Matthew M. Burg

Emotional and Physical Precipitants of Ventricular Arrhythmia

Background—Observational studies have suggested that psychological stress increases the incidence of sudden cardiac death. Whether emotional or physical stressors can trigger spontaneous ventricular arrhythmias in patients at risk has not been systematically evaluated. Methods and Results—Patients with implantable cardioverter-defibrillators (ICDs) were given diaries to record levels of defined mood states and physical activity, using a 5-point intensity scale, during 2 periods preceding spontaneously occurring ICD shocks (0 to 15 minutes and 15 minutes to 2 hours) and during control periods 1 week later. ICD-stored electrograms confirmed the rhythm at the time of shock. A total of 107 confirmed ventricular arrhythmias requiring shock were reported by 42 patients (33 men; mean age, 65 years; 78% had coronary artery disease) between August 1996 and September 1999. In the 15 minutes preceding shock, an anger level ≥3 preceded 15% of events compared with 3% of control periods (P <0.04; odds ratio, 1.83; 95% confidence intervals, 1.04 to 3.16) Other mood states (anxiety, worry, sadness, happiness, challenge, feeling in control, or interest) did not differ. Patients were more physically active preceding shock than in control periods. Anger and physical activity were independently associated with the preshock period. Conclusions—Anger and physical activity can trigger ventricular arrhythmias in patients with ICDs. Future investigations of therapies aimed at blocking a response to these stressors may decrease ventricular arrhythmias and shocks in these patients.

Depression and late mortality after myocardial infarction in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study

Objective: The Enhancing Recovery in Coronary Heart Disease study was a multicenter clinical trial in which patients with depression and/or low perceived social support after an acute myocardial infarction were randomly assigned to an intervention consisting of cognitive behavior therapy and, in some cases, sertraline, or to usual care. There was no difference in survival between the groups. A possible reason why the intervention failed to affect survival is that too many patients with mild, transient depression were enrolled. Another is that some patients died too soon to complete the intervention. This analysis evaluates whether there was a difference in late (ie, ≥6 months after the myocardial infarction) mortality among initially depressed patients who had a Beck Depression Inventory score ≥10 and a past history of major depression, and who completed the 6-month post-treatment assessment. It also examines the relationship between change in depression and late mortality. Methods: Out of the 1,165 (47%) of the Enhancing Recovery in Coronary Heart Disease study participants who met our criteria, 57 died in the first 6 months, and 858 (409 usual care, 449 intervention) completed the 6-month assessment. Cox regression was used to analyze survival. Results: The intervention did not affect late mortality. However, intervention patients whose depression did not improve were at higher risk for late mortality than were patients who responded to treatment. Conclusions: Patients whose depression is refractory to cognitive behavior therapy and sertraline, two standard treatments for depression, are at high risk for late mortality after myocardial infarction.

Enhanced Depression Care for Patients With Acute Coronary Syndrome and Persistent Depressive Symptoms: Coronary Psychosocial Evaluation Studies Randomized Controlled Trial

BACKGROUND Depressive symptoms are an established predictor of mortality and major adverse cardiac events (defined as nonfatal myocardial infarction or hospitalization for unstable angina or urgent/emergency revascularizations) in patients with acute coronary syndrome (ACS). This study was conducted to determine the acceptability and efficacy of enhanced depression treatment in patients with ACS. METHODS A 3-month observation period to identify patients with ACS and persistent depressive symptoms was followed by a 6-month randomized controlled trial. From January 1, 2005, through February 29, 2008, 237 patients with ACS from 5 hospitals were enrolled, including 157 persistently depressed patients randomized to intervention (initial patient preference for problem-solving therapy and/or pharmacotherapy, then a stepped-care approach; 80 patients) or usual care (77 patients) and 80 nondepressed patients who underwent observational evaluation. The primary outcome was patient satisfaction with depression care. Secondary outcomes were depressive symptom changes (assessed with the Beck Depression Inventory), major adverse cardiac events, and death. RESULTS At the end of the trial, the proportion of patients who were satisfied with their depression care was higher in the intervention group (54% of 80) than in the usual care group (19% of 77) (odds ratio, 5.4; 95% confidence interval [CI], 2.2-12.9 [P < .001]). The Beck Depression Inventory score decreased significantly more (t(155) = 2.85 [P = .005]) for intervention patients (change, -5.7; 95% CI, -7.6 to -3.8; df = 155) than for usual care patients (change, -1.9; 95% CI, -3.8 to -0.1; df = 155); the depression effect size was 0.59 of the standard deviation. At the end of the trial, 3 intervention patients and 10 usual care patients had experienced major adverse cardiac events (4% and 13%, respectively; log-rank test, chi(2)(1) = 3.93 [P = .047]), as well as 5 nondepressed patients (6%) (for the intervention vs nondepressed cohort, chi(2)(1) = 0.48 [P = .49]). CONCLUSION Enhanced depression care for patients with ACS was associated with greater satisfaction, a greater reduction in depressive symptoms, and a promising improvement in prognosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00158054.

Destabilizing Effects of Mental Stress on Ventricular Arrhythmias in Patients With Implantable Cardioverter-Defibrillators

BACKGROUND The incidence of sudden cardiac death increases in populations who experience disasters such as earthquakes. The physiological link between psychological stress and sudden death is unknown; one mechanism may be the direct effects of sympathetic arousal on arrhythmias. To determine whether mental stress alters the induction, rate, or termination of ventricular arrhythmias, we performed noninvasive programmed stimulation (NIPS) in patients with defibrillators and ventricular tachycardia (VT), which is known to be inducible and terminated by antitachycardia pacing, at rest and during varying states of mental arousal. METHODS AND RESULTS Eighteen patients underwent NIPS in the resting-awake state (nonsedated). Ten underwent repeat testing during mental stress (mental arithmetic and anger recall). Induced VT was faster in 5 patients (P=0.03). VT became more difficult to terminate in 5 patients during mental stress; 4 required a shock (P=0.03). There was no change in ease of induction with mental stress. There was no evidence of ischemia on ECG or continuous ejection fraction monitoring. Eight patients received a shock in the resting-awake state and did not perform mental stress. Four underwent repeat NIPS after sedation; 3 then had induced VT terminated with antitachycardia pacing. All patients with an increase in norepinephrine of >50% had alterations in VT that required shock for termination (P<0.01). CONCLUSIONS Mental stress alters VT cycle length and termination without evidence of ischemia. This suggests that mental stress may lead to sudden death through the facilitation of lethal ventricular arrhythmias.

Role of behavioral and psychological factors in mental stress-induced silent left ventricular dysfunction in coronary artery disease☆

OBJECTIVES We examined the relationship of the psychological profile to left ventricular dysfunction induced during mental stress. BACKGROUND The contribution of psychological factors to mental stress-provoked silent myocardial ischemia has not been explored. METHODS Thirty patients with chronic stable coronary artery disease and a reversible defect on stress thallium-201 imaging completed a psychological assessment by questionnaire and Structured Interview, serially administered mental stress and brief walking exercise. Blood pressure, electrocardiogram (ECG) and left ventricular indexes were obtained by ambulatory serial radionuclide ventriculography. Silent ventricular dysfunction was defined by a decrease > or = 0.05 in ejection fraction or > or = 1 mm in ST segment on the ECG in the absence of symptoms. RESULTS Of the 30 patients, 15 (Group I) had evidence of silent left ventricular dysfunction during mental arithmetic. The other 15 (Group II) showed no change. In addition, 18 of 30 patients had this dysfunction during the Structured Interview. Both ischemic and nonischemic groups developed comparable and significant increases in heart rate and blood pressure. Group I patients were distinguished by higher scores on measures of aggressive responding (p < 0.001), trait anger (p < 0.0001), hostile affect (p < 0.003) and an index of behavioral reactivity (p < 0.003) and a lower score on anger control (p < 0.001). No other variables, including historical and clinical indexes, discriminated between the two groups. CONCLUSIONS Patients with coronary artery disease and mental stress-provoked silent ventricular dysfunction were distinguished by a psychological profile consistent with emotional reactivity to social interaction and mental provocation, with anger as the predominant affective state. Patients with such a profile may be at risk of frequent silent left ventricular dysfunction.

Association of Anhedonia With Recurrent Major Adverse Cardiac Events and Mortality 1 Year After Acute Coronary Syndrome

CONTEXT Depression consistently predicts recurrent events and mortality in patients with acute coronary syndrome (ACS), but it has 2 core diagnostic criteria with distinct biological correlates-depressed mood and anhedonia (loss of pleasure or interest). OBJECTIVE To determine if depressed mood and/or anhedonia predict 1-year medical outcomes for patients with ACS. DESIGN Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within 1 week of admission, patients underwent a structured psychiatric interview assessing clinically impairing depressed mood, anhedonia, and major depressive episode (MDE). Also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity using the Beck Depression Inventory. SETTING Cardiac units of 3 university hospitals in New York and Connecticut. PARTICIPANTS Consecutive sample of 453 patients with ACS (age, 25-93 years; 42% women). MAIN OUTCOMES MEASURES All-cause mortality (ACM) and documented major adverse cardiac events (MACEs)-myocardial infarction, hospitalization for unstable angina, or urgent/emergency coronary revascularization)-actively surveyed for 1 year after admission. RESULTS There were 67 events (16 deaths and 51 MACEs; 14.8%): 108 (24%) and 77 (17%) patients had anhedonia and depressed mood, respectively. Controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16-2.14; P < .01) was a significant predictor of combined MACE and ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes (P < .05) when additionally controlling for MDE diagnosis or depressive symptom severity. Findings were confirmed using depressed mood and anhedonia subscores from the Beck Depression Inventory in place of clinician interview ratings. CONCLUSIONS Anhedonia identifies risk of MACE and ACM beyond that of established medical prognostic indicators, including MDE and depressive symptom severity. Correlates of anhedonia may add to the understanding of the link between depression and heart disease.

Negative emotion and coronary heart disease. A review.

This article reviews literature regarding the influence of negative emotions, specifically depression, anger/hostility, and anxiety on coronary heart disease (CHD). For each domain, evidence is presented demonstrating the deleterious effects of negative affect on health outcomes in patients with CHD. This is followed by a discussion of the manner in which emotional factors are transduced into cardiac health risk factors. The pathophysiological mechanisms by which negative emotions have been found to exert an influence on CHD are highlighted. Finally, a general overview of the outcomes of interventions designed to ameliorate the effects of these negative emotional states on cardiovascular health are reviewed. Several treatment studies are described in detail for the purpose of elaborating the types of multicomponent interventions that attempt to address negative emotions in populations with CHD.

Effects of mental stress on left ventricular and peripheral vascular performance in patients with coronary artery disease

OBJECTIVES We sought to investigate the mechanism of a mental stress-induced fall in left ventricular ejection fraction (LVEF) in patients with coronary artery disease. BACKGROUND Mental stress induces a fall in LVEF in a significant proportion of patients with coronary artery disease. This is accompanied by an increase in heart rate, blood pressure and rate-pressure product. Whether the mental stress-induced fall in LVEF is due to myocardial ischemia, altered loading conditions or a combination of both is not clear. METHODS Left ventricular (LV) function was studied noninvasively by serial equilibrium radionuclide angiocardiography and simultaneous measurement of peak power, a relatively afterload-independent index of LV contractility, in 21 patients with coronary artery disease (17 men, 4 women) and 9 normal subjects (6 men, 3 women) at baseline, during mental stress and during exercise. Peripheral vascular resistance (PVR), cardiac output (CO), arterial and end-systolic ventricular elastance (Ea, Ees,) and ventriculoarterial coupling (V/AC) were also calculated. Patients underwent two types of mental stress-mental arithmetic and anger recall-as well as symptom-limited semisupine bicycle exercise. RESULTS Nine patients (43%) had an absolute fall in LVEF of > or = 5% (Group I) in response to at least one of the mental stressors, whereas the remaining patients did not (Group II). Group I and Group II patients were similar in terms of baseline characteristics. Both groups showed a significant but comparable increase in systolic blood pressure (15+/-7 vs. 9+/-10 mm Hg, p=0.12) and a slight increase in heart rate (7+/-4 vs. 8+/-7 beats/min, p=0.6) and a comparable increase in rate-pressure product (2.2+/-0.9 vs. 1.9+/-1.2 beats/min x mm Hg, p=0.6) with mental stress. However, PVR increased in Group I and decreased in Group II (252+/-205 vs. -42+/-230 dynes x s x cm(-5), p=0.006), and CO decreased in Group I and increased in Group II (-0.2+/-0.4 vs. 0.6+/-0.7 liters/min, p=0.02) with mental stress. There was no difference in the change in peak power (p=0.4) with mental stress. With exercise, an increase in systolic blood pressure, heart rate, rate-pressure product and CO and a fall in PVR were similar in both groups. Of the two mental stressors, anger recall resulted in a greater fall in LVEF and a greater increase in diastolic blood pressure. Exercise resulted in a fall in LVEF in 7 patients (33%). However, exercise-induced changes in LVEF and hemodynamic variables were not predictive of mental stress-induced changes in LVEF and hemodynamic variables. Conclusions. Abnormal PVR and Ea responses to mental stress and exercise are observed in patients with a mental stress-induced fall in LVEF. Peripheral vasoconstrictive responses to mental stress contribute significantly toward a mental stress-induced fall in LVEF.

Posttraumatic stress disorder and risk for coronary heart disease: A meta-analytic review

OBJECTIVE The aim of this study was to estimate the association of posttraumatic stress disorder (PTSD) with risk for incident coronary heart disease (CHD). DESIGN A systematic review and meta-analysis were used as study designs. DATA SOURCES Articles were identified by searching Ovid MEDLINE, PsycINFO, Scopus, Cochrane Library, PILOTS database, and PubMed Related Articles and through a manual search of reference lists (1948-present). STUDY SELECTION All studies that assessed PTSD in participants initially free of CHD and subsequently assessed CHD/cardiac-specific mortality were included. DATA EXTRACTION Two investigators independently extracted estimates of the association of PTSD with CHD, as well as study characteristics. Odds ratios were converted to hazard ratios (HRs), and a random-effects model was used to pool results. A secondary analysis including only studies that reported estimates adjusted for depression was conducted. RESULTS Six studies met our inclusion criteria (N = 402,274); 5 of these included depression as a covariate. The pooled HR for the magnitude of the relationship between PTSD and CHD was 1.55 (95% CI 1.34-1.79) before adjustment for depression. The pooled HR estimate for the 5 depression-adjusted estimates (N = 362,950) was 1.27 (95% CI 1.08-1.49). CONCLUSION Posttraumatic stress disorder is independently associated with increased risk for incident CHD, even after adjusting for depression and other covariates. It is common in both military veterans and civilian trauma survivors, and these results suggest that it may be a modifiable risk factor for CHD. Future research should identify the mechanisms of this association and determine whether PTSD treatment offsets CHD risk.

Low perceived social support and post-myocardial infarction prognosis in the enhancing recovery in coronary heart disease clinical trial: the effects of treatment.

Objective: In post hoc analyses, to examine in low perceived social support (LPSS) patients enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial (n = 1503), the pattern of social support following myocardial infarction (MI), the impact of psychosocial intervention on perceived support, the relationship of perceived support at the time of MI to subsequent death and recurrent MI, and the relationship of change in perceived support 6 months after MI to subsequent mortality. Methods: Partner status (partner, no partner) and score (<12 = low support; >12 = moderate support) on the ENRICHD Social Support Instrument (ESSI) were used post hoc to define four levels of risk. The resulting 4 LPSS risk groups were compared on baseline characteristics, changes in social support, and medical outcomes to a group of concurrently enrolled acute myocardial infarction patients without depression or LPSS (MI comparison group, n = 408). Effects of treatment assignment on LPSS and death/recurrent MI were also examined. Results: All 4 LPSS risk groups demonstrated improvement in perceived support, regardless of treatment assignment, with a significant treatment effect only seen in the LPSS risk group with no partner and moderate support at baseline. During an average 29-month follow-up, the combined end point of death/nonfatal MI was 10% in the MI comparison group and 23% in the ENRICHD LPSS patients; LPSS conferred a greater risk in unadjusted and adjusted models (HR = 1.74–2.39). Change in ESSI score and/or improvement in perceived social support were not found to predict subsequent mortality. Conclusions: Baseline LPSS predicted death/recurrent MI in the ENRICHD cohort, independent of treatment assignment. Intervention effects indicated a partner surrogacy role for the interventionist and the need for a moderate level of support at baseline for the intervention to be effective. CAD = coronary artery disease; CHD = coronary heart disease; AMI = acute myocardial infarction; MI = myocardial infarction; ENRICHD = Enhancing Recovery in Coronary Heart Disease; LPSS = low perceived social support; ESSI = ENRICHD Social Support Instrument; UC = usual care; INT = intervention; DISH = Diagnostic Interview and Structured Hamilton; ECG = electrocardiogram; BDI = Beck Depression Inventory; HR = hazard ratio; CI = confidence interval.