Patient-Reported Outcomes in Adults With Congenital Heart Disease Following Hospitalization (from APPROACH-IS)

In this international study, we (1) compared patient-reported outcomes (PROs) in adults with congenital heart disease (CHD) who had versus had not been hospitalized during the previous 12 month, (2) contrasted PROs in patients who had been hospitalized for cardiac surgery versus nonsurgical reasons, (3) assessed the magnitude of differences between the groups (i.e., effect sizes), and (4) explored differential effect sizes between countries. APPROACH-IS was a cross-sectional, observational study that enrolled 4,028 patients from 15 countries (median age 32 years; 53% females). Self-report questionnaires were administered to measure PROs: health status; anxiety and depression; and quality of life. Overall, 668 patients (17%) had been hospitalized in the previous 12 months. These patients reported poorer outcomes on all PROs, with the exception of anxiety. Patients who underwent cardiac surgery demonstrated a better quality of life compared with those who were hospitalized for nonsurgical reasons. For significant differences, the effect sizes were small, whereas they were negligible in nonsignificant comparisons. Substantial intercountry differences were observed. For various PROs, moderate to large effect sizes were found comparing different countries. In conclusion, adults with CHD who had undergone hospitalization in the previous year had poorer PROs than those who were medically stable. Researchers ought to account for the timing of recruitment when conducting PRO research as hospitalization can impact results. In this international study, we (1) compared patient-reported outcomes (PROs) in adults with congenital heart disease (CHD) who had versus had not been hospitalized during the previous 12 month, (2) contrasted PROs in patients who had been hospitalized for cardiac surgery versus nonsurgical reasons, (3) assessed the magnitude of differences between the groups (i.e., effect sizes), and (4) explored differential effect sizes between countries. APPROACH-IS was a cross-sectional, observational study that enrolled 4,028 patients from 15 countries (median age 32 years; 53% females). Self-report questionnaires were administered to measure PROs: health status; anxiety and depression; and quality of life. Overall, 668 patients (17%) had been hospitalized in the previous 12 months. These patients reported poorer outcomes on all PROs, with the exception of anxiety. Patients who underwent cardiac surgery demonstrated a better quality of life compared with those who were hospitalized for nonsurgical reasons. For significant differences, the effect sizes were small, whereas they were negligible in nonsignificant comparisons. Substantial intercountry differences were observed. For various PROs, moderate to large effect sizes were found comparing different countries. In conclusion, adults with CHD who had undergone hospitalization in the previous year had poorer PROs than those who were medically stable. Researchers ought to account for the timing of recruitment when conducting PRO research as hospitalization can impact results. Patient-reported outcomes (PROs) are “any reports of the status of a patient's health condition that come directly from the patient, without interpretation of the patient's response by a clinician or anyone else.”1US Department of Health and Human Service Food and Drug AdministrationGuidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. FDA, Silver Spring, MD2009Google Scholar PRO research has gained traction among patients with congenital heart disease (CHD).2Moons P Patient-reported outcomes in congenital cardiac disease: are they as good as you think they are?.Cardiol Young. 2010; 20: 143-148Crossref PubMed Scopus (14) Google Scholar,3Bratt EL Moons P Forty years of quality-of-life research in congenital heart disease: temporal trends in conceptual and methodological rigor.Int J Cardiol. 2015; 195: 1-6Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar A large proportion of these patients fare well, and typically present for routine evaluation at outpatient clinics every 1 to 5 years, depending on their clinical scenario and complexity of the heart defect.4Landzberg MJ Murphy Jr., DJ Davidson Jr., WR Jarcho JA Krumholz HM Mayer Jr., JE Mee RB Sahn DJ Van Hare GF Webb GD Williams RG Task force 4: organization of delivery systems for adults with congenital heart disease.J Am Coll Cardiol. 2001; 37: 1187-1193Crossref PubMed Scopus (135) Google Scholar However, patients sometimes require hospital admission, either because of deteriorating clinical status or for elective assessment or interventional procedure. When PROs are measured during or following hospitalization, it may be presumed that scores would generally be worse than when completed during outpatients visit or from patients’ homes. Therefore, we aimed (1) to described PROs in individuals who had versus had not been hospitalized during the previous 12 months, (2) to contrast PROs in patients who had been hospitalized for cardiac surgery versus nonsurgical reasons, (3) to assess the magnitude of differences between the groups, and (4) to explore differential effect sizes between countries. This analysis is a substudy of APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease – International Study), a cross-sectional study conducted in 15 countries. The rationale and study protocol of APPROACH-IS were extensively described in a dedicated methods paper.5Apers S Kovacs AH Luyckx K Alday L Berghammer M Budts W Callus E Caruana M Chidambarathanu S Cook SC Dellborg M Enomoto J Eriksen K Fernandes SM Jackson JL Johansson B Khairy P Kutty S Menahem S Rempel G Sluman MA Soufi A Thomet C Veldtman G Wang JK White K Moons P Approach-Is consortiumInternational Society for Adult Congenital Heart DiseaseAssessment of patterns of patient-reported outcomes in adults with congenital heart disease - international study (APPROACH-IS): rationale, design, and methods.Int J Cardiol. 2015; 179: 334-342Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Briefly here, we included 4,028 adults (≥18 years) with CHD who were followed-up at a CHD center or included in a national/regional registry, and who had the physical, cognitive, and language capabilities required to complete self-report questionnaires.5Apers S Kovacs AH Luyckx K Alday L Berghammer M Budts W Callus E Caruana M Chidambarathanu S Cook SC Dellborg M Enomoto J Eriksen K Fernandes SM Jackson JL Johansson B Khairy P Kutty S Menahem S Rempel G Sluman MA Soufi A Thomet C Veldtman G Wang JK White K Moons P Approach-Is consortiumInternational Society for Adult Congenital Heart DiseaseAssessment of patterns of patient-reported outcomes in adults with congenital heart disease - international study (APPROACH-IS): rationale, design, and methods.Int J Cardiol. 2015; 179: 334-342Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar,6Apers S Kovacs AH Luyckx K Thomet C Budts W Enomoto J Sluman MA Wang JK Jackson JL Khairy P Cook SC Chidambarathanu S Alday L Eriksen K Dellborg M Berghammer M Mattsson E Mackie AS Menahem S Caruana M Veldtman G Soufi A Romfh AW White K Callus E Kutty S Fieuws S Moons P Approach-Is consortiumIsachdQuality of life of adults with congenital heart disease in 15 countries: evaluating country-specific characteristics.J Am Coll Cardiol. 2016; 67: 2237-2245Crossref PubMed Scopus (87) Google Scholar The study was conducted in keeping with the Declaration of Helsinki and was approved by the Institutional Review Board of the University Hospitals Leuven/KU Leuven, Belgium (coordinating center) and by the local institutional review boards of the participating centers (when required). For 3,969 patients (98.5%), information about inpatient cardiac admissions was available. Therefore, the current study was performed on this subsample. Informed consent was obtained from each patient. Three domains of PROs were assessed using self-report questionnaires: (1) perceived health status using the 12-item Short Form Health Survey (SF-12)7Ware JE Kosinski M Turner-Bowker DM Sundaram M Gandek B Maruish ME User's Manual for the SF-12v2 Health Survey.Second Edition. QualityMetric, Incorporated, Lincoln, RI2009Google Scholar and the EuroQol-5D Visual Analog Scale8EuroQolGroupEuroQol–a new facility for the measurement of health-related quality of life.Health Policy. 1990; 16: 199-208Crossref PubMed Scopus (10582) Google Scholar; (2) psychological functioning using the Hospital Anxiety and Depression Scale9Zigmond AS Snaith RP The hospital anxiety and depression scale.Acta Psychiatr Scand. 1983; 67: 361-370Crossref PubMed Scopus (28785) Google Scholar; and (3) QoL using a Linear Analog Scale10Moons P Van Deyk K De Bleser L Marquet K Raes E De Geest S Budts W Quality of life and health status in adults with congenital heart disease: a direct comparison with healthy counterparts.Eur J Cardiovasc Prev Rehabil. 2006; 13: 407-413Crossref PubMed Scopus (0) Google Scholar; and the Satisfaction With Life Scale.11Diener E Emmons RA Larsen RJ Griffin S The satisfaction with life scale.J Pers Assess. 1985; 49: 71-75Crossref PubMed Scopus (14834) Google Scholar Demographic data were collected through self-report questionnaires. Medical data were obtained through chart review, including (1) whether patients had cardiac inpatient hospitalizations over the previous 12 months and (2) the date of the most recent cardiac surgery. Online Table 1 provides an expanded definition of the domains as applied in APPROACH-IS as well as the interpretation of scores for the individual PRO measures. Data analysis was performed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, NY, USA). PRO scores were expressed as means and standard deviations. Other descriptive statistics were reported as medians and interquartile ranges, given that the data were not normally distributed. Inferential statistics were performed using the Chi square test for nominal or ordinal level data, and the Whitney U test for continuous data. To avoid inflation of type 1 error, we applied the false discovery rate according to Benjamini-Hochberg.12Benjamini Y Hochberg Y Controlling the false discovery rate - a practical and powerful approach to multiple testing.J R Stat Soc Ser B-Method. 1995; 57: 289-300Google Scholar A Benjamini-Hochberg adjusted p-level <0.05 was used as the cut-off for statistical significance. Statistical tests were two-sided. To express the magnitude of the difference between groups, we calculated standardized effect sizes (Cohen's d) for hospitalized patients compared with nonhospitalized patients. The following cut-off values for Cohen's d were used: 0.2 to 0.5 indicative of a small effect; >0.5 to 0.8 a moderate effect; and >0.8 a large effect.13Cohen J Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum, Hillsdale, NJ1988Google Scholar For the differential effect sizes across the countries, only countries in which at least 10 patients had been hospitalized were included in the analysis. Thus, Argentina, Malta, and the Netherlands were excluded from these comparative analyses. Overall, 16.8% of patients had been hospitalized for cardiac reasons during the previous 12 months. Of these patients, 22.8% were hospitalized for cardiac surgery. Demographic and clinical characteristics of patients who had inpatient cardiac admissions over the past year versus those who did not are shown in Table 1. Hospitalization for cardiac reasons was significantly associated with older age, not working, poorer functional class, complex CHD, cardiac surgery and catheter interventions in the past, heart failure, history of arrhythmias, having pacemakers or implantable cardioverter defibrillator, and history of depression, anxiety and other psychiatric disorders (Table 1). There were no significant differences in demographic variables or medical history according to reason for hospitalization, namely cardiac surgery versus other reason, except for the number of surgeries.Table 1Demographic and medical background of adults with congenital heart disease who had vs. had not been hospitalized in the previous 12 monthsVariableNo inpatient cardiac admissions over the past year 3301 (83.2%)Inpatient cardiac admissions over the past year 668 (16.8%)p Value‡Benjamini-Hochberg adjusted p-value.Inpatient cardiac admissions for cardiac operation152 (22.8%)Inpatient cardiac admissions not for cardiac operation 516 (77.2%)p Value‡Benjamini-Hochberg adjusted p-value.Women1,741 (53.0%)344 (51.5%)0.479†Chi square test;69 (45.4%)275 (53.3%)0.313†Chi square test;Median age years31 (IQR 24-41)33.0 (IQR 26-46)<0.001*Mann-Whitney U test;33 (IQR 26-44)33 (IQR 26-47)0.974*Mann-Whitney U test;Educational level0.071†Chi square test;0.432†Chi square than University square square or or or square square or with or Heart square square of heart square square of cardiac (IQR (IQR U (IQR (IQR U of catheter (IQR (IQR U (IQR (IQR U of heart square square not of square square medical square square square square square square square square of square square of anxiety square square of other psychiatric square square U Chi square Benjamini-Hochberg adjusted in a new patients who had been hospitalized during the previous scores on all PROs except for anxiety were significantly worse than scores of patients without hospitalizations 1). The Cohen's d for all significant PROs were between 0.2 and a small difference between the For the Cohen's d was than a negligible of PROs in patients who had been hospitalized for cardiac surgery with those who had been hospitalized for nonsurgical reasons that patients reported significantly better quality of on the and the satisfaction with life The effect sizes for these differences were than For the other PROs, the differences between and nonsurgical patients with hospitalization were When effect sizes of hospitalization no in different countries, intercountry differences were For the of the large effect sizes were in and In and the effect sizes were For the of the large effect sizes were found in and and a moderate effect in For health measured using the EuroQol-5D Visual Analog a large effect was in and moderate effect sizes in and The difference in of anxiety and depression between hospitalized versus nonhospitalized patients was negligible or small in most countries, except for and For quality of a moderate difference on the and on the Satisfaction with Life In the present study, we found that PROs were worse in patients who had been hospitalized in the previous year compared with those who had not been and that most differences were not the effect sizes were in countries the effect sizes were in the moderate to large that hospitalizations a differential impact on PROs in sizes were the for PROs that patients’ namely the and the EuroQol-5D Visual Analog Patients who underwent cardiac surgery demonstrated a better quality of life in the of hospitalization than those hospitalized for other reasons. The in this study was about would be a difference between hospitalized versus nonhospitalized patients and about the difference would This is of for and PRO measures. For administered PROs at hospital J A B M A K L Patient-reported outcomes at hospital from Heart a cross-sectional with a the study PubMed Scopus Google Scholar which is to study outcomes at this in and to explore whether they are of clinical outcomes or M A B L K Patient-reported outcomes among patients with cardiac from the J Cardiol. Full Text Full Text PDF PubMed Scopus Google B L K M Patient-reported outcomes are of and cardiac across cardiac from the J Prev Cardiol. PubMed Scopus Google Scholar However, this timing of data would not of the of a The present study that the timing of PRO assessment because PROs are about to standard worse among patients 1 year of the reason for hospitalization as patients who were hospitalized for cardiac reported quality of life that was standard better than those who were for other reasons. 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The present study is for when new PRO However, from a clinical it that a health status is the that PROs are worse in patients following hospitalization that is a for including cardiac and psychological and psychological may of Moons P S B C P J S and in patients with a PubMed Scopus Google JA White L of a on anxiety to Scopus Google Scholar The APPROACH-IS had methodological over patients from 15 countries were a of complete data were and and PRO were S Kovacs AH Luyckx K Thomet C Budts W Enomoto J Sluman MA Wang JK Jackson JL Khairy P Cook SC Chidambarathanu S Alday L Eriksen K Dellborg M Berghammer M Mattsson E Mackie AS Menahem S Caruana M Veldtman G Soufi A Romfh AW White K Callus E Kutty S Fieuws S Moons P Approach-Is consortiumIsachdQuality of life of adults with congenital heart disease in 15 countries: evaluating country-specific characteristics.J Am Coll Cardiol. 2016; 67: 2237-2245Crossref PubMed Scopus (87) Google P Kovacs AH Luyckx K Thomet C Budts W Enomoto J Sluman MA Jackson JL Khairy P Cook SC R Alday L Eriksen K Dellborg M Berghammer M Johansson B Mackie AS Menahem S Caruana M Veldtman G Soufi A Fernandes SM White K Callus E Kutty S Van L S APPROACH-IS Society of Adult Congenital Heart outcomes in adults with congenital heart disease: standard of and J Cardiol. Full Text Full Text PDF PubMed Scopus Google Scholar This large international data that are than or and to intercountry and the impact of on S Kovacs AH Luyckx K Thomet C Budts W Enomoto J Sluman MA Wang JK Jackson JL Khairy P Cook SC Chidambarathanu S Alday L Eriksen K Dellborg M Berghammer M Mattsson E Mackie AS Menahem S Caruana M Veldtman G Soufi A Romfh AW White K Callus E Kutty S Fieuws S Moons P Approach-Is consortiumIsachdQuality of life of adults with congenital heart disease in 15 countries: evaluating country-specific characteristics.J Am Coll Cardiol. 2016; 67: 2237-2245Crossref PubMed Scopus (87) Google P Kovacs AH Luyckx K Thomet C Budts W Enomoto J Sluman MA Jackson JL Khairy P Cook SC R Alday L Eriksen K Dellborg M Berghammer M Johansson B Mackie AS Menahem S Caruana M Veldtman G Soufi A Fernandes SM White K Callus E Kutty S Van L S APPROACH-IS Society of Adult Congenital Heart outcomes in adults with congenital heart disease: standard of and J Cardiol. Full Text Full Text PDF PubMed Scopus Google P Luyckx K J Kovacs AH Thomet C Budts W Enomoto J Sluman MA Jackson JL Khairy P R Alday L Eriksen K Dellborg M Berghammer M Johansson B Mackie AS Menahem S Caruana M Veldtman G Soufi A Fernandes SM White K Callus E Kutty S S Approach-Is Society for Adult Congenital Heart and as of patient-reported outcomes in adults with congenital heart disease the J Cardiol. Full Text Full Text PDF PubMed Scopus Google P Luyckx K Kovacs AH Thomet C Budts W Enomoto J Sluman MA Jackson JL Khairy P Cook SC Chidambarathanu S Alday L Eriksen K Dellborg M Berghammer M Johansson B Mackie AS Menahem S Caruana M Veldtman G Soufi A Fernandes SM White K Callus E Kutty S S Approach-Is International Society for Adult Congenital Heart and of and in adults from 15 countries with congenital heart J Cardiol. 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APPROACH-IS is a cross-sectional study, and be S Kovacs AH Luyckx K Alday L Berghammer M Budts W Callus E Caruana M Chidambarathanu S Cook SC Dellborg M Enomoto J Eriksen K Fernandes SM Jackson JL Johansson B Khairy P Kutty S Menahem S Rempel G Sluman MA Soufi A Thomet C Veldtman G Wang JK White K Moons P Approach-Is consortiumInternational Society for Adult Congenital Heart DiseaseAssessment of patterns of patient-reported outcomes in adults with congenital heart disease - international study (APPROACH-IS): rationale, design, and methods.Int J Cardiol. 2015; 179: 334-342Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar in most participating countries, only center in the which the of the a not be as patients without the or to complete the self-report questionnaires were for the S Kovacs AH Luyckx K Alday L Berghammer M Budts W Callus E Caruana M Chidambarathanu S Cook SC Dellborg M Enomoto J Eriksen K Fernandes SM Jackson JL Johansson B Khairy P Kutty S Menahem S Rempel G Sluman MA Soufi A Thomet C Veldtman G Wang JK White K Moons P Approach-Is consortiumInternational Society for Adult Congenital Heart DiseaseAssessment of patterns of patient-reported outcomes in adults with congenital heart disease - international study (APPROACH-IS): rationale, design, and methods.Int J Cardiol. 2015; 179: 334-342Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar However, a comparison of and in the of APPROACH-IS only small differences in demographic and clinical Mattsson E Johansson B Moons P Dellborg of and in patient-reported the of assessment of patterns of patient-reported outcomes in adults with congenital heart disease - international Young. PubMed Scopus Google Scholar we did not information on the between the hospitalization and the date of data on the number of hospitalizations in the 12 months, the of or the reason for hospital on the year of the cardiac we were to whether the hospitalization was for surgery. we did not because hospitalizations not be an of hospitalization is a for medical the of APPROACH-IS was as the comparison of versus nonsurgical be However, it is that were to type because all differences in effect sizes were In conclusion, adults with CHD 1 year of hospitalization had poorer PROs than those who not had a recent effect sizes were across participating countries. Patients who underwent cardiac surgery demonstrated a better quality of life compared with those hospitalized for nonsurgical reasons. 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