Chronic depression symptoms and salivary NOx are associated with retinal vascular dysregulation: The SABPA study.

BACKGROUND: Depression has been associated with impaired nitric oxide (NO)-mediated vasodilation and vascular dysregulation (VD). Whether depression and NO levels will disturb retinal haemodynamics is not clear. OBJECTIVES AND METHODS: Associations between the retinal vasculature, diastolic ocular perfusion pressure (DOPP) as measure of hypoperfusion, NO metabolites (NOx) and depression symptoms were assessed. Chronic VD risk markers [depression symptoms (Patient Health Questionnaire/PHQ-9 ≥ 10) and 24 h pulse pressure] were determined in a bi-ethnic cohort (n = 313; 48.6 ± 9 years; 53.9% men). At 3 year follow-up, retinal vessel calibre and retinopathy signs were quantified from digital images. Salivary NOx was obtained pre- and post-flicker light-induced provocation (FLIP). DOPP was defined as diastolic blood pressure minus intraocular pressure. RESULTS: Chronic VD risk was evident in Blacks opposed to acute risk in Whites (P < 0.05). At follow-up, retinopathy (Blacks 60.4%/Whites 39.6%), lower pre-FLIP (µM) and higher post-FLIP NOx (changes from baseline, %), arteriolar narrowing and wider venular calibre values were evident in Blacks compared to Whites, independent of confounders. A wider venular calibre, an index of stroke risk, was associated with chronic depression symptoms [cut point 248 MU: Area under the curve 0.61 (95% CI: 0.51, 0.72); 71% sensitivity; 55% specificity] as well as with hypoperfusion in the Blacks. In this group, arteriolar narrowing was associated with hypoperfusion; and attenuated arteriolar dilation with increased post-FLIP NOx responses. CONCLUSIONS: Chronic depression symptoms may alter NO regulation and facilitate VD. NO-mediated vasoconstriction presumably impeded perfusion, retinal haemodynamics and -remodelling; potentiating stroke risk in Blacks.

Randomized controlled trial of a nursing intervention to reduce emergency department revisits.

OBJECTIVE: To determine whether a nursing intervention delivered at emergency department (ED) discharge would reduce ED revisits. METHOD: A randomized study was conducted in the ED of a tertiary cardiac hospital in Montreal, Quebec. Between November 2006 and March 2010, 3,795 patients were assessed for eligibility based on two risk factors for ED revisits (≥1 ED visit in the past year and ≥6 medications); 132 were randomized to the experimental group (EG) and 133 to the control group (CG). The intervention included one nurse-patient meeting before leaving the ED, with two additional telephone contacts over the next 2 weeks. The primary outcome was time to ED revisits within 30 days after discharge. Secondary outcomes included time to ED revisits over 90, 180, and 365 days and hospitalizations over 30, 90, 180, and 365 days. RESULTS: A planned interim analysis that stopped the study with half of the planned sample showed that the time to ED revisits was similar in both groups at 30 days (p=0.81; revisits: 18.2% in EG, 19.6% in CG), 90 days (p=0.44), 180 days (p=0.98), and 365 days (p=0.75). The only difference identified was a lower hospitalization proportion at 180 days in the EG group (13.6% v. 24.1%; p=0.038). CONCLUSIONS: These findings are consistent with previous research showing that few ED-based interventions are successful in reducing ED returns. Factors other than those targeted by the intervention, including an improvement in usual care, may explain the findings.

The impact of an emergency department nursing intervention on continuity of care, self-care capacities and psychological symptoms: secondary outcomes of a randomized controlled trial.

BACKGROUND: As yet there is no firm evidence about the types of intervention that can reduce emergency room revisits. However, the literature on emergency room revisits suggests patient difficulties with managing their health problems and treatments after discharge may play a role. OBJECTIVES: We carried out a randomized trial of an emergency department-based nursing intervention, but results showed no reduction in revisits (primary outcome). This paper describes the secondary outcomes of the trial: patient perceptions of continuity of care, illness perceptions, self-care capacities, psychological symptoms and medication adherence 30 days after emergency room discharge. DESIGN: Randomized, controlled trial. SETTINGS: The trial was conducted in the emergency department of a tertiary cardiac hospital in Montreal, Canada between November 2007 and March 2010. PARTICIPANTS: The study involved 203 patients, including 108 in the experimental group and 95 in the control group. METHODS: The intervention included one nurse patient encounter before discharge and two phone calls in the 10 days after discharge. Participants provided data 30 days post-discharge on secondary outcomes potentially related to emergency department revisits. RESULTS: Although, as previously reported, the intervention had no impact on the primary outcome of emergency department revisits, the present study demonstrated a significant positive effect on patients' perceived continuity of care (p=.033), self-care capacities (p=.037), anxiety (p=.007) and depressive symptoms (p=.043), and the illness perceptions treatment control subscale (p=.037). No differences were found for other illness perception subscales or medication adherence (all p's>.05). CONCLUSION: Although the intervention did not influence emergency department revisits it did improve secondary outcomes, suggesting pathways for future research.

Cohort Profile: Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) prospective cohort study.

Adapting to an over-demanding stressful urban environment may exhaust the psychophysiological resources to cope with these demands, and lead to sympathetic nervous system dysfunction. The evidence that an urban-dwelling lifestyle may be detrimental to the cardiometabolic health of Africans motivated the design of the Sympathetic activity and Ambulatory Blood Pressure in African Prospective cohort study. We aimed to determine neural mechanistic pathways involved in emotional distress and vascular remodelling. The baseline sample included 409 teachers representing a bi-ethnic sex cohort from South Africa. The study was conducted in 2008-09 and repeated after 3-year follow-up in 2011-12, with an 87.8% successful follow-up rate. Seasonal changes were avoided and extensive clinical assessments were performed in a well-controlled setting. Data collection included sociodemographics, lifestyle habits, psychosocial battery and genetic analysis, mental stress responses mimicking daily life stress (blood pressure and haemostatic, cardiometabolic, endothelial and stress hormones). Target organ damage was assessed in the brain, heart, kidney, blood vessels and retina. A unique highly phenotyped cohort is presented that can address the role of a hyperactive sympathetic nervous system and neural response pathways contributing to the burden of cardiometabolic diseases in Africans.

Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

BACKGROUND: Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. METHODS AND RESULTS: Writing group members were approved by the American Heart Association's Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. CONCLUSIONS: Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.

Bridging the transition from hospital to home: effects of the VITAL telehealth program on recovery for CABG surgery patients and their caregivers.

The purpose of this randomized trial was to determine whether coronary artery bypass graft surgery patients and their caregivers who received telehealth follow-up had greater improvements in anxiety levels from pre-surgery to 3 weeks after discharge than did those who received standard care. Secondary outcomes included changes in depressive symptoms and patients' contacts with physicians. No group differences were noted in changes in patients' anxiety and depressive symptoms, but patients in the telehealth group had fewer physician contacts (p = .04). Female caregivers in the telehealth group had greater decreases in anxiety than those in standard care (p < .001), and caregivers of both genders in the telehealth group had greater decreases in depressive symptoms (p = .03).

Centralized, stepped, patient preference-based treatment for patients with post-acute coronary syndrome depression: CODIACS vanguard randomized controlled trial.

IMPORTANCE: Controversy remains about whether depression can be successfully managed after acute coronary syndrome (ACS) and the costs and benefits of doing so. OBJECTIVE: To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs. DESIGN: Multicenter randomized controlled trial. SETTING: Patients were recruited from 2 private and 5 academic ambulatory centers across the United States. PARTICIPANTS: A total of 150 patients with elevated depressive symptoms (Beck Depression Inventory [BDI] score ≥10) 2 to 6 months after an ACS, recruited between March 18, 2010, and January 9, 2012. INTERVENTIONS: Patients were randomized to 6 months of centralized depression care (patient preference for problem-solving treatment given via telephone or the Internet, pharmacotherapy, both, or neither), stepped every 6 to 8 weeks (active treatment group; n = 73), or to locally determined depression care after physician notification about the patient's depressive symptoms (usual care group; n = 77). MAIN OUTCOME MEASURES: Change in depressive symptoms during 6 months and total health care costs. RESULTS: Depressive symptoms decreased significantly more in the active treatment group than in the usual care group (differential change between groups, -3.5 BDI points; 95% CI, -6.1 to -0.7; P = .01). Although mental health care estimated costs were higher for active treatment than for usual care, overall health care estimated costs were not significantly different (difference adjusting for confounding, -$325; 95% CI, -$2639 to $1989; P = .78). CONCLUSIONS: For patients with post-ACS depression, active treatment had a substantial beneficial effect on depressive symptoms. This kind of depression care is feasible, effective, and may be cost-neutral within 6 months; therefore, it should be tested in a large phase 3 pragmatic trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01032018.

Cardiac resynchronization therapy in patients with heart failure and a QRS complex <120 milliseconds: the Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial.

BACKGROUND: Although the benefits of cardiac resynchronization therapy are well established in selected patients with heart failure and a prolonged QRS duration, salutary effects in patients with narrow QRS complexes remain to be demonstrated. METHODS AND RESULTS: The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial is a randomized, double-blind, 12-center study that was designed to compare the effects of active and inactive cardiac resynchronization therapy in patients with severe left ventricular dysfunction and a QRS duration <120 milliseconds. The trial was interrupted prematurely by the Data Safety and Monitoring Board because of futility and safety concerns after 85 patients were randomized. Changes in exercise duration after 12 months were no different in patients with and without active cardiac resynchronization therapy (-0.7 minutes [95% confidence interval (CI), -2.9 to 1.5] versus 0.8 minutes [95% CI, -1.2 to 2.9]; P=0.31]. Similarly, no significant differences were observed in left ventricular end-systolic volumes (-6.4 mL [95% CI, -18.8 to 5.9] versus 3.1 mL [95% CI, -9.2 to 15.5]; P=0.28) and ejection fraction (3.3% [95% CI, 0.7-6.0] versus 2.1% [95% CI, -0.5 to 4.8]; P=0.52). Moreover, cardiac resynchronization therapy was associated with a significant reduction in the 6-minute walk distance (-11.3 m [95% CI, -31.7 to 9.7] versus 25.3 m [95% CI, 6.1-44.5]; P=0.01), an increase in QRS duration (40.2 milliseconds [95% CI, 34.2-46.2] versus 3.4 milliseconds [95% CI, 0.6-6.2]; P<0.0001), and a nonsignificant trend toward an increase in heart failure-related hospitalizations (15 hospitalizations in 5 patients versus 4 hospitalizations in 4 patients). CONCLUSIONS: In patients with a left ventricular ejection fraction ≤35%, symptoms of heart failure, and a QRS duration <120 milliseconds, cardiac resynchronization therapy did not improve clinical outcomes or left ventricular remodeling and was associated with potential harm. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00900549.

Quality of life and functional capacity in patients with atrial fibrillation and congestive heart failure.

OBJECTIVES: This study sought to assess the impact of rhythm- versus rate-control treatment strategies and of underlying rhythm on quality of life and functional capacity in patients with atrial fibrillation (AF) and congestive heart failure (CHF). BACKGROUND: Although intention-to-treat and efficacy analyses have demonstrated similar cardiovascular outcomes in patients with AF and CHF randomized to rhythm or rate control, effects on quality of life remain to be determined. METHODS: The AF-CHF (Atrial Fibrillation and Congestive Heart Failure) trial randomized 1,376 patients to rhythm- or rate-control strategies. For this pre-specified substudy, Medical Outcomes Short Form-36 questionnaires were administered at baseline and 4 months. Six-min walk tests were conducted at baseline, 3 weeks, 4 months, and 1 year. RESULTS: Quality of life improved across all domains to a similar extent with rhythm and rate control. However, a higher proportion of time spent in sinus rhythm was associated with a modestly greater improvement in quality of life scores. Six-min walk distance (p = 0.2328) and New York Heart Association functional class (p = 0.1712) improved to a similar degree with rhythm and rate control. A higher proportion of time spent in sinus rhythm was associated with a greater improvement in New York Heart Association functional class (p < 0.0001) but not in 6-min walk distance (p = 0.1308). CONCLUSIONS: Improvements in quality of life and functional capacity were similar in patients with AF and CHF randomized to rhythm- versus rate-control strategies. By contrast, sinus rhythm was associated with beneficial effects on New York Heart Association functional class and modest gains in quality of life. (Atrial Fibrillation and Congestive Heart Failure [AF-CHF]; NCT88597077).

Design and baseline data from the vanguard of the Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS) randomized controlled trial.

This paper describes the rationale and design of the vanguard for the Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS), a multicenter, randomized, controlled trial of a patient preference-based, stepped care protocol for persistent depressive symptoms after acute coronary syndrome (ACS). The overall aim of the vanguard phase was to determine whether the patient-preference, stepped care protocol, which is based on the intervention used in the recent Coronary Psychosocial Evaluation Studies (COPES) trial, was feasible in patients with recent ACS who were recruited from 5 geographically diverse sites. Innovative design features of this trial include randomization to either initial patient-preference of treatment or to a referred care arm in which the primary care provider decided upon care. Additionally, delivery of psychotherapy was accomplished by telephone, or webcam, depending upon patient preference. The vanguard phase provides estimates of eligibility and screening/enrollment ratios, patient acceptance of screening, and retention. In this report, we describe the innovative features and the baseline results of the vanguard phase of CODIACS. The data from this vanguard study will be used to finalize planning for a large, phase III clinical trial designed to evaluate the effect of treatment on depressive symptoms, coronary events, and death.

Anxiety sensitivity moderates prognostic importance of rhythm-control versus rate-control strategies in patients with atrial fibrillation and congestive heart failure: insights from the Atrial Fibrillation and Congestive Heart Failure Trial.

BACKGROUND: Patients with high anxiety sensitivity (AS) become extremely anxious with heart rate increases, palpitations, and symptoms of psychological arousal. AS predicts panic attacks. In atrial fibrillation (AF), AS correlates with symptom preoccupation and reduced quality of life. We assessed whether AS is associated with outcomes of rhythm-control versus rate-control in congestive heart failure (CHF) patients with AF. METHODS AND RESULTS: Before random assignment, 933 participants (172 women) in the Atrial Fibrillation and Congestive Heart Failure Trial completed the Anxiety Sensitivity Inventory (ASI). Cox proportional hazards models showed no main effects of treatment (P=0.61) or AS (P=0.72) for time to cardiovascular death, but these factors interacted significantly (P=0.020). High AS patients (upper quartile, ASI ≥33) randomly assigned to rhythm-control had significantly lower cardiovascular mortality than those receiving rate-control (hazard ratio, 0.54; 95% confidence interval, 0.32-0.93; P=0.022). With lower ASI scores (<33), treatments did not differ (hazard ratio, 1.12; 95% confidence interval, 0.83-1.51; P=0.46). The interaction between treatment and dichotomized ASI scores remained significant (P=0.009) after adjustment for covariates including age, sex, hypertension, diabetes, creatinine, ejection fraction, time since first diagnosis of AF, New York Heart Association functional class, depression symptoms, marital status, and baseline ß-blockers, angiotensin-converting enzyme inhibitors, oral anticoagulants, and implantable cardioverter-defibrillators. CONCLUSIONS: Atrial fibrillation and congestive heart failure patients with high AS had better long-term prognosis with rhythm- than rate-control. If replicated, AS should be considered in treatment selection. Research is also needed concerning mechanisms and possible joint AS-AF treatments. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT88597077.

Randomized controlled trial of tailored nursing interventions to improve cardiac rehabilitation enrollment.

BACKGROUND: Short hospital stays for patients with acute coronary syndromes (ACSs) reduce the opportunity for risk factor intervention during admission. After discharge, cardiac rehabilitation can decrease the recurrence of coronary events by up to 25%. However, it remains underused. OBJECTIVES: The aim of this study was to determine whether a nursing intervention focused on individual ACS patients' perceptions of their disease and treatment would increase rehabilitation enrollment after discharge. METHOD: A total of 242 ACS patients admitted to a specialized tertiary cardiac center were randomized to either the intervention or usual care (n = 121 in both groups). The intervention included one nurse-patient meeting before discharge with 2 additional contacts over the 10 days after discharge (mean duration = 40 minutes per contact). The primary outcome was enrollment in a free rehabilitation program offered to all participants 6 weeks after discharge. Secondary outcomes included illness perceptions; family support; anxiety level; medication adherence; and cardiac risk factors including lack of exercise, smoking, body mass index, and diet. RESULTS: The sample was composed of a majority of male, married workers who experienced a myocardial infarction or unstable angina without severe complications. The mean hospital stay in both groups was 3.6 days. There was a significantly higher rate of rehabilitation enrollment in the intervention group (45%) than in the control group (24%; p = .001). For the secondary outcomes, only the personal control dimension of illness perceptions was improved significantly with the intervention. DISCUSSION: Progressive, individualized interventions by nurses resulted in greater rehabilitation enrollment, thereby potentially improving long-term outcome.

A pilot randomized trial of a smoking cessation nursing intervention in cardiac patients after hospital discharge.

BACKGROUND: One fifth of Canadians are smokers despite the availability of community-based smoking cessation programs. It was hypothesized that offering a post-discharge smoking cessation program to cardiac patients would decrease smoking rates at six months. METHOD: This pilot randomized study explored the feasibility, acceptability and preliminary efficacy of a smoking cessation intervention delivered by a smoking cessation nurse specialist (SCNS) to cardiac patients after hospital discharge. SAMPLE: Participants (N=40) were randomized to either a postdischarge telephone intervention delivered weekly for the first month and then monthly until the third month (experimental group [EG]), or referral to usual community care (control group [CG]). FINDINGS: The researchers confirmed the feasibility of recruitment and acceptability of the intervention, but dfficulty with follow-up. The intention-to-treat analysis showed similar smoking cessation rates in both groups at six months (25% EG versus 30% CG; p = 0.72). CONCLUSION: An intensifed follow-up protocol, or a more intensive, comprehensive and multidisciplinary intervention might be required, given the characteristics of the smokers.

Depressive Symptoms and 24-Hour Ambulatory Blood Pressure in Africans: The SABPA Study.

Disturbances in circadian rhythm might play a central role in the neurobiology of depression. We examined the association between depressive symptoms and 24-hour ambulatory BP in a sample of 405 (197 black and 208 Caucasian) urbanized African teachers aged 25 to 60 yrs (mean 44.6 ± 9.6 yrs). Depressive symptoms were assessed using the self-administered 9-item Patient Health Questionnaire (PHQ-9). After adjusting for age, sex, and ethnicity, participants with severe depressive symptoms (PHQ-9 ≥ 15) had higher odds of hypertension defined from ambulatory BP and/or use of antihypertensive medication (odds ratio = 2.19, 95% CI, 1.00-4.90) in comparison to participants with no symptoms. Compared to Caucasians with no depressive symptoms, those with severe symptoms had blunted nocturnal systolic BP drop of 4.7 mmHg (95% CI, -0.5 to 10.0, P = 0.07). In summary, depressive symptoms were associated with the circadian BP profile in black and Caucasian Africans.

Left ventricular versus simultaneous biventricular pacing in patients with heart failure and a QRS complex ≥120 milliseconds.

BACKGROUND: Left ventricular (LV) pacing alone may theoretically avoid deleterious effects of right ventricular pacing. METHODS AND RESULTS: In a multicenter, double-blind, crossover trial, we compared the effects of LV and biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LV ejection fraction ≤35%, QRS ≥120 milliseconds, and symptoms of heart failure. A total of 211 patients were recruited from 11 centers. After a run-in period of 2 to 8 weeks, 121 qualifying patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. The greatest improvement in New York Heart Association class and 6-minute walk test occurred during the run-in phase before randomization. Exercise duration at 75% of peak Vo(2) (primary outcome) increased from 9.3±6.4 to 14.0±11.9 and 14.3±12.5 minutes with LV and BiV pacing, respectively, with no difference between groups (P=0.4327). LV ejection fraction improved from 24.4±6.3% to 31.9±10.8% and 30.9±9.8% with LV and BiV pacing, respectively, with no difference between groups (P=0.4530). Reductions in LV end-systolic volume were likewise similar (P=0.6788). The proportion of clinical responders (≥20% increase in exercise duration) to LV and BiV pacing was 48.0% and 55.1% (P=0.1615). Positive remodeling responses (≥15% reduction in LV end-systolic volume) were observed in 46.7% and 55.4% (P=0.0881). Overall, 30.6% of LV nonresponders improved with BiV and 17.1% of BiV nonresponders improved with LV pacing. CONCLUSION: LV pacing is not superior to BiV pacing. However, nonresponders to BiV pacing may respond favorably to LV pacing, suggesting a potential role as tiered therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00901212.

[A pre assessment for nursing intervention to support tobacco cessation in patients hospitalized for cardiac problems: a pilot study (So-Live)]. / Evaluation préliminaire d'une intervention infirmière de soutien a la cessation tabagique chez des patients hospitalisés pour un problème cardiaque: etude pilote (So-Live).

OBJECTIVE: The aim of this study was to evaluate the effect of a smoking cessation intervention provided after discharge from a specialized cardiac hospital. DESIGN: A randomized pilot study (N = 40); after discharge, the experimental group (EG) received 6 phone calls from a nurse specialized in tobacco cessation counselling. RESULTS: Patients in the EG showed improved scores on two aspects of illness representations (perceive their illness as chronic and reported less negative emotional representations). No significant difference in smoking cessation was observed at 6 months (p = 0.72). CONCLUSION: The non-significant difference may be explained in part by the smoking characteristics within this sample exemplifying the more nicotine dependent "hard core" smokers who persist in their smoking habits despite the serious health consequences incurred by continued smoking. This population of smokers may require a more intensive, specialized intervention to achieve smoking cessation.

Evaluation of resynchronization therapy for heart failure in patients with a QRS duration greater than 120 ms (GREATER-EARTH) trial: rationale, design, and baseline characteristics.

BACKGROUND: Heart failure is considered an epidemic of the modern era. In selected candidates on optimal medical therapy, cardiac resynchronization therapy (CRT) has emerged as a valuable adjunctive treatment. Despite its demonstrated salutary effects on clinical evolution, left ventricular (LV) function, and overall survival, at least 30% of patients fail to respond to CRT. METHODS: The Greater Evaluation of Resychronization Therapy for Heart Failure (GREATER-EARTH) (ClinicalTrials.gov Identifier NCT00901212) is a randomized, double-blind, multicentre study involving 11 centres across Canada and compares LV CRT with biventricular CRT in patients with severe LV dysfunction and a QRS duration>120 ms. RESULTS: This article describes the rationale and design of the study and presents the baseline characteristics of all randomized patients. The primary outcome consists of the effects of CRT on submaximal exercise tolerance (treadmill test), and secondary outcomes explore mechanisms of asynchrony and effects of CRT on asynchrony and LV function. CONCLUSION: The study was initiated in November 2003, with the last patient randomized on February 12, 2009. As expected, follow-up was in February 2010 and the results are presently being analyzed in March 2010.

The efficacy of omega-3 supplementation for major depression: a randomized controlled trial.

OBJECTIVE: To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode (MDE). METHOD: Inclusive, double-blind, randomized, controlled, 8-week, parallel-group trial, conducted October 17, 2005 through January 30, 2009 in 8 Canadian academic and psychiatric clinics. Adult outpatients (N = 432) with MDE (Mini-International Neuropsychiatric Interview, version 5.0.0, criteria) lasting at least 4 weeks, including 40.3% taking antidepressants at baseline, were randomly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid (EPA) and 150 mg/d of docosahexaenoic acid (DHA) or matched sunflower oil placebo (2% fish oil). The primary outcome was the self-report Inventory of Depressive Symptomatology (IDS-SR(30)); the secondary outcome was the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: The adjusted mean difference between treatment and placebo was 1.32 points (95% CI, -0.20 to 2.84; P = .088) on the IDS-SR(30) and 0.97 points (95% CI, -0.012 to 1.95; P = .053) on the MADRS. Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group (P = .035). For patients without comorbid anxiety disorders (n = 204), omega-3 supplementation was superior to placebo, with an adjusted mean difference of 3.17 points on the IDS-SR(30) (95% CI, 0.89 to 5.45; P = .007) and 1.93 points (95% CI, 0.50 to 3.36; P = .008) on the MADRS. CONCLUSIONS: In this heterogeneous sample of patients with MDE, there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms. However, there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders. TRIAL REGISTRATION: controlled-trials.com Identifier: ISRCTN47431149.

First episode of major depressive disorder and vascular factors in coronary artery disease patients: Baseline characteristics and response to antidepressant treatment in the CREATE trial.

OBJECTIVE: The CREATE trial reported that coronary artery disease (CAD) patients suffering from a first depression derived less benefit from citalopram relative to placebo than those with a recurrent depression. The present investigation sought to determine whether the differential benefit of citalopram between those with a first depression and those with recurrent depression could be explained by indicators of vascular depression and cardiac disease severity. METHODS: Secondary analyses of data from CREATE, a 12-week, randomized placebo-controlled trial of 284 patients with major depressive disorder and CAD were used. Recurrence subgroups were compared on baseline characteristics reflecting vascular depression and cardiac disease severity. Outcome measures were the mean change from baseline to 12 weeks on the 24-item Hamilton Depression Rating Scale administered centrally by telephone. ANCOVA was used to assess the potential interaction of each baseline variable with citalopram/placebo treatment in predicting outcomes. RESULTS: Few baseline differences differentiated patients with a first versus recurrent depression, and none accounted for the differential treatment efficacy in these subgroups. Patients with a cardiac event in the past 6 months (P=.02) and taking angiotensin-converting enzyme inhibitors (P=.03) experienced less change with citalopram relative to placebo. Older age, worse functional status, taking beta-blockers, presence of angina (all P<.05), and later age of first depression (P=.05) predicted smaller changes in depression, independent of treatment assignment. CONCLUSIONS: There was limited evidence that the lack of improvement with citalopram relative to placebo in CAD patients with a first depression can be attributed to vascular depression.