Management of Ventricular Irritability in the Ambulatory Setting
The discovery of ventricular ectopy in the outpatient setting raises concerns about serious underlying heart disease and the possibilities of cardiac arrest and sudden death. At issue is how much danger the ventricular irritability poses, a critical determination because treatment is also fraught with risk. In some instances, pharmacologic suppression of ventricular irritability may actually increase risk of sudden death rather than reduce it. Management of ventricular ectopy is shifting from reliance on antiarrhythmic drugs to implantation of cardioverter-defibrillators, which have demonstrated promising results in preventing cardiac arrest and sudden death. Determining the optimal approach to management in this period of change requires close consultation with a cardiologist experienced in treating ventricular dysrhythmias. The primary care physician’s principal tasks are to identify high-risk patients, arrange timely cardiac consultation, help patients to choose the treatment option best suited to their needs, and monitor therapy. Knowledge of the relative benefits of antiarrhythmic drugs and implantable defibrillators is essential to therapeutic decision making. Close monitoring and long-term follow-up by the primary physician help to ensure safe and effective management.
Premature ventricular contractions (PVCs) are ubiquitous and commonly found among patients both with and without underlying heart disease. In studies of the general population, at least one PVC per routine electrocardiogram (ECG) was found in 1% of Air Force recruits, 4% of life insurance applicants, 7% of men greater than 34 years of age, and 40% to 75% of normal persons subjected to 24 to 48 hours of continuous ambulatory (Holter) monitoring. The incidence and prevalence of PVCs increase with age and with exercise. There is no evidence that moderate intake of caffeine increases the frequency or severity of ventricular dysrhythmias in normal individuals or patients with heart disease, even those with preexisting serious ventricular ectopy.
In the ambulatory setting, ventricular irritability usually presents in one of several ways: as an incidental finding on routine examination or ECG; as an ECG finding in a patient being evaluated for palpitations, dizziness, or syncope; or as a complication of underlying heart disease noted on resting ECG, exercise stress test, or Holter monitoring. Frequent PVCs are defined as greater than 60 ectopic beats/h; complex ventricular ectopy is characterized by multiforms, repetitive forms, bigeminy, or R on T. Ventricular tachycardia (VT) refers to three or more PVCs in a row; in the monomorphic type, all QRS complexes are identical; in polymorphic VT (e.g., torsades de pointes), the QRS complexes are all different. Nonsustained VT refers to brief, selflimited runs of VT; sustained VT persists in the absence of intervention. Prognosis is a function of the presence and severity of any underlying heart disease and the nature of the ventricular ectopic activity.
Benign Ventricular Arrhythmias
Initially, prospective studies of large populations of ambulatory men were believed to have shown a correlation between PVCs on routine ECG and subsequent sudden death; however, when these results were reexamined controlling for other cardiac risk factors, PVCs were not found to be an independent determinant of cardiac death in the general population. Asymptomatic healthy subjects, even those with frequent or complex PVCs, showed no increased mortality on long-term follow-up. Regardless of the presence and persistence of worrisome ventricular irritability, such patients have prognoses no different from those of other healthy people; there is no increased risk of cardiac death.
Other natural history surveys also emphasized that, in the absence of important cardiac risk factors, people with PVCs are at no greater risk for cardiac death than the general population. However, the presence of such risk factors (e.g., hypertension,
coronary heart disease, heart failure, cardiomegaly, left ventricular hypertrophy, early repolarization, bundle-branch block, family history of early sudden death) places the patient with PVCs at increased risk.
coronary heart disease, heart failure, cardiomegaly, left ventricular hypertrophy, early repolarization, bundle-branch block, family history of early sudden death) places the patient with PVCs at increased risk.
Potentially Adverse Ventricular Arrhythmias
In comparison with patients free of underlying heart disease, the situation is more worrisome for patients with a variety of cardiac problems.
In the Setting of Recent Myocardial Infarction
In the Coronary Drug Project study of greater than 2,000 survivors of myocardial infarction, the occurrence of even a single PVC on a routine ECG taken 3 months or more after the infarct was associated with a doubling of the mortality rate during the 3-year follow-up period. The features most predictive of mortality are high frequency of PVCs (>30/hour over a 24-hour period) and presence of complex ventricular ectopy, especially repetitive beats (33 consecutive complexes). Prognosis is particularly poor in the setting of a failing left ventricle (ejection fraction <0.4). For patients with recent myocardial infarction, reduced ejection fraction, and nonsustained VT, the rate for cardiac arrest or sudden death approaches 20% at 2 years and exceeds 30% at 5 years.
In the Setting of Remote Myocardial Infarction
In this context, the frequency and complexity of PVCs also influence prognosis. The absence of ventricular irritability on a 1-hour ECG recording performed 3 to 9 months postinfarction is associated with a 6% risk of sudden cardiac death over 5 years, compared with 12% in patients with unifocal PVCs and 25% in those with complex ventricular ectopy. Complex ventricular ectopy (e.g., multifocal PVCs, nonsustained VT) has the strongest influence on risk for sudden cardiac death in this population (see later discussion).
In the Setting of Other Forms of Underlying Heart Disease
The situation is similar in other forms of structural heart disease that cause myocardial scarring and abnormal wall motion. Patients with hypertrophic or congestive cardiomyopathy, hemodynamically significant valvular disease, congenital heart disease with ventricular hypertrophy, hypertensive LV hypertrophy, and revascularization or valve surgery have been found to be at significantly increased risk of sudden death if they experience frequent or complex PVCs, especially in the context of a reduced ejection fraction. The ventricular ectopy is not merely a manifestation of the underlying heart disease but is an independent predictor of prognosis. Patients with substance abuse, particularly cocaine and alcohol, may manifest ventricular dysrhythmias due to underlying myocardial injury.
Persons without structural heart disease are also at risk. QT interval prolongation, be it congenital or acquired, predisposes to malignant ventricular dysrhythmias (e.g., torsades de pointes; see later discussion), as does Brugada’s syndrome (right bundle branch block, ST segment elevation in the early precordial leads). Concern has arisen from reports of an association between idiopathic ventricular fibrillation (VF) and early repolarization on ECG (especially when present in the inferolateral leads); 1% to 5% of the population manifests early repolarization changes on resting ECG, a finding previously considered harmless but potentially important in young men with a history of unexplained syncope or family history of sudden death.
In the Recovery Phase of Exercise Stress Testing
Frequent or complex ventricular ectopy that occurs during the recovery period of exercise stress testing may have a worrisome prognosis. In a large-scale observational study from the Cleveland Clinic, patients who manifested frequent (≥7 beats/min) or complex ventricular ectopy during the recovery period of exercise stress testing had an increased risk of death (adjusted hazard ratio, 1.5) that was independent of other cardiac risk factors. Ventricular ectopy that occurred during stress testing but not in the recovery period did not confer similar independent mortality risk when corrected for confounding variables. Patients with frequent ventricular ectopy during recovery had increased risk of underlying coronary disease and left ventricular systolic dysfunction.
Malignant Ventricular Arrhythmias
The main determinants of adverse prognosis in patients with ventricular ectopy are the presence of underlying heart disease and a failing left ventricle (see prior discussion). Each of these factors is an independent predictor of survival. The complexity of the ventricular ectopy is also a determinant of prognosis, especially in patients with heart disease and LV failure, where VT portends an especially high risk of cardiac sudden death.
Nonsustained Ventricular Tachycardia
Nonsustained VT is a worrisome arrhythmia characterized by runs of VT that spontaneously revert to sinus rhythm within several beats. Unless there is hemodynamic compromise, nonsustained VT may be asymptomatic. In the context of chronic coronary artery disease and LV dysfunction, it represents a malignant form of electrical instability that is an independent risk factor for sudden death, increasing risk fivefold to 30% at 2 years. It has a more benign form, found in young patients with no demonstrable heart disease and characterized by resolution with exercise, no associated symptoms, and a regular, relatively slow rate (<150 beats/min) with uniform cycle length and QRS morphology.
Recurrent Sustained Ventricular Tachycardia and Sudden Cardiac Death
Recurrent sustained VT is a very dangerous ventricular arrhythmia, especially when it occurs in the context of LV dysfunction. Untreated, the 1-year mortality rate is about 40%; prognosis is poorest in symptomatic patients with compromised LV function. The arrhythmia is characterized by repeated episodes of VT, some of which may persist for up to several hours. Many patients become symptomatic due to a fall in cardiac output, which can lead to syncope, near-syncope, angina, or dyspnea. Coronary artery disease and cardiomyopathy account for almost 90% of cases. About 1% of postinfarction patients experience this arrhythmia during the first year of follow-up.
QT-Interval Prolongation—Torsades de Pointes
Torsades de pointes is a rapid, polymorphic VT that often deteriorates into VF. The characteristic feature is a QRS axis that twists about the ECG baseline, going from positive to negative and back again. The arrhythmia occurs in the context of QT-interval prolongation, whether congenital or acquired. This is a very malignant ventricular dysrhythmia most commonly seen as an acquired condition in patients with electrolyte abnormalities (especially hypokalemia or hypomagnesemia) and use of drugs that prolong the QT interval (Table 29-1).
TABLE 29-1 Some Drugs Associated with Prolongation of the QT Interval | ||||||||
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Drugs that Prolong the QT Interval (see Table 29-1).
Many commonly prescribed noncardiac drugs are proarrhythmic by virtue of prolonging the QT interval. Risk of sudden death occurs only during use of the drug and increases with dose and serum concentration. Patients with underlying cardiovascular disease or high cardiovascular risk manifest greatest susceptibility. Risk also increases with electrolyte abnormalities, use of antiarrhythmics, or when an agent that prolongs the QT interval is used in conjunction with one that impairs its mitochondrial metabolism (Table 29-1). Of particular epidemiologic importance are the antipsychotic agents, both typical and atypical, used increasingly in elderly patients (who are already likely to be at increased cardiovascular risk by virtue of age). Also important in this regard are the macrolide antibiotics, including the very widely prescribed azithromycin.
Congenital QT Prolongation.
In the congenital form of QT prolongation, patients are young and have no evidence of structural heart disease but may have a family history of early (before age 30 years) sudden death in first-degree relatives, a personal history of prior syncope (especially in the setting of stress) or deafness, and ECG findings of QT prolongation, T-wave alternans, and notched T waves in at least three leads.
Commotio Cortis
This leading cause of sudden death among young athletes results from a blunt, often harmless-appearing, blow to the chest in persons with no known cardiovascular disease. Most victims are men. Cardiovascular collapse occurs almost instantaneously, although some may remain active for a few seconds before collapsing due to sustained VT or VF. The purported mechanism is concentration of the energy of the blow to a small area of the precordium altering the electrical stability of the myocardium and leading to VT and fibrillation. There is no contusion of the heart muscle or pericardium. Determining factors include location of the blow directly over the heart and timing within 10 to 20 msec on the upstroke of the T wave, just before its peak, which is a brief but electrically vulnerable period. Other determinants include hardness of the projectile or striking object, small diameter, direct angle of attack, and compliant chest wall. Relation to QT interval length remains unknown.
Brugada’s Syndrome
This hereditary electrical disorder of myocardial sodium channels leads to VF and sudden cardiac death. It represents one of the important causes of cardiac sudden death in young persons and is characterized by its typical electrocardiographic pattern of right bundle branch block and persistent ST segment elevations in the right precordial leads.
Probability of Occult Heart Disease in Asymptomatic Persons with Premature Ventricular Contractions
As long as the asymptomatic patient with PVCs has no evidence of underlying heart disease, the prognosis appears fine, but what is the probability of occult heart disease in an otherwise apparently healthy patient presenting with frequent or complex PVCs? The best approximation is that risk is not high. In a study of such patients subjected to coronary catheterization and angiography, only one fourth were found to have significant coronary artery disease (defined as >50% luminal narrowing). The characteristics of the ventricular ectopy did not differentiate those with coronary disease from those without it. These asymptomatic patients were treated with modest doses of beta-blocking agents and had normal survival rates after 5 years of follow-up. On the other hand, patients with syncope of unknown origin who manifest complex ventricular irritability and signs of underlying heart disease have a high risk of further syncope and cardiac death, especially if they demonstrate inducible sustained VT on electrophysiologic study (EPS).
