Gaine S. et al.emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension.Eur Respir J. 2013; Google Scholar Scores for the SF-36 physical component score (PCS) and mental component score (MCS) were calculated using standard methodology with a potential range from to the general is for with higher scores to health-related quality of Scores for the EmPHasis-10 range from to with scores to analysis was for and were for and a was for the three groups, a was for and a for the group were (P < a and were for the between-group for was for using a for of were calculated as an for PTE surgery or Survival analysis outcome was using from the of consent up to months of follow-up for the group and after by median age and by with for the by median age and were studies have differences in outcomes by and in age groups, than R.L. M. Elliott C.G. et survival in patients with pulmonary arterial hypertension: the and with assessment 2019; Full Text Full Text PDF Scopus Google Scholar Patients were for or at study for those the months of Cox proportional hazards models were with a significant of in the analyses were as the as the vs Health functional and Health and as or ≤ 30 as vs > 30 right cardiac and pulmonary vascular unadjusted Cox proportional hazards model with group in the model (operated group as the was completed with three model adjusted for and model adjusted for of right and cardiac on in the with survival in with and arterial of with and inclusion of all that were significant (P < in the the SF-36 SF-36 and EmPHasis-10 outcomes, analysis was for the scores and scores from baseline at study (mean with were for scores and scores from baseline by group and and in an were after by median analysis was the of patients with an in scores to or more than the for these using a in score of ≥ for the SF-36 and SF-36 and ≤ for the S.C. The in the for patients with pulmonary arterial hypertension.Am J Respir Crit Care Med. 2012; PubMed Scopus Google M. T. et as a measure of health-related quality of life in pulmonary arterial hypertension: data from Respir J. 2021; Scopus Google Scholar and were calculated (P from the Mixed model repeated measures analyses were for the SF-36 SF-36 and EmPHasis-10 The for model includes the patients who had baseline outcome and at follow-up in the model were the scores of the outcomes from baseline at months and in the model were baseline outcome and of was as a for for was in the was < The of that were adjusted for in the models were the in the survival as Patient-reported outcome scores also were after by median of the of PH medical and on results were not of the of relative to survey analyses were using version for of patients with CTEPH were from 30 PH in the United age was 59 and the cohort was patients were classified as operated underwent 566 inoperable 96 and operable but no surgery 88 patients were and had rates of or a of vs patients in the inoperable and operable but no surgery groups, and the operated group more patients, the was not significant across the three was in the inoperable group. patients undergoing PTE surgery, surgery was a median of months from was in patients from and patients from the inoperable patients from the operable but no surgery and patients from the operated group. 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Chin K. et al.Results from the United States Chronic Thromboembolic Pulmonary Hypertension Registry: enrollment characteristics and 1-year follow-up.Chest. 2021; 160: 1822-1831Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar; the long-term survival results as as and quality-of-life in the current study higher survival for patients with CTEPH who underwent PTE vs the inoperable group and vs the operable but no surgery group and in health-related quality-of-life patients with CTEPH who underwent PTE vs changes in patients in the inoperable and operable but no surgery The a disease-specific and the a health-related quality-of-life were used in this study to assess symptoms and health-related quality of have to in some by symptoms and that are whereas provide a for both and of that patients with CTEPH in the US CTEPH Registry a baseline on EmPHasis-10 scores and significant in baseline health on SF-36 and SF-36 longitudinal follow-up, scores on both improved for all three CTEPH but the improvements were in patients who underwent of the current study is the inclusion of patients treated both and CTEPH studies that have on a single and after V. health-related quality of life after surgery in patients with chronic thromboembolic pulmonary Life Scopus Google Scholar, M. K. N. et patient-reported outcomes are improved by pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.Eur Respir J. Scopus Google Scholar, J. S. L. et of the and SF-36 in pulmonary Med. 2013; 13: PubMed Scopus Google Scholar The further into inoperable and operable but no surgery groups vs inclusion of a single no surgery group is an potential when patients who underwent surgery with those who did patients who undergo surgery to with of the from this study, is that in symptoms and quality of life to for patients with CTEPH undergoing PTE surgery vs both the inoperable and operable but no surgery The in SF-36 and EmPHasis-10 results also to for this with patients showed that or the differences for S.C. The in the for patients with pulmonary arterial hypertension.Am J Respir Crit Care Med. 2012; PubMed Scopus Google M. T. et as a measure of health-related quality of life in pulmonary arterial hypertension: data from Respir J. 2021; Scopus Google Scholar Patients in the operated group showed a of mortality with those in the inoperable and operable but no surgery groups, and this significant in of the with the quality-of-life results that patients to for PTE surgery as the cohort studies also have long-term survival for patients with CTEPH undergoing PTE surgery vs S.R. Swift A.J. Billings C.G. et al.The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.Eur Respir J. 2018; 52Crossref PubMed Scopus (60) Google M. Lang I. Pepke-Zaba J. et al.Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry.Circulation. 2016; 133: 859-871Crossref PubMed Scopus (424) Google R. Kiely D.G. Gibbs J.S. et al.Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension.Am J Respir Crit Care Med. 2008; 177: 1122-1127Crossref PubMed Scopus (339) Google Scholar and vs R.L. J. of for pulmonary arterial hypertension: Full Text Full Text PDF PubMed Scopus Google Scholar the current study, these were and were to potential or a mortality also was after for potential in the by et M. Lang I. Pepke-Zaba J. et al.Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry.Circulation. 2016; 133: 859-871Crossref PubMed Scopus (424) Google Scholar in a study by et S.R. Swift A.J. Billings C.G. et al.The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.Eur Respir J. 2018; 52Crossref PubMed Scopus (60) Google Scholar from the United patients surgery choice than no surgery of also showed survival rates vs operated In the current study, also that survival was with Health functional of and and of right and pulmonary vascular Although of these are these results the of mortality in this patient including both CTEPH as as age and with a higher of patients in the current study underwent PTE surgery, with in the operated group vs to in S.R. Swift A.J. Billings C.G. et al.The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.Eur Respir J. 2018; 52Crossref PubMed Scopus (60) Google M. Lang I. Pepke-Zaba J. et al.Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry.Circulation. 2016; 133: 859-871Crossref PubMed Scopus (424) Google R. Kiely D.G. Gibbs J.S. et al.Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension.Am J Respir Crit Care Med. 2008; 177: 1122-1127Crossref PubMed Scopus (339) Google Scholar a of patients classified as inoperable and also more patients classified as operable in surgery was not this in patient or is Although these the of patients in the current study also underwent at rates and at rates with a recent S. D’Armini A.M. M. et for chronic thromboembolic pulmonary hypertension: results of the prospective CTEPH 2021; PubMed Scopus Google Scholar In that study, significant was with at as has been characteristics vs patients in the operated group to to have and to more patients vs inoperable and operable but no surgery also that patients in the operated group were more to vs patients in the operable but no surgery group. survival at 3 years in the current study years was vs that in this in was larger in the inoperable and operable no surgery groups, outcomes across studies have been S.R. Swift A.J. Billings C.G. et al.The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.Eur Respir J. 2018; 52Crossref PubMed Scopus (60) Google M. Lang I. Pepke-Zaba J. et al.Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry.Circulation. 2016; 133: 859-871Crossref PubMed Scopus (424) Google R. Kiely D.G. Gibbs J.S. et al.Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension.Am J Respir Crit Care Med. 2008; 177: 1122-1127Crossref PubMed Scopus (339) Google Scholar in the current study, survival at 3 years was in the inoperable group and in the operable no surgery group vs in the inoperable group and in the operable but no surgery group in the cohort by et S.R. Swift A.J. Billings C.G. et al.The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.Eur Respir J. 2018; 52Crossref PubMed Scopus (60) Google Scholar in Although this to differences in the patient in the treatment of CTEPH also potentially is approved as medical for patients with CTEPH with inoperable or PH after PTE surgery, and is used for patients with CTEPH with on in both a the clot surgically as a patient is a good for surgery more surgical a to review and to and in the is CTEPH is In the current study, the of to adjudication were as CTEPH on review of with the reasons were imaging more with and no evidence of CTEPH on imaging patients also significant in with a median of months from to diagnosis in this the for a of in patients with dyspnea as as the for improved of the differences in imaging characteristics for vs chronic S. in chronic thromboembolic pulmonary Thorac PubMed Scopus Google Scholar patients with a diagnosis of surgically CTEPH but who did not undergo surgery, the reasons were that the patient surgery and the of surgery the reasons are to those in the study by et S.R. Swift A.J. Billings C.G. et al.The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.Eur Respir J. 2018; 52Crossref PubMed Scopus (60) Google Scholar in the reasons for operable patients not undergoing surgery were and for surgery were not to evaluate the of PH medical and on the of the of these relative to survey and for patients were at some potential for in those who were and this have to the of operable patients in this study. to by including and by including that did not surgery, but not all patients are to PH for models were to for the of the of not for and potentially to the of in both surgical and improvements were time in all three patient groups, with the improvements in patients undergoing observed a higher of for patients with CTEPH in the inoperable and operable but no surgery groups relative to the operated and this after for and baseline study was by a from to The of the University of California, San

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