Premature Ventricular Complexes and the Role of Catheter Ablation in Current Times

Introduction

Premature ventricular complexes (PVCs) are electrical activity originating within the ventricles leading to early depolarization of ventricles. PVCs are generally detected on electrocardiography (ECG), ambulatory monitoring devices, and hospital telemetry. PVCs are commonly found in patients with or without structural heart disease, and their frequency increases with age. Most patients with PVCs are asymptomatic, and management consists of monitoring and lifestyle changes. Symptomatic patients can present with palpitations, syncope or dizziness, increased fatigue, or shortness of breath. Some patients can have an increased risk of arrhythmias or reversible cardiomyopathy. Symptomatic management can involve antiarrhythmic drugs (AADs) or catheter ablation; PVC ablation is also routinely done in our electrophysiology lab. In this article, we present two cases of PVC ablation, briefly discussing PVCs and their management, including catheter ablation.

Case #1

A 78-year-old woman presented to the electrophysiology clinic with symptoms of palpitations, shortness of breath, and fatigue for the last two years. She denies any orthopnea, paroxysmal dyspnea, or syncopal episodes. She previously had a transthoracic echocardiogram (TTE) showing an ejection fraction of 55%. She underwent a coronary angiogram demonstrating elevated wedge pressure and mild non-obstructive coronary artery disease. She had a previous diagnosis of hyperlipidemia, hypertension, and recently diagnosed heart failure with preserved ejection fraction. She takes hydrochlorothiazide, losartan, aspirin, metoprolol, and furosemide, but continues to have symptoms despite the optimization of medical therapy. Her ECG in the clinic showed sinus rhythm, left ventricular hypertrophy, and frequent PVCs in a trigeminy pattern. The PVCs had a left bundle branch morphology with an early transition, tall R wave in the lead II, III, and AVF. Based on these qualities, our initial thought was that the PVCs were originating from the right ventricular outflow tract (RVOT). Given her frequent PVCs on ECG, she had a Holter monitor placed, which showed a total PVC burden of 31%. The patient was offered AADs, but she refused medical therapy. Given the severity of symptoms with underlying heart failure with preserved ejection fraction, she was offered PVC ablation.

After obtaining informed consent, she was taken to the electrophysiology laboratory. An octapolar catheter was placed in the coronary sinus in the left anterior oblique position, and a quadripolar catheter was placed in the His position. We advanced an irrigated tip catheter (THERMOCOOL Catheter, Biosense Webster, Inc., a Johnson & Johnson company) to the RVOT, and using the CARTO 3 system (Biosense Webster, Inc., a Johnson & Johnson company), the activation map identified PVCs originating from the postero-septal portion of the RVOT. We noticed that the activation was not early enough, and unipolar electrogram did not show negative deflection. We then went retrogradely to the left ventricle and mapped the left ventricle. The PVC was then localized to the left coronary cusp with the earliest activation of -30 milliseconds and a good negative unipolar electrogram (Figure 1). After applying multiple radiofrequency lesions of 30 Watts, the PVC was eliminated. After waiting for more than 30 minutes, we were not able to find a single clinical PVC and decided to stop the procedure.

At one- and six-month follow-up, she showed no sign of PVC recurrence on her Holter monitor, and her symptoms improved significantly with complete resolution of palpitations.

Case #2

A 71-year-old man with a history of mitral valve repair and hyperlipidemia was followed in the electrophysiology clinic for palpitations that had taken place for many years. He was found to have 20,000 PVCs with a total PVC burden of 20% during 24-hour Holter monitoring. His echocardiogram showed an ejection fraction of 55%, and his angiogram showed non-obstructive coronary artery disease. He was started on high-dose metoprolol, which decreased his ectopic burden to 12%, and his symptoms improved. More recently, the patient started complaining of palpitations despite being continued on the same dose of metoprolol. A repeat Holter monitor demonstrated a recurrence of increased PVC burden to 21%. His TTE showed a decrease in ejection fraction to 45%. The patient was started on amiodarone, which briefly controlled his symptoms but was discontinued due to adverse events. He refused trial of other AADs. Given his PVC burden, uncontrolled symptoms, decreased ejection fraction, and intolerance to AADs, the patient was deemed a candidate for catheter ablation.

On the day of the procedure, his ECG showed sinus rhythm with right bundle branch block (RBBB) and frequent PVCs. The PVCs had an RBBB morphology with an inferior axis and S wave in lead II and III. After proper consent, the patient was brought to the electrophysiology lab. A quadripolar catheter was placed in the His potential position, and another quadripolar catheter was advanced to the high right atrial and then to the right ventricle apex. A 3.5 mm irrigated catheter was advanced to the left ventricle in a retrograde fashion. We obtained both activation and voltage maps using the CARTO 3 mapping system, and the PVC was identified along the aortic-mitral continuity (AMC) (Figure 2). It is to be noted that we initially identified three different PVCs, but only the AMC persisted. The AMC location was then confirmed using pace mapping. A total of 16 radiofrequency lesions were applied to that location, after which no further PVCs were noted. We then used isoproterenol infusion as well as ventricular burst pacing, but no further PVCs or ventricular tachycardia (VT) were obtained. We then created a voltage map of the entire left ventricle, and the procedure was completed.

At one- and three-month follow-up, this patient remains asymptomatic and PVC free on the Holter monitor, with repeat TTE showing a modest increase in ejection fraction to 50%.

Incidence, Prevalence and Pathophysiology

In the Atherosclerosis Risk in Communities (ARIC) study, PVCs are present in >6% of the population on a two-minute ECG. The prevalence was different depending on the age groups, sex, and ethnicity, and was strongly associated with hypertension.¹ Longer monitoring such as 24-hour ambulatory ECG shows almost 50% of people with PVCs without any structural heart disease.² Cardiac conditions frequently associated with PVCs include heart failure, myocardial ischemia, myocarditis, congenital heart disease, left ventricular hypertrophy, idiopathic ventricular tachycardia, and arrhythmogenic right ventricular dysplasia.³ PVCs are also sometimes seen with non-cardiac conditions such as pulmonary diseases (chronic obstructive pulmonary disease, pulmonary hypertension), endocrine disorders (thyroid, adrenal hormonal abnormalities), illicit drugs (cocaine), smoking, alcohol, and medications (beta agonist or inotropes).⁴ Factors like autonomic tone, anxiety, electrolyte disturbances, hypoxia, and ischemia also affect the occurrence and frequency of PVCs. The majority of the time, PVCs originate from the RVOT, while other less common foci are left ventricular outflow tract, epicardial tissues adjacent to aortic sinuses of Valsalva, left ventricular Purkinje system, left ventricle summit, atrioventricular valve annulus, and the papillary muscles.⁵

PVCs and Arrhythmias

Studies have found PVCs to be associated with increased risk of mortality, especially in patients with recent myocardial infarction.⁶ Increased frequency and complexity of PVCs were associated with higher risks of ventricular tachycardia, ventricular fibrillation, and cardiac death. Following this, the Cardiac Arrhythmia Suppression Trial (CAST) was designed to evaluate the use of AADs (encainide, flecainide, or moricizine) to suppress PVCs after MI. Unfortunately, increased mortality was noted in the antiarrhythmic group compared to the placebo despite the suppression of PVCs.^7,8 Increased death was thought to be due to the pro-arrhythmogenic effects of the AADs. PVCs were then thought to be benign, but later studies revealed PVCs are associated with increased risk of atherosclerotic disease, stroke, sudden cardiac death, and left ventricular dysfunction or cardiomyopathy.^1,9

PVCs and Cardiomyopathy

In 1998, Duffee et al showed that suppression of PVCs in patients with presumed idiopathic dilated cardiomyopathy could lead to improvement of left ventricular function.¹⁰ Since then, multiple studies have shown PVCs as an independent risk factor for cardiomyopathy. The diagnosis of PVC-induced cardiomyopathy (PIC) can be made clinically by the presence of frequent PVCs and lack of other causes for cardiomyopathy.¹¹ Even in patients with structural heart disease, the presence of frequent PVCs can contribute to worsening cardiomyopathy. The exact pathophysiology is still unknown; the proposed mechanism of PIC involves ventricular dyssynchrony and tachycardia-induced cardiomyopathy. Risk factors for PIC include not only increased frequency but also the duration of exposure, longer QRS complex, epicardial origin PVCs, and male sex. Studies have shown PVC burden of >15-25% has increased risk of cardiomyopathy, though many patients with similar burden have normal ejection fraction; even low PVC burden of 4-5% may sometimes be associated with cardiomyopathy.^3,11

Diagnostic Evaluation

Initial workup involves a focused history and physical exam of symptoms, duration, any associated factors, and specific questions about heart failure symptoms. Laboratory workup includes a complete metabolic panel, including electrolytes, blood counts, and hormonal workups such as thyroid and catecholamine levels. All patients should get an ambulatory ECG or Holter monitor to assess the PVC morphologies, frequency, diurnal variation, burden, and symptom correlation. A routine transthoracic echocardiogram (TTE) to document ejection fraction and look for any structural heart disease should be performed. Ischemic workup such as a stress test or angiogram can be tailored depending on the patient presentation. Cardiac magnetic resonance and positron emission tomography (PET) can be further utilized to identify structural heart disease, even in a patient with a normal TTE or angiogram.

Management: Lifestyle and Medical

The first step in the management of PVCs involves the identification of any secondary causes that are either causing the PVCs or making them worse, such as electrolyte imbalances, metabolic disorders, or coronary artery disease. Lifestyle modification such as quitting smoking, limiting alcohol or caffeine consumption, and managing stress and anxiety can improve symptoms in some patients. Initial medical management consists of beta-blockers or calcium channel blockers, which have an excellent safety profile and are shown to be effective in at least some patients. Compared to beta-blockers or calcium channel blockers, antiarrhythmic drugs are shown to achieve a higher success rate in PVC suppression. Class IC antiarrhythmics such as flecainide and propafenone are effective in PVC suppression, but their use is limited in patients with structural or coronary artery disease. In those patients, amiodarone, dofetilide, and sotalol are safe, but they all have their own side effect profile, especially with long-term use.^11,12

Management: Catheter Ablation

Compared to AADs, catheter ablation of PVCs is much more effective and has a sustained long-term effect. The success rate of radiofrequency catheter ablation ranges from 65-90%, even in long-term follow-up.^13-15 Current guidelines recommend catheter ablation in patients with PIC who failed or are unable to tolerate AADs or based on patient preference. Successful predictors of ablation include RVOT origin and monomorphic PVCs. PVCs originating from epicardial or papillary muscle and multiple PVC morphologies are indicators of possible ablation failure.^11,15 Successful catheter ablation is associated with some improvement in ejection fraction in the majority of patients. Guidelines also recommend considering catheter ablation in patients with structural heart disease in whom frequent PVCs are likely contributing to increased cardiomyopathy and in ventricular tachycardia or fibrillation, which are focally triggered by a PVC. Consensus is yet to be achieved about the use of catheter ablation for PVCs in symptomatic patients with normal ejection fraction. Some authors recommend using catheter ablation as a last resort after exhausting all antiarrhythmic drugs, or in highly symptomatic patients.¹⁵

Catheter ablation technique is based on identifying and localizing the PVCs, and this can be achieved using activation mapping or pace mapping techniques. Once localized, the earliest focal endocardial or epicardial electrical signal preceding the targeted PVC is ablated.¹⁵ In order to effectively localize these foci, increased frequency of PVCs are required on the day of the procedure. Some useful strategies involve discontinuation of AADs a few days before the procedure, limiting intraoperative sedatives, and using chemical induction agents such as isoproterenol, epinephrine, or phenylephrine during the procedure.¹⁵ In recent years, multielectrode mapping catheters are now used frequently; these catheters can get data from multiple sites for every beat, and thus, have better resolution and speed of mapping. Multielectrode catheters include the THERMOCOOL, Livewire catheter (Abbott), Advisor HD Grid Mapping Catheter, Sensor Enabled (Abbott), and Orion Mapping Catheter (Boston Scientific). Some of these catheters can be used with the CARTO system, while others can be used with the Rhythmia HDx Mapping System (Boston Scientific). Historically, radiofrequency ablation has been the preferred method of ablation; other techniques include needle ablation, ethanol ablation, and cryoablation. Cryoablation might have better efficacy in specific anatomical structures such as the papillary muscles. Another emerging method is the use of stereotactic radiotherapy; this technique requires accurate localization of the PVC substrate beforehand.¹⁵

PVCs originating from the epicardium, LV summit, intramural location, papillary muscles, and para-Hisian region can be difficult to ablate. Improvement in ablation and mapping techniques has increased the success rates of these anatomically difficult foci ablation. In some cases, the coronary venous system or surgical access can be attempted to achieve ablation. Overall, catheter ablation is a safe procedure with a reported complication rate of 2.4%. Common complications include hematomas, pseudoaneurysms, or arteriovenous fistulas, as well as cardiac complications such as pericardial effusion or tamponade, valvular or coronary artery injuries, and damage to the conduction system.^11,12,15

Conclusion

PVCs can present in many ways. They can be benign or symptomatic, associated with arrhythmias, or present with heart failure. A practical approach involving appropriate diagnostic workup should be utilized in every patient before deciding on management. Patients who are asymptomatic and with normal ejection fraction can be monitored periodically with ambulatory monitoring and with TTE. If PVCs are symptomatic, causing cardiomyopathy, or associated with risk of ventricular arrhythmias, they can be treated with either medical management or catheter ablation. 

Disclosures: The authors have no conflicts of interest to report regarding the content herein.   

1. Simpson RJ Jr, Cascio WE, Schreiner PJ, et al. Prevalence of premature ventricular contractions in a population of African American and white men and women: the Atherosclerosis Risk in Communities (ARIC) study. Am Heart J. 2002;143(3):535-540.
2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary: a report of the American College of Cardiology / American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2018;15(10):e190-e252.
3. Laplante L, Benzaquen BS. A review of the potential pathogenicity and management of frequent premature ventricular contractions. Pacing Clin Electrophysiol. 2016;39(7):723-730.
4. Kerola T, Dewland TA, Vittinghoff E, et al. Modifiable predictors of ventricular ectopy in the community. J Am Heart Assoc. 2018;7(22):e010078.
5. Sharma E, Arunachalam K, Di M, Chu A, Maan A. PVCs, PVC-induced cardiomyopathy, and the role of catheter ablation. Crit Pathw Cardiol. 2017;16(2):76-80.
6. Ruberman W, Weinblatt E, Goldberg JD, Frank CW, Shapiro S. Ventricular premature beats and mortality after myocardial infarction. N Engl J Med. 1977;297(14):750-757.
7. Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321(6):406-412.
8. Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992;327(4):227-233.
9. Massing MW, Simpson RJ Jr, Rautaharju PM, Schreiner PJ, Crow R, Heiss G. Usefulness of ventricular premature complexes to predict coronary heart disease events and mortality (from the Atherosclerosis Risk In Communities cohort). Am J Cardiol. 2006;98(12):1609-1612.
10. Duffee DF, Shen WK, Smith HC. Suppression of frequent premature ventricular contractions and improvement of left ventricular function in patients with presumed idiopathic dilated cardiomyopathy. Mayo Clin Proc. 1998;73(5):430-433.
11. Latchamsetty R, Bogun F. Premature ventricular complex-induced cardiomyopathy. JACC Clin Electrophysiol. 2019;5(5):537-550.
12. O'Quinn MP, Mazzella AJ, Kumar P. Approach to management of premature ventricular contractions. Curr Treat Options Cardiovasc Med. 2019;21(10):53.
13. Stec S, Sikorska A, Zaborska B, Krynski T, Szymot J, Kulakowski P. Benign symptomatic premature ventricular complexes: short- and long-term efficacy of antiarrhythmic drugs and radiofrequency ablation. Kardiol Pol. 2012;70(4):351-358.
14. Ling Z, Liu Z, Su L, et al. Radiofrequency ablation versus antiarrhythmic medication for treatment of ventricular premature beats from the right ventricular outflow tract: prospective randomized study. Circ Arrhythm Electrophysiol. 2014;7(2):237-243.
15. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Europace. 2019 May 10. pii: euz132.