Premature Ventricle Contractions in Heart Failure: A Closer Examination

Premature ventricular contractions (PVCs) are “early depolarizations of the myocardium, originating in the ventricle.”¹ Once regarded as benign, PVCs—even in the absence of structural heart disease—are now regarded as more insidious, potentially causing or contributing to cardiomyopathy and heart failure.²

Asymptomatic PVCs are often detected incidentally³ and have been described in 1% of the general population on standard ECG and in 40% to 75% on 24 to 48 hour ambulatory ECG recording.⁴ The prevalence of PVCs tends to be age-dependent, ranging from <1% in children under 11 years to 69% in individuals >75 years.¹

“Nearly everyone has PVCs from time to time,” observed Daniel Cantillon, MD, medical director of the Central Monitoring Unit at Cleveland Clinic in Ohio. “But they become pathological in patients with an excessive number.”

Symptomatic patients may describe PVCs as “palpitations,” “hard heartbeats,” “chest-thumping,” a “catch” or “skipped” heartbeats, according to Dr Cantillon, who is associate professor of medicine at the Cleveland Clinical Lerner Medical School. Symptoms typically include dyspnea, chest pain, fatigue, lightheadedness, dizziness, or syncope.³

A guide to PVC nomenclature can be found in Table 1.

Pathophysiology of PVCs

In PVCs, ventricular myocytes spontaneously depolarize to create an extra systole that creates mechanical dyssynchrony with the cardiac cycle.^2,3 Affected cells are triggered by cyclic adenosine monophosphate-mediated and calcium-dependent delays in after-depolarizations.³

The most common sites of origin for ventricular ectopy, in the absence of structural heart disease, are the left or right outflow tracts (RVOTs) or the epicardial tissues immediately adjacent to the aortic sinuses of Valsalva.³ Most foci are located in the RVOT. Fascicular PVCs originate from within the left ventricular His-Purkinje system.³ Other sites of origin for PVCs include ventricular tissues adjacent to the aortomitral continuity, the tricuspid annulus, the mitral valve annulus, papillary muscles, and other Purkinje-adjacent structures.³

PVCs can be associated with a variety of underlying cardiac conditions, including coronary artery disease, nonischemic dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), cardiac amyloidosis and sarcoidosis, and hypertrophic cardiomyopathy.³ Frequent PVCs can cause cardiomyopathy through complex transient alterations in intracellular calcium and membrane ionic currents, heart rate dynamics, hemodynamic parameters, and myocardial and peripheral vascular autonomic stimulation and inhibition.¹

To Intervene or Not to Intervene?

“The main question is whether and when to intervene,” said Rakesh Latchamsetty, MD, electrophysiologist at the University of Michigan Hospital and clinical lecturer at the University of Michigan Health System. “The 2 primary indications for intervention are whether the patient has disruptive symptoms, and the development of cardiomyopathy.”

The decision is complex and based on a variety of factors, Dr Latchamsetty explained. For example, the potential impact caused by PVCs is not necessarily based on simple arithmetic (ie, the number of daily PVCs). “A person can be symptomatic, even with a low PVC burden. On the other hand, there are patients with a large number of PVCs who are asymptomatic.”

In fact, being asymptomatic might represent a greater risk for the development of cardiomyopathy, since an asymptomatic patient is less likely to seek help, leading to a longer duration of exposure time.²

Dr Cantillon agreed. “Risk must be evaluated on a case-by-case basis, taking into account the frequency, location, and morphologic characteristics of the PVCs. Asymptomatic PVCs that are strung together in runs of ventricular tachycardia pose a higher risk of tachycardia-related cardiomyopathy and heart failure than symptomatic isolated PVCs.”

There is no consensus regarding a cutoff point above which a high PVC burden requires treatment, Dr Latchamsetty noted. He cited a 2010 study suggesting that cardiomyopathy was seen in the majority of patients when a PVC burden exceeded 24%.⁵ “I would consider anyone with an untreated PVC burden of 20% at a high risk of ultimately developing a cardiomyopathy, but even someone with a PVC burden of 10% warrants regular follow up.”

Again, Dr Cantillon agreed, stating that the lack of clear consensus creates significant “unanswered questions in the field, especially in dealing with asymptomatic patients with monomorphic PVCs, no evidence of structural heart disease, and an intermediate-to-high burden of 10% to 30%.”

Both experts emphasized that a thorough and careful diagnostic evaluation will help to inform the decision (Table 2).

Intervention Options

“The big controversy in this field is whether to pursue a conservative expectant approach—follow-up and monitoring, possibly with medical suppressive therapies—or to proceed directly to ablation,” Dr Cantillon said.

It is reasonable to begin with behavioral modification if structural heart disease or metabolic abnormalities have been ruled out, Dr Latchamsetty said. Patients should identify and avoid personal triggers, such as caffeine, stimulants, alcohol, smoking, stress, anti-fatigue supplements, and dehydration.³ Since stress increases catecholamine production, Cantillon noted that mind/body approaches such as yoga can be helpful.

Some noncardiac medications may be associated with increased risk of ventricular arrhythmias, and their use must be evaluated, in conjunction with the patient’s primary care physician or specialist. Medication classes containing certain potentially arrhythmia-inducing agents include antibiotics, antidepressants, stimulants, antipsychotics, and antiemetics.^6,7

Patients without structural heart disease who have a high PVC burden and do not wish to undergo pharmacotherapy or ablation must be followed closely, Dr Cantillon emphasized.

Pharmacotherapies

Patients who do not respond to behavioral interventions can be candidates for medical therapy, Dr Latchamsetty said.

Beta-blockers are the cornerstone of PVC suppression because they reduce intracellular cyclic adenosine monophosphate, thereby decreasing automaticity.³ Cardioselective beta-blockers include atenolol, betaxolol, metoprolol, and nadolol. With the exception of propranolol, noncardioselective beta-blockers are less commonly prescribed.³

Nondihydropyridine calcium channel blockers are particularly effective for PVC suppression in patients without structural heart disease and considered to be the “drugs of choice” in treating fascicular PVCs, Dr Cantillon said. Agents include verapamil and diltiazem. Since both agents reduce the resting heart rate and slow atrioventricular nodal conduction, they should be used cautiously in patients with congestive heart failure.³

Antiarrhythmic drugs must be used with caution because they can also be proarrhythmic.⁸ For example, flecainide and encainide have been linked with arrhythmic-related mortality.⁸ Sotalol can be effective in suppressing PVCs because it has both beta-blocker and antiarrhythmic properties. However, it also can trigger QT prolongation. As a precaution, patients can begin treatment in the hospital, where they can be monitored continuously. Amiodarone is less likely to cause QT prolongation, but has other short- and long-term side effects.³

The Role of Catheter Ablation

According to Dr Cantillon, catheter ablation is “safe and effective” and may be “curative” in many cases. However, the point at which ablation should be recommended is still under debate.⁹ “The question is in asymptomatic patients with an intermediate burden—say, 10% to 30%.”

The number or frequency of PVCs may help determine the utility of ablation. “A higher percentage of PVCs makes ablation more amenable,” Dr Latchamsetty observed. “If the burden is low, or the PVCs do not happen consistently, we may have challenges finding where they originate during an ablation.” In cases like these, he said, he would usually try pharmacotherapy first and consider ablation if pharmacotherapy was not effective.

A second factor is the number of morphologies, he added. “If there are only 1 or 2, we are more likely to find and eliminate them. But if they are coming with equal distribution from many locations, finding and eliminating all of the relevant PVCs may be more difficult. We often try pharmacotherapy first in such patients.”

Radiofrequency (RF) ablation and cryoablation are both used for PVCs, Dr Cantillon said, noting that there are no clinical guidelines recommending one method over the other. “We generally prefer RF because it is a more effective cauterizing mechanism. Cryoablation carries a higher recurrence rate. But if the PVC focus originates near a critical structure, there is the concern of delivering an irreversible lesion to the site. Cryoablation may be more appropriate because the area can be un-frozen, if necessary, without irreversible harm.”

Conclusion

PVCs are treatable and carry a good prognosis.¹ Emerging research is changing the approach to treatment and will provide clearer guidelines regarding the critical decisions and dilemmas in the field, Dr Latchamsetty said.

Table 1: PVC Nomenclature

Bigeminy	Every other beat is a PVC
Trigeminy	Every third beat is a PVC
Quadrigeminy	Every fourth beat is a PVC
Unifocal	Arises from a single ectopic focus; each PVC is identical.
Multifocal	Arising from ≥2 ectopic foci; multiple QRS morphologies
Couplet	2 consecutive PVCs
Triplet	3 consecutive PVCs
Nonsustained ventricular tachycardia	<3 sequential PVCs
Sustained ventricular tachycardia (SVT)	≥3 sequential PVCs

Reference: Gertsch M. The ECG Manual: An Evidence-Based Approach. New York, NY: Springer Publishing Company; 2008.

Table 2: Diagnostic Workup for PVCs

Personal and family history	Symptoms   Medications: Prescription OTC sympathomimetics Nonprescription supplements, elixirs, and beverages, especially those designed to treat fatigue or increase alertness Illicit substances (eg, cocaine, amphetamine)
Patient’s medical/surgical history	Particular emphasis:   Structural heart disease Pulmonary disorders Endocrine disorders
Family history	Particular emphasis   Sudden death in first-degree relatives Heritable cardiac conditions Coronary artery disease at early age
Physical examination	Potential underlying structural heart disease   Inspection/palpation of thyroid Skin changes or neurological findings that can reveal a clinical disorder with cardiac manifestations (eg, muscular dystrophy)
Assessment of cardiac rhythm	12-lead ECG   Ambulatory Holter monitoring (24-28 hours) 30-day ambulatory event monitor Mobile outpatient telemetry
Noninvasive cardiac evaluation	Surface echocardiography   Exercise treadmill test Advanced noninvasive cardiac imaging (reserve for special clinical indications—eg, suspected cardiac sarcoidosis, infiltrative heart disease, cardiomyopathies) CT MRI PET

PVC=premature ventricular contraction; OTC=over-the-counter; ECT=electrocardiogram; CT=computed tomography; MRI=magnetic resonance imaging; PET=positron-emission tomography.

Reference: Cantillon DJ. Evaluation and management of premature ventricular complexes. Cleve Clin J Med. 2013;80(6):377-387.

References

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