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.
