1. Introduction
The importance of investigating cardiovascular disease (CVD) in frail patients has been identified as a priority for care, the main interest being the recognition and implications of frailty on the cardiac outcomes [
1]. Frailty is defined as a syndrome having as its main characteristics the reduced biological reserve and functional decline of the whole organism, which lead to an increased vulnerability of the individual, even to minor stressors [
2]. Although frailty is related to chronological age and is often referred to older people, not all frail people are aged. Some medical conditions could increase the frail status, even in younger population.
Identifying frail syndrome in CVD patients or in those undergoing cardiac surgery has relevant implications for clinical practice. Clinical outcomes of CVD tend to be worse among frail individuals who have a higher rate of morbidity and mortality [
3]. The presence of frailty may reduce the benefits of surgery in some cardiac diseases because of competing risks. Falls, functional impairment, health resource utilization, and hospitalizations are conditions related to a pre-frail and frail status, and to adverse outcomes in CVD. Therefore, a frailty assessment should be included in the global evaluation of CVD patients in order to improve the clinical decision-making and planning of therapeutic actions.
A broad range of psychological and social characteristics have been investigated in relation to CVD and risk-related factors. Depression, anxiety and/or psychological distress have also been related to a higher risk of coronary disease, sudden cardiac death, stroke, and all-cause mortality [
4].
The negative impact of depression among cardiac patients has been long clinically recognized and reported in many studies [
5]. Major depressive disorder, current depressive symptoms, and a history of depression are all associated with an increased risk of CVD morbidity and mortality. Depression in patients with CVD is associated with a worse health-related quality of life (QoL). QoL, recurrent cardiac events, a risk of hospital readmissions, and a risk of functional decline and mortality, with a long-term impact on the cardiac function outcomes. High rates of sudden cardiovascular death in depressed patients have been also reported [
6,
7]. Among coronary patients, higher levels of anxiety have been associated with a poorer prognosis and greater recurrence of cardiac events post-myocardial infarction [
8,
9].
The relationship between frailty, psychological factors and their cumulative impact on the outcomes and prognosis in CVD has been paid increasing attention in the last decade. Still, little literature is available in this regard. The investigation of how frailty, depression and anxiety influence the outcomes and prognosis of cardiac disease may contribute to a broader understanding and an increasing awareness on the part of clinicians and healthcare professionals to include an assessment of the psychological factors in the global cardiac evaluation.
5. Discussion
The purpose of this paper was to highlight the impact of depression and anxiety, and of frailty on the clinical outcomes (readmission and mortality, functional decline, QoL) in HF patients. Due to the limited data published on this subject, the mission of the article was only partially accomplished. In this paper we covered, under the global term psychological distress, the level of depression and anxiety perceived by an individual.
Generally, frailty is considered highly prevalent in elderly patients with CVD, being mainly related to a high risk of adverse outcomes, including disability, lower quality of life, hospitalization, admission in nursing facilities, and mortality [
18]. The prevalence of frailty in HF patients is higher than that in the general population and ranges from 15% to 74%. Knowing that frailty can predict negative outcomes in HF patients that can result in disability and/or mortality is of great importance in clinical practice to identify the individuals at risk of frailty and to implement the appropriate measures to reverse this condition’s effects, if possible. The frail HF patients experience different levels of psychological distress due to, on the one hand, the prognostic, and on the other hand the potential complications that could occur in the course of the disease.
The prevalence of depression is high and may be increasing in individuals with HF. Evidence shows a prevalence of depression among patients with HF that ranges from 15% to 36% [
42]. Moderately and severely depressed patients with HF are reported to have a significantly higher mortality than HF patients with mild depression or non-depressed patients. Those reporting severe depression are four times more likely to die within 2 years compared with non-depressed patients. Higher depression rates have been identified in the hospitalized HF patients (ranging from 13.9% to 77.5%) compared to outpatients with HF (ranging from 13% to 48%). Three predictors for depression in CHF hospitalized patients have been identified: functional impairment, the severity of illness and comorbid psychiatric disorder [
43]. Hospitalized depressed patients with CHF, untreated for a depressive condition, result in a worse prognosis, higher demands on health service use and a higher readmission rate associated with increased adverse clinical outcomes. Depression is also related to the severity of HF symptoms; the baseline functional status, including a limitation in the activities of daily living and dyspnea at rest, are reported as being strongly related to depression [
44]. Friedman and Griffin reported significant correlations between depression severity and increased physical symptoms or decreased physical functioning [
45]. In the study conducted by Uchmanowicz and Gobbens, the frail syndrome has been correlated with a higher score of depression and anxiety [
46]. The average values of the HADS-anxiety and HADS-depression were significantly higher in the frail group compared to the non-frail group of patients. Significant positive correlations have been found between the TFI scores and HADS-anxiety (r = 0.60,
p < 0.001), and the HADS-depression (r = 0.66,
p < 0.001) results. This means that increased levels of frailty measured by the TFI scale are accompanied by an increase in the level of anxiety and depression. The results from this study showed a deterioration of QoL in HF patients who had an increase in their level of anxiety and depression, as well as a high frailty-related score. Depression is also related with a higher frequency of readmissions in the hospital in HF patients versus those without depressive symptoms. No data regarding the impact of combined frailty and coexisting depression and anxiety on the clinical outcomes in HF patients, such as the readmission rate or mortality, have been provided in this study.
Depression and anxiety are strongly related to hospitalization, the use of health care resources and recurrent events involving frequent readmissions [
41]. The prevalence of depression and anxiety is high in chronic patients with HF (10–60% depression; 11–45% anxiety). Comorbid depression and anxiety are associated with an increased mortality and health care utilization.
Anxiety appears to be a less investigated dimension in the study of HF. The existing evidence suggests a prevalence of anxiety as high as 63% in HF patients. Few researchers have reported that the presence of anxiety symptoms is an independent predictor of a worsening functional status and more frequent hospitalizations. The association of anxiety with HF patient outcomes has been little investigated, and the results are inconsistent. It appears that anxiety predicted a functional status at 1 year in patients with HF, but not rehospitalization or mortality [
47]. Other research findings showed that in patients with recent acute myocardial infarction and depressed left ventricular function, anxiety was associated with a higher incidence of adverse cardiac events and cardiac death in the subsequent 6–10 years [
41,
46]. High levels of depression and anxiety are considered risk factors for first and subsequent events (readmissions in the hospitals) in HF patients, as presented in the study conducted by Sokorelli et al. [
48]. It has been shown that the first adverse event in HF patients is related to the presence of both medical and psychological factors. The results of the study showed a higher rate of unplanned readmissions due to at least one cardiac event (52%) and a mortality rate of 19% at a 1-year follow-up. The presence of frailty, anxiety and depression were powerful predictors of the outcome of both the first and recurrent events. Some research data showed a statistical relationship between the presence of frailty and the need for HF hospitalization, but not a statistically significant relationship between depressive symptoms and need for HF hospitalization.
A moderate-to-severe depression and anxiety, cognitive deterioration and the presence of frailty along with medical circumstances such as an increasing age, past history of a cardiac disease, LVEF < 40%, and increasing urea and creatinine at discharge, are all associated with the risk of a first event. The HF patients with a moderate-to-severe level of depression have a 1.7 times higher risk for the first event and a 1.8 times higher risk for the recurrent events, while those with a similar level of anxiety have, respectively, a 1.7 and 1.4 times higher risk [
48]. In this study, it was found that both depression and anxiety are related to the risk of recurrent events [
49]. These findings contradict other data reported that has not shown any association between anxiety and mortality, with only depression being associated with negative outcomes and mortality [
44].
Denfeld et al. highlighted the importance of also assessing affective symptoms in HF patients, besides physical frailty [
50]. The results showed that physically frail patients with HF have significantly worse dyspnea and wake disturbances as physical symptoms, and a high-related level of depression, compared with those who are not physically frail. Despite the evidence that high levels of depression in HF frail patients interfere with the physical status, having a negative potential upon the cardiac functioning, anxiety has not been identified in such a way in this study. The authors emphasized the important role of a physical frailty assessment in clinical practice, along with both physical and affective symptoms experienced by patients with HF. The study conducted by Son and Seo showed that depressive symptoms are the most critical predictor of physical frailty in older adults with HF [
51]. The detection of depressive symptoms in older adults with HF may alarm clinicians about the risk of physical frailty in this population [
52]. Therefore, depressive symptoms should be assessed and managed as a comorbid condition for monitoring physical frailty in older adults with HF.
Including both types of symptoms in the assessment of HF patients may raise awareness in the early identification of patients with more advanced HF, especially in circumstances where worse symptoms are associated with an impaired cognition and physical capacity. A worst prognostic is given by the association of frailty with comorbidities that could lead to physical deterioration, cognitive impairment and a psychological dependence resulting in a high risk of non-compliance with HF treatment. Any depressive condition presented in HF patients alters their perception of QoL and affects the health status which, in turn, may negatively impact the patient’s self-care. Zhang et al. showed that psychological distress, including stress, anxiety and depression, accounted for 13% of the variability of the overall QoL total score (the second of seven clusters of importance) [
53].
6. Conclusions
Psychological distress and the frailty status play a key role in predicting the clinical outcomes in patients with heart failure. Still, limited data are available in this regard, and further research in this field is required.
Frail syndrome in HF patients is an independent predictor for adverse events and for mortality. In HF patients, high levels of depression and anxiety, along with frailty, may impede the recovery and worsen the prognostic of the disease without an appropriate management of these comorbidities. As risk factors for the occurrence of the recurrent events, depression and anxiety events, along with frailty and cognitive impairment, negatively impact the QoL in HF patients. In the absence of carefully monitoring the emotional status related to any exacerbation of the disease, the long-term results of the therapeutic interventions might be less efficient in frail patients with HF, compromising their QoL and increasing the risk of rehospitalization and mortality. Psychological support should be focused on the limitation of the negative effects of depression and anxiety on the prognosis of the disease and of survival in patients with heart failure.