Ventricular arrhythmias originate in the specialized conducting tissue distal to the bifurcation of the bundle of His or in true ventricular myocardium. Accordingly, they are characterized by prolonged ventricular depolarization (i.e., wide QRS complex) and/or an alteration in the sequence of ventricular activation (i.e., a change in the QRS vector) and/or alterations in the timing sequence of consecutive QRS complexes (prematurity, escape rhythms). The caution implied by the “and or” modifiers is intentional because no one criterion or set of criteria are totally sensitive and specific for arrhythmias of ventricular origin. On occasion, PVCs demonstrate narrow QRS complexes, have vectors not different from the normal QRS vector, or have timing little change from the normal timing sequence. The majority of impulses originating in the ventricles have QRS of at least 0.12 s and a shift in the QRS vector, and most single PVCs or initiating beats for runs of ventricular ectopic activity are premature. They may fail to conduct to the atria or may demonstrate retrograde atrial activation. In either case the sinus cycle is usually not interrupted, resulting in a fully compensatory pause (figure 94-35A,B ). The pause is characterized by an interval between the P wave of the sinus impulse immediately before the PVC and the first sinus P wave after the PVC equal to twice the sinus cycle length (figure 94-35A ). If the sinus rate is relatively slow, PVCs may be interpolated between two sinus beats with no alteration of the sinus cycle length (figure 94-35B ). Exceptions to the compensatory pause rule do occur (figure 94-35C ) and occasionally complicate diagnostic criteria. PVCs that presumably originate in the fascicles of the specialized conducting system may have more narrow QRS complexes with only slight alterations in the QRS vector.

The common form of PVCs are coupled to the preceding sinus beat by a fixed coupling interval. This generalization has exceptions in that PVCs having different QRS morphology may have different coupling intervals, and PVC’s having the same morphology in a given patient may have different coupling intervals under different pathophysiologic conditions. The pattern of fixed coupling has led to a concept of a physiological relationship between the sinus beat and the PVC and is used as an argument in favor of a reentant or triggered mechanism for common PVCs. In contrast, “parasystolic rhythms” refer to an independent ectopic rhythm, with the focus of origin being protected in the sense that descending impulses cannot enter and reset the parasystolic focus but can create a field of refractoriness around it limiting the rate and timing of existing impulses. Thus, the parasystolic focus, automatic in nature, can deliver impulses to the myocardium but cannot be reset by impulses originating elsewhere. Accordingly, the ECG reflects the presence of parallel competing pacemakers, the sinus node and a protected automatic ectopic ventricular focus, creating the classic triad of (1) variable coupling between sinus beats and ectopic QRS complexes, (2) fusion beats, and (3) a fixed common denominator of interectopic intervals between manifest parasystolic extrasystole (figure 94-35d). In recent years, however, classic concepts of parasystole have been altered by the discovery that parasystole may be modulated by relationships between the parasystolic focus and impulses originating in the sinus node. Sinus impulses occurring early in the parasystolic cycle tend to shorten the cycle length of the parasystolic focus, whereas those arriving in the latter half of the cycle length of a parasystolic focus. Parasystolic patterns may also occur with atrial extrasystolic activity.

Management of PVCs

PVCs in the Absence of Significant Structural Heart Disease
Prematue ventricular contractions occur in many healthy individuals. In the absence of heart disease there is little or no increase risk, and the risk-benefit ratio of antiarrhythmic therapy does not support routine treatment. For the patient who complains of disturbing palpitations due to the PVCs, however, the clinician may have to attempt to relieve the symptom. Reassurance and avoidance of potentially aggravating factors (e.g., tobacco, coffee, caffeine- containing soft drinks, environmental stress stimulants) should be tried before specific pharmacologic therapy. For the latter, mild anxiolytic drugs or beta-adrenergic blockers (which may sedate, reduce PVC frequency, and decrease the strength of postextrasystolic impulses causing the perception of palpitations) are preferred. When used for this purpose, low doses of beta-adrenergic blockers are often sufficient—e.g., 5 to 20 mg of propanolol qid or an equivalent dose of other preparations. The endpoint, relief of symptoms, may not necessarily be accompanied by significantly reduced PVC frequency. The frequency of PVCs may be modulated by underlying heart rate, and thus manipulations of sympathetic and parasympathetic balance may be useful. Because of their side-effect profiles, class1 antiarrhythmic agents are rarely indicated in this clinical setting, and the class111 agent, amiodarone, is unnecessarily potent. Premature ventricular contractions are often more prominent with pregnancy and premenstrually and increase in frequency with age. There may be an urge to be more aggressive in the management of patients who have advanced forms of PVC (i.e., salvos, nonsustained VT) or a high frequency of PVCs (30 or more PVCs per hour) in the absence of structural disease. On the other hand, Kennedy et al. reported no increase risk of death in a cohort of such persons followed for a mean of over six years .

The occurrence of PVCs in patients with “mitral valve prolapse” (MVP) has gained special attention for three reasons: (1) the high prevalence of MVP, (2) the prevalence of PVCs in patients with the MVP, and (3) the very small risk of sustained VT or VF. Annoying palpitations are a common complaint, but the arrhythmia does not require treatment in the vast majority. There are limited data suggesting that the patients at highest risk for serious ventricular arrhythmias can be subgrouped by the presence of nonspecific ST- T wave changes in leads11, 111, and AVF in conjunction with advanced grades of ventricular arrhythmias and redundancy of the mitral valve echocardiographically. The approach the treatment of patients with benign forms of PVCs in MVP should be no different than that outlined for individuals with no structural abnormalities. Beta-adrenergic blocking agents are often sufficient to control the symptoms, and membrane-active antiarrhythmic drugs should be avoided. Patients at risk for more serious arrhythmias, as outlined above, may require more aggressive treatment; membrane- active drugs are considered for use in this special situation for patients with salvos or nonsustained VT. The rare MVP patient who has sustained VT or survived after VF is managed by the approaches generally used for these potentially lethal arrhythmias in other clinical settings.

PVCs in Acute Syndromes

PVCs are nearly ubiquitous in acute myocardial infarction, but the threshold for treatment remains unsettled. Lown and others’ original concept of “warning arrhythmias” remains an indication for aggressive treatment, even though the predictive value of such warn arrhythmias remains unsubstantiated. Other opinions range from routine treatment with lidocaine of all patients with acute infarctions to prevent PVCs as well as VT or VF to threshold for treatment at various frequencies of manifest PVCs. Suppression of PVCs in acute myocardial infarction is usually accomplished with intravenous lidocaine ( a bolus of 5omg to 100mg followed by a continuous infusion of 2 to 4mg / minute), with intravenous procainamide as a second choice (100mg every five minutes to a total of 500 to 750mg followed by a n infusion of 1 to 4mg/ minute). Both drugs have significant side effects, especially with improper dosing. Furthermore, although their “routine” use is supported by practice, these drugs have not been shown to change hospital mortality in patients for whom prompt medical attention and electrical defibrillation are available. Lidocaine levels and binding both increase during the course of acute myocardial infarction , theoretically rendering free drug level stable. The practice of tapering the lidocaine infusion to avoid toxicity is not appropriate if free drug concentrations represent active drug and does not rise. Caution is warranted until these points are confirmed.

A number of other acute cardiac syndromes are associated with the emergence of PVCs. Transit acute ischemic syndromes have a higher incidence of PVCs that are accompanied by a risk of sustained VT or VF. The primary intervention for controlling PVCs in these settings is the control of transient ischemia. On first contact, however, the use of intravenous lidocaine or procainamide to suppress ischemic arrhythmias is justified. Clinical settings characterized by myocardial reperfusion—e.g., Prinzmetal’s angina , thrombolysis in acute myocardial infarction, balloon deflation during percutaneous transluminal coronary angioplasty ( PTCA) may be accompanied by risk of reperfusion arrhythmias. These arrhythmias are usually transient and self limiting but may evolve into sustained VT or VF. Although there are theoretical and experimental reasons to suspect that Ca2+- mediated electrophysiologic disturbances occur during reperfusion, intravenous lidocaine is currently used to treat reperfusion arrhythmias. It is used in the same dose and infusion techniques as in acute myocardial infarction and maybe use prophylactically during thrombolysis or P T CA.

Severe heart failure and acute pulmonary edema are commonly accompanied by frequent and advanced forms of PVCs and as in acute myocardial infarction with low- output states, the PVCs are considered secondary to the hemodynamic abnormality (figure 94-35e). The use of antiarrhythmic agents while the hemodynamic status is being stabilized is appropriate but may only have a limited success until adequate hemodynamic control is achieved.

Acute and subacute myocarditis and myopericarditis are commonly accompanied by PVCs and sustained VT or VF may occur infrequently, even in the absence of heart failure. Frequent PVCs, and salvos or nonsustained VT, are usually treated until the carditis has resolved. In those patients who have not had sustained VT or VF, conventional antiarrhythmic agents are given orally and titrated to suppression of PVCs if possible or at least to suppression of salvos. Antiarrhythmic therapy is continued for minimal of two months, and then the patient is monitored off of arrhythmic drugs. If advanced forms do not reappear, the drug is not restarted; if they do they reappear, treatment is continued for another two to three months, after which the same procedure is carried out. Myocarditis is only rarely followed by frequent or complex forms of PVCs is beyond six months. Virtually all other acute cardiac syndromes and many acute systemic disorders may be associated with PVCs that will abate with resolution of the initiating abnormality. In most systemic disorders , PVC’s did not require antiarrhythmic therapy.

PVCs in Chronic Cardiac Diseases

Chronic PVCs carry a different connotation in patients with established heart disease than in those free of disease. Sudden and total death rates are increased in patients who have frequent or repetitive PVCs in the major categories of chronic cardiac disease in the United States-- chronic ischemic heart disease, hypertensive heart disease, and the cardiomyopathies. When frequent PVCs and/or salvos or runs of non sustained VT are accompanied by a reduced ejection fraction(EF), the risk of sudden death is distinctively elevated. Bigger et al. observed a 42- percent 2 year mortality for postmyocardial infarction patients with salvos or nonsustained VT and an EF of less than 30 percent compared to a 12- percent 2 year mortality for patients with salvos or nonsustained VT and an EF of 50 percent or more. The 2-year rate fell to 7 percent for patients with only a single PVCs and an EF of50 percent or more .
Attitudes and approaches to the management of frequent and repetitive forms of chronic PVCs after myocardial infarction have changed dramatically since the results of CAST were published. Previous studies, as well as CAST, had demonstrated that PVCs suppression was feasible in these patients, but CAST demonstrated clearly a significant excess risk of sudden and total cardiovascular mortality among the treatment groups receiving the 2 class1C agents(flecainide and encainide) evaluated in the study, and CAST11 demonstrated a trend toward increased mortality rates for moricizine. Metaanalyses of data derived from previous smaller randomized studies testing the effect of antiarrhythmic drugs on mortality after by myocardial infarction also suggested an adverse effect of most antiarrhythmic drugs when used in the post- myocardial infarction patient. Accordingly, drugs used in CAST are now contraindicated in post-myocardial infarction patients with asymptomatic or mildly symptomatic PVCs, and there is a trend away from the use of any membrane-active antiarrhythmic agent in such patients. Beta-adrenoceptor blocking agents, however, have a beneficial effect on long term outcome in the post-myocardial patient. In addition, they are effective in suppressing repetitive forms of PVCs in many patients and significantly reduce total PVC frequency in some. Beta blockers, therefore, have evolved as a drug category of choice for post-myocardial infarction patients with asymptomatic or mildly symptomatic PVCs. While no properly randomized study directed to a sudden and total death outcome as a result the PVC suppression using beta-adrenoceptor blocking agents has been reported, the existing randomized mortality data from the post-myocardial infarction population at large demonstrates beneficial effects. The management problem becomes more difficult for postmyocardial infarction patients with symptomatic repetitive forms of PVC, especially when accompanied by a low EF. Such patients have a higher risk of sudden death, and it is not known whether or not the CAST data should be extrapolated to this population as well. Because of CAST, the class 1C agents are generally avoided in these patients, but clinicians may use other antiarrhytmic drugs if they are well tolerated and no adverse effects observed soon after the initiation of therapy. Regardless of EFs, beta-adrenergic blocking agents can be tried initially; if they are effective and well tolerated, they are preferred treatment even in this category. Another approach is the use of antiarrhythmic therapy guided by the results of programmed electrical stimulation in patients who have coronary heart disease , Low EFs, nonsustained VT clinically, and induced VT during invasive electrophysiological testing. The reported results appear beneficial,but the interpretation is limited, as in most electoral physiologically guided data for such patients, by the absence of concurrent placebo- controlled observations. The identification of patients at increased risk of developing VT orVF may be enhanced by the identification of late potentials by sigma leverage electrocardiography .

Chronic PVCs are very common in patients with advanced idiopathic dilated cardiomyopathy and in patients with hypertrophic cardiomyopathy, and both groups have a high risk of arrhythmic sudden death. In some reports, more than 90 percent of patients with dilated cardiomyopathy have frequent PVCs and over 50% have salvos or nonsustained VT. Efficacy of arrhythmic therapy for both suppression of chronic PVCs and prevention of the VT and VF is unclear and perhaps is quite limited in these patient categories. Nonetheless, treatment remains customary even though it is not known whether or not the CAST data can be extrapolated to this group.

When treatment is prescribed, the patient should be hospitalized for initiation of antiarrhythmic therapy because of proarrhytmic risk in cardiomyopathy. Secondary ventricular arrhythmias in patients who have chronic heart failure ( figure 94-35e) may respond to control of heart failure. In one carefully designed study, treatment with angiotensin converting enzyme inhibitor had a very favorable effect on both parameters of heart failure and ventricular ectopy. When antiarrhythmic drugs are to be used. the selection of a drug or drug combination for high-risk patients with chronic PVCs is complex. The class1A drugs are moderately effective but have a high incidence of allergic reactions (e.g., procainamide), intolerable side effects(e.g., quinidine), or significant myocardial of depression in patients with a reduced EF (e.g., disopyramide). Moricizine appears to be better tolerated, but all have significant risk of proarrhythmic effects, although the majority of these events are not life threatening. Among the class 1B agents (e.g., tocainide , mexletine). efficacy might be quite good in some patients, but there is a high incidence of uncomfortable side effects; the proarrhythmic incidence is lower. The currently approved 1C agents (flecainide, encainide, propafenone) are very effective in reducing ectopy and are well tolerated in patients with normal or minimally depressed left ventricular dysfunction. Their use is limited for patients with recent myocardial infarction by the adverse outcome observed in CAST and more generally by the fact that the incident of proarrhythmic effects and myocardial depression is highest in the subgroup at greatest need for intervention-i.e., those with repetitive forms and impaired left ventricular function. The long term benefits of class1A agents in respect to reducing death rates, in patient group other than the type enrolled in CAST and CAST11, are unknown at present. In regard to proarrhythmic risk,there are differences among the various groups . Class1A drugs are predominantly associated with classical proarrhythmia (torsade de pointes), which usually appears shortly after initiation of therapy. Class111 have the same pattern of proarrhythmia. The common denominator between Class1A and Class111 drugs, which likely contributes to this concordant proarrhythmic pattern, is moderate to marked prolongation of repolarization. In contrast, the class 1C drugs, which have minimal effect on repolarization, have a low rate of classic proarrhythmia. They may, however, worsen clinical arrhythmias or generate a new rapid sinusoidal VT (figure 9c). In addition, the excess death rate in CAST, attributed to proarrhythmia, extended over the entire period of drug exposure rather than close in time to the start of treatment. A possible explanation for this pattern is a tendency for the class1C drugs to interact with sporadic intercurrent events, such as transient ischemia or left ventricular dysfunction. Such an explanation is consistent with disturbed conduction patterns (depolarization) contributing to proarrhythmia rather than repolarization abnormalities.

Combining drug classes has been found to be effectiveed by some, although carefully controlled studies are limited; combinations such as class 1A and a class 1B drug may be tried. The class 11 drugs, beta-adrenergic blocking agents, have been mentioned earlier and many consider them the first choice of therapy even if the EF is not normal. They may be used in combination with class1 drugs in some patients. Class 111 drugs have only been approved for the used in life-threatening arrhythmias, although amiodarone may be appropriate for selected patients with longer runs a nonsustained VT and advanced left ventricular dysfunction. The available data on amiodarone is promising, but the specific benefits for patients with clinical nonsustained VT is unclear. The class1V drugs, calcium-entry blockers, have no role in the treatment of chronic PVCs. With any of these drugs or drug combination, attention to underlying heart disease and systemic factors is necessary. Treatment of limiting episodes of transient ischemia, maximizing left ventricular function, maintaining electrolyte balance, and controlling blood pressure, all may act in concert with antiarrhythmic agents to limit the risk of cardiac morbidity and mortality in patients with chronic PVCs. The endpoint of treatment (see table 1) of high risk chronic PVC’s is not fully understood. The pharmcodynamics of PVC suppression differ from those of VT prevention, and quantitative PVC’s suppression is difficult to achieve. Suppression of advance forms of PVCs (couplets, salvos, nonsustained VT) appears to be an acceptable and achievable endpoint for high risk patients with these forms on baseline ambulatory monitoring, even if quantitative PVC suppression cannot be achieved. General guidelines include suppression of 70 to 80 percent of total PVCs on a 24 hour ambulatory monitor and complete suppression of salvos and nonsustained VT.

Myerburg,R.J.,M.D. and Others,Recognition,Clinical Assessment,and
Management of Arrhythmias and Conduction Disturbances,THE HEART,8th