Effects of Insula Resection on Autonomic Nervous System Activity.

BACKGROUND: The insula is an essential component of the central autonomic network and plays a critical role in autonomic regulation in response to environmental stressors. The role of the insula in human autonomic regulation has been primarily investigated following cerebrovascular accidents, but interpretation of these findings is complicated by lack of control over time-related processes preceding and following cerebrovascular accidents. Surgical resection of tumors in the insula provides unique information about the neural circuits of autonomic dysregulation and subsequent cardiac arrhythmias. METHODS: This study examined autonomic modulation in 2 unique cases during tumor resection of the right and left insula, respectively (WHO grade II low-grade astrocytoma). The patients were monitored for changes in heart rate variability and cardiac arrhythmias before and during tumor resection. RESULTS: Right insular tumor resection was accompanied by significantly increased parasympathetic activity followed by bradyarrhythmias. Removal of the left insula did not change autonomic indices. CONCLUSIONS: These findings suggest that the right insula plays a critical role in parasympathetic autonomic modulation and subsequent cardiac arrhythmias. Additional research is needed to establish the long-term effects of right versus left insula resection as related to autonomic dysregulation and adverse brain-heart interactions, particularly in patients at risk of cardiac arrhythmias.

Emotional, neurohormonal, and hemodynamic responses to mental stress in Tako-Tsubo cardiomyopathy.

Tako-Tsubo cardiomyopathy (TTC) is characterized by apical ballooning of the left ventricle and symptoms and signs mimicking acute myocardial infarction. The high catecholamine levels in the acute phase of TTC and common emotional triggers suggest a dysregulated stress response system. This study examined whether patients with TTC show exaggerated emotional, neurohormonal, and hemodynamic responses to mental stress. Patients with TTC (n = 18; mean age 68.3 ± 11.7, 78% women) and 2 comparison groups (healthy controls, n = 19; mean age 60.0 ± 7.6, 68% women; chronic heart failure, n = 19; mean age 68.8 ± 10.1, 68% women) performed a structured mental stress task (anger recall and mental arithmetic) and low-grade exercise with repeated assessments of negative emotions, neurohormones (catecholamines: norepinephrine, epinephrine, dopamine, hypothalamic-pituitary-adrenal axis hormones: adrenocorticotropic hormone [ACTH], cortisol), echocardiography, blood pressure, and heart rate. TTC was associated with higher norepinephrine (520.7 ± 125.5 vs 407.9 ± 155.3 pg/ml, p = 0.021) and dopamine (16.2 ± 10.3 vs 10.3 ± 3.9 pg/ml, p = 0.027) levels during mental stress and relatively low emotional arousal (p <0.05) compared with healthy controls. During exercise, norepinephrine (511.3 ± 167.1 vs 394.4 ± 124.3 pg/ml, p = 0.037) and dopamine (17.3 ± 10.0 vs 10.8 ± 4.1 pg/ml, p = 0.017) levels were also significantly higher in patients with TTC compared with healthy controls. In conclusion, catecholamine levels during mental stress and exercise were elevated in TTC compared with healthy controls. No evidence was found for a dysregulated hypothalamic-pituitary-adrenal axis or hemodynamic responses. Patients with TTC showed blunted emotional arousal to mental stress. This study suggests that catecholamine hyper-reactivity and not emotional hyper-reactivity to stress is likely to play a role in myocardial vulnerability in TTC.

Is it possible to differentiate between Takotsubo cardiomyopathy and acute anterior ST-elevation myocardial infarction?

INTRODUCTION: Several studies have investigated the ability of the twelve-lead electrocardiogram (ECG) to reliably distinguish Takotsubo cardiomyopathy (TC) from an acute anterior ST-segment elevation myocardial infarction (STEMI). In these studies, only ECG changes were required - ST-segment deviation and/or T-wave inversion - in TC whereas in acute anterior STEMI, ECGs had to meet STEMI criteria. In the majority of these studies, patients of both genders were used even though TC predominantly occurs in women. The aim of this study is to see whether TC can be distinguished from acute anterior STEMI in a predominantly female study population where all patients meet STEMI-criteria. METHODS: Retrospective analysis of the ST-segment changes was done on the triage ECGs of 37 patients with TC (34 female) and was compared to the triage ECGs of 103 female patients with acute anterior STEMI. The latter group was divided into the following subgroups: 46 patients with proximal, 47 with mid and 10 with distal LAD occlusion. Three ST-segment based ECG features were investigated: (1) Existing criterion for differentiating anterior STEMI from TC: ST-segment depression >0.5mm in lead aVR+ST-segment elevation ≤1mm in lead V1, (2) frontal plane ST-vector and (3) mean amplitude of ST-segment deviation in each lead. RESULTS: The existing ECG criterion was less accurate (76%) than in the original study (95%), with a large difference in sensitivity (26% vs. 91%). Only a frontal plane ST-vector of 60° could significantly distinguish TC from all acute anterior STEMI subgroups (p<0.01) with an overall diagnostic accuracy of 81%. The mean amplitude in inferior leads II and aVF was significantly higher for patients with TC compared to all patients with acute anterior STEMI (p<0.01 and p<0.05 respectively) and the mean amplitude in the precordial leads V1 and V2 was significantly lower compared to proximal and mid LAD occlusion (p<0.01). CONCLUSIONS: Given the consequences of missing the diagnosis of an acute anterior STEMI the diagnostic accuracy of the ECG criteria investigated in this retrospective study were insufficient to reliably distinguish patients with TC from patients with an acute anterior STEMI. To definitely exclude the diagnosis of an acute anterior STEMI coronary angiography, which remains the gold standard, will need to be performed.

Positive affect, anhedonia, and compliance with self-care in patients with chronic heart failure.

OBJECTIVE: Optimal self-care is crucial in patients with chronic heart failure (HF). While the focus of research has been on negative mood states, adequate psychological resources may be required to successfully engage in HF self-care. Therefore, the longitudinal associations of multiple positive affect measures in explaining HF self-care including consulting behavior were examined while adjusting for depressive symptoms and potential covariates (e.g., disease severity). METHODS: In this prospective cohort study, 238 patients (mean age: 66.9 ± 8.6 years, 78% men), with chronic HF completed questionnaires at baseline and 1-year follow-up. Positive affect was assessed with the Positive and Negative Affect Schedule (PANAS) and the Global Mood Scale (GMS). Anhedonia, i.e. diminished interest or pleasure, was assessed with a subscale of the Hospital Anxiety and Depression Scale (HADS). The 9-item European Heart Failure Self-care Behaviour scale was completed to assess HF self-care including consultation behavior. RESULTS: Linear mixed modeling results showed that anhedonia was most strongly associated with both poor self-care (estimate=-.72, P<.001) and consulting behavior (estimate=-.44, P<.001) over time, after adjustment for covariates and depressive symptoms. GMS positive affect was related to better HF self-care adjusting for standard depressive symptoms but not when adjusting for anhedonia. PANAS positive affect was not independently related to self-care. CONCLUSION: Anhedonia was associated with worse compliance with self-care among chronic HF patients over time, irrespective of disease severity and depression. Associations between positive affect and self-care were dependent on the measures used in multivariable analyses.

The relationship between Type D personality, affective symptoms and hemoglobin levels in chronic heart failure.

BACKGROUND: Anemia is associated with poor prognosis in heart failure (HF) patients. Contributors to the risk of anemia in HF include hemodilution, renal dysfunction and inflammation. Hemoglobin levels may also be negatively affected by alterations in stress regulatory systems. Therefore, psychological distress characterized by such alterations may adversely affect hemoglobin in HF. The association between hemoglobin and Type D personality and affective symptomatology in the context of HF is poorly understood. AIM: To examine the relationship between Type D personality and affective symptomatology with hemoglobin levels at inclusion and 12-month follow-up, controlling for relevant clinical factors. METHODS: Plasma levels of hemoglobin and creatinine were assessed in 264 HF patients at inclusion and at 12-month follow-up. Type D personality and affective symptomatology were assessed at inclusion. RESULTS: At inclusion, hemoglobin levels were similar for Type D and non-Type D HF patients (p = .23), and were moderately associated with affective symptomatology (r = -.14, p = .02). Multivariable regression showed that Type D personality (ß = -.15; p = .02), was independently associated with future hemoglobin levels, while controlling for renal dysfunction, gender, NYHA class, time since diagnosis, BMI, the use of angiotensin-related medication, and levels of affective symptomatology. Change in renal function was associated with Type D personality (ß = .20) and hemoglobin at 12 months (ß = -.25). Sobel mediation analysis showed significant partial mediation of the Type D - hemoglobin association by renal function deterioration (p = .01). Anemia prevalence increased over time, especially in Type D patients. Female gender, poorer baseline renal function, deterioration of renal function and a longer HF history predicted the observed increase in anemia prevalence over time, while higher baseline hemoglobin was protective. CONCLUSION: Type D personality, but not affective symptomatology, was associated with reduced future hemoglobin levels, independent of clinical factors. The relation between Type D personality and future hemoglobin levels was mediated by renal function deterioration.

Positive affect dimensions and their association with inflammatory biomarkers in patients with chronic heart failure.

BACKGROUND: In cardiac patients positive affect has found to be associated with improved clinical outcomes, with reduced inflammation being one of the potential mechanisms responsible. METHODS: Positive affect was assessed using The Global Mood Scale (GMS), Positive and Negative Affect Schedule (PANAS), and Hospital Anxiety and Depression Scale (HADS) in patient with chronic heart failure (N=210; 67 ± 9 years, 79% men). Markers of inflammation (TNFα, sTNFr1, sTNFr2, IL-6 and CRP) were measured and averaged at three consecutive time points. RESULTS: The positive affect dimensions of the GMS and PANAS were significantly associated with lower averaged levels of sTNFr2, TNFα and IL-6 (p<.1), even after adjustment for clinical and lifestyle confounders. Positive affect of the HADS was significantly associated with lower averaged levels of hsCRP (p<.1), but was no longer significant after correction for lifestyle confounders and depressive symptoms. CONCLUSION: Positive affect is associated with reduced inflammation in patients with heart failure.

Symptoms of anxiety and cardiac hospitalizations at 12 months in patients with heart failure.

OBJECTIVE: Heart failure (HF) is a leading cause of hospitalization. Clinical and socio-demographic factors have been associated with cardiac admissions, but little is known about the role of anxiety. We examined whether symptoms of anxiety were associated with cardiac hospitalizations at 12 months in HF patients. METHODS: HF outpatients (N = 237) completed the Hospital Anxiety and Depression Scale (HADS) at baseline (i.e., inclusion into the study). A cutoff ≥8 was used to indicate probable clinical levels of anxiety and depression. At 12 months, a medical chart abstraction was performed to obtain information on cardiac hospitalizations. RESULTS: The prevalence of symptoms of anxiety was 24.9% (59/237), and 27.0% (64/237) of patients were admitted for cardiac reasons at least once during the 12-month follow-up period. Symptoms of anxiety were neither significantly associated with cardiac hospitalizations in univariable logistic analysis [OR = 1.13, 95% CI (0.59-2.17), p = 0.72] nor in multivariable analysis [OR = 0.94, 95% CI (0.38-2.31), p = 0.89]. New York Heart Association (NYHA) functional class III [OR = 3.00, 95% CI (1.08-8.12), p = 0.04] and a history of HF-related hospitalizations [OR = 1.18, 95% CI (1.01-1.38), p = 0.03] were independently associated with 12-month cardiac admissions. CONCLUSIONS: The current study found no significant association between symptoms of anxiety and cardiac hospitalizations at 12 months in HF patients. In contrast, clinical indicators (i.e., NYHA class III and a history of HF-related hospitalizations) were significantly associated with admissions due to a cardiac cause. Future studies are warranted to investigate the importance of symptoms of anxiety in HF using a larger sample size and a longer follow-up duration.

Type D personality and course of health status over 18 months in outpatients with heart failure: multiple mediating inflammatory biomarkers.

BACKGROUND: The distressed (Type D) personality is associated with poor health status (HS) and increased inflammatory activation in heart failure (HF). We tested whether multiple inflammatory biomarkers mediated the association between Type D personality and the course of self-reported HS over 18 months. METHODS: HF outpatients (n=228, 80% male, mean age 67.0±8.7 years), filled out the Type D questionnaire (DS14) at inclusion and the Short Form-12 (SF12) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 0, 6, 12, and 18 months. Blood samples at inclusion were analyzed for high sensitive C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and its soluble receptors (sTNFr1, sTNFr2). A multiple mediation latent growth model was tested using structural equation modeling. RESULTS: Type D personality (prevalence=21%) was associated with poorer HS (all scales p<0.001), deterioration of mental HS (p<0.001), and higher TNF-α and sTNFr2 levels in the full mediation model. A higher inflammatory burden was associated with a poorer baseline level and a deterioration of generic physical, mental and disease-specific HS. No mediating effects were found for the multiple inflammatory biomarkers on the association between Type D and baseline self-reported HS, whereas change in physical HS was significantly mediated by the group of five inflammatory biomarkers (p=0.026). CONCLUSIONS: Only the association between Type D personality and change in self-reported physical health status was significantly mediated by inflammatory biomarkers. Future research should investigate whether the association between Type D personality and poor health status may be explained by other biological or behavioral factors.

Beyond Type D personality: reduced positive affect (anhedonia) predicts impaired health status in chronic heart failure.

OBJECTIVE: Type D personality has been associated with impaired health status in chronic heart failure (CHF), but other psychological factors may also be important. AIM: To determine whether non-Type D patients with low positive affect and Type D patients report lower health status, compared with non-Type D patients with high positive affect at 12-month follow-up in chronic heart failure. METHODS: Consecutive CHF outpatients (n = 276) filled out the Short Form-12 (health status) and Health Complaints Scale (disease-specific complaints) at inclusion and 12-month follow-up, and the DS14 (Type D personality) and positive affect (Global Mood Scale) at inclusion. Three groups were composed: non-Type D patients without anhedonia, non-Type D patients with anhedonia, and Type D patients. RESULTS: After controlling for demographic and clinical confounders, and scores at inclusion, anhedonic non-Type D patients reported lower mental health status (beta = -.19, P < .004), and more feelings of disability (beta = .10, P = .04), marginally lower physical health status (beta = -.11, P = .07), and equal levels of cardiac symptoms (beta = .04, P = .43), when compared with non-Type D's without anhedonia. Type D patients reported lower levels of impaired mental health status, more cardiac symptoms and feelings of disability (-.31 < beta < .17, all Ps < .05). A trend was shown for physical health status (beta = -.11, P = .09). CONCLUSION: Non-Type D patients low on positive affect and Type D patients report lower levels of health status in CHF, compared with non-Type D patients with high positive affect. Future studies need to determine whether lack of positive affect is associated with impaired clinical outcome.

Psychological predictors of prognosis in chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is an increasingly prevalent condition with high mortality and morbidity rates. This review examines the role of depression, anxiety, and social support on prognosis in CHF. METHOD AND RESULTS: Prospective studies that examined mortality as an outcome, and assessed depression, anxiety, or social support as associates were included. Methodological qualities were evaluated. In total, 25 studies were identified. Concerning depression, 6 of 15 studies of inpatients, 10 of 11 studies of outpatients, and 1 study of a mixed sample found associations between depression and prognosis, with greater associations rendered by depressive symptomatology in outpatients. Anxiety was not associated with prognosis in one inpatient study and one outpatient study. There was a univariable trend in one outpatient study for anxiety to be associated with prognosis. In two of six studies of inpatients and in two of four studies of outpatients, social support was associated with prognosis. On the basis of methodological quality, studies on depression showed mixed results, no conclusions could be drawn for anxiety because this association was not investigated soundly, and the quality of the social network was not associated with outcome. CONCLUSION: Evidence suggests that depressive symptoms and social support might be associated with prognosis in CHF outpatients, independently of biomedical risk factors. With respect to anxiety, no conclusions can be drawn. Future studies are warranted to disentangle associations with psychological factors.