Introduction

There have been numerous attempts at defining the concept of quality of life (QoL) due to its multidimensionality and subjectivity. QoL is influenced by socioeconomic status, functioning in everyday life, life satisfaction and many other factors depending on the evaluation context [1, 2]. The term health-related quality of life (HRQoL) describes the impact of disease or chronic conditions on QoL. Key aspects of HRQoL are the following: physical status and functioning; psychological status and individual well-being; social interactions; and economic status [3]. Medical interventions, such as organ transplantation, can influence HRQoL positively. To incorporate impacts of disease as reported by the patient and to evaluate effects of interventions, adequate measures to determine HRQoL are needed. Assessment tools of HRQoL can be classified as disease-, population-, dimension or utility-specific, individualised or generic (Table 1; [4,5,6,7]). Assessment tools of disease-specific HRQoL focus on patient populations with specific diseases or chronic conditions, such as heart failure.

Table 1 Frequently used health-related quality of life (HRQoL) assessment tools
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Background

In patients with chronic heart failure, an increased risk of hospital admission, increased symptom prevalence and symptom burden has been linked to poor HRQoL [8, 9]. Gender, age, exercise, and social support have been stated as influencing factors of HRQoL in patients with heart failure [10]. Heart transplant candidates are a special subgroup among patients with cardiac disease, since one requirement of transplantation is having symptoms of congestive heart failure with severe limitations of physical activity (New York Heart Association [NYHA] class IV). Therefore, HRQoL is adversely affected by limited physical functioning in this population [11]. HRQoL after heart transplantation is influenced by physical, psychological and sociodemographic factors.

Methods

We conducted this systematic review to determine (1) posttransplant HRQoL in heart transplantation (HTx) patients and (2) influencing factors of HRQoL.

Studies including at least one measure to assess HRQoL in adult heart transplant recipients were systematically reviewed in a literature research on PubMed, PsycINFO and PSYNDEX. This systematic review was conducted in accordance with the PRISMA (Preferred reporting items for systematic reviews and meta-analyses) statement [12]. A systematic literature review of studies addressing the domains of HRQoL in HTx patients and using validated HRQoL scales was conducted on PubMed, PsycINFO and PSYNDEX in November 2017. Further information on the search strategy can be found in Fig. 1. Studies published in English between 1 November 2007 and 1 November 2017 and available in full text were included to ensure relevance. Posttransplant HRQoL studies at any length of follow-up as well as cross-sectional, prospective and mixed methods studies were eligible. Articles which did not report data collection methods or inclusion/exclusion criteria, did not use validated measures of HRQoL, focused on HRQoL before transplantation and in transplantation of other solid organs, or only assessed psychological status in terms of distress or functional status without considering HRQoL were excluded. Additionally, case reports, systematic reviews, and meta-analyses were excluded because only studies directly assessing HRQoL and addressing a larger number of HTx patients were eligible for inclusion. Overall, 739 articles were found through database researching. Titles and abstracts were screened by the authors to identify eligible studies after removal of duplicates. Full-text articles were assessed in all cases where inclusion criteria were met. Any disagreements in the selection of studies were resolved by discussion. The study selection process and reasons for exclusion are described in Fig. 1.

Fig. 1
figure 1

Flowchart of study selection process and exclusions. HRQoL health-related quality of life

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Studies were evaluated by using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement to ensure quality [13]. A maximum of 22 points can be reached within STROBE. Studies reaching scores above 19 points were considered as having very high quality, 18–15 points as high quality, 14–11 points as moderate quality and 10 points or less as low quality. Retrieved data regarding sample size, sample characteristics, domains of HRQoL, and influencing factors of HRQoL were collected in supplemental Table 1.

Results

22 studies met the inclusion criteria: 14 studies with a cross-sectional design, 6 studies with a prospective design and 2 mixed-methods studies were included. The studies assessed between 12 and 555 HTx patients, with an average sample size of 119.78 patients. Participants in these studies were mostly male (range 62.8–100%). The age within groups ranged from 43 ± 13 years to 61.2 ± 11.4 years. Frequently reported underlying diagnoses as a reason for HTx were nonischaemic cardiomyopathy and dilated cardiomyopathy. Three studies used the same data sample of 555 HTx patients transplanted between 1990 and 1999 in four American medical centres [14,15,16]. For more information on each study, see supplemental Table 1.

Most frequently, generic measurements for HRQoL were found. The SF-36 was used (8 times); the abbreviated form SF-12 was encountered once. Secondly, WHOQoL-BREF was applied (7 times; Table 2). Overall, 49 different scales were used in 20 samples, covering a total of 2697 patients.

Table 2 Overview of the selected studies
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Changes of HRQoL over time

Cross-sectional studies

Two cross-sectional studies reported the stability of HRQoL using WHOQoL-BREF and SF-36 at one, three, four to five, and five years posttransplant (Fig. 2; [17, 18]). Only one cross-sectional study highlighted a decrease in 5Q-5D Visual Analog Scale (VAS) scores from 6, 12, 36, 60 months to 10 years after transplant (p = 0.011; Fig. 3). Overall QoL improved significantly in a comparison of one sample 6 months posttransplant to another sample 120 months posttransplant (77.72 to 80.51, p = 0.017) [19].

Fig. 2
figure 2

Changes in SF-36 subscales over time (data of Kugler et al. [22], patients 1 to 2 and 6 to 8 months after transplant n = 54; Saeed et al. [18], patients 1, 3, and 5 years after transplant, n = 80, n = 127, n = 116; Galeone et al. [20], patients > 20 years after transplant, n = 81). PF physical functioning, RP role physical, BP bodily pain, GH general health, VT vitality, SF social functioning, RE role emotional, MH mental health

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Fig. 3
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Changes in 5Q-5D VAS over time (data of Delgado et al. [19], patients 6 months, 1, 3, and 5 years after transplant, n = 52, n = 57, n = 66, n = 62, n = 66; Saeed et al. [18], patients 1, 3, and 5 years after transplant, n = 80, n = 127, n = 116)

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Significantly lower scores in all aspects of SF-36, indicating worse HRQoL, except for mental health at 1, 3 and 5 years posttransplant in comparison to the age- and gender-matched general population were determined in one cross-sectional British study [18]. In their cross-sectional comparison of 81 HTx patients who survived longer than 20 years posttransplant (mean time since transplant 23 ± 3 years) to 52 HTx patients (surviving 6 ± 5 years posttransplant), Galeone et al. reported significantly lower SF-36 scores in the physical functioning (61 vs 74), general health (49 vs 58), vitality (49 vs 58) and social functioning (61 vs 77) and in the physical (57 vs 67) and mental component summary (58 vs 68) in the older patient sample (all below p < 0.05) [20].

Prospective studies

Kugler et al. described a significant increase in the physical and psychosocial domains of HRQoL (according to SF-36) from before transplant to 60 months after transplant without providing exact data on SF-36 subscales [21]. From 4–8 weeks to 5–7 months posttransplant, only an increase in the role physical subscale of SF-36 was found (75.1 vs 87.5, p < 0.03) [21]. According to Jakovljevic et al. [23], HRQoL, measured with the Minnesota Living with Heart Failure Questionnaire (MLHFQ), was significantly better at 3, 6, and 12 months posttransplant (p < 0.05, scores decreasing from 72 to 29, indicating better overall HRQoL) in comparison to patients with a left ventricular assist device (LVAD).

Changes in physical function and bodily pain

With regard to physical function, HRQoL increased significantly in HTx patients in comparison to LVAD patients at 12 months [22, 23]. Scores regarding bodily pain differed when compared to general population norms [22, 24]. At 6 months posttransplant, a significant improvement of bodily pain was reported with better scores than a general population sample [22], whereas patients with a mean time of 4.5 years since transplant had significantly worse scores regarding bodily pain than the general population [24].

Influence of sociodemographic factors on HRQoL

Satisfaction with the physical (58.3% vs 62.8%) and psychological domains (58.3% vs 65.1%) of HRQoL was lower in female patients, whereas female patients were more satisfied with social relations (100% vs 53.5%) and environmental factors (83.3% vs 65.1%) [25]. Delgado et al. reported a negative association of female gender with EQ-5D scores [19]. There was no statistically significant difference in SF-12 scores between female and male patients in one cross-sectional study [26]. In adults older than 60 years, a greater satisfaction with QoL and social support (according to the QLI) was reported in comparison to adults younger than 45 years and aged between 45 and 59 years (p < 0.001) [15].

Influence of psychological factors on HRQoL

Demoralized patients had significantly lower scores in all domains of WHOQoL-BREF, indicating worse HRQoL, than nondemoralized patients (all domains below p ≤ 0.01) [27]. Depression (Beck’s Depression Inventory [BDI] score >8) is negatively correlated with the physical (WHOQoL-BREF, r = −0.45, p < 0.01), social (r = −0.49, p < 0.05) and psychological domains (r = −0.30, p > 0.01) of HRQoL in one study and to physical and mental component summaries in another (SF-36, r = −0.56, r = −0.66, p < 0.05, p < 0.01) [28, 29]. Depressed patients had significantly lower scores in all SF-36 domains (all below p < 0.0013) [30].

At one year and over five years posttransplant, family support was a predictor of the physical (p < 0.01) and psychosocial domains (p < 0.01) of HRQoL. The influence of tangible support on physical (r = 0.29, p < 0.05), social (r = 0.28, p < 0.05) and environmental (r = 0.26, p < 0.05) domains of HRQoL (WHOQoL-BREF) measured by Interpersonal Support Evaluation List (ISEL) is shown. ISEL total score and belonging were associated with physical (r = 0.31, p < 0.05; r = 0.35, p < 0.01) and social domains of HRQoL (r = 0.37, p < 0.01; r = 0.41, p < 0.01), and ISEL appraisal with social QoL (r = 0.28, p < 0.05) [31]. Self-perceived family support was a predictor of the physical and mental component summary in multivariate analysis [28]. Satisfaction with emotional, tangible, and social support was associated with better HRQoL (low scores indicating more satisfaction, r = −0.60, r = −0.50, r = −0.54, p < 0.0001) [16].

All domains of WHOQoL-BREF were correlated with different coping strategies (positive correlation with focus on problem and negative correlation with focus on emotion). Psychological, social and environmental domains were associated with focus on social support [32]. Overall HRQoL (WHOQoL-BREF) correlated significantly with sense of coherence (r = 0.66), optimism (r = 0.53), and self-efficacy (r = 0.62; all p < 0.004) [33].

Influence of physical factors on HRQoL

Holtzman et al. assessed pain in a sample of 92 HTx patients [24]. 10.9% of patients reported having severe or very severe pain. In contrast to one general population sample, patients with at least a mild level of pain reported significantly worse scores in all domains of SF-36, indicating worse HRQoL, whereas HTx patients with no or little pain described having similar levels of social functioning, role interference due to emotional difficulties, and mental health [24].

Patients with severe gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale >1) reported lower scores in all SF-36 domains [34]. Phan et al. [26] underlined high levels of sexual dysfunction (50% of women and 78% of men, mean age 61.2 ± 11.4 years). Patients with sexual dysfunction had significant lower subscores of SF-12 in general health (41.1 vs 52.8, p = 0.02), physical health (38.6 vs 50.0, p = 0.02), physical functioning (38.2 vs 50.0, p = 0.01) and physical role limitation (39.5 vs 50.3, p = 0.01) than patients without sexual dysfunction. Additionally, a poor perceived impact of oral health on HRQoL was reported (mean score 24.43 of a total 196 points) [35].

At 5–10 years after transplant, social and economic satisfaction, domains of QLI, were a significant predictor of survival (hazard ratio 0.05, range 0.00–0.75, p = 0.03) in multivariate analysis, as were education, coexisting cardiovascular and hematologic illnesses, NYHA classes I and II, compliance with the medical regimen, cumulative infections and being married. Patients surviving 5–10 years after heart transplant reported significantly better HRQoL than nonsurviving patients (higher scores in all domains of QLI) [14].

Discussion

Regarding the development of HRQoL, the stability of HRQoL up to 10 years posttransplant is to be highlighted. Two cross-sectional studies support the long-term stability of QoL up to 5 years posttransplant. In comparison to a general population sample, significantly lower scores in all aspects of SF-36 except for mental health at 1, 3 and 5 years posttransplant were determined. In summary, older patients were more satisfied with HRQoL. Demoralized and depressed patients had lower scores in all SF-36 domains. Satisfaction with social, emotional, tangible and family support was associated with better overall HRQoL scores and physical and psychosocial domains. Several coping strategies (focus on problem, focus on social support) correlated with better HRQoL. Pain, sexual dysfunction and gastrointestinal symptoms have a negative impact on HRQoL. Social and economic satisfaction, components of QLI, were significant predictors of survival at 5–10 years after transplantation. Generic scales such as SF-36 (8 times) and WHOQoL-BREF (7 times) were encountered most often in data assessment.

The impact of gender on HRQoL in HTx patients is difficult to determine since gender is rarely analyzed separately. The majority of assessed patients in all studies were male, and results regarding gender differences were inconclusive. Small gender differences in HRQoL of heart failure patients have been reported [36, 37]. The examination of a possible gender difference is therefore of particular interest.

Conway et al. described in their review of qualitative studies of HRQoL in HTx patients that HTx patients tend to have negative psychological experiences, such as depression. Psychological well-being was positively influenced by social support in their analysis [38]. Our results regarding the impact of depression and family and social support on HRQoL support these findings.

Greater symptom burden, including pain, sexual dysfunction, and several gastrointestinal symptoms, and prevalence, lower age and higher NYHA classification were predictors of worse HRQoL in heart failure patients [9]. Again, our results highlight the negative impact of pain, gastrointestinal symptoms, sexual dysfunction and poor oral health on overall HRQoL.

Nonsurviving heart failure patients in a 3-year follow-up study reported worse overall HRQoL (according to MLHFQ) and a decrease in physical functioning, physical role limitation, bodily pain and general health (Medical Outcome Study 36-item General Health Survey, RAND36) than survivors at baseline [7]. Similar results for HTx patients surviving 5–10 years have been described [14].

Limitations

Most of the included studies had a cross-sectional design. Cause and effect relations cannot be determined in this study design, limiting validity and assessment of confounding bias. Regarding this analysis, a potential selection bias must be addressed, since the selected articles only regard adult HTx patients in the context of HRQoL. In addition, only a small sample of articles was chosen. This reduces generalizability. Furthermore, articles not published in English or with a qualitative approach were excluded.

Conclusion

This systematic review has reported the development of posttransplant HRQoL in HTx patients, influencing factors of HRQoL, and frequently used assessment tools of HRQoL. Further research regarding possible gender differences in HRQoL of HTx patients is needed. The negative impact of psychological and physical factors, such as depression, pain, gastrointestinal symptoms, and sexual dysfunction, on HRQoL of HTx patients is to be considered in clinical research and patient care. Research about other possible influencing factors on HRQoL of HTx patients, that have already been reported in heart failure patients, needs to be conducted since our review does not provide information on important sociodemographic characteristics such as education and marital status [39]. With regard to the scales used, a lack of sensitivity of SF-36 and QLI in a small sample of cardiac patients has been reported [40]. Generic scales to assess HRQoL were mainly used, which are likely to have a lower sensitivity than disease-specific scales. In only one patient sample, the QLI cardiac version was used for data collection. For this reason, small changes in QoL were possibly not detected. Therefore, disease specific scales need to be incorporated in future research to specify results. Awareness of various influencing factors, such as pain and sexual dysfunction, on HRQoL in HTx patients is required to improve screening and communication with patients.