7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Premature ventricular complexes: Treatment and prognosis : Antonis S Manolis, MD : Hugh Calkins, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 07, 2022. INTRODUCTION Premature ventricular complexes/contractions (PVCs; also referred to premature ventricular beats, premature ventricular depolarizations, or ventricular extrasystoles) are common and occur in a broad spectrum of the population. This includes patients without apparent structural heart disease as well as those with any form of cardiac disease, independent of severity. The approach to risk assessment and treatment of PVCs along with information on prognosis will be presented here. Discussion of the prevalence, mechanisms, clinical presentation, and approach to diagnostic testing for patients with known or suspected PVCs, as well as review of supraventricular premature beats, are presented separately: (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation".) (See "Supraventricular premature beats".) RISK ASSESSMENT The management of the patient with PVCs depends on whether the initial evaluation indicates that the patient is at high versus low risk of complications including cardiomyopathy, heart failure exacerbation, and ventricular tachyarrhythmias. High-risk features will indicate more intensive treatment and monitoring. https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 1/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate Our approach, outlined below, is in general agreement with the published recommendations of multiple professional societies [1-3]. Symptoms Most patients with PVCs have no symptoms; only a minority describe bothersome symptoms (usually palpitations). These PVC-related symptoms are described separately. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Symptoms'.) Patients with no or mild PVC symptoms and none of the other risk factors described below can typically be reassured by their providers that PVCs are usually self-limiting, rarely life- threatening, and in most cases do not require treatment. (See 'Asymptomatic patients with low premature ventricular complex burden' below.) Patients with significant and/or persistent PVC-related symptoms should be treated to reduce the PVC burden; the treatment approach will depend upon the presence or absence of other risk factors. (See 'Patient with symptoms and/or high premature ventricular complex burden' below and 'Premature ventricular complex burden' below.) Symptoms of syncope (especially with no prodrome or preceded by palpitations), chest pain, or dyspnea are uncommonly reported in patients with PVCs and signal underlying cardiac structural or electrical conduction system disease. These symptoms may identify a higher-risk patient and require specific evaluation. (See 'Underlying or associated cardiac disease' below.) Family history A detailed family history should be taken regarding coronary heart disease, sudden death, or arrythmia and cardiomyopathy. A family history of sudden cardiac death or arrest or an inherited arrythmia syndrome identifies the patient to be at higher risk for electrical or structural heart disease, which in turn requires a more specific evaluation. (See 'Further testing in selected patients' below.) Premature ventricular complex burden In all patients, it is important to assess and then continue to monitor for reduction in PVC burden throughout treatment. High PVC burden is a predictor of PVC-induced cardiomyopathy, heart failure, and mortality, and therefore requires more aggressive therapy [4]. Monitoring can usually be done with 24- to 48-hour continuous electrocardiographic monitoring. (See "Ambulatory ECG monitoring", section on 'Continuous ambulatory ECG (Holter) monitor'.) PVC burden is classified as: https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 2/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate Low: <1 percent or 1000 PVCs/day Intermediate burden: >1 to <15 percent PVCs/ day High: >15 percent or 15,000 PVCs/day Premature ventricular complex characteristics PVC characteristics such as origin and morphology can be considered when determining whether a patient is at high or low risk for cardiomyopathy or malignant arrythmia. Even when the PVCs seem to be idiopathic in a patient with a previously normal heart, some PVCs can still be potentially malignant (ie, cause cardiomyopathy, or trigger sudden death) [5-7]. PVC morphology is also of value as it can predict the ablation target and response to PVC catheter ablation. (See 'Catheter ablation' below.) Characteristics associated with higher risk include increased QRS duration [8,9] (these are often of epicardial origin [10-12]) ( waveform 1), interpolated PVCs [13] ( waveform 2), PVCs involving the Purkinje system (these can trigger ventricular fibrillation and have a short coupling interval figure [14-16]), and polymorphic PVCs [17] ( waveform 3). PVCs with highly variable coupling interval (>60 ms) have been identified as originating in unusual areas (aortic sinuses of Valsalva, great cardiac vein) and have been associated with a higher risk for cardiac events [18]. In the same context, greater PVC coupling interval heterogeneity has been associated with both reduced LV function and an increased risk of developing heart failure [19]. Right and left ventricular outflow tract PVCs morphologies have also been associated with malignant ventricular arrhythmias [5,20,21] ( waveform 4 and waveform 5). In patients without apparent heart disease, frequent, complex, and polymorphic PVCs have been associated with worse prognosis [22-24]. Older studies suggested these PVCs were associated with a twofold increase in myocardial infarction or death in males [22,24]. A newer study in a Taiwanese population suggested a smaller magnitude of effect; multiform PVCs were associated with a 20 percent increased risk of mortality and 10 percent increased risk for hospitalization [17]. Underlying or associated cardiac disease PVCs can be the first manifestation of cardiac disease, including coronary artery disease, cardiomyopathy, and inherited arrhythmia syndromes (eg, long QT syndrome, arrhythmogenic right ventricular cardiomyopathy). In addition, patients with a high PVC burden can develop a cardiomyopathy. In some people with inherited arrythmia syndromes, PVCs can trigger ventricular tachyarrhythmia. (See "Congenital long QT syndrome: Pathophysiology and genetics", section on 'Triggered activity' and "Brugada syndrome: Epidemiology and pathogenesis", section on 'Ventricular arrhythmias and phase 2 reentry' and "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'R-on-T phenomenon'.) https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 3/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate If a patient has a left ventricular ejection fraction (LVEF) <50 percent (regardless of symptoms) and a high PVC burden, the LVEF reduction is assumed to be related to frequent PVCs (also called PVC-induced cardiomyopathy [25,26]). In one series of 245 patients with PVC-induced cardiomyopathy, independent predictors for development of PVC-induced cardiomyopathy were male sex, high PVC burden, lack of symptoms, and epicardial PVC origin [27]. (See 'Premature ventricular complex cardiomyopathy' below.) Evaluation in most patients In order to assess PVC burden and the presence of structural heart disease, all patients should undergo: A 12-lead electrocardiogram (ECG). Twenty-four-hour Holter monitoring. An echocardiogram should be performed if there are high-risk symptoms, frequent PVCs, or if there is any suspicion of underlying or new structural heart disease (including PVC cardiomyopathy) and/or high-risk information from other risk assessments such as abnormal 12-lead ECG or family history of heart disease and especially of sudden cardiac death. (See 'Symptoms' above and 'Family history' above and 'Premature ventricular complex burden' above and 'Premature ventricular complex characteristics' above.) When ambulatory ECG monitoring is indicated, a monitoring period of 24 to 48 hours is typically sufficient to identify PVCs and quantify the overall PVC burden. A variety of ambulatory ECG monitoring techniques are available, but for most patients Holter monitoring or patch monitoring will be the preferred approach. (See "Ambulatory ECG monitoring".) Further testing in selected patients Specific symptoms and/or high-risk features are reasons to get further cardiac testing. If obstructive coronary disease is suspected (on the basis of symptoms or risk factors), or the PVCs are effort related, the patient should also undergo: Exercise stress testing Among patients with effort-related symptoms and who are suspected to have obstructive coronary disease, exercise stress testing can evaluate ischemia [28] and provide useful prognostic information. (See "Prognostic features of stress testing in patients with known or suspected coronary disease".) PVCs occurring during exercise may be secondary to underlying ischemia or could represent adrenergic or catecholamine-sensitive arrhythmias (eg, inherited channelopathies) [29]. For patients whose PVCs are induced by exercise, exercise testing in https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 4/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate conjunction with ambulatory monitoring can be used to assess the effectiveness of antiarrhythmic drug treatment. For patients with exercise-related PVCs, further cardiac testing for underlying cardiovascular disease should be undertaken that may include additional cardiac tests, such as stress testing with imaging, cardiac magnetic resonance imaging (CMR), and electrophysiology testing [30-32]. More commonly, however, PVCs are suppressed during exercise and reemerge in the ensuing recovery period. Cardiac magnetic resonance imaging Selected patients (ie, those with high-risk PVC features, a family history of sudden death or cardiomyopathy, and/or cardiomyopathy of uncertain etiology) may require CMR [33]. CMR can be particularly useful in diagnosing hypertrophic cardiomyopathy, cardiac sarcoid, arrhythmogenic right ventricular cardiomyopathy, and amyloid cardiomyopathy. CMR is generally obtained if these conditions are suspected based on baseline ECG and/or echocardiogram characteristics, family history, and exercise history. We do not routinely use CMR imaging for all patients with frequent PVCs due to limited availability of this test, high cost, lack of expertise in cardiac MRI imaging, and the lack of prospective randomized trials demonstrating that a CMR-based strategy improves outcomes, including mortality. CMR is used selectively and can be center dependent, based on local availability and expertise. Screening with CMR may be useful before further invasive electrophysiology assessment and therapeutic decision-making are undertaken. For instance, CMR may play a role in evaluating need for implantable cardioverter-defibrillator (ICD) in patients with PVC cardiomyopathy. (See 'Implantable cardioverter-defibrillator' below.) Observational studies in patients with frequent PVCs have shown that myocardial abnormalities on CMR are commonly seen (ie, in 15 to 35 percent of such patients) and are associated with adverse cardiac outcomes [34-36]. Among an international cohort of 518 patients (mean age 44 years) with frequent (>1000/24 hours) PVCs and otherwise negative diagnostic work-up, myocardial abnormalities were found in 85 patients (16 percent) [34]. In a single-center observational study, 255 patients with frequent PVCs (>5 percent per 24 hours) who had a contrast-enhanced CMR for work-up of PVCs were followed for the composite outcome (mortality, ventricular fibrillation, sustained ventricular tachycardia, or reduction in left ventricular ejection fraction of 10 percent) [35]. Thirty-five percent of patients had a myocardial abnormality on CMR, and the composite outcome occurred in 5.9 percent. After a median follow-up of 36 months, the incidence of the composite https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 5/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate outcome was higher among patients with myocardial abnormalities versus a normal CMR (20 versus 3.6 percent; hazard ratio 4.35, 95% CI 1.34-14.15). Electrophysiology testing Electrophysiology testing is used only in selected patients with higher-risk PVC features as a risk stratification tool to guide therapy or in patients undergoing catheter ablation procedure (ie, as treatment for frequent symptomatic PVCs refractory to medical therapy or in whom the PVCs have resulted in cardiomyopathy). (See "Invasive diagnostic cardiac electrophysiology studies" and 'Implantable cardioverter- defibrillator' below.) MANAGE TRIGGERS AND RISK FACTORS Prior to initiating therapy, correctable causes or triggers should be identified and, where possible, corrected ( table 1). Patients with hypertension often have PVCs, and if there is left ventricular hypertrophy, outcomes are often worse. These patients should have their blood pressure controlled, preferably with a beta blocker and/or an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker, and receive treatment for concurrent left ventricular dysfunction/heart failure if present. Efforts should be made to avoid hypokalemia, which can result from the diuretic class of antihypertensive agents [37]. (See "Choice of drug therapy in primary (essential) hypertension" and "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Associated conditions'.) MANAGEMENT OF HIGH-RISK PATIENTS High-risk patients have any of the following conditions: high (>10 to 15 percent) PVC burden, PVC-induced cardiomyopathy, preexisting cardiac structural or electrical conduction system disease, history of syncope, and abnormalities on cardiac magnetic resonance (CMR) imaging even in the presence of a normal LVEF [34,38,39]. Management in these patients is required to reverse or reduce the risk of developing a cardiomyopathy and to reduce the risk of ventricular arrhythmias and sudden cardiac death ( algorithm 1). Premature ventricular complex cardiomyopathy If a patient has an LVEF <50 percent (regardless of symptoms), and a high PVC burden, the LVEF reduction is assumed to be related to frequent PVCs, and the diagnosis is PVC-induced cardiomyopathy [25,26]. (See "Premature https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 6/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'PVC-induced cardiomyopathy' and 'Underlying or associated cardiac disease' above and 'Premature ventricular complex burden' above.) In such patients, treatment is aimed towards reducing PVC burden, which can in turn avert or reverse the cardiomyopathy. Even patients who already have an implantable cardioverter- defibrillator (ICD) benefit from PVC reduction and ablation. Some patients with PVC-induced cardiomyopathy will exhibit signs and symptoms of heart failure that may require treatment with heart failure medications. However, the definitive treatment is to suppress or ablate the PVCs. (See "Arrhythmia-induced cardiomyopathy", section on 'Frequent ventricular ectopy' and "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'PVC-induced cardiomyopathy'.) Calcium channel blockers should generally be avoided in patients with cardiomyopathy. (See "Drugs that should be avoided or used with caution in patients with heart failure", section on 'Calcium channel blockers'.) Beta blockers The first-line therapy to reduce PVC burden is beta blockers. An exception may be those with heart failure who may proceed directly to catheter ablation. Commonly used beta blockers to treat PVCs include metoprolol and carvedilol. Typical starting doses, alternatives, and maximum dosages for PVC treatment are given in a table ( table 2). Once given, the patient should be monitored for a reduction in symptoms that correspond with a reduction in PVCs, titrating the medication as necessary. Repeat ambulatory ECG monitoring is typically obtained after three months of treatment to determine if the patient has responded to beta blockers. If symptoms and PVC burden have been reduced and are not high, the beta blocker should be continued. If after one month of maximal beta blocker therapy there is no symptom relief or decrease in PVC burden, a catheter ablation is usually considered (especially if PVCs are monomorphic, making them more amenable to ablation). Alternatively, some patients are treated with antiarrhythmic drugs. Efficacy of beta blockers Beta blockers are effective at reducing PVC symptoms. This is because beta blockers reduce the post-extrasystolic potentiation via the Starling mechanism (increased inotropy related to the increased stroke volume) associated with the PVC. Beta blockers can also prevent PVC recurrence. However, it should be recognized that they have no direct effects on the ventricular myocardium. Therefore, beta blockers are https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 7/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate most likely to suppress PVCs that result from excess sympathetic stimulation or are catecholamine sensitive. In an observational study, beta blockers were reported to reduce PVC burden in one-third of patients taking them [40]. Similar findings (a 21 to 36 percent PVC reduction) were reported by other studies [41,42]. Weaning Sometimes, a patient will prefer to stop the beta blocker after symptom relief is achieved. In this case, one can try to wean the beta blocker after 6 to 12 months of medication treatment. The dose can be gradually reduced and a 24-hour Holter recording can be repeated periodically. It is preferable to keep the patient on at least a low-dose beta blocker if they are willing, as this may prevent PVC reoccurrence. (See 'Premature ventricular complex burden' above.) Catheter ablation Catheter ablation is an effective option ( algorithm 2) to reduce or eliminate PVCs in patients who do not respond to beta blocker therapy [41,43-49] and may be first-line treatment in those with heart failure. In a multicenter study of 1185 patients undergoing PVC ablation, 85 percent did not require the use of antiarrhythmic medications at two years following ablation [27]. In patients with PVC-induced cardiomyopathy, PVC ablation can lead to left ventricular function recovery. In a multicenter study of 245 patients with PVC-induced cardiomyopathy who underwent ablation, the LVEF increased from 38 to 50 percent after ablation [27]. The decision to recommend radiofrequency catheter ablation versus antiarrhythmic therapy in a particular patient will depend on clinical factors (ie, predictors of procedural success) and on patient preference. Some patients will not want to undergo an invasive catheter ablation procedure. Not all centers have catheter ablation expertise. Reasonable attempts should be made to refer appropriate patients to centers with catheter ablation expertise. Predictors of procedural success Clinical variables that identify patients most likely to respond to catheter ablation and/or less likely to experience complications include [37]: Unifocal PVCs. High PVC burden. (See 'Premature ventricular complex burden' above.) Right ventricular outflow tract (RVOT) origin. PVCs of right ventricular origin (left bundle branch block inferior axis) will have left bundle branch inferior axis morphology on 12- lead ECG ( waveform 5). For such patients, we have a lower threshold to do catheter ablation, as ablation of PVCs in the right ventricle requires only venous access. In https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 8/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate contrast, PVCs arising in the LV outflow tract or LV require retrograde aortic or transeptal access and have a higher associated procedural risk. In a 2014 meta-analysis of small nonrandomized studies of patients with idiopathic PVCs originating from the RVOT, catheter ablation was associated with a reduction in PVC burden (97 percent mean reduction) along with an improvement in LVEF (mean increase 10 percent) [50]. Heterogeneity across studies limited the certainty of these effect estimates. The majority of patients with PVC-induced LV dysfunction have a recovery of LV function within four months. In some patients, recovery of LV function may take longer; an epicardial origin of PVCs and/or a significantly longer PVC-QRS width are more often present in patients with delayed recovery of LV function than in patients with early recovery of LV function. In a study of 75 patients with frequent idiopathic PVCs and PVC-induced cardiomyopathy submitted to successful PVC ablation, the majority (68 percent) had a recovery of LV function within four months [48]. Patients with delayed recovery of LV function were more likely to have epicardial origin of PVCs (54 versus 4 percent) and longer PVC-QRS width (170 21 versus 159 16 ms) compared with those with an earlier recovery. Similarly, in a study of 114 patients, mean PVC- QRS was 173 ms for those with irreversible LV dysfunction versus 158 ms for those with reversible LV dysfunction (odds ratio 5) [51]. Predictors of ablation failure include multiple PVC morphologies, epicardial or papillary muscle origins, and decreased/short earliest local activation time [27,52]. PVC ablation complications Regardless of whether venous or arterial access is needed, vascular complications are a potential risk of the procedure. Ablation of PVCs originating in the LV require arterial access, and therefore, circulatory complications of stroke, myocardial infarction, and mitral or aortic valve damage can occur. Myocardial perforation and cardiac tamponade or coronary artery injury are potentially lethal complications [53,54]. In a study of 1185 patients undergoing catheter ablation for PVCs, the major complication rate was 2.4 percent, with the most common complications related to vascular access [27]. Nine patients (0.8 percent) had pericardial tamponade requiring pericardiocentesis, and a single patient experienced permanent atrioventricular block. No patients died or experienced stroke. In another study, among 1231 patients undergoing PVC ablation, the overall complication rate was 2.7 percent, with cardiac tamponade being the most common complication (27 percent of all complications or an overall rate of 0.7 percent) [54]. Two ablation-related deaths occurred; one patient died from coronary artery injury during the procedure, and the other died from infectious endocarditis. Location (LV and epicardium) was the main predictor of complications, with RVOT predicting fewer complications. https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 9/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate Potential risks of catheter ablation are discussed separately. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) Expected timeframe for recovery of LVEF Repeat cardiac monitoring should be performed post-procedure at approximately three months to assess PVC burden. Also, a repeat echocardiogram should be performed three months after the PVC ablation to assess for LV function recovery. Most patients experience complete LVEF recovery after three to six months post-ablation [55]. In about one-third of patients, recovery is delayed and can take up to three to four years [48]. Predictors of delayed recovery included epicardial-origin PVCs [27] and increased intrinsic QRS duration [56]. Antiarrhythmic therapy If a patient is not an optimal candidate for, or prefers not to have, an invasive ablation procedure, an antiarrhythmic agent can be tried. In patients with structural heart disease, including those with PVC cardiomyopathy, there are limited safe and efficacious antiarrhythmic drugs [37,50]. Preferred agents for patients with underlying heart disease are amiodarone and ranolazine: Amiodarone Amiodarone is the least proarrhythmic agent in patients with structural heart disease, although there are substantial risks of organ toxicities with long-term use. Trials of amiodarone use in patients with PVCs and prior myocardial infarction or heart failure have demonstrated a reduction in PVCs and in arrhythmic mortality (6.9 versus 4.5 percent; relative risk 0.49; 95% CI 0.05-0.72) but not overall mortality ( figure 1) [57]. However, routine amiodarone therapy in asymptomatic patients is not recommended because of the limited benefit and potential side effects [57-59]. Oral loading doses of 400 to 1200 mg/day in divided doses (up to a total loading dose of 6 to 10 grams) can be used. The usual maintenance dose should be the lowest effective dose; this is usually 200 mg daily but can be as low as 100 mg daily. (See "Amiodarone: Clinical uses", section on 'Amiodarone for ventricular arrhythmias'.) Ranolazine Ranolazine, an oral antianginal medication that has I and IKr-blocking Na properties, is approved for patients with chronic stable angina. Observational studies [60] and case reports/series [61-63] suggest that ranolazine may be a safe and effective treatment for PVCs; however, no randomized trials have been performed to confirm these results. In one cohort of 59 patients with ventricular ectopy with or without cardiac disease, ranolazine reduced PVCs by 71 percent (from 13,329 to 3837 per day) [60]. Ventricular https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 10/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate bigeminy and couplets were each reduced by 80 percent, and ventricular tachycardia was reduced by 90 percent. Safety and efficacy of ranolazine for ventricular tachycardia were studied in the MERLIN- TIMI 36 trial (ventricular tachycardia lasting 3 beats, 52 versus 61 percent; relative risk 0.86, 95% CI 0.82-0.90) [64] without causing significant proarrhythmia [65]. Starting dose is 500 mg orally twice daily; maximum daily dose 1000 mg twice daily. Class IC drugs may be proarrhythmic in patients with coronary artery disease and/or significant myocardial dysfunction; therefore, they should not be used in these patients [66,67]. In patients with a prior myocardial infarction, the use of flecainide and other class IC antiarrhythmic drugs ( table 3) for PVCs has been associated with increased mortality due to proarrhythmia ( figure 2 and figure 3) [66,67]. Flecainide and propafenone (class IC antiarrhythmic drugs ( table 3)) have been successfully used in patients with suspected PVC-induced cardiomyopathy who have failed previous catheter ablation attempts [68], but they should not be generally used in this setting due to safety concerns. The use of these drugs in lower-risk patients is discussed below. (See 'Subsequent therapy' below.) Implantable cardioverter-defibrillator In patients with PVC-induced cardiomyopathy and very low LVEF (<35 percent) that would otherwise meet primary prevention criteria for an ICD, elimination of the PVCs can generally restore LV function and obviate the need for ICD implantation [69]. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions", section on 'Primary prevention'.) However, when the etiology of nonischemic cardiomyopathy is not clear, which can be the case before PVCs are eliminated and the LVEF normalizes, there remains a concern about the risk of sudden cardiac death. Thus, preprocedural CMR followed by an electrophysiology study with programmed ventricular stimulation, particularly in CMR-positive patients, may be considered [30]. In the absence of CMR-defined myocardial fibrosis/scarring and/or inducible ventricular tachycardia during an electrophysiology study, one can wait for improvement in LVEF following PVC elimination, withholding the ICD and reevaluating the patient within six months of ablation. (See "Determining the etiology and severity of heart failure or cardiomyopathy", section on 'Cardiovascular magnetic resonance' and "Premature ventricular complexes: Clinical presentation and diagnostic evaluation" and "Invasive diagnostic cardiac electrophysiology studies".) Preexisting cardiac disease Patients with coronary artery disease, cardiomyopathy, or electrical conduction system disease who have PVCs are considered high risk. High-risk PVC https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 11/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate characteristics, including morphology and origin, are discussed above. (See 'Premature ventricular complex characteristics' above.) For patients with underlying structural heart disease, it is important to reduce the PVC burden if it is high (ie, >15 percent or 15,000 PVCs/day) in order to lower the risk of developing PVC- induced cardiomyopathy. The first-line therapy for these patients is to reduce PVC burden with beta blockers. If after two to four weeks of beta blocker therapy, there is no decrease in PVC burden and/or there is a persistent reduction in LVEF, catheter ablation is usually considered next [27,37,41,43-50]. (See 'Catheter ablation' above.) Generally, treating the underlying condition often improves and can reduce PVC burden. For an inherited cardiomyopathy or arrythmia syndrome, referral to a genetic counselor is also appropriate. Heart failure Patients with dilated cardiomyopathy or heart failure have a reported 70 to 95 percent prevalence of PVCs [70]. The evaluation and management of PVCs in such patients are discussed separately. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".) Coronary artery disease The management of PVCs differs in patients with acute and chronic coronary syndrome. Acute coronary syndrome For persons with PVCs in the setting of acute coronary syndromes, the best antiarrhythmic approach is the use of antiischemic therapies (reperfusion/revascularization) combined with a beta blocker. As mentioned, treatment with ranolazine may significantly lower the incidence of ventricular arrhythmias in patients with a non-ST-elevation acute coronary syndrome, as shown in MERLIN-TIMI 36 trial [64]. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Management' and "Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment", section on 'Ventricular premature beats'.) Chronic coronary syndrome In patients who have had past myocardial infarctions, PVCs, particularly if frequent (more than 10 per hour) or complex (ie, repetitive forms, primarily nonsustained ventricular tachycardia), appear to be associated with a worse prognosis. Most patients with a prior myocardial infarction will be taking a beta blocker as part of standard therapy for their underlying disease, which may be associated with a https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 12/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate reduction in PVCs [71,72]. (See "Beta blockers in the management of chronic coronary syndrome" and "Primary pharmacologic therapy for heart failure with reduced ejection fraction".) Amiodarone is the preferred antiarrhythmic drug in patients with symptomatic PVCs despite beta blocker therapy. Attempted suppression of PVCs with class IC antiarrhythmic drugs in patients with coronary artery disease has been associated with increased mortality ( figure 2). (See 'Antiarrhythmic therapy' above and "Amiodarone: Clinical uses", section on 'Amiodarone for ventricular arrhythmias'.) In cases of complex and/or symptomatic ventricular arrhythmia, an electrophysiology study with programmed ventricular stimulation may better guide therapy. In patients with inducible sustained ventricular tachycardia, an ICD will be needed [73]. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions", section on 'Secondary prevention'.) Patients with cardiac resynchronization therapy (CRT) Patients with a CRT device need to have effective biventricular pacing greater than 98 percent of all ventricular beats in order to have a mortality reduction [74]. Frequent PVCs compromise effective biventricular pacing and diminish clinical response to CRT [75]. Hence, a more aggressive approach to suppress PVCs is recommended in these patients. (See "Implantable cardioverter- defibrillators: Overview of indications, components, and functions".) Hypertension This is discussed elsewhere. (See 'Manage triggers and risk factors' above.) Long QT syndrome This is discussed elsewhere. (See "Congenital long QT syndrome: Treatment".) Brugada syndrome This is discussed elsewhere. (See "Brugada syndrome or pattern: Management and approach to screening of relatives".) Hypertrophic cardiomyopathy This is discussed elsewhere. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".) Arrhythmogenic right ventricular cardiomyopathy This is discussed elsewhere. (See "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis".) Cardiac sarcoidosis This is discussed elsewhere. (See "Management and prognosis of cardiac sarcoidosis".) https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 13/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate Amyloid cardiomyopathy This is discussed elsewhere. (See "Amyloid cardiomyopathy: Treatment and prognosis".) MANAGEMENT OF LOW-RISK PATIENTS Low-risk patients are those in whom cardiomyopathy and/or inherited arrythmia syndrome has been reasonably excluded. Our approach to treatment in low-risk patients differs according to whether there are significant PVC-related symptoms. Specific PVC-related symptoms are discussed elsewhere. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Symptoms'.) Asymptomatic patients with low premature ventricular complex burden For patients with a low burden of PVCs (<1 percent or 1000 PVCs/day), no underlying apparent structural heart disease, and no symptoms, neither medical therapy nor catheter ablation are required; observation and reassurance along with eliminating possible triggers are appropriate ( algorithm 2 and algorithm 3) [49]. While PVCs have been associated with increased risk of cardiovascular death and other adverse outcomes, there is no clear evidence that PVC suppression or elimination with beta blockers, non-dihydropyridine calcium channel blockers, antiarrhythmic drugs, or catheter ablation improves overall survival in patients who have no symptoms, no heart disease, and no sustained ventricular arrhythmias. Patient with symptoms and/or high premature ventricular complex burden Most low-risk patients with significant symptoms from their PVCs will require medical therapy or ablation in an effort to reduce or eliminate symptoms ( algorithm 2 and algorithm 3). Patients with high PVC burden (>15 percent or 15,000 PVCs/day) also benefit from treatment even in the absence of bothersome symptoms to lower their risk of PVC-induced cardiomyopathy. PVC-induced cardiomyopathy typically takes several months or a few years to develop. In a study of 240 patients referred for PVC ablation, symptom duration of 30 to 60 months, as well as symptom duration >60 months, independently predicted impaired LV function (odds ratio 4.0, 95% CI 1.1-14.4 and 20.1, 95% CI 6.3-64.1, respectively) [76]. In a low-risk patient who has more noticeable symptoms in a quiet environment, such as at night while lying in bed, counseling them to move around and increase their heart rate may alleviate symptoms and provide reassurance to the patient. https://www.uptodate.com/contents/premature-ventricular-complexes-treatment-and-prognosis/print 14/50 7/6/23, 3:35 PM Premature ventricular complexes: Treatment and prognosis - UpToDate The decision to recommend antiarrhythmic medication or radiofrequency catheter ablation in a particular patient will depend on many clinical factors and also on patient preference. Some patients will not want to undergo an invasive catheter ablation procedure. Potential risks of the catheter ablation are discussed elsewhere. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) Initial therapy Prior to initiating therapy, correctable causes or triggers should be identified and corrected ( table 1). Beta blockers For low-risk patients with symptomatic and/or a high burden of PVCs, we suggest first-line therapy with a beta blocker. (See 'Beta blockers' above.) Non-dihydropyridine calcium channel blockers In patients without a reduced LVEF, a non-dihydropyridine calcium channel blocker can be substituted if beta blockers are not tolerated or are not successful in reducing symptoms. A table lists specific agents with dosages ( table 2). Non-dihydropyridine calcium channel blockers may be particularly effective in patients without apparent structural heart disease when PVCs are often due to triggered activity of calcium-dependent mechanisms. One example of this is PVCs of fascicular origin (relatively narrow QRS, right bundle branch block-like, left axis deviation) ( waveform 6). Calcium channel blockers may also be preferred to beta blockers if hypertension treatment is needed. Patients should be evaluated for PVCs burden with periodic examinations and continuous ECG monitoring, usually for 24 to 48 hours. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Ambulatory monitoring'.) If symptoms and PVC burden have been reduced and are not high, treatment should be continued. If a patient prefers to stop or reduce their medications, a trial of weaning and/or stopping may be done after 6 to 12 months. (See 'Premature ventricular complex burden' above and 'Beta blockers' above.)