The present study aimed to investigate the role of three distinct symptoms of heart-focused anxiety (avoidance, attention, and fear), in relation to general anxiety, depression and physical health in patients referred to cardio-genetic counseling and at higher risk than the average person for serious arrhythmias and SCD because of a personal or a family history of an inherited cardiac disorder (familial LQTS or familial HCM). First, the levels of general anxiety, depression, and physical health in the patients were investigated in comparison to expected scores of the general population, further, the scores of general anxiety, depression, physical health, and heart-focused anxiety of patients with familial LQTS were compared to the scores of patients with familial HCM, and finally, the independent influence of avoidance, attention, and fear were examined in relation to general anxiety, depression, and physical health.
General anxiety, depression, physical health, and heart-focused anxiety
High levels of general anxiety may be one of the major psychological problems among patients referred to genetic counseling for inherited cardiac disorders. In this study, approximately one quarter of the sample had clinical anxiety symptoms, whereas 13.5% scored above cut-off for depression. Further, the mean general anxiety scores were found to be significantly higher in the patients as compared to expected scores of the general population, whereas there were no significant differences in depression scores. The same pattern was found when analyzing patients at genetic risk in comparison to expected scores, this in contrast to previous findings among HCM mutation carriers without manifest disease [11], and in LQTS carriers without abnormal ECG [12]. In the previous reports, baseline data (i.e. before the patients had attended genetic counseling) were not analyzed, as in the present study, which may have biased their findings [11, 12]. In addition, when comparing general anxiety and depression scores in patients with familial LQTS to familial HCM no significant differences were found, which was somewhat unexpected since previous research on patients with familial HCM especially has identified poor health-related quality of life in both mental an physical domains [16]. This may suggest that the overall level of general anxiety before receiving genetic counseling is determined by other factors than disease status or the inherited cardiac disorder in question in the present sample. Heart-focused anxiety may be one of the important reasons for elevated general anxiety in patients referred to genetic investigation and counseling for familial LQTS or familial HCM. Common for the patients with familial LQTS and familial HCM receiving genetic investigation and counseling, is a disease threat that runs in the family. The patients may have experienced other family members' disease or have a family history of SCD, factors that are known to cause high levels of heart-focused anxiety [31]. For example, in the present sample 28% of the patients had experienced a sudden cardiac death in a first or second degree relative. Patients with this experience and patients uncertain whether other relatives had undergone genetic testing had higher levels of heart-focused anxiety up to one year after genetic counseling, whereas satisfaction with the procedural parts of genetic counseling predicted decreased levels of heart-focused anxiety over time [23]. Therefore, it is possible that satisfaction with genetic counseling also will lead to decreased levels of general anxiety, however the different subgroups may show different patterns with that, as previous research has indicated[11, 12].
In the present study, patient-reported physical health was overall as expected in a general population. However, physical health differed according to disease status. As expected, patients with a clinical diagnosis of either LQTS or HCM reported poorer physical health compared to expected scores of the general population, whereas patients at genetic risk reported somewhat better physical health. The manifestation of cardiac symptoms may be more likely in the group that already have been diagnosed, especially among the patients with HCM, who in addition to the risk of arrhythmias, can experience quite debilitating cardiac symptoms, which is the most likely explanation of the poorer physical health reported. This was further supported in the subgroup analyses. However, patients at genetic risk also have a substantial risk of having inherited the condition (50% for first-degree relatives), and thus a significant risk that sensations and stimuli from the heart can be potentially life threatening, which is a possible explanation why they presented with similar elevated general anxiety levels as the patients with a clinical diagnosis. However, we did not expect that they would report better physical health than the general population, but this phenomenon has been previously observed in similar populations [11], and may be caused by confounding factors such as younger age in the sample as compared to that of the norm population, or again, the experience of family members' illness, or SCD may cause individuals to value their own health more.
Symptoms of heart-focused anxiety independently related to general anxiety, depression, and physical health
To address the overall aim of the study, the question posed is to what extent levels of general anxiety, depression, and physical health could have been independently influenced by the three distinct symptoms of heart-focused anxiety (avoidance, attention, and fear).
Partially consistent with the hypothesis, the result showed that avoidance and fear were symptoms of heart-focused anxiety that were significantly related to general anxiety, depression, and physical health, but attention was not. Specifically, patients who had higher levels of avoidance and fear were more likely to report higher levels of general anxiety, depression, and poorer physical health. A somewhat larger effect was observed for fear compared to avoidance in predicting general anxiety and depression, whereas avoidance had a stronger association to physical health.
The interpretation of the role of avoidance is not straight forward. Cardio-protective avoidance has been described as one of the cardinal symptoms of heart-focused anxiety [17, 32, 33]. Besides the fact that our findings showed that avoidance was uniquely related to general anxiety and depression, it is in fact one of the recommendations to this patient group [8]. "Cardio-protective avoidance" may equate to good patient adherence to appropriate medical recommendations. That is, a patient who has been given a diagnosis or are at genetic risk of either LQTS or HCM will often be coached to avoiding competitive athletic activity to prevent arrhythmia or sudden cardiac death, as cardio- protective avoidance. Avoidance of such activities does in that case not signify fearful symptoms, rather, appropriate adjustments to the limitations imposed by the disease, in line with our finding that higher avoidance scores is strongly related to poorer physical health, beyond the effects of gender, age, having children, clinical diagnosis and a recent SCD of a relative, as well as fear and attention. Interestingly, even if avoidance may be perceived as a an adaptive coping response or as a preventive measure, avoidance is also strongly related to higher levels of general anxiety and depression, which indicates that avoidance includes more than being an adaptive coping response. Thus, the current findings suggest that avoidance may be part of a psychological process highly influential in the production of general anxiety and depression, in addition to its relation to poorer patient-reported physical health.
This has implications for the genetic counseling of these patients. By addressing avoidance in the patient, the counselor will have access to important information to target intervention, and can provide information about that normal activities are not harmful. This may be important to prevent a vicious circle for the patients since avoidance may disrupt not only physical activity but also social life and occupational life functioning if such avoidance escalates [33]. In predicting avoidance, a mutation negative result was related to decreased avoidance [23]. Information about consequences of genetic testing may therefore be of influence, since a mutation positive test result will emphasize certain activity restrictions, while a negative more or less can rule out the recommendations.
Addressing fear of SCD is according to genetic counseling literature the main concern of psychological counseling in LQTS and HCM patients [13]. Results from the hierarchical regression analyses show that besides from significant effects of recent SCD in the family and cardio-protective avoidance, fear about heart sensations is the symptom that is strongest associated to general anxiety and depression, giving support to that this is a concern also to be reckoned with in genetic counseling of these patients. This tally also with previous research which found that perceived risk of SCD were associated with higher levels of general anxiety, depression and poorer physical health and that perceived risk of symptoms were associated with impaired mental health [11].
In contrast to the two other symptoms, heart- focused attention did not make a unique contribution in explaining the health outcomes even if attention was strongly correlated to general anxiety in particular. This may be due to the high intercorrelation with fear. Finally, gender, age, presence of a diagnosis of LQTS or HCM, and a relative's recent SCD, made significant contributions to the final models. In line with research of anxiety and gender, male gender was associated to less anxiety [34]. Not surprisingly, increasing age and clinical diagnosis of either LQTS or HCM was related to poorer physical health, and finally, a recent SCD in the family was related to higher levels of general anxiety and depression.
Study limitations and strenghts
The design of this study shares the limitations that all cross-sectional designs have regarding control, causality and generalizability. Our sample size was relatively small, but the data was, however, collected at three different hospitals in three different health regions of Norway to reduce possible influence of community characteristics. The two patient groups (i.e. patients with familial LQTS and patients with familial HCM) differ from each other in some characteristics; however in the genetic counseling setting it is interesting to analyze them together since they are very similar with regard to the risk they are living with, they share some common disease manifestations, and LQTS and HCM are both autosomal dominant disorders with variable penetrance and disease expression. An important issue in discussing the findings in the present study is whether the research sample is representative of a greater population and what kind of biases might influence the results. Ideally we would like to generalize the findings in our study to all subjects undergoing genetic counseling for LQTS and HCM. The proportion of decliners in the study was 26.6%. The Regional Committee for Medical and Health Research Ethics did not allow collecting information for individuals who did not consent to research. Therefore, it was not possible to compare respondents from non-respondents. The comparison of general anxiety and depression scores with expected scores of the general population was a clear strength of study, since assessing symptoms based only on cut-off points may be of little clinical significance.
Finally, the study group consisted of both patients with a clinical diagnosis and patients at genetic risk, which can be regarded as very different groups. However, controlling for this in the analyses showed that this was meaningful for the study's findings, as it was confirmed that being clinically affected only had a significant relationship to patient-reported physical health, whereas it did not relate to levels of general anxiety and depression.