Noninvasive detection of risk for emotion-provoked myocardial ischemia.

OBJECTIVES: To test an easily administered, noninvasive technology to identify vulnerability to mental stress ischemia. BACKGROUND: Myocardial ischemia provoked by emotional stress (MSI) in patients with stable coronary artery disease (CAD) predicts major adverse cardiac events. A clinically useful tool to risk stratify patients on this factor is not available. METHODS: Patients with documented CAD (n = 68) underwent single photon emission CT myocardial perfusion imaging concurrent with pulse wave amplitude assessment by peripheral arterial tonometry (PAT) during a mental stress protocol of sequential rest and anger stress periods. Heart rate and blood pressure were assessed, and blood was drawn for catecholamine assay, during rest and stress. MSI was defined by the presence of a new perfusion defect during anger stress (n = 26) and the ratio of stress to rest PAT response was calculated. RESULTS: Patients with MSI had a significantly lower PAT ratio than those without MSI (0.76 +/- 0.04 versus 0.91 +/- 0.05, p = .03). An ROC curve for optimum sensitivity/specificity of PAT ratio as an index of MSI produced a sensitivity of 0.62 and a specificity of 0.63. Among patients taking angiotensin converting enzyme (ACE) inhibitors, the sensitivity and specificity of the test increased to 0.86 and 0.73, respectively; 90% of patients without MSI were correctly identified. CONCLUSIONS: PAT in concert with ACE inhibition may provide a useful approach to assess risk for MSI. Future studies should help determine how best to utilize this approach for risk assessment in the clinical setting.

Implantable cardioverter-defibrillator shocks increase T-wave alternans.

INTRODUCTION: While implantable defibrillator shocks save lives, shock can lead to ventricular arrhythmias. However, the mechanism of shock-related proarrhythmia remains unclear. We evaluated the impact of ICD shock on repolarization instability, a factor associated with ventricular arrhythmogenesis. METHODS AND RESULTS: Sixty-five patients with ICDs underwent ambulatory ECG monitoring during defibrillation testing 3 months postimplant. TWA was analyzed continuously in the time domain during baseline, sedated, and post-shock states. RR, QRS, and QT intervals and catecholamines were also measured continuously. Adequate pre- and post-shock Holter data were recorded in 55 patients, 48 male, mean 64 +/- 12 years, 50 with coronary disease, 48 with prior spontaneous or induced arrhythmia. TWA significantly increased after shock, from 9.6 +/- 0.5 to 11.9 +/- 0.6 microV, as did QRS duration, epinephrine, and norepinephrine levels, compared with sedated and baseline states. RR intervals decreased minimally. TWA changes with shock were not associated with RR or QRS duration changes, but were associated with changes in epinephrine. CONCLUSIONS: ICD shock, even in the sedated state, increases repolarization instability as measured by TWA, an effect mediated in part by sympathetic stimulation. This association between shock and TWA may have important mechanistic and clinical implications for optimization of defibrillation therapy.

C-reactive protein and vulnerability to mental stress-induced myocardial ischemia.

Myocardial ischemia provoked in the laboratory during mental stress (MSI) in patients with stable coronary artery disease (CAD) predicts subsequent clinical events. The pathophysiology of MSI differs from that of exercise ischemia, and the mechanisms tying MSI to poor prognosis are not known. C-reactive protein (CRP) is a risk marker for cardiovascular events in patients with CAD, but little is known regarding the relationship of CRP to MSI. The purpose of this study was to examine the association of CRP to risk of MSI in CAD patients. Eighty-three patients with stable CAD underwent simultaneous single-photon emission computed tomography (SPECT) imaging with technetium-99m tetrofosmin myocardial perfusion imaging (MPI) and transthoracic echocardiography (TTE), at rest and during MS induced by laboratory mental stress. Serum CRP levels were measured 24 h after MS. MSI was defined by the presence of a new perfusion defect on SPECT and/or new regional wall motion abnormality on TTE during MS. Of the 83 patients, 30 (36%) developed MSI. There was no difference in gender, sex, BMI, histories of diabetes, hypertension, smoking, lipid profile, medications used (including statins, beta-blockers, ACE inhibitors, and aspirin), or hemodynamic response during MS between those with and without MSI. In univariate logistic regression analysis, each unit (1 mg/L) increase in CRP level was associated with 20% higher risk of MSI (OR 1.2, 95% CI 1.01-1.39, P=.04). This relationship remained in multivariate models. These data suggest that levels of CRP may be a risk marker for MSI in patients with CAD.

Benefits of cardiac rehabilitation in patients with implantable cardioverter-defibrillators: a patient survey.

OBJECTIVES: To determine whether participation in an outpatient cardiac rehabilitation (OCR) program increases exercise levels and decreases shocks in patients with implantable cardioverter-defibrillators (ICDs). DESIGN: Retrospective comparative survey. SETTING: University tertiary-care ICD clinic. PARTICIPANTS: Patients with ICDs and coronary artery disease. INTERVENTION: Participation in OCR (nonrandomized). MAIN OUTCOME MEASURES: Exercise levels and OCR participation were determined through a telephone survey of patients with ICDs. The incidence of shock-treated arrhythmia was determined by review of charts and ICD data storage disks. RESULTS: Of 82 patients (85% men; mean age, 61+/-8 y), 28 (34%) participated in OCR after receiving an ICD. There was no difference in age, sex, ejection fraction, or length of follow-up between OCR and non-OCR groups. Median intensity of regular exercise was 5.3 metabolic equivalents (METS) for OCR patients versus 3.5 METS for non-OCR patients (P<.02). In follow-up (mean, 48+/-3 mo), non-OCR patients were more likely to receive any shock, shocks during exercise, or shocks for ventricular arrhythmia during exercise than OCR patients (all P<.05). Non-OCR remained a predictor of shock after adjustment for exercise limitation (P<.05). CONCLUSIONS: OCR patients exercised more and had fewer shocks. Physicians and health plans should encourage ICD patients to participate in OCR.

Effects of psychologic stress on repolarization and relationship to autonomic and hemodynamic factors.

INTRODUCTION: Psychological stress can precipitate ventricular arrhythmias in patients with ICDs, as well as sudden death. However, the physiologic pathways remain unknown. We sought to determine whether psychological stress induced in the laboratory setting alters indices of repolarization associated with arrhythmogenesis. METHODS AND RESULTS: Patients with ICDs and a history of ventricular arrhythmia underwent ambulatory ECG monitoring during a laboratory mental stress protocol (anger recall and mental arithmetic). Continuous changes in repolarization indices which have correlated with temporal and spatial myocardial heterogeneity of repolarization, including T-wave alternans (TWA), T-wave amplitude (Tamp), and T-wave area (Tarea) were analyzed in the time domain. In the 33 patients (85% male, 88% with coronary artery disease, mean ejection fraction 30%), norepinephrine, epinephrine, BP, and HR increased during mental stress. TWA increased from 22 (interquartile range 16-27) at baseline to 29 (21-38) uV during mental stress (P < 0.001). Changes in TWA correlated with changes in HR, systolic BP, and catecholamines. Tamp and Tarea also increased with mental stress (P < 0.01) but did not correlate with changes in other variables. CONCLUSION: Psychological stress increased TWA, Tamp, and Tarea. Autonomically mediated repolarization changes may be a pathophysiologic link between emotion and arrhythmia in susceptible patients.