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.

Clinical and induced ventricular tachycardia in a patient with myotonic dystrophy.

A 20 year old patient with myotonic dystrophy presented with hemodynamically significant ventricular tachycardia at a rate of 230 beats/min requiring cardioversion. Two days later, the identical tachycardia was reproducibly initiated and terminated in the electrophysiology laboratory using two extrastimuli in the right ventricle. Trials of procainamide and quinidine were not successful in controlling the induced rhythm and amiodarone was administered. On restudy with amiodarone, ventricular fibrillation was induced using a single extrastimulus. This case suggests that ventricular tachyarrhythmias may contribute to the known cardiac morbidity and mortality in myotonic dystrophy.

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.

The automatic implantable cardioverter-defibrillator: efficacy, complications and survival in patients with malignant ventricular arrhythmias.

Ninety-four patients underwent surgery for automatic implantable cardioverter-defibrillator implantation. Ninety patients were discharged from the hospital with the device and were followed up for a mean period of 17 +/- 10 months. Forty-six patients experienced at least one discharge of the device under circumstances consistent with a malignant ventricular arrhythmia. One sudden death occurred. Complications included perioperative death (3 patients), post-operative ventricular tachycardia (12 patients) and atrial fibrillation (8 patients), perioperative myocardial infarction (1 patient) and device discharges for sinus tachycardia and supraventricular arrhythmias (17 patients). Six and 12 month survival rates by life table analysis were 98.7 and 95.4%, respectively. Thus, the automatic implantable cardioverter-defibrillator is a highly effective and relatively low risk treatment modality for patients with refractory life-threatening ventricular arrhythmias.

Ventricular fibrillation in patients without significant structural heart disease: a multicenter experience with implantable cardioverter-defibrillator therapy.

OBJECTIVES: This study was undertaken to characterize the outcome of survivors of ventricular fibrillation with no or minimal structural heart disease who received an implantable cardioverter-defibrillator. BACKGROUND: The prognosis among survivors of ventricular fibrillation with minimal or no structural cardiac abnormalities remains unclear. Since the advent of implantable cardioverter-defibrillators, this question takes on added importance. METHODS: This 10-center retrospective study provided information on 28 survivors of ventricular fibrillation (mean age 42 years) with minimal or no structural abnormalities who were treated with an implantable cardioverter-defibrillator. RESULTS: Ventricular tachyarrhythmias (polymorphic in all but one patient) were induced during baseline programmed stimulation in 39% of patients. During a median 30.6-month follow-up period after implantable cardioverter-defibrillator implantation, there were no cardiac deaths and two noncardiac deaths. Sixteen patients experienced 36 shock episodes (total 88 shocks). The majority of shocks were classified as "indeterminate"; one patient received 47 "spurious" shocks during one shock episode and each of four patients received one "appropriate" shock. Ventricular arrhythmias were not inducible in any of these latter four patients. CONCLUSIONS: Survivors of ventricular fibrillation with minimal or no structural cardiac abnormalities receiving an implantable cardioverter-defibrillator have an excellent 3-year survival rate. The occurrence, albeit infrequent, of appropriate implantable cardioverter-defibrillator shocks in this group suggests that these patients have a potential risk of recurrent cardiac arrest whose fatal outcome may be avoided by implantable cardioverter-defibrillator therapy.

The short- and long-term prognosis of patients with transmural and nontransmural myocardial infarction.

To compare the long-term prognosis in patients surviving transmural with patients surviving nontransmural myocardial infarctions, the records of 188 consecutive patients with clinical histories and enzyme elevations consistent with acute infarction were reviewed. According to standard electrocardiographic criteria the patients were divided into two groups: 148 with transmural myocardial infarction (group 1) and 40 with nontransmural myocardial infarction (group 2). Of the patients who survived hospitalization, follow-up data were obtained on 119 of 124 patients in group 1 and 36 of 37 patients in group 2 at a mean follow-up period of 36 months. In group 2, the patients had a high incidence of sudden death after discharge (33 per cent in group 2 versus 15 per cent in group 1, p less than 0.02) as well as a significantly higher incidence of death from all cardiac causes (41.6 per cent in group 2 versus 24.3 per cent in group 1, p less than 0.05). Furthermore, the patients in group 2 still alive at the end of the follow-up period had an increased incidence of angina pectoris and of recurrent infarction. The data suggest that patients with nontransmural myocardial infarction carry a particularly guarded prognosis.

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.

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.

Relations between ventricular refractoriness and regional myocardial blood flow after acute coronary occlusion.

Myocardial ischemia has been associated with dispersion of ventricular refractory periods and this dispersion has been related to the ventricular arrhythmias seen with coronary occlusion. This study relates the degree of change in measured ventricular refractory period with the degree of regional myocardial blood flow abnormality after coronary occlusion. When regional myocardial blood flow is less than 70% of that of nonischemic areas, refractory periods are significantly (P less than 0.001) shortened. The greatest change in refractory periods occurs in areas with a regional myocardial blood flow that is 21 to 40% of that of nonischemic areas. Marked (less than 20%) and minimal (61 to 80%) reductions in regional myocardial blood flow are associated with less, but still significant, shortening of ventricular refractory periods. Thus dispersion of refractoriness can be related to the inhomogeneity of regional myocardial blood flow after acute coronary occlusion. Interventions designed to salvage ischemic myocardium by increasing regional myocardial blood flow may affect dispersion of ventricular refractory periods in complex and divergent ways.

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.

Electrophysiologic studies in the denervated transplanted human heart. II. Response to norepinephrine, isoproterenol and propranolol.

Five patients who had received a transplanted human heart 1 to 3 years previously were studied to determine the effects of norepinephrine, isoproterenol and propranolol on the atrioventricular (A-V) conduction system. Using the His bundle technique, atrial, His bundle and ventricular electrograms were recorded, and central aortic pressure was monitored during the administration of these drugs. Norepinephrine was given by continuous infusion to four patients in doses ranging from 4 to 8 mug/min, with the systolic arterial pressure increasing by an average of 72 mm Hg. Concomitantly, there was an average increase in the rate of the donor atrium of 32 beats/min, and a reflex slowing of the recipient atrium of 23 beats/min. The A-H interval shortened by an average of 27 msec. Isoproterenol dose-response curves were performed in three patients, with the maximal dose being 5.2 mug by intravenous bolus infusion. The rate of the donor atrium increased by an average of 40 beats/min, and that of the recipient atrium by 18 beats/min. The A-H time shortened by an average of 25 msec, with a drop in systolic blood pressure averaging 23 mm Hg. Propranolol (7 mg intravenously) was given to three patients and the peak doses of norepinephrine and isoproterenol were again infused. Beta adrenergic blockade was achieved at this dose of propranolol since there was only a minimal increase in the donor atrial rate after infusion of the drug. The A-H interval was not altered by catecholamine infusion after achievement of beta blockade. However, the levels of systolic hypertension noted after infusion of norepinephrine was not altered by propranolol. The denervated transplanted human heart appears to respond normally to norepinephrine and isoproterenol, and the electrophysiologic effects of these agents are blocked by propranolol. Extensive investigative work in the denervated canine model has demonstrated the presence of the alpha and beta cardiovascular receptors. Although the automonic nervous system is important in cardiac performance, this work is the first validation in man that (1) the functional integrity of the beta receptor is maintained even when the autonomic nerves are absent, and (2) the intrinsic properties of the sinus and atrioventricular nodes are the keystone in stabilizing cardiac electrophysiology after denervation.

Predictors of automatic implantable cardioverter defibrillator discharge for life-threatening ventricular arrhythmias.

Data from 100 patients with life-threatening ventricular arrhythmias and automatic implantable cardioverter defibrillators (AICDs) were analyzed to determine if clinical, angiographic and electrophysiologic variables are predictive of AICD discharge. During a median follow-up period of 18 months, 45% of patients experienced greater than or equal to 1 device discharge during a documented ventricular arrhythmia or in association with presyncope or syncope ("appropriate" AICD discharge). Univariate predictors of appropriate AICD discharge included depressed left ventricular ejection fraction (p = 0.0007), inducible sustained ventricular arrhythmia at electrophysiologic study performed in the absence of antiarrhythmic drugs (p = 0.009), fewer number of extrastimuli required for induction at this study (p = 0.001), inducible sustained arrhythmia at electrophysiologic study performed on the discharge antiarrhythmic regimen (p = 0.0005) and fewer extrastimuli required for this induction (p less than 0.0001). Multivariate analysis identified the induction of a sustained ventricular arrhythmia by 1 or 2 extrastimuli during electrophysiologic study performed on the discharge regimen as the only independent predictor among the variables analyzed (p less than 0.0001). The probability of appropriate AICD discharge at 18 months was 86% for patients who had a sustained arrhythmia induced with 1 or 2 extrastimuli versus 15% for those requiring 3 extrastimuli for arrhythmia induction and 13% for patients without inducible sustained arrhythmias.

Influence of patient characteristics in the selection of patients for defibrillator implantation (the AVID Registry). Antiarrhythmics Versus Implantable Defibrillators.

The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial is a prospective, randomized study of treatment for life-threatening ventricular arrhythmias. Patients who are eligible for the main trial but who are not enrolled for any reason are followed in a registry. The objective of the present study was to determine whether there are identifiable patient characteristics among these registry patients that may influence whether a patient is treated with an implantable defibrillator. The 914 patients in the registry were divided into 2 groups according to whether the primary treatment was an implantable defibrillator. The mean age of defibrillator patients was 60 years, compared with 65 years in the nondefibrillator group (p <0.001). Only 11.2% of defibrillator recipients were minorities, whereas the percentage of minorities in the nondefibrillator group was 18.7% (p <0.003). A history of recurrent ventricular fibrillation was more likely in the group treated with defibrillators (8.9% vs 4.4%, p <0.01), whereas a history of atrial fibrillation or diabetes mellitus were both significantly more likely in the nondefibrillator group. Among defibrillator patients, a higher proportion had ventricular fibrillation as the index arrhythmia; patients with ventricular tachycardia were significantly more likely to be treated without devices. In this prospective but nonrandomized cohort of patients treated for life-threatening ventricular arrhythmias, older age, minority status, and comorbidity reduced the chances that a patient would be treated with a defibrillator.

Procainamide accumulation kinetics in the immediate postmyocardial infarction period.

The rate of change of plasma procainamide concentration during 36 hours of constant-rate intravenous infusion was examined in five acute myocardial infarction patients. It was observed that a steady-state plasma concentration was established in about 16 hours, which is consistent with simulations of plasma concentrations based on pharmacokinetic constants obtained from studies in young healthy volunteers. However, the steady-state level that was attained in these patients was markedly higher than that which the simulations predicted. Thus, on the average, acute myocardial infarction patients have lower total body clearances of procainamide than normal volunteers.

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.

A critical appraisal of indications for the implantable cardioverter defibrillator (ICD).

The implantable cardioverter defibrillator (ICD) is a remarkably effective therapy for reducing sudden cardiac death in patients with malignant ventricular arrhythmias. The indications for implantation of the ICD were approved in 1985 by the United States Food and Drug Administration; it could be implanted in patients who have experienced cardiac arrest or in those with recurrent ventricular arrhythmias which are not suppressed by anti-arrhythmic drugs in the electrophysiology laboratory. These established indications have not changed in the last seven years. In the near future, the release of third-generation ICDs (with antitachycardia pacing) will likely further expand indications for the device. Many patients with stable ventricular tachycardia who have not had syncope or cardiac arrest will receive a third-generation defibrillator. Also, three clinical trials now in progress--CABG-PATCH, Multicenter Automatic Defibrillator Implantation Trial (MADIT) and Multicenter Unsustained Tachycardia Trial (MUSTT)--are studying "pre-event" patients with low ejection fraction and electrical instability; some of the patients in each trial are being prospectively randomized to the ICD. Within the next five years we will have a better understanding of the role of ICD therapy in such patients. Until these studies are completed, it is important that the indications for the ICD not be expanded.