Craig A. McPherson

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.

Failure to Improve Left Ventricular Function After Coronary Revascularization for Ischemic Cardiomyopathy Is Not Associated With Worse Outcome

Background-Preoperative identification of viable myocardium in patients with ischemic cardiomyopathy is considered important because CABG can result in recovery of left ventricular (LV) function. However, the hypothesis that lack of improvement of LV function after CABG is associated with poorer patient outcome is untested. Methods and Results-Outcome was compared in patients with ischemic LV dysfunction (LVEF </=0.30) with and without improvement in LVEF after CABG. Of 135 consecutive patients, 128 (95%) survived CABG and 104 (77%) had pre- and post-CABG LVEF assessment. Of these 104 patients, 68 (65%) had >0.05 increase in LVEF (group A) and 36 (35%) had no significant change, or </=0.05 decrease in LVEF (group B) compared with pre-CABG LVEF. No significant differences existed in age, gender, comorbidities, baseline symptoms, baseline LVEF, or intraoperative variables between groups A and B. Group A increased LVEF from 0.24+/-0.05 to 0.39+/-0.1 (P<0.005). In Group B, LVEF did not change significantly postoperatively, 0.24+/-0.05 to 0.23+/-0.06 (P=NS). Postoperative improvement in angina and heart failure scores were similar between the 2 groups. Survival free of cardiac death was similar for both groups (93% in group A and 94% in group B, P=NS) at a mean follow-up of 32+/-23 months. Conclusions-Lack of improvement of global LVEF after CABG is not associated with poorer outcome compared with that of patients with improved LVEF, presumably because effective revascularization of ischemic myocardium, even without improvement in ventricular function, protects against future infarction and death.

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.

Electrophysiologic effects of thrombolytic therapy in patients with a transmural anterior myocardial infarction complicated by left ventricular aneurysm formation

To assess the effects of early thrombolytic therapy on the incidence of clinical and induced ventricular arrhythmias in high risk postmyocardial infarction patients, 32 patients with a transmural anterior myocardial infarction complicated by left ventricular aneurysm formation were prospectively evaluated. Sixteen patients (Group A) received routine care because of contraindication to thrombolytic therapy or other factors and 16 (Group B) received either tissue plasminogen activator or streptokinase within 6 h of the onset of chest pain. The two groups were similar in left ventricular ejection fraction (mean +/- SD, 28 +/- 9% [Group A] versus 30 +/- 8% [Group B]) and occurrence of spontaneous nonsustained ventricular tachycardia, new bundle branch block and congestive heart failure. Group B patients had higher peak creatine kinase MB levels (446 +/- 336 versus 205 +/- 120 IU; p = 0.017) and earlier time to peak creatine kinase values (13.4 +/- 6.6 versus 19.1 +/- 6.1 h; p = 0.006). Twenty patients who had no clinical sustained ventricular arrhythmias underwent electrophysiologic study 13 +/- 6 days after infarction. Ventricular tachycardia was induced during the study in 7 (88%) of 8 Group A patients, but in only 1 (8%) of 12 Group B patients given thrombolytic therapy (p = 0.0008). During a mean follow-up period of 11 +/- 8 months, eight Group A patients (50%) died suddenly or were resuscitated from sustained ventricular tachycardia; all Group B patients are alive and have had no clinical arrhythmic events (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian variation of sustained ventricular tachycardia in patients with coronary artery disease and implantable cardioverter-defibrillators.

While previous studies using epidemiological data and ambulatory ECG monitoring have shown peak occurrence of sudden death and nonsustained ventricular tachycardia in the morning, none have examined circadian variation of potentially life-threatening ventricular tachycardia (VT), nor has any study observed circadian behavior of any arrhythmias in individuals followed longitudinally. We used the event memory of multiprogrammable implantable cardioverter- defibrillators to evaluate the circadian pattern of sustained VT over time. Methods and ResultsData were reviewed from 32 consecutive patients with coronary artery disease and sustained VT who had received the Ventak PRX (CPI, Inc) cardioverterdefibrillator between May 1991 and August 1993 and had experienced at least one episode of VT terminated by their device. Mean follow-up was 14±7 months. Among the 2558 episodes recorded by the device logs, VT occurrence peaked between 6 AM and noon (P = .007 by ANOVA among four 6-hour time periods). Harmonic regression revealed a morning peak at 9 AM (P < .01). This morning peak occurred in patients with both frequent and infrequent events. Among 21 patients who experienced more than four VT events, 8 (38%) had an AM peak of VT occurrence (>35% of VT between 6 AM and noon). Neither age, ejection fraction, event frequency, presenting arrhythmia, nor drug therapy distinguished patients who displayed the AM VT peak. ConclusionsIn patients with coronary artery disease, sustained VT displays circadian variation with peak frequency in the morning, similar to that for sudden death. Individual patients who display specific patterns of circadian variation over time can be identified using defibrillator logs. Investigation of circadian variation of other phenomena to elucidate mechanisms of VT should focus on these patients.

Anger-Induced T-Wave Alternans Predicts Future Ventricular Arrhythmias in Patients With Implantable Cardioverter-Defibrillators

OBJECTIVES This study sought to determine whether T-wave alternans (TWA) induced by anger in a laboratory setting predicts future ventricular arrhythmias in patients with implantable cardioverter-defibrillators (ICDs). BACKGROUND Anger can precipitate spontaneous ventricular tachycardia/ventricular fibrillation and induce TWA. Whether anger-induced TWA predicts future arrhythmias is unknown. METHODS Sixty-two patients with ICDs underwent ambulatory electrocardiography during a mental stress protocol, 3 months after the ICD was implanted. T-wave alternans was analyzed using time-domain methods. After a > or =1 year follow-up, ICD stored data was reviewed to determine incidence of ICD-terminated ventricular tachycardia/ventricular fibrillation. RESULTS Patients with ICD-terminated arrhythmias during follow-up (n = 10) had higher TWA induced by anger, 13.2 microV (interquartile range [IQR] 9.3 to 16 microV), compared with those patients without future ventricular arrhythmias, 9.3 microV (IQR 7.5 to 11.5 microV, p < 0.01). Patients in the highest quartile of anger-induced TWA (>11.9 microV, n = 15) were more likely to experience arrhythmias by 1 year than those in the lower quartiles (33% vs. 4%) and during extended follow-up (40% vs. 9%, p < 0.01 for both). In multivariable regression controlling for ejection fraction, prior clinical arrhythmia, and wide QRS, anger-induced TWA remained a significant predictor of arrhythmia, with likelihood in the top quartile 10.8 times that of other patients (95% confidence interval: 1.6 to 113, p < 0.05). CONCLUSIONS Anger-induced TWA predicts future ventricular arrhythmias in patients with ICDs, suggesting that emotion-induced repolarization instability may be 1 mechanism linking stress and sudden death. Whether there is a clinical role for anger-induced TWA testing requires further study.

The Goldman algorithm revisited: prospective evaluation of a computer-derived algorithm versus unaided physician judgment in suspected acute myocardial infarction.

BACKGROUND It has been nearly a decade since Goldmans computer-driven algorithm to predict myocardial infarction was validated. Despite the potential to avoid admission of patients without acute myocardial infarction (AMI) to the coronary care unit (CCU), the routine use of computer-generated protocols has not been widely adopted. METHODS Two hundred consecutive patients admitted to a university-affiliated community hospital with the suspected diagnosis of AMI as determined by physicians without the aid of the Goldman protocol underwent a blinded prospective evaluation to assess the performance of the Goldman algorithm in predicting the presence of AMI. Over the same time period, the Goldman algorithm was applied by retrospective chart review in 762 patients with non-AMI admitting diagnoses. Prospective history, physical examination, and electrocardiographic data were obtained within 24 hours of admission to the CCU by a physician blinded to each patients clinical course. Retrospective chart reviews were conducted for 762 patients with chest pain given with non-AMI diagnoses. RESULTS The diagnosis of AMI was confirmed in 68.5% (137/200) of patients with suspected AMI admitted to the CCU. In prospective parallel evaluations the Goldman algorithm predicted the presence of AMI in 167 (83.5%) of these 200 patients. All 137 confirmed patients with AMI were correctly identified by the Goldman algorithm. All major in-hospital complications occurred in the 137 patients who were diagnosed as having AMI. Of the 762 patients with chest pain with non-AMI diagnoses, only 27 (3.5%) sustained an AMI. The Goldman algorithm predicted the presence of AMI in 85% (23/27) of these patients. Adherence to the use of Goldmans algorithm in the triage of chest pain could have prevented 16.5% of CCU admissions for AMI. CONCLUSIONS Routine adherence to the Goldman algorithm for the evaluation of patients with acute chest pain could have decreased the number of CCU admissions for suspected AMI by 16. 5%. Because major in-hospital complications occurred only in patients with AMI, this strategy would result in significant cost savings to our health care system without jeopardizing patient safety.

Evaluation by serial electrophysiologic studies of an abbreviated oral loading regimen of amiodarone

Optimal loading and maintenance regimens for amiodarone are undefined. Serial electrophysiologic testing was used in 25 patients with ventricular tachycardia to assess the adequacy of a 1-week oral loading regimen at 1,200 mg/day, to modify maintenance dosing at the conclusion of loading, and to evaluate the appropriateness of maintenance dosing after 2 months of therapy. During the loading period, highly significant (p less than 0.001) increases occurred in the AH interval (88 +/- 22 vs 120 +/- 31 ms), HV interval (49 +/- 10 vs 61 +/- 11 ms), AV nodal Wenckebach cycle length (390 +/- 92 vs 537 +/- 147 ms), ventricular refractory period (247 +/- 17 vs 276 +/- 23 ms), mean ventricular tachycardia cycle length (254 +/- 38 vs 298 +/- 52 ms) and return cycle length (294 +/- 55 vs 360 +/- 87 ms). Ventricular tachycardia inducibility decreased in only a minority of cases, and when observed in association with a more than 10% increase in ventricular refractory period, resulted in a lower maintenance dose. After 2 months of maintenance therapy no additional change occurred in any of these parameters except for an increase in ventricular tachycardia cycle length (298 +/- 52 vs 330 +/- 65 ms, p less than 0.017). Ventricular tachycardia inducibility again showed no consistent response. It is concluded that patients can be discharged after 1 week of therapy with oral amiodarone loading at 1,200 mg/day and that maintenance dosing modified by electrophysiologic assessment results in steady perpetuation of the cardiac amiodarone effect, as indicated by the time course of change in electrophysiologic variables consistently affected.

Troponin-T Elevation After Implanted Defibrillator Discharge Predicts Survival

Background: Cardiac troponin T (cTnT) elevations have been reported to occur after implantable cardioverter-defibrillator (ICD) discharges, but their prognostic significance is unknown. Objective: To evaluate whether cTnT elevations occurring after ICD discharges have an impact on survival. Design: Prospective observational study. Patients: 174 patients (mean (SD) age 68 (12) years, 32 women) who received spontaneous (n = 66) or induced (n = 108) ICD discharges were studied. The mean (SD) left ventricular ejection fraction was 29 (11)%. Main outcome measures: Troponin T was measured between 12 and 24 h after ICD discharge. Patients received between 1 and 19 discharges (mean (SD) 2.4 (2.4)), with total delivered energy ranging from 6 to 288 J (mean (SD) 41 (63) J). The relationship between cTnT levels and all-cause mortality was assessed in univariate and multivariate analyses. Results: During a median follow-up period of 41.8 months (range 3–123), 56 patients died. Patients with a post-discharge cTnT level of ⩾0.05 ng/ml had worse survival than those with cTnT <0.05 ng/ml. The significant relationship between raised cTnT and survival was retained in Cox multivariate analysis adjusted for total ICD energy delivered during an arrhythmia episode, age, sex, presence of coronary artery disease, left ventricular ejection fraction and serum creatinine. Conclusions: Elevation of troponin T after ICD discharge, even when it occurs after device testing, is a risk factor for mortality that is independent of other common clinical factors that predict survival in such patients.

Mechanisms and relevance of arrhythmias induced by high-current programmed ventricular stimulation

Programmed ventricular stimulation was performed at 10 mA with up to 3 extrastimuli in 15 patients studied for indications other than sustained ventricular tachycardia and with no sustained arrhythmias induced at twice diastolic threshold. Stimulation with 10 mA produced 6 new instances of ventricular fibrillation (VF), 1 of which may have been clinically relevant. No sustained ventricular tachycardia was induced. VF was induced with triple extrastimuli in 5 of 6 cases. The increased arrhythmogenicity of 10-mA stimulation was related to shortened ventricular refractory periods (S2 267 +/- 21 vs 231 +/- 22 ms, p less than 0.0001; S3 217 +/- 15 vs 178 +/- 15 ms, p less than 0.0005) and did not occur without at least 2 extrastimulus coupling intervals being less than was possible at twice diastolic threshold. Stimulation with 10 mA also resulted in greater increments in extrastimulus local conduction time (27 +/- 19 vs 54 +/- 15 ms, p less than 0.001) and intraventricular conduction time (27 +/- 17 vs 45 +/- 18 ms, p less than 0.005) as coupling intervals were shortened from 360 ms to just beyond ventricular refractoriness. VF was induced more frequently in patients with cardiomyopathy (p less than 0.05). Thus, the increase in arrhythmogenicity with 10-mA stimulation with triple extrastimuli is predominantly manifest as VF, which occurs with considerable frequency and is of uncertain clinical significance. This technique should be used with great caution, and only after other stimulation modalities have been attempted.