Premature Ventricular Complex

Etiology

Identifying the etiological cause requires a thorough history and physical examination. While most PVCs occur spontaneously without an identifiable cause, several known etiologies exist. PVCs can arise from numerous risk factors or causes, with some occurring benignly due to excessive adrenergic stimulation. PVCs stem from a broad range of cardiac and noncardiac conditions, lifestyle factors, and demographic risks. While some PVCs are benign and self-limited, understanding their etiology is vital for appropriate evaluation and management. Common known etiologies include excess caffeine consumption, excess catecholamines,[6] high levels of anxiety, and electrolyte abnormalities. 

Noncardiac conditions like hypercapnia, hyperthyroidism, anemia, and sleep deprivation can provoke PVCs, as can acute cardiac events, eg, myocardial infarction, myocarditis, myocardial contusion, mitral valve prolapse, and cardiomyopathies (particularly hypertrophic and dilated forms). Structural heart diseases that disrupt conduction pathways are frequent culprits. Other factors include various medications, electrolyte abnormalities, and hypoxia. The following describes several etiologies of PVCs:

• Illicit drug abuse (eg, alcohol, amphetamines, and cocaine)
• Various medications eg, digoxin, tricyclic antidepressants, sympathomimetics, aminophylline, caffeine
• Electrolyte imbalance, including hypokalemia, hypomagnesemia, or hypercalcemia
• Hypoxia
• Hypercapnia
• Acute myocardial infarction
• Cardiomyopathies mainly hypertrophic and dilated cardiomyopathy
• Myocarditis
• Myocardial contusion
• Mitral valve prolapse [6]

Risk factors for Premature Ventricular Complexes

Specific populations and demographic factors exhibit a higher risk for PVCs, including:

• Advanced age
• Male gender
• Hypertension
• African American
• hypomagnesemia
• Bundle branch block
• Hypokalemia
• Underlying ischemic heart disease [7]

Epidemiology

Studies on the prevalence of PVCs often derive from ECG or Holter monitor databases, where higher rates are expected due to the clinical setting. Early research showed a prevalence of 7.8 per 1000 over a 48-second ECG, with rates increasing with age. More recent studies, eg, the Cardiovascular Health Study, found PVCs in 1.8% to 5.2% of participants using 10-second ECGs, with prevalence rising with more extended monitoring. A 24-hour Holter monitoring detected PVCs in 69% of healthy adults in 1 study and nearly all elderly participants in another. Longer monitoring and newer wearable technologies reveal even higher detection rates, emphasizing the increasing prevalence of PVCs with age and extended observation durations.[1]

According to the Framingham Heart Study, the prevalence of PVCs was found to be higher in 1-hour continuous ECG monitoring, with 33% being men and 32% women with no history of any coronary artery disease. For those patients with coronary artery disease, the prevalence was comparatively higher, with 58% in men and women 49%.[8] The variability in the reported data differs due to the different monitoring techniques and duration used to calculate PVC prevalence. Several factors are involved in this diversity, including coronary heart disease, African-American ethnicity, male gender, older age, hypertension, faster sinus rates, lower serum potassium or magnesium levels, and lower education level.[9]

Pathophysiology

The pathophysiological mechanisms for underlying PVCs are often unclear, with multiple processes potentially contributing. The primary mechanisms thought to result in PVCs include triggered activity, automaticity, and reentry. Identification of the pathophysiological is essential as this informs the management approach.[1]

Triggered activity arises during the early depolarization phase due to exceeding the cell membrane activation threshold. The PVCs associated with bradycardia are often caused by this mechanism, along with other factors like electrolyte abnormalities, ischemia, and digoxin toxicity. Caffeine and catecholamines may exacerbate this mechanism, while β-blockers, adenosine, and calcium channel blockers can reduce its effects.[1][10][1]

Automaticity involves PVCs originating from abnormal cardiomyocyte activity, often showing parasystole. The enhanced automaticity characteristically results from an ectopic ventricular focus that fires spontaneously. A variety of stimuli, including myocardial ischemia, electrolyte imbalance, and heightened adrenergic state, can cause enhanced automaticity.[1]

Though usually linked to sustained arrhythmias, reentry can also cause PVCs. It requires 2 distinct pathways with unidirectional block, often involving scars, fibrosis, or abnormal conduction in specific regions. This mechanism is seen in phenomena like bundle-branch or fascicular PVCs.[1]

History and Physical

Clinical Features of Premature Ventricular Complexes

Most often, PVCs are asymptomatic. However, some patients report fatigue, palpitations, lightheadedness, or dizziness. In patients with preexisting heart disease, frequent PVCs can cause dyspnea, angina, and palpitations. Patients may often report a sense of abnormal neck pulsation with palpitations when they experience PVCs. PVCs rarely cause hemodynamic compromise, leading to presyncope or syncope, mainly if sustained or frequent runs occur. In asymptomatic individuals, PVCs may be initially identified on a routine physical exam by an irregular rhythm consisting of a premature beat followed by a compensatory pause with subsequent return of regular rhythm or cardiac auscultation revealing a sharp first heart sound or splitting of S2 or on a routine office electrocardiogram.

In some cases, PVCs are the first manifestation of underlying structural heart disease. For this reason, in all patients with PVCs, one must perform a detailed clinical history of 12-lead EKG and chest x-ray. The indication for further evaluation by Holter monitoring, stress test, or echocardiogram depends on whether PVCs persist after the initial assessment of suspected structural heart disease or the onset of complex forms of ventricular arrhythmias.

For over 20 years, the accepted view is that the presence of PVCs in the absence of structural heart disease presents a favorable, benign prognosis, even when they arise frequently. Therefore, treatment strategies for PVCs are planned according to the frequency of occurrence and symptoms. In some cases, very frequent PVCs can produce cardiomyopathy, being an indication for treatment, even in the absence of symptoms. However, the clinical importance of frequent PVCs in patients without any left ventricular dysfunction is still unclear.

Evaluation

Electrocardiograph Evaluation

The initial workup should start with a resting ECG. The PVC is electrocardiographically defined as a premature QRS complex with an abnormal morphology and duration greater than 120 milliseconds. A large T-wave classically follows it with discordant deflection (opposite polarity) from the QRS complex. Typically, no preceding P waves are present; however, the impulse generated from the PVCs can often be propagated in a retrograde fashion to the atria and can cause a classic compensatory pause following the PVC. This pause is due to the atrioventricular (AV) nodal blockade due to depolarization from the retrograde impulse and subsequent refractory period of the AV node. Though the sinus node fires at the appropriate time, its impulse is not propagated, as the AV node has been rendered refractory, thus causing an R-R interval that is precisely double the intrinsic R-R interval.

Usually, a PVC is followed by a full compensatory pause because the sinus node timing is not interrupted; 1 sinus P-wave is not able to reach the ventricles because they are still refractory from the PVC; the following sinus impulse thus occurs on time based on the sinus rate. In contrast, premature atrial contractions (PACs) are usually associated with an incomplete pause because the PAC usually enters the sinoatrial node and resets its timing, which enables the following sinus impulse to appear earlier than expected. Not all PVCs, however, get followed by a pause. If a PVC occurs early enough, especially with prolonged heart rates, it may appear sandwiched between the 2 normal heartbeats. This phenomenon is called an "interpolated PVC." The sinus impulse following the PVC is conducted with a longer PR interval because of the retrograde concealed conduction by the premature ventricular impulse into the AV-node junction, slowing the subsequent conduction of the sinus impulse.

The morphology of the QRS complex can be a means to determine the origin of the PVC. Left and right ventricular outflow tracts are the most common sites of origin of PVCs and account for approximately two-thirds of all PVCs. The electrocardiographic morphology can similarly determine the ectopic origin of the source of ventricular tachycardia. PVCs with the morphology of a typical left bundle branch block (LBBB) and an inferior axis originate from the right ventricular outflow tract, while PVCs with the morphology of a standard right bundle branch block (RBBB) and an inferior axis originate from the left ventricular outflow tract. PVCs can originate from numerous other locations, eg, the ventricular free wall, ventricular septum, aortic cusp, tricuspid or mitral annuli, pulmonary artery, fascicles, or papillary muscles. 

Individuals with multiple abnormal QRS complexes are classified as having multifocal PVCs, which are more common than unifocal PVCs. PVCs are also definable by the pattern in which they occur relative to intrinsic beats. Bigeminy indicates a PVC following a single, standard QRS complex, whereas trigeminy indicates a PVC following 2 normal QRS complexes. Multiple successive PVCs also have a distinct annotation; 2 PVCs successively a couplet, 3 PVCs successively a triplet, and more than 3 successive PVCs classify as a run of PVCs or ventricular tachycardia. 

When more than 3 consecutive PVCs are present, the term used is nonsustained ventricular tachycardia, and the term sustained ventricular tachycardia is used when the duration lasts >30 seconds. Couplets can be further defined by the interval between the ectopic PVCs and the subsequent usually conducted beat from the sinoatrial node. A stable interval between the PVCs and a regular beat is called fixed coupling. Variable coupling is when these intervals change from beat to beat. PVCs are considered "frequent" if they occur >30 times per hour or >20% of total heartbeats.

In addition to a resting ECG, the clinician should obtain ambulatory ECG monitoring for a minimum of 24 hours with a device such as a Holter monitor. If patients are particularly symptomatic, and the initial 24-hour monitoring is unrevealing, an event recorder or loop recorder can provide prolonged monitoring. In patients with PVCs, the ECG may reveal other findings that include:

• Electrolyte abnormalities (peaked T waves, QT prolongation)
• Left ventricular hypertrophy
• With an old MI, one may see Q waves, loss of R waves, and a bundle branch block
• Acute ischemia may present with ST-segment elevation/depression and/or T-wave inversion

Additional Diagnostic Studies

Evaluating for an underlying electrolyte abnormality, with specific attention to serum potassium and magnesium levels, is also reasonable. Additional laboratory evaluation with urine drug screen, thyroid stimulating hormone level, cardiac biomarkers (troponin), and serum digoxin level merit consideration when indicated. In most patients, especially those who are symptomatic, evaluation with a transthoracic echocardiogram should be considered to evaluate for underlying structural cardiac abnormalities. Further evaluation with exercise/chemical stress testing, nuclear myocardial perfusion imaging, coronary angiography, and cardiac magnetic resonance imaging (MRI) should also be considered on a case-by-case basis for each patient.

Treatment / Management

Medical Management

Patients with PVCs in the setting of underlying structural heart disease should receive guideline-directed medical therapy (GDMT) as indicated in their specific disease process. Treatment is a consideration in patients who are symptomatic with a high burden of ectopic beats or who have frequent episodes of nonsustained ventricular tachycardia. Most notably, PVCs that transform into ventricular fibrillation (usually mediated by the R-on-T phenomenon) should receive immediate defibrillation. If treatment is indicated, β-blockers are typically first-line therapy. Catecholamine-sensitive or exercise-induced PVCs have an excellent response to the initiation of β-blocker therapy. PVCs in the setting of CHF or myocardial infarction should be treated with β-blockers as first-line therapy, as directed by GDMT.

Similarly, nondihydropyridine calcium channel blockers can be a consideration in patients with a contraindication for β-blockers. Patients can start antiarrhythmic treatment with class Ic agents (eg, flecainide or propafenone) when their symptoms have not improved after initiation of β-blocker or calcium channel blocker therapy. However, these agents are proarrhythmic, increase mortality, and are contraindicated in patients with preexisting coronary artery disease. For this specific patient population, amiodarone has proven to be effective in suppressing PVCs; however, due to adverse effect profiles, the administration should generally be reserved under close clinical monitoring for patients with underlying structural heart disease or coronary disease and significant symptomatology.

Ablation Therapy

Patients who cannot tolerate the therapy should be referred to an electrophysiologist for consideration of ablation. PVC ablation is also the recommended intervention in patients who develop PVC-induced cardiomyopathy, especially in those with a significant PVC burden.[11] The definition of high PVC burden is >10,000 ectopic ventricular beats or >10% of all beats recorded on 24-hour ambulatory monitoring.

The accepted thinking is that cardiomyopathy is more likely in patients whose PVCs have a very wide QRS complex, the beats arise from the epicardium, or in patients with PVC occurring higher than a quarter of all beats on 24-hour Holter monitor (PVC burden of over 25%). This cardiomyopathy is generally considered to be reversible after ablation; however, some degree of left ventricular systolic dysfunction may rarely persist after the ablation of the ectopic focus.[12] Patients who have already developed cardiomyopathy due to high-frequency PVCs should also have a referral for radiofrequency ablation, as evidenced by a 2014 meta-analysis demonstrating that catheter ablation of PVCs originating from the right ventricular outflow tract significantly reduced ventricular ectopy burden and improved left ventricular ejection fraction. Ablation may also be indicated in patients with frequent PVCs that interfere with cardiac resynchronization therapy.[13](B3)

Several cardiology societies have provided guidelines on the utilization of ablations for patients with PVCs. The 2019 AHA, American College of Cardiology, and Heart Rhythm Society Guideline for Management of Patients with Ventricular Arrhythmia and the Prevention of Sudden Cardiac Death recommends that catheter ablation may be useful for patients with reduced left ventricular ejection fraction suspected to have been caused by frequent PVCs defined as >15% of all beats who failed to respond or could not tolerate antiarrhythmic medications.[14](B3)

The 2015 European Society of Cardiology Guidelines recommends considering ablation therapy for patients with reduced left ventricular ejection fraction and frequent symptomatic PVCs or nonsustained ventricular tachycardia.[15] Additionally, the European Heart Rhythm Association/Heart Failure Association recommends that patients with heart failure with reduced ejection fraction and a high burden of PVCs, defined as >10,000 PVCs in 24 hours, should be aggressively treated with catheter ablation if they have failed, declined, or are intolerant to antiarrhythmic therapy especially if a single dominant PVCs morphology is identified.[16][17][18][19][16](B3)

Differential Diagnosis

Differentiating PVCs from other arrhythmias can be challenging because several arrhythmias may mimic PVCs, including:

• Aberrant PACs
• Fusion beats
• Premature junctional contractions
• Idioventricular escape rhythms
• Sustained and nonsustained ventricular tachycardia
• Bigeminy, trigeminy, or quadrigeminy 
• Supraventricular tachycardia
• Atrial fibrillation
• Sinus arrhythmia

Prognosis

In almost all heart diseases, due to the high incidence and complexity, PVCs can be the major cause of mortality in coronary artery disease and dilated cardiomyopathy. According to the MRIFT and Framingham Heart Study, frequent occurrence of PVCs correlates with an increased risk of sudden cardiac death.[20][21] As these studies lack the diligent measures taken to investigate underlying heart disease, they are under great criticism because they can halve the death outcome. 

The benign premature ventricular contractions that occur occasionally do not interfere with the average lifespan, but their frequent occurrence implies an ominous prognosis. Patients with a previous myocardial infarction with frequent PVCs are prone to sudden cardiac death. However, patients treated either with medication or catheter ablation therapy can improve and recover from the LV dysfunction.[4]

The characteristics of PVCs that confer poor prognosis include:

• An "arrhythmic burden" with >500 PVCs in 24 hours on Holter monitoring
• PVC morphologies with LBBB or RBBB
• PVCs with intermediate or superior axis and wide QRS complexes
• Short-coupled PVCs
• PVCs superimposed on preceding T-waves
• PVCs induced by adrenergic stimulation

Healthy patients without structural heart disease who experience infrequent PVCs have the same prognosis as the general population. However, those with frequent PVCs (>1000/day) are at risk of developing dilated cardiomyopathy.[22] For those with heart disease, PVCs are an indicator of increased mortality risk.[23]

PVCs occurring during a period of exercise have a varying prognosis, depending on when they occur. If the PVCs arise during exercise, the prognosis is very good. If they occur during the recovery phase of exercise, the long-term mortality risk is higher than in the general population.[24]

Complications

Frequent PVCs are often associated with complications if remain unattended, which include:

• Left ventricular dysfunction
• Dilated cardiomyopathy
• Sustained ventricular tachycardia
• Sudden cardiac arrest