Association between type D personality, depression, and oxidative stress in patients with chronic heart failure.

OBJECTIVE: To examine whether markers of oxidative stress differ as a function of Type D personality, depression, and chronic heart failure (CHF) etiology. Type D (distressed) personality and depression are related to poor cardiac prognosis. Because patients with CHF are characterized by increased oxidative stress, this may be a candidate mechanism responsible for the adverse prognosis in emotionally distressed patients with CHF. METHODS: Serum levels of xanthine oxidase (XO), inducible heat shock protein (Hsp)70, and deoxyribonucleic acid damage marker 8-OHdG were measured in 122 patients, and effects of Type D, depression, and etiology were assessed. RESULTS: CHF patients with Type D personality had lower levels of Hsp70 than non-Type D patients (6.48 ng/mL versus 7.85 ng/mL, p = .04, d = 0.26), and in case of an ischemic etiology, higher levels of XO (13.57 ng/mL versus 9.84 ng/mL, p = .01, d = 0.98). There were no significant univariate differences for depression. When adding depression as an additional independent variable in the Type D analysis, the effect of Type D personality remained significant (F = 5.460, p = .02) and was independent of depression (F = 0.942, p = .33). The ratio of XO to Hsp70 was significantly higher in Type D patients with CHF as compared with non-Type D patients (6.14 versus 2.83, p = .03, d = 0.39), independent of etiology class. CONCLUSION: CHF patients with Type D personality are characterized by an increased oxidative stress burden, apparent in the decreased antioxidant levels and an increased oxidative stress ratio.

Incidence and prognostic significance of sustained ventricular tachycardias in heart failure patients implanted with biventricular pacemakers without a back-up defibrillator: results from the prospective, multicentre, Mona Lisa cohort study.

AIMS: The aim of this study was to investigate the 12-month incidence, predictive factors, and prognosis of sustained ventricular tachycardia (VT) in chronic heart failure patients implanted with biventricular pacemakers without a back-up defibrillator (CRT-P), assessed by continuous intracardiac ventricular electrograms. METHODS AND RESULTS: The Mona Lisa study, a prospective, multicentre, cohort study, designed to determine the incidence of sustained VT and its prognostic impact in CRT-P recipients within the year after implant enrolled 198 patients with moderate or severe chronic heart failure, despite optimal pharmacological therapy. An independent committee reviewed the data from all arrhythmic episodes as well as causes of death according to predefined criteria. During a mean follow-up of 9.8 +/- 3.1 months after implantation, 8 patients experienced at least one episode of sustained VT [4.3%; 95% confidence interval (CI), 1.1-7.5] and 21 deaths occurred, giving a 12-month mortality rate of 11.7% (95% CI, 6.4-16.9). The presence of sustained VT was associated with a high risk of sudden cardiac death (SCD) and the lowest 12-month overall survival (P < 0.0001). CONCLUSION: The incidence of sustained VT remains relatively low in the first year after CRT-P implantation, but when present appears closely associated with short-term adverse outcomes, especially SCD. This emphasizes the possible value of remote monitoring to detect high-risk patients for urgent upgrading.

Vital exhaustion in chronic heart failure: symptom profiles and clinical outcome.

OBJECTIVE: The aim of this study was to examine the components of vital exhaustion (VE) in chronic heart failure (CHF) patients and to examine whether psychological symptom profiles based on these components are differently associated with health status and cardiac rehospitalization. METHODS: Consecutive CHF patients (N=381) were assessed for VE at baseline using the Maastricht Questionnaire and assessed for health status at 6-month follow-up using the Minnesota Living with Heart Failure Questionnaire. Information on cardiac rehospitalization was obtained from the patients' medical records. RESULTS: Principal component analysis revealed four essential features of VE: fatigue, cognitive-affective depressive symptoms, sleep difficulties, and lack of concentration. Latent class cluster analysis using these components identified three subgroups with different symptom profiles: a subgroup without VE, a first vitally exhausted subgroup (VE1; fatigue and lack of concentration, but with a relative absence of cognitive-affective depressive symptoms and sleep difficulties), and a second more severe, vitally exhausted subgroup (VE2; elevated levels of all components). Both vitally exhausted subgroups were more likely to have impaired health status (VE1: beta=.36, P<.001; VE2: beta=.71, P<.001). VE2 was also associated with an increased risk of cardiac rehospitalization at 6-month follow-up (odds ratio=2.98; 95% confidence interval=1.01-8.83; P=.049). CONCLUSIONS: VE in CHF comprised four components (fatigue, cognitive-affective depressive symptoms, sleep difficulties, and lack of concentration) from which three different symptom profiles were derived. Subgroups with symptoms of VE were associated with adverse clinical outcome in CHF. In clinical practice, these results may help identify distinct groups of patients with potentially differential risks of adverse health outcomes.

Symptoms of fatigue in chronic heart failure patients: clinical and psychological predictors.

OBJECTIVE: To examine the role of clinical and psychological characteristics as predictors of fatigue in CHF. BACKGROUND: Little is known about predictors of fatigue in CHF. Next to heart failure characteristics, depressive symptoms and type-D personality may explain individual differences in fatigue. METHODS: At baseline, 136 CHF outpatients (age

Vagus-brain communication in atherosclerosis-related inflammation: a neuroimmunomodulation perspective of CAD.

The current understanding of the pathophysiology of atherosclerosis leading to coronary artery disease (CAD) emphasizes the role of inflammatory mediators. Given the bidirectional communication between the immune and central nervous systems, an important question is whether the brain can be "informed" about and modulate CAD-related inflammation. A candidate communicator and modulator is the vagus nerve. Until now, the vagus nerve has received attention in cardiology mainly due to its role in the parasympathetic cardiovascular response. However, the vagus nerve can also "inform" the brain about peripheral inflammation since its paraganglia have receptors for interleukin-1. Furthermore, its efferent branch has a local anti-inflammatory effect. These effects have not been considered in research on the vagus nerve in CAD or in vagus nerve stimulation trials in CAD. In addition, various behavioural interventions, including relaxation, may influence CAD prognosis by affecting vagal activity. Based on this converging evidence, we propose a neuroimmunomodulation approach to atherogenesis. In this model, the vagus nerve "informs" the brain about CAD-related cytokines; in turn, activation of the vagus (via vagus nerve stimulation, vagomimetic drugs or relaxation) induces an anti-inflammatory response that can slow down the chronic process of atherogenesis.

Decreased impact of post-myocardial infarction depression on cardiac prognosis?

OBJECTIVE: A recent meta-analysis suggests that the impact of post-myocardial infarction (MI) depression on cardiac prognosis has decreased over the last decade. We tested whether depression still significantly affects prognosis in the present health care situation. METHODS: Four hundred ninety-four MI patients were screened for depression. Patients with depression were compared with patients without on cardiovascular events (fatal or nonfatal) during an average follow-up of 2.5 years. Demographic characteristics and cardiac risk factors were controlled for. RESULTS: We found that depression was associated with the occurrence of cardiovascular events in both univariate [hazard ratio (HR), 1.84; 95% confidence interval, 1.24-2.72] and multivariate analysis (HR, 1.56; 1.02-2.38). CONCLUSIONS: Depression still has an independent impact on cardiac prognosis after MI, but this influence is smaller than found in early studies. Improvements in general care for MI and better recognition and treatment of post-MI depression may have decreased the impact of depression on prognosis.

Dose escalation trial of the efficacy, safety, and pharmacokinetics of a novel fibrinolytic agent, BB-10153, in patients with ST elevation MI: results of the TIMI 31 trial.

BACKGROUND: Currently available fibrinolytic agents are limited by their ability to restore normal blood flow in only half of patients, the risk of reocclusion, and the risk of intracranial hemorrhage. The genetically engineered agent BB-10153 is activated by thrombin, not plasminogen activator enzymes, which limits its activity to the site of thrombus which may in turn reduce the risk of systemic bleeding. BB-10153 also has a relatively long half-life of 3-4 hours, which may also limit the potential for early reocclusion [1, 2]. METHODS: The study was a phase II, open-label, multi-center, dose escalation, single-dose administration study to determine the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of BB-10153 in ST segment elevation MI (STEMI). STEMI patients (n = 50) received a single dose of BB-10153 at one of six dose levels (1.0, 2.0, 3.0, 5.0, 7.5 and 10 mg/kg). The primary endpoint was TIMI flow grade (TFG) 3 at 60 minutes following the intravenous bolus of BB-10153. RESULTS: Mean area under the curve for drug concentration ranged from 48.0 microg.h/mL in the 1 mg/kg dose group to 788.6 microg.h/mL in the 10 mg/kg dose group. Likewise, mean Cmax generally increased with dose over the entire dose range, from 4.9 microg/mL in the 1 mg/kg dose group to 139.6 microg/mL in the 10 mg/kg dose group. The mean apparent terminal half-life (t1/2) was 4.4 hours (range 2.2 to 7.6 hours). Few patients in the 1-3 mg/kg dosage groups achieved TFG 3 on the one-hour post-dose angiogram (4/20, 20%), and no patients achieved complete ST segment resolution. The 5, 7.5 and 10 mg/kg doses were associated with similar rates of TIMI grade 3 flow of approximately three per seven patients. Pooling TFG 3 data from the 5, 7.5 and 10 mg/kg groups yielded a TIMI grade 3 flow rate of 34% (n = 10/29; range 29-43%). No patients experienced 30-day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during the study. One patient experienced recurrent angina and developed recurrent myocardial ischemia requiring urgent revascularization. Three patients sustained TIMI major bleeding events (one in 1 mg/kg group, two in 7.5 mg/kg group), six patients sustained TIMI minor bleeds (one in the 2, 3, 7.5 and 10 mg/kg groups, two in the 5 mg/kg group), twp patients sustained TIMI minimal bleeds (one in each of the 2 and 10 mg/kg groups) and no patients sustained intracranial hemorrhage (ICH). CONCLUSION: In a dose escalation study of a single intravenous bolus, the novel fibrinolytic agent, BB-10153 was associated with a rise in the mean area under the curve and Cmax for drug concentration over the dose range 1 to 10 mg/kg. Higher doses were associated with a range of TIMI grade 3 flow of 29-43%, and no patients experienced 30-day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during the study. In a dose escalation study of a single intravenous bolus, the novel fibrinolytic agent, BB-10153 was associated with a rise in the mean area under the curve and Cmax for drug concentration over the dose range 1 to 10 mg/kg. Higher doses were associated with a range of TIMI grade 3 flow of 29-43%, and no patients experienced 30-day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during the study.

The distressed (type D) personality is independently associated with impaired health status and increased depressive symptoms in chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a serious condition that is associated with impaired health status and a high prevalence of depressive symptoms. To date, little is known about the determinants of health status and depressive symptoms in CHF. Therefore, the aim of this study was to assess whether Type D personality is associated with impaired health status and increased depressive symptoms in heart failure patients, independent of disease characteristics. METHODS: Eighty-four patients (63 men and 21 women, mean age=65.9+/-12.1 years) with systolic CHF completed four questionnaires to assess Type D personality (14-item Type D Personality Scale [DS14]), health status (Minnesota Living with Heart Failure Questionnaire [MLWHFQ]), depressive symptoms (Center for Epidemiological Studies Depression Scale [CES-D]) and mood status (Global Mood Scale [GMS]) when visiting an outpatient heart failure clinic. Information on clinical variables was obtained from patients' medical records. RESULTS: Type D patients were more likely to experience impairment in health status (18/38=47%) as compared to non-Type Ds (11/46=24%), P=0.027. They also more often reported symptoms of depression; namely 18 of 38=47% versus 6 of 46=13%, P=0.001. When controlling for severity and etiology of CHF, age and gender, Type D remained a significant associate of impaired health status [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.12-7.78] and depressive symptoms (OR 6.3, 95% CI 2.08-19.12). CONCLUSIONS: Type D was associated with impaired health status and increased depressive symptoms in CHF patients. These preliminary findings demonstrate the value of including personality factors in CHF research.

A prospective randomized trial comparing stenting with off-pump coronary surgery for high-grade stenosis in the proximal left anterior descending coronary artery: three-year follow-up.

OBJECTIVES: This study was done to identify the best treatment for an isolated high-grade stenosis of the proximal left anterior descending coronary artery (LAD). BACKGROUND: Percutaneous transluminal coronary angioplasty with stenting (PCI) and off-pump coronary artery bypass grafting (surgery) are used to treat single-vessel disease of a high-grade stenosis of the proximal LAD. Midterm results of both treatments are compared in this prospective randomized study. METHODS: In a single-center prospective trial, we randomly assigned 102 patients with a high-grade stenosis of the proximal LAD (American College of Cardiology/American Heart Association classification type B2 or C) to PCI (n = 51) or surgery (n = 51). Primary composite end point was freedom from Major Adverse Cardiac and Cerebrovascular Events (MACCE) at follow-up, including death, myocardial infarction, cerebrovascular accident, and repeat target vessel revascularization (TVR). Secondary end points were angina pectoris class and need for antianginal medication at follow-up. Analysis was by intention-to-treat (ITT) and received treatment (RT). RESULTS: Mean follow-up time was three years (90% midrange, two to four years). Incidence of MACCE was 23.5% after PCI and 9.8% after surgery; p = 0.07 ITT (24.1% vs. 8.3%; p = 0.04 RT). After surgery a significantly lower angina pectoris class (p = 0.02) and need for antianginal medication (p = 0.01) was found compared to PCI. Target vessel revascularization was 15.7% after PCI and 4.1% after surgery (p = 0.09). CONCLUSIONS: At three-year follow-up (range, two to four years), a trend in favor of surgery is observed in regard to MACCE-free survival with a significantly lower angina pectoris status and significantly lower need for antianginal medication.

Minimally invasive coronary artery bypass grafting versus percutaneous transluminal coronary angioplasty with stenting in isolated high-grade stenosis of the proximal left anterior descending coronary artery: six months' angiographic and clinical follow-up of a prospective randomized study.

OBJECTIVE: We sought to compare minimally invasive coronary artery bypass grafting (surgical intervention) with percutaneous transluminal coronary angioplasty with primary stenting (stenting) in patients having an isolated high-grade stenosis (American College of Cardiology/American Heart Association classification type B2 or C) of the proximal left anterior descending coronary artery. At 6 months, both procedures were compared on the basis of quantitative angiography and clinical outcome. METHODS: Both treatments were compared in a single-center, prospective, randomized study. The primary end point of this study was quantitative angiographic outcome at 6 months. The secondary end point was 6-month clinical outcome. Statistical analysis was performed in accordance with the intention-to-treat principle. RESULTS: From March 1997 to September 1999, patients with angina pectoris caused by an isolated high-grade stenosis of the proximal left anterior descending coronary artery were randomly assigned to surgical intervention (n = 51) or stenting (n = 51). At 6 months, quantitative coronary angiography showed an anastomotic stenosis rate of 4% after surgical intervention and a restenosis rate of 29% after stenting (P <.001). Periprocedural events did not significantly differ between surgical intervention and stenting. After surgical intervention, 2 patients died; no patients died after stenting. After 6 months, no significant difference was found for major adverse cardiac or cerebral events and need for repeat target vessel revascularization. After 6 months, return of angina pectoris, physical work capacity, and use of antianginal drugs did not significantly differ between treatments. CONCLUSIONS: After 6 months, surgical intervention had a significantly better angiographic outcome than stenting in patients with an isolated high-grade stenosis of the proximal left anterior descending coronary artery. Clinical outcome did not significantly differ between treatments.