PVCs are caused by abnormal impulse formation or re-entry in the ventricular myocardium or Purkinje system. Characteristics of PVCs include the premature appearance of an abnormal QRS complex (>120m/sec) with a broad, opposite T-wave and no preceding P-wave.¹  

Left ventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT) are the most common originator sites of PVCs, accounting for >60% of all cases. RVOT accounts for 70%–80% of cases. Other sites include fascicles, papillary muscles, mitral and tricuspid annuli, and the epicardium.^1,2,4,5 

PVC often incidentally discovered 

Patients are often asymptomatic, and PVC may be incidentally discovered during a physical exam or on routine screening electrocardiogram (ECG). Acute symptoms include palpitations, chest pain, shortness of breath, lightheadedness, or dizziness.²  

Progressive symptoms resulting from the cumulative impact that frequent PVCs can have on myocardial contractility, include dyspnoea on exertion, orthopnoea, and oedema and should be an indication for further investigation. Patients living with pre-existing heart disease who experience frequent PVCs may present with symptoms such as dyspnoea, angina, presyncope, syncope, and even haemodynamic compromise.²    

What tests should be done to confirm a diagnosis? 

The initial workup for patients living with suspected PVCs includes a thorough history, physical exam, resting ECG, and at least 24-hours of ambulatory ECG monitoring. If symptoms persist and the initial monitoring is inconclusive, extended monitoring with a 48-hour monitor, event recorder, or implantable loop recorder is recommended.²  

Symptomatic patients should undergo a transthoracic echocardiogram to check for structural abnormalities, focusing on ejection fraction, LV chamber size, valvular issues, and regional wall motion. Additional tests like stress testing, nuclear myocardial perfusion imaging, coronary angiography, and cardiac magnetic resonance imaging (MRI) may be necessary in some cases.² 

Cardiac MRI is useful for diagnosing arrhythmogenic right ventricular cardiomyopathy, infiltrative diseases, or confirming left ventricular non-compaction cardiomyopathy. Evaluating electrolyte imbalances, specifically potassium and magnesium levels, is also reasonable. Further lab tests, including urine drug screens, thyroid-stimulating hormone levels, cardiac biomarkers, and serum digoxin levels, should be considered when indicated.²  

How are PVCs categorised? 

PVCs can be categorised by their pattern relative to normal beats: Bigeminy (a PVC follows each normal QRS complex), trigeminy (a PVC follows every two normal QRS complexes), and multiple successive PVCs. Two consecutive PVCs are called a couplet, three are a triplet, and more than three successive PVCs are termed VT.²  

Couplets are further defined by the interval between the PVC and the subsequent normal beat: Fixed coupling if the interval is stable, and variable coupling if it changes. PVCs are considered frequent if they occur >30 times per hour or constitute more than 20% of total heartbeats.² 

What causes PVC? 

Studies show that various lifestyle factors can increase the risk of PVCs. These include stress, caffeine, illicit drug use (eg cocaine), excessive alcohol intake, cigarette smoking, sleep disturbances, and physical exercise - even in healthy, asymptomatic individuals.^1,2  

Caffeine and illicit drugs stimulate the heart, while excessive alcohol and nicotine use disrupt electrical pathways, both leading to PVCs. Obesity, insomnia, and stress levels are also linked to higher PVC rates due to autonomic system imbalances.¹ 

PVC can also be caused by electrolyte abnormalities (most commonly hypokalaemia and hypomagnesaemia), volume overload, and hypoxia. Furthermore, the American Heart Association cautions that many commonly used pharmaceutical agents can cause or worsen arrhythmias. Some anti-arrhythmic drugs (AADs), antimicrobials, psychotropic medications, methadone, and a growing list of drugs from other therapeutic classes such as neurological drugs, anti-cancer agents, and others can prolong the QT interval.^2,6 

How do you treat symptomatic PVC? 

According to Marcus, if PVC burden is low, no underlying structural heart disease is found, reassurance alone may suffice. It should be noted that patients with HF and PVCs tend to have a higher PVC burden, which is a significant risk factor for cardiomyopathy including sudden cardiac death.⁷  

Although there is currently not a definitive threshold for PVC burden, studies do however, suggest that PVC-induced cardiomyopathy is more likely at burdens of 16% to 24%, with most cases occurring at burdens exceeding 10%.⁷  

Catheter ablation is recommended as first-line treatment due to its high success rate and low complication risk.  Successful ablation typically involves a combination of activation and pace-mapping guided by fluoroscopy, electro-anatomical mapping, and intracardiac echocardiography.⁸ 

However, like any invasive procedure, the potential benefits of catheter ablation must be carefully weighed against the risk of major complications, which may occur in up to 3% of patients. These complications include vascular issues such as femoral pseudoaneurysm, arteriovenous fistula, or groin hematoma, as well as cardiac perforation leading to tamponade, intraprocedural stroke, or even death.⁸  

When considering catheter ablation, factors such as pharmacological alternatives, patient comorbidities, the anatomical location of the PVC, and the operator's experience should all be considered.⁸ 

In cases where symptoms are present, beta-blockers are typically the initial pharmacological treatment. For patients with a slow baseline heart rate or increased PVC burden due to bradycardia, beta-blockers (BBs) with intrinsic sympathomimetic activity may be particularly beneficial.⁸  

Alternatively, in patients intolerant to BBs without HF, non-dihydropyridine calcium channel blockers (CCBs) may be considered due to their relatively low adverse effect profile.⁸ 

Second-line treatment includes the use of antiarrhythmic drugs (AADs) such as flecainide or propafenone. Class I and III AADs have shown higher rates of PVC reduction compared to BBs or CCBs. However, Class I AADs were traditionally contraindicated in patients with LV dysfunction or significant structural heart disease.⁸  

Nevertheless, in a small cohort of patients with suspected PVC-induced cardiomyopathy who had previously undergone unsuccessful ablation procedures, treatment with class IC AADs effectively suppressed PVCs with no adverse events during follow-up. In this cohort, the mean PVC burden decreased significantly, and LV ejection fraction improved.⁸ 

Treating patients with no underlying structural heart disease 

Idiopathic PVCs occur in the absence of structural heart disease or inherited ion channelopathies.  These PVCs have a focal mechanism related to delayed afterdepolarisations and triggered activity. Stress or exertion often triggers these adrenergically mediated arrhythmias.⁹ 

PVCs originating in the RVOT usually appear in patients without structural heart disease. They may present in the form of isolated or incessant PVC, or as tachycardia (up to 80% of idiopathic VT). PVCs originating in the left fascicles are rare.  In patients with a cardiomyopathy suspected to be caused by frequent and predominately monomorphic PVCs, catheter ablation is recommended.^3,6,10 

Pharmacological management of idiopathic PVCs aims to reduce cyclic adenosine monophosphate (cAMP) levels, which are elevated in these conditions.⁹  

The latest European Society of Cardiology (ESC) guidelines recommend the following for idiopathic PVC:  Beta-blockers, non-dihydropyridine CCBs or sodium channel blockers when catheter ablation is not available, not desired, or is particularly risky in symptomatic patients with idiopathic PVCs from the RVOT or the left fascicles. Catheter ablation or flecainide should be considered in symptomatic patients with idiopathic PVCs from an origin other than the RVOT or the left fascicles.^3,7,10 

When these medications are ineffective or poorly tolerated, other AADs like flecainide, propafenone, sotalol, and amiodarone may be considered. Flecainide is noted for its high efficacy and tolerability in treating PVCs, though it is contraindicated in patients with structural heart disease due to the risk of re-entrant VAs.^9,11,12 

Conclusion 

PVCs are more prevalent than commonly perceived, affecting between 1%-4% of the population. Despite historically being viewed as benign, emerging evidence suggests PVCs significantly elevate the risk of adverse CV outcomes. 

Effective diagnosis and management of PVCs require a comprehensive approach. Pharmacological management typically starts with beta-blockers or CCBs, with AADs reserved for cases refractory to initial therapy.  

Catheter ablation has emerged as a first-line treatment option for patients with PVCs originating from specific sites. However, the decision to pursue catheter ablation must be carefully considered, weighing the potential benefits against the risks of major complications.  

Ultimately, a tailored approach that considers individual patient factors, symptomatology, and risk profile is essential for optimising outcomes in individuals living with PVCs.  

References 

1. Tungar IM, Reddy MMRK, Flores SM, et al. The Influence of Lifestyle Factors on the Occurrence and Severity of Premature Ventricular Contractions: A Comprehensive Review. Current Problems in Cardiology, 2024. 
2. Koester C, Ibrahim AM, Cancel M, Labedi MR. The Ubiquitous Premature Ventricular Complex. Cureus, 2020. 
3. Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). European Heart Journal, 2022. 
4. Xiong Y, Zhu H. Electrocardiographic characteristics of idiopathic ventricular arrhythmias based on anatomy. Ann Noninvasive Electrocardiol, 2020. 
5. Chen H, Xiao F, Ju W, et al. Premature Ventricular Contractions from the Left Anterior Fascicle: Electrocardiographic and Electrophysiological Characteristics, Mapping Strategy, and Immediate and Long-Term Catheter Ablation Results. Front Cardiovasc Med, 2022. 
6. Tisdale JE, Chung MK, Campbell KB, et al.  Drug-Induced Arrhythmias: A Scientific Statement from the American Heart Association. Circulation, 2020. 
7. Marcus GM. Evaluation and Management of Premature Ventricular Complexes. Circulation, 2020. 
8. Panizo JG, Barra S, Mellor G, Heck P, Agarwal S. Premature Ventricular Complex-induced Cardiomyopathy. Arrhythm Electrophysiol Rev, 2018. 
9. Muser D, Tritto M, Mariani MV, et al. Diagnosis and Treatment of Idiopathic Premature Ventricular Contractions: A Stepwise Approach Based on the Site of Origin. Diagnostics (Basel). 2021   
10. Infante ED, León RC, Borrego I, et al. Ablation of Premature Ventricular Contractions Originating in the Right Ventricular Outflow Tract Using Non-Contact Mapping. Revista Española de Cardiología, 2011. 
11. Kojić D, Radunović A, Bukumirić Z, et al. Idiopathic premature ventricular complexes treatment: Comparison of flecainide, propafenone, and sotalol. Clin Cardiol, 2023. 
12. Lavalle C, Trivigno S, Vetta G, et al. Flecainide in Ventricular Arrhythmias: From Old Myths to New Perspectives. J Clin Med, 2021.