Annotated Abstracts of Journal Articles
2015, 2nd Quarter
Annotations by Christopher Celano, MD, Jeff Huffman, MD, FAPM, and Scott R. Beach, MD
ANNOTATION (Christopher Celano)
The Finding: The authors performed a secondary analysis of data from the Heart Failure Health-Related Quality of Life Collaborative Registry to determine the prospective relationships between depressive symptoms/diabetes and mortality/cardiac rehospitalizations in 663 patients with heart failure (HF). When looking at depressive symptoms and diabetes individually, only depressive symptoms were associated with mortality and rehospitalizations; diabetes was not. However, a combination of elevated depressive symptoms (PHQ-9 score ≥ 10) and diabetes was associated with higher rates of mortality and cardiac rehospitalizations than either one alone. These relationships remained significant even when controlling for sociodeomgraphic, medical, and medication-related variables.
Strengths and Weaknesses: The main strengths of the study were its moderate sample size, its prospective design, and its systematic approach to obtaining information about cardiac rehospitalizations and mortality. Its main limitation was the likely inclusion of too many covariates (14 in the fully adjusted model) in the Cox regression analyses. This especially was the case when looking at mortality as an outcome, as only 47 individuals died during the follow-up period. Ultimately, this raises the significant possibility of overfitting in the regression analyses. Therefore, the results of the study should be interpreted with caution.
Relevance: The results of these analyses suggest that depression is strongly associated with mortality and cardiac rehospitalization in patients with heart failure. This increases the focus on depression as a potential risk factor of poor outcomes in patients with cardiac disease. While depression’s negative effects on cardiac health have been established in the post-acute coronary syndrome (post-ACS) population (leading to the American Heart Association’s 2014 recommendation that it be considered a risk factor for mortality in the post-ACS population), this manuscript extends those findings to patients with heart failure. It also raises the question of whether screening for depression in heart failure is worthwhile, and it provides support for other studies to determine whether the treatment of depression may improve cardiac outcomes in this high risk cohort. Finally, it suggests that patients with both depression and diabetes are at particularly high risk for poor cardiac outcomes and likely should be identified and closely monitored by clinicians.
Background: More than 22% of individuals with diabetes mellitus have concomitant heart failure (HF), and the prevalence of diabetes in those with HF is nearly triple that of individuals without HF. Comorbid depressive symptoms are common in diabetes and HF. Depressive symptoms are an independent predictor of mortality in individuals with diabetes alone, as well as those with HF alone and are a predictor of rehospitalization in those with HF. However, the association of comorbid HF, diabetes and depressive symptoms with all-cause mortality and rehospitalization for cardiac causes has not been determined.
Objective: The purpose of this study was to evaluate the association of comorbid HF, diabetes and depression with all-cause mortality and rehospitalization for cardiac cause.
Method: Patients provided data at baseline about demographic and clinical variables and depressive symptoms; patients were followed for at least 2 years. Participants were divided into four groups based on the presence and absence of diabetes and depressive symptoms. Cox regression analysis was used to determine whether comorbid diabetes and depressive symptoms independently predicted all-cause mortality and cardiac rehospitalization in these patients with HF.
Results: Patients (n=663) were primarily male (69%), white (76%), and aged 61±13 years. All-cause mortality was independently predicted by the presence of concomitant diabetes and depressive symptoms (HR 3.71; 95% CI 1.49 to 9.25; p=0.005), and depressive symptoms alone (HR 2.29; 95% CI 0.94 to 5.40; p=0.05). The presence of comorbid diabetes and depressive symptoms was also an independent predictor of cardiac rehospitalization (HR 2.36; 95% CI 1.27 to 4.39; p=0.007).
Conclusions: Comorbid diabetes and depressive symptoms are associated with poorer survival and rehospitalization in patients with HF; effective strategies to regularly evaluate and effectively manage these comorbid conditions are necessary to improve survival and reduce rehospitalization rates.
ANNOTATION (Jeff Huffman)
The Finding: The authors found that about 1/3 of ICD patients had elevated anxiety scores on the BAI, and about 1/4 had elevated scores on a measure of generalized anxiety disorder. Not surprisingly, more ICD shocks, and more recent shocks, were associated with higher anxiety. In addition, in a very small randomized pilot trial for high-anxiety ICD patients, the authors found that a low-burden, three-session CBT intervention appeared to lead to sustained beneficial effects on anxiety, compared to almost no change in anxiety in patients who were randomized to usual care.
Strengths and Weaknesses: The main strength of the observational component of the study was systematic inclusion of a substantial number of ICD patients, with use of validated scales to assess anxiety and ICD acceptance, as well as collection of numerous variables to assess their association with anxiety. The main strength of the trial was its novelty—utilizing an intervention to help high-anxiety ICD patients—as well as the practical, low-burden nature of the intervention. The pilot trial had several important weaknesses, especially the very small sample sizes (with only 8 CBT patients and 6 usual care patients in the final primary analysis, a loss of nearly 50% of the participants), seriously limiting any conclusions that can be drawn about the intervention. Furthermore, the majority of eligible patients for the study declined (41 out of 70 declined), so in the end, of 70 eligible patients, 14 patients enrolled and provided full data.
Relevance: Anxiety in ICD patients is a sticky and complex clinical problem. Patients with ICDs are often anxious because of very real fears of the distress and pain associated with sudden firing of the ICD, and this anxiety can substantially limit function. This study confirms that a meaningful proportion of ICD patients have elevated anxiety, and their simple, practical intervention has shown some promise in reducing anxiety in this important cohort. Clearly, further study is needed to determine whether this intervention remains efficacious in larger, carefully controlled studies before such an intervention could be clinically implemented.
Purpose: Stress and anxiety are potential consequences from arrhythmias and implantable cardioverter defibrillator (ICD) shocks that can contribute to substantial morbidity. We assessed anxiety associated with an ICD and whether cognitive behavioral therapy (CBT) reduces anxiety.
Methods: The study consisted of two parts: part 1 (N=690) was a prospective cross-sectional observational study of consecutive ICD patients. Patients completed the Beck Anxiety Inventory (BAI), Generalized Anxiety Disorder Scale (GAD-7), Florida Shock Anxiety Scale (FSAS), and Florida Patient Acceptance Survey (FPAS) psychometric tests. Part 2 (N=29) was a pilot randomized controlled trial of CBT (three sessions in 3 months) vs. usual care (UC) in patients with BAI ≥ 19 from part 1.
Results: The median BAI and GAD-7 scores were 5 and 2, respectively. By BAI scores, 64.5 % had minimal and 3.9 % had severe anxiety. By GAD-7 scores, 73.0 % had low probability of anxiety and 2.9 % had high anxiety. Higher anxiety levels were associated with recent (p=0.017) and total number of shocks (p=0.002). Any shock was associated with fear about shocks (FSAS, p<0.001) and reduced patient ICD acceptance (FPAS, p=0.019). In the pilot trial of CBT, median BAI scores decreased from 24.5 to 11 at 1 year (p=0.031) in the CBT group and GAD-7 scores from 12.5 to 7 (p=0.063); no significant changes in anxiety scores were observed in the UC group.
Conclusions: Severe anxiety was present in a small proportion of ICD patients, but higher anxiety was associated with recent and total number of shocks. The small pilot study suggested that a simple program of CBT might lower moderate-high anxiety with lasting effects to 1 year and supports the need for a larger trial to validate these results.
ANNOTATION (Scott Beach)
The authors examined the association of cluster disorders (stress disorders and fear disorders), individual disorders (major depression, generalized anxiety disorder (GAD), panic disordcer) and symptoms (anhedonia, negative affectivity, and anxious arousal) with major adverse cardiovascular and cerebrovascular events (MACCE) in the five years following coronary artery bypass graft surgery. They found that baseline generalized anxiety disorder, but not other distress disorders such as major depression or fear disorders such as panic disorder, was associated with increased rates of MACCE. They also found that specific negative symptoms were not independently associated with MACCE.
Strengths and Weaknesses: The main strength of the study is the delineation of disorders at the diagnostic and cluster level, as well as the measurement of symptom dimensions. Other strengths included the use of standardized screening tools, a relatively long follow-up period (mean 4.6 years), and inclusion of medical covariates in the analyses. Weaknesses of the study included a racially and ethnically homogenous sample, assessment of psychiatric disorders prior to surgery with no reassessment during the study period, relatively low total number of MACCE, and lack of information about psychiatric treatment received. Oddly, according to the structured interview, GAD could not be diagnosed in the presence of major depression (despite high comorbidity between these disorders), so patients having comorbid depression and anxiety were not included in the GAD analysis. Additionally, the prevalence of generalized anxiety disorder and panic disorder was nearly 5 times higher than in the general population, raising the question of whether these entities were overdiagnosed in the setting of significant pre-surgical anxiety.
Relevance: Negative emotions have been associated with MACCE, though it has remained unclear whether the association pertains most to specific disorders, cluster disorders, or specific symptoms. The findings here suggest that generalized anxiety disorder is specifically associated with MACCE, whereas other diagnoses and symptoms are not. Psychiatric interventions targeting GAD may therefore be indicated for patients undergoing CABG, though further study is needed to determine whether such treatments reduce the risk of MACCE in this population.
Background: Although depression and anxiety have been implicated in risk for major adverse cardiovascular and cerebrovascular events (MACCE), a theoretical approach to identifying such putative links is lacking. The objective of this study was to examine the association between theoretical conceptualisations of depression and anxiety with MACCE at the diagnostic and symptom dimension level.
Methods: Before coronary artery bypass graft (CABG) surgery, patients (N=158; 20.9 % female) underwent a structured clinical interview to determine caseness for depression and anxiety disorders. Depression and anxiety disorders were arranged into the distress cluster (major depression, dysthymia, generalized anxiety disorder, post-traumatic stress disorder) and fear cluster (panic disorder, agoraphobia, social phobia). Patients also completed the self-report Mood and Anxiety Symptom Questionnaire, measuring anhedonia, anxious arousal and general distress/negative affect symptom dimensions. Incident MACCE was defined as fatal or non-fatal; myocardial infarction, unstable angina pectoris, repeat revascularization, heart failure, sustained arrhythmia, stroke or cerebrovascular accident, left ventricular failure and mortality due to cardiac causes. Time-to-MACCE was determined by hazard modelling after adjustment for EuroSCORE, smoking, body mass index, hypertension, heart failure and peripheral vascular disease.
Results: In the total sample, there were 698 cumulative person years of survival for analysis with a median follow-up of 4.6 years (interquartile range 4.2 to 5.2 years) and 37 MACCE (23.4 % of total). After covariate adjustment, generalized anxiety disorder was associated with MACCE (hazard ratio [HR]=2.79, 95 % confidence interval [CI] 1.00-7.80, p=0.049). The distress disorders were not significantly associated with MACCE risk (HR=2.14; 95 % CI .92-4.95, p=0.077) and neither were the fear-disorders (HR=0.24, 95 % CI .05-1.20, p=0.083). None of the symptom dimensions were significantly associated with MACCE.
Conclusions: Generalized anxiety disorder was significantly associated with MACCE at follow-up after CABG surgery. The findings encourage further research pertaining to generalized anxiety disorder, and theoretical conceptualizations of depression, general distress and anxiety in persons undergoing CABG surgery.