The impact of transvenous cardioverter-defibrillator implantation on quality of life, depression and optimism in dialysis patients: report on the secondary outcome of QOL in the randomized controlled ICD2 trial

We found that in patients on dialysis, implantation of an implantable cardioverter-defibrillator (ICD), which is a device that can detect and treat life-threatening heart rhythm disturbances, did not affect quality of life, mood or dispositional optimism significantly in the first year after implantation.

This new data is important because it can help physicians to decide what the best, possibly life-saving, treatment is for the approximately 2 million patients suffering from end-stage kidney disease worldwide. Unfortunately, kidney failure requiring chronic dialysis treatment is associated with an increased risk of death and poses a major negative effect on a patient's physical and mental well-being. Preventive implantation of an ICD is not uncommon in these patients. However, the physical and psychological impact of preventive ICD implantation in these vulnerable patients is unknown. It was our goal to shed light on this by using three questionnaires (SF-36, GDS-15 and LOT-R) to map the physical and mental condition of 177 dialysis patients with an age of 55–81 years, with moderate to normal cardiac function. After filling out the questionnaires, 80 patients received an ICD, while the remaining 91 patients received standard care. One year later, all patients were asked again to complete the same three questionnaires. The results of the patients with an ICD were compared with the patients without an ICD, and we found no differences between both groups.

The incidence of end-stage renal disease (ESRD) in the United States in 2017 was 370 per million/year [1]. ESRD poses a high burden of disease, causing physical and psychological harm [2‐5]. Dialysis treatment, although life-saving, is often perceived as burdensome and negatively impacts quality of life (QOL); patients on chronic dialysis are at high risk of anxiety and depression [2, 6‐12]. Patients treated with dialysis are reported to be at high risk of malignant ventricular tachyarrhythmia, although reports in the literature likely overestimate sudden cardiac death incidence in this population [1, 13, 14]. Patients known to have life-threatening arrhythmias or sudden cardiac arrest survivors may be eligible for prophylactic use of an implantable cardioverter-defibrillator (ICD) to increase life expectancy [15‐18]. ICD implantation can impact psychological well-being of ICD-patients by reduction of anxiety with regard to sudden cardiac death by providing reassurance or feelings of security. On the other hand, in a subgroup of ICD-recipients, an ICD is also known to cause adverse psychological events like anxiety and depression [19‐22]. ICD-patients report that living with an ICD can introduce a number of physical and psychological adjustment issues, such as fear of defibrillation, fear of driving or (temporary) loss of driver’s license, fear of isolation, fear of device failure and fear of sexual- or physical activity [23]. Anxiety following device implantation could lead to alteration of leisure-time activities, e.g. refraining from enjoyed activities such as sports or hobbies, which in turn could lead to diminished QOL. Even partners of ICD patients can experience psychological distress levels as high as that of ICD-recipients [24]. An ICD shock can be experienced as extremely traumatizing. Likewise, dialysis treatment is known to cause psychological distress and to negatively impact QOL [25]. Comorbidity and the risk of complications in this vulnerable group make it unclear how these (potentially) life-saving therapies concomitantly affect physical and mental well-being, which are important but under-exposed variables. Our study group previously described the value of prophylactic ICD therapy in patients on chronic dialysis with left ventricular ejection fraction (LVEF) ≥ 35% [14]. Presently, however, the effect of an ICD implantation on the physical and mental state of patients on dialysis is unknown. The purpose of the current prespecified substudy of the randomized controlled ICD2 trial was to prospectively evaluate the impact of ICD implantation on QOL, mood or dispositional optimism in patients on maintenance dialysis.

Previously we reported on the quantitative data of the impact of ICD therapy in patients undergoing dialysis, with respect to survival and adverse effects, by executing a randomized clinical trial [14]. In this paper, we report on the longitudinal assessment of the physical and mental disease burden of ICD-recipients on dialysis (n = 80) versus patients undergoing dialysis without an ICD (n = 91), using three validated self-report questionnaires. In this per-protocol subanalysis of the ICD2 trial we found that in ESRD patients undergoing dialysis, ICD implantation did not (negatively or positively) affect QOL, mood or dispositional optimism in the first year post-implantation. Multiple regression analysis showed that a kidney transplantation during the 1-year follow-up period significantly contributed to changes in depression from baseline to follow-up (p = 0.047), with patients who had a transplantation reporting less depression at follow-up. Additionally, patients receiving a transplantation reported better General Health at 1-year follow-up.

To the best of our knowledge, we are the first to report on the impact of an ICD on QOL in this population. Early recognition (of patients at high risk) of adverse psychological events is of paramount importance for timely intervention. In comparison with other reports of QOL in ICD-recipients or reports of QOL among patients on dialysis, our trial consists of a relatively large population (n = 188) [21, 22]. Also, the follow-up duration of the current study of 12 months offers valuable insights. Moreover, our trial design included a proper control group. Also, we assessed the preimplantation scores of the three questionnaires, which is an important strength of this trial. Reliable and valid screening devices were used for measuring mental well-being and certain traits that influence coping behaviour. The fact that we have not been able to demonstrate an effect of ICD implantation on the mentioned scales does not seem to be based on an underpowerment of this study. As we are the first to perform a prospective evaluation of the effect of ICD therapy on the physical and mental state of patients with ESRD we cannot compare our results with other reports from the literature.

Multiple studies evaluating QOL in patients on dialysis report high rates of depression and anxiety [6, 7, 33]. Kim et al. assessed QOL among hemodialysis patient and found similar health-related QOL scores compared to our results [33]. Also, Nagasawa and colleagues evaluated the effect of QOL on medication compliance among 92 dialysis patients and found QOL-scores comparable to QOL-scores in this report [7]. Adaptation distress among ICD-recipients in the general population has also been described in several reports [11, 23]. However, these reports mostly concern cross-sectional data, or longitudinal data with small sample size, and are lacking a proper control group without an ICD. Also, consensus regarding the relationship of QOL and ICD implantation is lacking because of equivocal trial outcomes [11, 21‐23, 34]. Kamphuis et al. assessed QOL and depressive symptoms in a 12-month longitudinal study among 132 ICD-recipients versus 35 patients without ICD and found clinically significant depressive symptoms in 22–66% of ICD recipients throughout the first year [21]. Lewin et al. conducted an RCT to assess the effect of cognitive behavioural rehabilitation on QOL and depression in 192 patients scheduled to receive an ICD and after 6 months following ICD-implantation [35]. However, this study group did not include a control group that did not undergo ICD-implantation. Also, both randomization groups were not comparable with regard to baseline QOL and depression scores [35]. Friedman et al. mapped the QOL and anxiety among 48 ICD recipients in a cross-sectional study and found that younger patients were at the highest risk of psychological distress and poor QOL [22]. Irvine et al. performed a randomized controlled trial to assess the impact of ICD implantation on QOL among 317 patients known with sustained ventricular arrhythmias randomized to receive ICD implantation (n = 157) or amiodarone (n = 160). Authors found, after a follow-up of 12 months, that QOL improved in the ICD group [36]. Conversely, Schron et al. compared QOL outcomes among 416 patients randomized for ICD implantation versus 384 patients receiving anti-arrhythmic drugs and found no significant difference over 1-year follow-up [37]. Magyar-Russel et al. reviewed 42 studies that assessed (symptoms of) depression among ICD recipients, of which only 5 were longitudinal cohort reports, all suggesting no change over time [11]. Fitchet et al. performed an RCT among 12 ICD recipients and found 12 week cardiac rehabilitation can improve anxiety and depression rates [38]. Sears et al. performed an RCT to assess the effect of psychological treatment on depression and QOL among 30 ICD-recipients that received an ICD-shock within 1 year following device implantation. The investigators found that depression, and QOL improved significantly from baseline to postintervention in all participants and concluded that structured interventions for shocked ICD patients involving ICD education and cognitive-behavioural strategies can reduce psychological distress and improve QOL [20].

Our trial had some limitations. Firstly, as in any trial, we had patients from the main trial that did not want to participate in this substudy. The baseline characteristics of the subgroup with completed questionnaires at baseline and 1-year follow-up are depicted in Table 1, in addition to the baseline characteristics of the complete per protocol population. This table shows that both populations are very similar, as expected. Secondly, although the LOT-R is a widely used, and well-validated questionnaire to measure dispositional Optimism, we found a low internal validity in our population, especially for the subscale measuring Optimism. As can be seen in Table 3 the Cronbach’s alphas for Optimism (α = 0.50 at baseline, α = 0.53 at follow up) and Pessimism at follow up (α = 0.61) yielded a lower internal consistency than expected. One explanation for this is the limited number of items the subscales consist of. An additional explanation for the low internal consistency of the subscale Optimism, both at baseline and at follow-up, is the fact that the intercorrelations between the items the subscale consists of are quite low. Thirdly, absence of significant findings may be the result of the limited sample size. However, with respect to reports in literature, our population is relatively large and has a control group. Also, we performed a sensitivity analysis and found that for all QOL outcomes the differences in changes in QOL outcomes between the treatment arms were both quantitatively (in terms of effect sizes) and quantitatively (in terms of statistical significance) similar. Furthermore, our population consisted of a highly selective patient group. Consequently, results may not be generalizable to the overall dialysis/ICD population. However, we found approximately equal levels of QOL in our dialysis population compared with reports in the literature [5, 24, 33]. Also, we did not include patients with a class I indication for ICD implantation according to the current guidelines. The long-term effect of ICD implantation in dialysis patients has not been charted, as follow up in our trial was performed following a time span of 1 year. The poor prognosis of this vulnerable patient group would lead to high rate of missing values because of high mortality in case of longer follow-up. Furthermore, prospective collection of multiple extensive questionnaires can be experienced as bothersome by patients, which does not benefit the response rate. However, distress levels may change over time. It could be hypothesized that after longer follow up an ICD could provide feelings of safety and results in a better QOL due to less anxiety through better adaptation. Conversely, feelings of anxiety for imminent shock and occurrence of adverse events, could lead to a further decrease in QOL after longer follow-up. We did not map the social support of patients.

In conclusion, in the current trial we shed light on the physical and psychological well-being of ESRD patients on dialysis undergoing prophylactic ICD implantation for primary prevention. Our data suggests that ICD implantation does not seem to influence QOL, negatively or positively, among dialysis patients during 1-year follow-up. Based on these results, we believe that our study provides evidence that in case of a hard indication for preventive ICD implantation, this procedure should not be withheld in this population. Further study is warranted for evaluation of long-term implication of an ICD in this vulnerable patient group.