Adult Congenital Heart Disease Patients Experience Similar Symptoms of Disease Activity
Background—There is a lack of objective data on the symptoms characterizing disease activity among adults with congenital heart disease (ACHD). The purpose of this study was to elicit the most important symptoms from patients across the spectrum of ACHD and to examine whether reported symptoms were similar across the spectrum of ACHD as a foundation for creating a patient-reported outcome measure(s).
Methods and Results—We constructed a 39-item survey using input from physicians specializing in ACHD to assess the symptoms patients associate with disease activity. Patients (n=124) prospectively completed this survey, and the results were analyzed based on underlying anatomy and disease complexity. A confirmatory cohort of patients (n=40) was then recruited prospectively to confirm the validity of the initial data. When grouped based on underlying anatomy, significant differences in disease-related symptom rankings were found for only 6 of 39 symptoms. Six symptoms were identified which were of particular significance to patients, regardless of underlying anatomy. Patients with anatomy of great complexity experienced greater overall symptom severity than those with anatomy of low or moderate complexity, attributable exclusively to higher ranking of 5 symptoms. The second patient cohort had symptom experiences similar to those of the initial cohort, differing in only 5 of 39 symptoms.
Conclusions—This study identified 6 symptoms relevant to patients across the spectrum of ACHD and remarkable homogeneity of patient experience, suggesting that a single disease-specific patient-reported outcome can be created for quality and outcome assessments.
- adult congenital heart disease
- disease-specific symptoms
- outcome assessment
- patient-reported outcome
- quality of life
WHAT IS KNOWN
Adult congenital heart disease is growing in prevalence.
No systematic investigation of disease-specific symptoms of disease activity has been performed in this population.
WHAT THE STUDY ADDS
This study provides systematic investigation of symptoms of greatest importance to adult congenital heart disease patients.
It also provides a solid foundation on which to begin construction of a patient-reported outcome tool.
There is a pressing need for a method to evaluate the quality of care for adult congenital heart disease (ACHD). This unique population of patients has grown significantly over the past 20 years, and currently, the number of ACHD patients in the United States is estimated to be over 1.2 million—far exceeding the number of children with congenital heart disease.1,2 Nevertheless, little data are available to guide ACHD specialists in quantifying patient-reported outcomes (PROs) for this group. Without the ability to reproducibly evaluate PROs, ACHD research will continue to fall short in optimizing management paradigms to improve patients’ daily lives. To address this inability to quantify the impact of ACHD on patients’ lives, a reliable tool for assessing disease-specific PROs in ACHD is needed.3
Derivation of an ACHD-specific PRO tool, however, is a complex process. The ACHD population is characterized by variability in not only anatomic diagnosis, but also in genetic background and in early life medical and surgical care. This heterogeneity would be anticipated to result in a broad diversity of disease-related symptoms, and it is not clear whether a single tool for all patients with ACHD would be adequate to evaluate PROs in the ACHD population or whether unique tools for each type of ACHD would be needed. Furthermore, there is little data available to indicate which symptoms are typically experienced by ACHD patients as a group. To resolve these questions, it is necessary to conduct a systematic evaluation of disease-specific symptoms experienced by ACHD patients across the anatomic spectrum. Accordingly, we investigated patients’ symptoms by surveying both ACHD healthcare providers and ACHD patients regarding disease-specific symptoms. The purpose of this investigation was to begin to define the key concepts to be incorporated into an ACHD-specific PRO and to determine whether similar symptoms were relevant across a broad spectrum of ACHD patients with differing pathophysiological abnormalities.
We conducted a prospective survey of both ACHD physicians and patients to identify important ACHD-related symptoms. Developing a PRO with appropriate content validity requires eliciting symptoms and limitations from patients through qualitative research methods; however, patients with ACHD are so diverse that we first needed to determine whether a single measure, or multiple PROs, would be needed. This question demanded assessing the prevalence and importance of symptoms across the spectrum of ACHD. Although such efforts generally use the extant literature to define initial items to include in such surveys, there are few detailed descriptions of patients’ symptoms in ACHD. We thus sought to first generate a list from experienced clinicians, with open-ended responses from patients, so that the design of future focus groups and interview guides could be developed. The protocol for this study was reviewed and approved by the institutional review boards at both Washington University and Massachusetts General Hospital (MGH).
The first step in creating a pool of potentially important symptoms was to survey physicians specializing in the care of ACHD patients. To identify physicians experienced in the care of ACHD patients, we approached the ACHD physician members of the Alliance for Adult Research in Congenital Cardiology (a multi-institutional ACHD research consortium) and asked them to provide a list of symptoms typically elicited at the time of ACHD patient visits and which they believed were related to ACHD. Six providers from 6 different institutions with broad US geographic representation offered to participate in this study. A total of 39 symptoms were identified. No physician-proposed symptoms were excluded with the goal of being as exhaustive as possible.
The next step was to solicit feedback from patients on the importance and relevance of the 39 identified symptoms and to expand this list by having patients contribute additional suggestions. Using the list of symptoms generated, we constructed an ACHD patient survey. This survey included the following demographic variables: sex, age, offspring, long-term relationship status, presence of an implantable cardiac defibrillator, and primary cardiac diagnosis. Patients were then asked to rank both the importance and the frequency with which they experienced each symptom identified as a part of the physician survey. Symptom impact and frequency were scored on separate 5-point Likert scales (Figure 1). To ensure that the symptom list was exhaustive, patients were also asked to provide a list of symptoms not identified by physicians or included on the survey, but which were of significance to them. Patients were approached nonselectively to complete the survey at the annual meeting of the Adult Congenital Heart Association (ACHA) in Chicago, Illinois, from September 5 to 7, 2014 (100 participants), as well as in the Center for Adults with Congenital Heart Disease at Washington University School of Medicine (24 participants). In both settings, patients were approached by a study investigator at a research table (at the ACHA meeting) or at a regularly scheduled outpatient cardiology visit (at Washington University) and offered participation in the study.
Confirmatory Patient Cohort
To confirm the results of the patient survey, patients seen in the ACHD clinic at MGH over a 4-week period in April and May 2015 were consecutively approached and invited to participate in the study. Forty patients agreed to participate and completed the survey. These results were then compared with the initial sample.
Basic descriptive statistics were evaluated on all survey responses, overall and stratified by lesion complexity. Using the diagnoses provided by subjects, survey responses were then grouped into low, moderate, and high anatomic complexity based on the 2008 guidelines statement for the care of ACHD from the American College of Cardiology/American Heart Association. Symptom impact score for each survey item within each subject was compared between groups using the Kruskal–Wallis test.4 Again using the diagnoses provided by subjects, the survey responses were then pooled into 1 of 7 groups depending on underlying diagnosis and presumed associated long-term disease-specific sequelae as described in Table 1. A composite score, derived by multiplying symptom impact and frequency score, for each survey item within each subject was then compared for each individual survey item between groups using analysis of variance (ANOVA), treating Likert scaled data as continuous measures. Data within groups were summarized by the mean±standard deviation (SD) for this analysis. To confirm these initial findings, given the small sample sizes in certain groups and non-normal distribution, data were treated as ordinal values and compared using the Kruskal–Wallis test. Ordinal data for this test were summarized by the median and interquartile range. These 2 methods for evaluating the data yielded similar results, and we therefore used the ANOVA analysis for identification of differences between the 7 diagnostic groups.
Finally, we conducted an analysis to further investigate the significance of differences in relative symptom importance between groups. In this analysis, impact and frequency scores for each survey item within each subject were multiplied and standardized. To standardize, we averaged the composite score for each subject over all 39 items. We then subtracted this average from the composite score for each individual item to generate a standardized score for each item. We derived this analysis because our goal was to identify symptoms of particular importance to subjects. ACHD has significant heterogeneity in terms of clinical status, lesion complexity, and degree of disability. In an asymptomatic individual, any symptom at all might be deemed important, whereas in a chronically ailing individual, or one with significant chronic limitation, many symptoms would be anticipated to be present much of the time, certain of which would have a greater and certain of which would have a lesser impact on their quality of life. Our goal was to use the employed technique to permit direct comparison of the scores between the asymptomatic and the chronically ailing patient with the goal of identifying symptoms of particular importance, regardless of baseline clinical status. ANOVA was used to compare the standardized data between groups.
Comparison of the test cohort survey data to the confirmatory cohort was performed in a similar fashion to the group-wise comparison in the test cohort: we first compared composite item scores between the 2 groups using ANOVA. We thereafter compared the standardized composite score for each item, derived as earlier, between the 2 groups using ANOVA. For all analysis, significance was assigned at P≤0.05. Trend toward significance was defined as 0.05<P<0.1. All analyses were conducted using SAS Software v 9.3 (SAS Institute Inc, Cary, NC).
One hundred and twenty-four patients completed the symptom survey in the test cohort which had broad representation of ACHD lesions (Table 1). The mean age of participants was 42.7±14.2, and 67% were female. Other clinical and demographic characteristics of these patients are found in Table 2. Among test group participants, 26 (21%) had lesions of low complexity, 53 (43%) had lesions of moderate complexity, and 45 (36%) had lesions of great complexity.
Symptom Severity by Anatomy
We next sought to identify lesion-specific symptoms by separating patients into 7 groups, pooling together patients with lesions believed by ACHD providers to produce similar symptoms. Notably, there were few differences between the groups in symptoms rated as most troublesome. Among the 39 symptoms, significant differences were found in 6, and a trend toward different symptoms being most troublesome between groups was found for 2 (Table 3). On inspection of the symptoms with significant differences using analysis standardized to the mean overall score in each patient, the symptom “shortness of breath (windedness, trouble breathing) when I do things” scored greater than the mean score for all items in all groups except group 1. “Bluish or dusky colored skin” was rated highly only among patients in group 7. “Passing out or fainting” scored less than the mean score for all items in all groups, although to varying degrees. “Having to go to the hospital or emergency room” scored greater than the mean in groups 3 and 4. “Concerns with sexual function” scored greater than the mean in groups 3 and 7. “Concern about my ability to care for my children” scored greater than the mean in groups 1 and 4. Among symptoms for which there was a trend toward difference between groups, “monitoring a blood thinning medication” scored greater than the mean in groups 2 and 6, whereas “feeling like I am not as attractive/handsome/beautiful as other people” scored greater than the mean only in group 7 (Table 4). Symptoms of particular importance in all groups included trouble sleeping; fatigue; low energy levels; anxiety or stress about my health; depression, sadness, or feelings of helplessness or hopelessness; and cost of medical care, including medications or tests.
Beyond the 39 symptoms proposed by physicians, there were 11 symptoms identified by 9 participants which were not listed on the survey (Table 5). None of these were mentioned by >1 participant.
Symptom Severity by ACHD Complexity
Patients with lesions of great complexity reported a greater impact of symptoms related to heart disease (Table 6). This difference was attributable to significantly higher impact scores for the symptoms “bluish or dusky colored skin” (P=0.001), “having to go to the hospital or emergency room” (P<0.001), “concerns with sexual function” (P=0.018), “feeling mentally slower than other people” (P=0.001), and “feeling I am different than other people” (P=0.027). The only symptom for which there was a significant difference between patients with low and moderate complexity was “uncertainty about the future” (P=0.028).
To confirm the relative importance of the symptoms identified in the study cohort and the frequency with which they occurred, an independent confirmatory sample of 40 ACHD patients was recruited from MGH. Demographic characteristics of this confirmatory cohort are found in Table 2. When compared with the initial patient group, the confirmatory cohort was significantly less symptomatic, with an average score across all symptoms of 3.9±1.8, as compared with 6.2±2.2 in the initial group, and higher scores for all of the 39 symptoms were observed (Table 7). To compare symptoms of particular importance between the 2 groups, we analyzed the standardized composite score. The confirmatory cohort largely confirmed the relative importance of the symptoms identified as of significance in the test cohort as shown in Figure 2. We found that the confirmatory cohort differed from the test cohort in only 5 of the 39 total symptoms. Among these, “sleepiness” and “headaches”, which had been identified as important symptoms in the initial cohort, were found to be of greater importance in the confirmatory cohort. The symptom “defibrillator or implantable cardiac defibrillator firing” was found to be of below average importance in both the test and confirmatory cohorts. The symptom “concern about my children having health problems like mine” was of greater importance in the confirmatory cohort than the test cohort. The symptom “feeling I am different than other people” was found to be of greater importance in the initial cohort than in the confirmatory cohort.
A critical goal in optimizing care for the growing population of ACHD patients is to be able to quantify and monitor the symptoms among patients with disease. Before developing a formal PRO, however, it is critically important to elicit the most important symptoms to assess. In the present study, we identified a group of symptoms of particular importance to patients with ACHD and examined how the frequency and importance of these symptoms varied across the spectrum of ACHD. Unexpectedly, the symptoms of greatest significance to ACHD patients are largely similar and independent of underlying cardiac diagnosis. To the best of our knowledge, the present study is the first to objectively investigate the patient-reported importance of ACHD-related symptoms. This study suggests that a single PRO might be feasible for evaluation of ACHD as a composite group.
Lesion-Specific Differences in Symptoms Are Few
Among the differences we found between patients with differing underlying cardiac anatomy, the symptom “shortness of breath (windedness, trouble breathing) when I do things” was rated highly by all patients, except those with left ventricular outflow tract obstructions (group 1). This finding is unexpected given that a classic symptom of left ventricular outflow tract stenosis is dyspnea with activity. The fact that members in group 1 of the test cohort did not rate this symptom highly may indicate that a great proportion of the patients had been adequately repaired with no residual obstruction. The present study was not designed to investigate this further because clinical and diagnostic data were not obtained.
“Having to go to the hospital or emergency room” was of particular concern in patients with single ventricle and transposition of the great vessels. Given that these have been demonstrated to be the most common lesions found among ACHD patients who experienced an emergency admission, this finding is not surprising.5 Nevertheless, although of greater concern for only certain groups of ACHD patients, hospitalization is an important event for patients and would be reasonable to include in a PRO.
“Concerns with sexual function” was rated as important, specifically by patients with either single ventricle or Eisenmenger’s syndrome. The reasons underlying this may be complex, potentially involving both self-image and physical capacity. There is conflicting data in the literature as to whether ACHD patients experience decreased sexual function compared with the general population; however, women with complex lesions or cyanosis have been shown to have particularly impaired function.6–8 Because our study population was predominantly female, this may explain why this emerged as such an important symptom.
“Concern about my ability to care for my children” was rated differently between groups and was most highly rated among those with left ventricular outflow tract obstruction and transposition of the great arteries. The reasons for observed differences may be because of both the prevalence of offspring in each group and lesion-specific perception of future health risk. It would be interesting to perform an analysis of the importance of this symptom among those who do versus those who do not have offspring, but this was beyond the scope of the present study. We would hypothesize that concern over ability to care for children is directly related to the concepts “uncertainty about the future” and “anxiety or stress about my health”, both of which were found to be significant for all groups, among patients with children.
“Bluish or dusky colored skin” and “feeling like I am not as attractive/handsome/beautiful as other people” were relevant only in the relatively small group of Eisenmenger syndrome patients, likely because of the physically apparent manifestations of the disease. We will, therefore, consider using these as symptoms to be assessed specifically when evaluating patients in this group.
The trend toward increased importance of “monitoring a blood-thinning medication” among patients with shunt lesions or truncus arteriosus is interesting and unexpected. This finding may reflect a disproportionately high burden of atrial arrhythmias in the sample of shunt patients in the case of the former and a high prevalence of mechanical valves among the latter. We did not collect the data that would be required to confirm these speculations as a part of the present study.
Disease Complexity Is Associated With Overall Symptom Burden
We found, not surprisingly, that overall symptom burden is greater among patients with disease of great complexity as compared with those with less complex ACHD.9,10 Some of the specific symptoms responsible for this difference are intuitive. For example, given that patients with cyanotic heart disease and Eisenmenger’s syndrome are categorized as having disease of great complexity, it is logical that “blueish or dusky colored skin” would be of particular concern for the group of ACHD patients with complex anatomy. In addition, patients with complex disease are known to be at greater risk for hospitalization compared with those with anatomy of low or moderate complexity, which might explain why “having to go to the hospital or emergency room” was of particular concern in this group.5,11 The other differences detected between patients with anatomy of varying complexity are for symptoms that may be related to self-image, physical capacity, perceived health status, or overall psychological state and will need to be explored in future research.
Differences Between the Study and Confirmatory Cohort
The patients in the confirmatory cohort were overall less symptomatic than those in the test cohort across all symptoms queried. The reasons for this are not clear. Although the test cohort included a greater percentage of patients with lesions of great complexity, we demonstrated in the test cohort that the overall increased symptom burden associated with disease complexity was attributable to a narrow group of symptoms, whereas the observed symptom burden is significantly lower for 22 of 39 symptoms in the confirmatory cohort. This might reflect that differences in participant’s clinical experiences at MGH, however, is most likely to be because the politically active patients at the ACHA were more likely to be forthcoming in reporting symptoms and more comfortable with self-advocacy. Nevertheless, when standardized to average score, there were few differences in survey responses between the study and confirmatory cohorts, confirming the relative importance of the symptoms identified in the test cohort.
Among the 5 symptoms found to be significantly different between the 2 groups after standardization, we found “sleepiness” and “headaches” to score greater than the mean in both the study and confirmatory cohorts, although to differing degrees, and “defibrillator or implantable cardiac defibrillator firing” to be of less than the mean importance in both groups, also to differing degrees.
We found the symptom “feeling I am different than other people” to be of greater significance in the study cohort than in the confirmatory cohort. This symptom is psychologically complex and may reflect early life experience, external evidence of disease, including operative scars or variability in physical appearance related to genetic syndromes, as well as overall current psychological state. One possible explanation for the observed difference between groups might be the greater number of patients with complex disease, including cyanotic disease in the study cohort versus the confirmatory cohort. Nevertheless, given the psychological complexity associated with self-image, we cannot draw definitive conclusions.
The symptom “concern about my children having health problems like mine” was likely of greater importance to the confirmatory cohort because they were more likely to have children, although other variables may also have been responsible.
There are several potential limitations that should be considered in interpreting our findings. First, the majority of survey respondents were attendees of the ACHA meeting, which would be anticipated to yield a more informed and potentially more affluent patient group than the general ACHD population. Furthermore, only interested patients agreed to complete the survey. The impact of these factors on reported symptoms is difficult to quantify. Nevertheless, the similarity of the responses in the clinic cohort at MGH is reassuring. Another potential concern is that although ACHD has a slight male preponderance, the majority of participants in the present study were female. This may suggest a biased sample. Finally, patients were categorized into groups based on underlying anatomy and repair. Although the anatomic diagnosis of participants recruited from Washington University and MGH were confirmed, those of participants at the ACHA meeting were based on self-report and were therefore potentially incorrect or incomplete. The data presented here is exploratory, hypothesis-generating, and largely descriptive in nature. This study is not intended to suggest that the survey used is adequate to track PROs.
The present study investigated, for the first time, the patient-reported disease-related symptoms of greatest importance to ACHD patients. Patients generally experience similar symptoms regardless of underlying anatomy. Based on these findings, we think that a single PRO can be developed for patients with ACHD. In future work, we will employ focus groups and cognitive debriefing exercises with the goal of reducing the number of items and developing a PRO with good content validity.
Dr Stefanescu was supported by the National Institutes of Health T32HL007604 training grant in Cardiovascular research. The manuscript contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
This article was handled independently by John J. Ryan, MD, as a Guest Editor. The editors had no role in the evaluation or in the decision about its acceptance.
- Received July 8, 2015.
- Accepted January 17, 2016.
- © 2016 American Heart Association, Inc.
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