Emotional stressors trigger cardiovascular events.

AIMS: To describe the relation between emotional stress and cardiovascular events, and review the literature on the cardiovascular effects of emotional stress, in order to describe the relation, the underlying pathophysiology, and potential therapeutic implications. MATERIALS AND METHODS: Targeted PUBMED searches were conducted to supplement the authors' existing database on this topic. RESULTS: Cardiovascular events are a major cause of morbidity and mortality in the developed world. Cardiovascular events can be triggered by acute mental stress caused by events such as an earthquake, a televised high-drama soccer game, job strain or the death of a loved one. Acute mental stress increases sympathetic output, impairs endothelial function and creates a hypercoagulable state. These changes have the potential to rupture vulnerable plaque and precipitate intraluminal thrombosis, resulting in myocardial infarction or sudden death. CONCLUSION: Therapies targeting this pathway can potentially prevent acute mental stressors from initiating plaque rupture. Limited evidence suggests that appropriately timed administration of beta-blockers, statins and aspirin might reduce the incidence of triggered myocardial infarctions. Stress management and transcendental meditation warrant further study.

Comparison of dilated cardiomyopathy and coronary artery disease in patients with life-threatening ventricular arrhythmias: Differences in presentation and outcome in the AVID registry.

BACKGROUND: The etiology of structural heart disease in patients with life-threatening arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) may define clinical characteristics at presentation, may require that different therapies be administered, and may cause different mortality outcomes. METHODS: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) registry, baseline clinical characteristics, treatments instituted, and ultimate mortality outcomes from the National Death Index were obtained on 3117 patients seen at participating institutions with VT/VF, irrespective of participation in the randomized trial. By use of these data, 2268 patients with coronary artery disease (CAD) were compared with 334 patients with dilated nonischemic cardiomyopathy (DCM). RESULTS: The CAD group was 7 years older and had a higher percentage of males. DCM patients were more likely to be African American, have severely compromised left ventricular function (52% vs 39%), and have a history of congestive heart failure symptoms (62% vs 44%). Patients with CAD were more likely to be treated with b-blockers and calcium channel blockers and less likely to be treated with angiotensin-converting enzyme inhibitors. Patients with DCM were more likely to be treated with diuretics, warfarin, and an implantable cardioverter defibrillator for VT/VF (54% vs 48% for CAD); the use of other antiarrhythmic therapies did not differ between the 2 groups. Two-year survival was not significantly different between the groups (76.6% [95% CI 74.6%-78.7%] vs 78.2% [95% CI 73.6%-82.9%]). CONCLUSIONS: In AVID registry patients with VT/VF, demographic and clinical characteristics were different between patients with CAD and those with DCM. Despite these differences, overall survival was similar in these 2 groups.

Survival benefit with an implanted defibrillator in relation to mortality risk in chronic coronary heart disease.

Although improved patient survival has been reported in several randomized trials with the implanted cardioverter-defibrillator, <15% of patients treated with defibrillators during trials receive life-saving benefit from this therapy. We evaluated the survival benefit from defibrillator therapy in relation to the severity of the mortality risk in patients with coronary heart disease. Using data from the Multicenter Automatic Defibrillator Implantation Trial, we partitioned the study population into high- and low-risk subsets for each of 3 physiologically meaningful risk factors (ejection fraction, QRS duration, and history of heart failure requiring therapy). Risk of death was evaluated by Cox proportional-hazards regression analyses in patients with single and multiple risk factors. The defibrillator was associated with a significant (p = 0.002) reduction in mortality only in high-risk subsets with ejection fraction <0.26, QRS duration > or =0.12 second, and history of heart failure requiring treatment. The Cox hazard ratio for the risk of death progressively increased >1.0 as a function of the number of risk factors present. Defibrillator therapy was associated with a progressive reduction in the hazard ratio <1.0 (improved survival) at each increased level of mortality risk. Patients at the highest mortality risk (all 3 risk factors; hazard ratio 4.33) achieved the largest mortality reduction (hazard ratio 0.20) from defibrillator therapy. In patients with chronic coronary heart disease, the magnitude of the survival benefit from the implanted defibrillator is directly related to the severity of cardiac dysfunction and its associated mortality risk.

Matching cardiac rhythm management technology to patient needs: pacing/ablation/implantable cardioverter defibrillators.

Data from 2 decades of clinical electrophysiologic studies have allowed great progress in the evaluation and treatment of patients with sustained ventricular arrhythmias and the appropriate identification of those patients at high risk for subsequent sudden death. The goals of treatment of the patient with ventricular arrhythmias are to suppress symptoms and prevent a fatal event. The steps in providing such therapy include (1) defining the cardiac anatomy; (2) assessing arrhythmia risk through noninvasive or invasive testing; and (3) prescribing treatment based on these results. Patients may be separated into high- and low-risk groups to help identify appropriate treatment. Although low-risk groups may benefit from reassurance or medications such as beta-blockers or verapamil, high-risk groups have been more difficult to treat. Recent randomized trials of implantable cardioverter defibrillators (ICDs) for ventricular arrhythmias suggest that they may provide better protection for high-risk patients than do antiarrhythmic medications.

Atrial fibrillation: nonpharmacologic approaches.

Various nonpharmacologic interventions are available for patients with atrial fibrillation (AF) who are refractory to standard drug therapy. Atrioventricular junctional ablation and permanent pacing is a very effective therapy for patients with AF and a poorly controlled ventricular response. The surgical MAZE procedure has been performed on small numbers of patients but is remarkably successful in restoring and maintaining sinus rhythm. The role of permanent pacing as treatment for paroxysmal AF is undergoing evaluation and dual-site atrial pacing appears particularly promising in reducing the number of episodes of paroxysmal AF. Certainly the most exciting frontier in the treatment of AF is radiofrequency catheter ablation procedures. Our understanding of the mechanisms of paroxysmal AF and chronic AF has expanded enormously in the past 5 years. Radiofrequency lesions in pulmonary veins using standard technology will cure many cases of paroxysmal AF. However, catheter systems under development offer a great promise of treating most paroxysmal and chronic AF within the next few years. These developments will revolutionize our approach to this ever more prevalent clinical problem.

A low amplitude His-bundle potential predicts failure of the right-sided approach for atrioventricular junction ablation.

In 30 patients with drug refractory atrial fibrillation-flutter who underwent radiofrequency (RF) ablation of the atrioventricular (AV) junction, 23 were successfully ablated using the conventional right-sided approach (group A). Seven patients required a left-sided approach (group B) after multiple applications from the conventional right-sided approach failed to produce complete AV block. The amplitude of the His-bundle potential recorded at the ablation site differed significantly between the 2 groups (0.23+/-0.11 mV in group A vs 0.12+/-0.04 mV in group B; p<0.005). Also, the amplitude of the His-bundle potential recorded in the standard position across the tricuspid annulus differed significantly between the 2 groups (0.27+/-0.35 mV in group A vs 0.11+/-0.44 mV in group B; p<0.007). There was no significant difference in the amplitude of the ventricular potential between the 2 groups. The probability of successful ablation of the AV junction with a conventional right-sided approach was 6 out of 12 patients (50%) if the His amplitude was <0.12mV, and 17 out of 18 patients (94%) if the His amplitude was >0.12mV (p<0.005). Patients in group B had a mean of 20.5+/-13.0 failed right-sided RF applications (5-33 applications), but required a mean of only 2 subsequent RF applications for success on the left side (1-6 applications). The His-amplitude recorded from the left side using the same catheter was significantly greater than that on the corresponding right-side (0.22+/-0.09 mV on the left side vs 0.12+/-0.04 mV on the right side: p<0.05). Total mean fluoroscopic time was 62+/-12min for group B and 20+/-13min for group A patients. In patients that underwent RF ablation of the AV junction, a maximum His amplitude <0.12 mV predicted a success rate of approximately 50% in the present study. An early switch to a left-sided approach may avoid multiple RF applications and prolonged fluoroscopic time in patients with a low amplitude His-bundle potential.

Other primary prevention trials-what is clinically and economically necessary?

There are a number of important primary prevention implantable cardioverter defibrillator (ICD) trials underway which will help define the role of the ICD in high risk patients. High risk is defined by low ejection fraction, although a number of electrical markers (e.g., the signal averaged ECG and invasive electrophysiologic test) are also under evaluation. The trials currently underway (including SCD-HEFT, MADIT II, and the CABG-PATCH substudy) are analyzing patients with either coronary or idiopathic cardiomyopathy who have an EF of 35% or under. Patients are randomized to either ICD therapy or no antiarrhythmic drug therapy. Maximal congestive heart failure therapy with ACE inhibitors and beta blockers is used in both arms of each trial. At the conclusion of these trials we should have a better understanding of which group of presumably high risk patients, if any, will benefit from the ICD. Another group of high risk patients that is being encountered more frequently: those who have a high risk diagnosis. These patients are present in such small numbers that a large randomized trial is impossible. As many of these patients are receiving ICDs, a national registry of firing rates will be helpful.

In-hospital versus out-of-hospital presentation of life-threatening ventricular arrhythmias predicts survival: results from the AVID Registry. Antiarrhythmics Versus Implantable Defibrillators.

OBJECTIVES: This study describes the outcomes of patients from the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study Registry to determine how the location of ventricular arrhythmia presentation influences survival. BACKGROUND: Most studies of cardiac arrest report outcome following out-of-hospital resuscitation. In contrast, there are minimal data on long-term outcome following in-hospital cardiac arrest. METHODS: The AVID Study was a multicenter, randomized comparison of drug and defibrillator strategies to treat life-threatening ventricular arrhythmias. A Registry was maintained of all patients with sustained ventricular arrhythmias at each study site. The present study includes patients who had AVID-eligible arrhythmias, both randomized and not randomized. Patients with in-hospital and out-of-hospital presentations are compared. Data on long-term mortality were obtained through the National Death Index. RESULTS: The unadjusted mortality rates at one- and two-year follow-ups were 23% and 31.1% for patients with in-hospital presentations, and 10.5% and 16.8% for those with out-of-hospital presentations (p < 0.001), respectively. The adjusted mortality rates at one- and two-year follow-ups were 14.8% and 20.9% for patients with in-hospital presentations, and 8.4% and 14.1% for those with out-of-hospital presentations (p < 0.001), respectively. The adjusted long-term relative risk for in-hospital versus out-of-hospital presentation was 1.6 (95% confidence interval [CI] 1.3-1.9). CONCLUSIONS: Compared with patients with out-of-hospital presentations of life-threatening ventricular arrhythmias not due to a reversible cause, patients with in-hospital presentations have a worse long-term prognosis. Because location of ventricular arrhythmia presentation is an independent predictor of long-term outcome, it should be considered as an element of risk stratification and when planning clinical trials.

Design and results of the antiarrhythmics vs implantable defibrillators (AVID) registry. The AVID Investigators.

BACKGROUND: The Antiarrhythmics Versus Implantable Defibrillators (AVID) Study compared treatment with implantable cardioverter-defibrillators versus antiarrhythmic drugs in patients with life-threatening ventricular arrhythmias (VAs). AVID maintained a Registry on all patients, randomized or not, with any VA or unexplained syncope who could be considered for either of the treatment strategies. Trial-eligible arrhythmias were the categories of VF cardiac arrest, Syncopal VT, and Symptomatic VT, below. METHODS AND RESULTS: Of 5989 patients screened, 4595 were registered and 1016 were randomized. Mortality follow-up through 1996 was obtained on the 4219 Registry patients enrolled before 1997 through the National Death Index. Crude mortality rates (mean+/-SD, follow-up, 16.9+/-11.5 months) were: VF cardiac arrest, 17.0% (n=1399, 238 deaths); Syncopal VT, 21.2% (n=598, 127 deaths); Symptomatic VT, 15.8% (n=1065, 168 deaths); Stable (asymptomatic) VT, 19.7% (n=497, 98 deaths); VT/VF with transient/correctable cause, 17.8% (n=270, 48 deaths); and Unexplained syncope, 12.3% (n=390, 48 deaths). CONCLUSIONS: Patients with seemingly lower-risk or unknown-risk VAs (asymptomatic VT, and VT/VF associated with a transient factor) have a (high) mortality similar to that of higher-risk, AVID-eligible VAs. The similar (and poor) prognosis of most patients with VT/VF suggests the need for reevaluation of a priori risk grouping and raises the question of the appropriate arrhythmia therapy for a broad range of patients.

Management of ventricular arrhythmias: detection, drugs, and devices.

OBJECTIVE: To review evaluation and treatment of patients with ventricular arrhythmias, based on recent studies, with an emphasis on randomized controlled trials. DATA SOURCES: MEDLINE search of English-language publications of ventricular arrhythmias and their references from 1966 through April 27, 1998. References to articles were also scanned to broaden the search. STUDY SELECTION: Randomized controlled trials and all large nonrandomized trials of arrhythmias and arrhythmia therapy were reviewed. In addition, studies that led to changes in approach to patients with arrhythmias were reviewed. DATA EXTRACTION: We reviewed articles jointly for pertinent studies and information. DATA SYNTHESIS: The goals of treatment of the patient with ventricular arrhythmias are to suppress symptoms and prevent a fatal event. The steps in providing such therapy include defining the cardiac anatomy, assessing arrhythmia risk through noninvasive or invasive testing, and prescribing treatment based on these results. Patients may be separated into high- and low-risk groups to help identify appropriate treatment. While low-risk groups may benefit from reassurance or medications such as beta-blockers or verapamil, high-risk groups have been more difficult to treat. Recent randomized trials of implantable cardioverter defibrillators for ventricular arrhythmias suggest that they may provide better protection for high-risk patients than do antiarrhythmic medications. CONCLUSIONS: Treatment and understanding of risk from ventricular arrhythmias have advanced substantially in recent years. Classifying patients as being at high or low risk for fatal arrhythmias allows the physician to identify appropriate treatments for the high-risk patient without exposing the low-risk patient to unnecessary treatment-related risks.

A review of the implantable cardioverter defibrillator trials.

Clinical ventricular tachycardia and ventricular fibrillation are associated with a high recurrence rate, and through the 1980s and the early 1990s a variety of therapies have been proposed including the implantable cardioverter defibrillator (ICD). Over the past decade it has been recognized that prospective randomized trials are imperative if the proper role for any therapy is to be defined. The Antiarrhythmic Versus Implantable Defibrillator (AVID) trial recently was concluded and helped define the role of the ICD in high-risk patients. Other trials are studying patients at high risk for sudden death who have not yet had a clinical event. The recently concluded Multicenter Automatic Defibrillator Implantation Trial and CABG Patch Trial helped determine the proper role of the ICD in various pre-event high-risk subsets. These trials are summarized in detail.

Efficacy of low-energy T wave shocks for induction of ventricular fibrillation in patients with implantable cardioverter defibrillators.

The efficacy of low-energy T wave shocks for induction of ventricular fibrillation (VF) was evaluated in 33 patients undergoing implantable cardioverter defibrillator (ICD) implantation (33 sessions) or predischarge ICD testing (20 sessions). To induce VF, the ventricle was paced for eight cycles at a 400-ms cycle length (S1-S1), and the T wave was scanned with a monophasic shock (S2) delivered via the defibrillating lead system. Of 294 attempts, the T wave shocks induced VF in 65%, nonsustained ventricular tachycardia in 10%, and less than five ventricular beats in 25%. As compared with the failed T shocks, the mean energy of successful T wave shocks was higher and the S1-S2 coupling interval was shorter. When the S2 timing was examined in relation to the T wave peak, the VF induction efficacy was 37% for shocks delivered more than 70 ms before the T wave peak, 82% for shocks delivered 30-70 ms before the T wave peak, and 50% for shocks delivered less than 30 ms before or just after the T wave peak (P < .001). Thus, in patients undergoing ICD implantation or ICD conversion testing, the use of low-energy T wave shocks is an effective and safe method to provoke VF.

Baseline characteristics of patients in the coronary artery bypass graft (CABG) Patch Trial.

BACKGROUND: Patients with left ventricular dysfunction who undergo coronary artery bypass graft (CABG) surgery frequently have late sudden cardiac death. The CABG Patch Trial is a prospective, randomized, multicenter clinical trial that randomized patients at high risk at the completion of CABG surgery to implantation of an epicardial implantable cardioverter defibrillator (ICD) or to no antiarrhythmic treatment. The trial was designed to determine whether prophylactic implantation of an ICD at the time of CABG surgery would result in a lower total mortality in long-term follow-up. METHODS: Patients undergoing CABG surgery were eligible for the trial if they were younger than 80 years, had a left ventricular ejection fraction less than 0.36, and had an abnormal signal averaged electrocardiogram. Patients with a history of sustained ventricular tachycardia or ventricular fibrillation were excluded from the trial. All patients were scheduled to undergo follow-up at 3-month intervals until 42 months after surgery. RESULTS: Randomization of patients in the trial ended in February 1996. During the recruitment period 71,855 patients were screened, 1,422 were eligible, 1,055 were enrolled (signed consent forms), and 900 patients (76% of eligible patients) were randomized. The mean age of the 446 patients in the ICD group was 64 years versus 63 years for the 454 patients in the control group. A total of 87% of the participants in the ICD group were men versus 82% in the control group (p = NS). Most of the patients had a history of hypertension (55%), smoking (78%), and hypercholesterolemia (54%). Half of the patients had clinical heart failure, and the mean ejection fraction for both patient groups was 0.27 +/- 0.06. No difference was seen in the history of myocardial infarction (83%), congestive heart failure (50%), or atrial (11%) or ventricular (17%) arrhythmias between the two groups. Major clinical characteristics (age, sex, number of previous infarctions, incidence of heart failure, and mean left ventricular ejection fraction) were almost identical to those found in another ICD primary prevention trial, the Multicenter Automatic Defibrillator Implantation Trial (MADIT). CONCLUSIONS: A high risk sample of patients was enrolled in The CABG Patch Trial, as shown by examination of their baseline characteristics.