European Journal of General Practice, 2014; 20: 134–138
Clinical Lesson
Are premature ventricular contractions always harmless?
R. A. G. Winkens1,2, P. F. Höppener2, J. A. Kragten3, M. P. Verburg4 & H. F. J. M. Crebolder2 1Diagnostic
Centre, Department of Integrated Care, Maastricht University Medical Centre, the Netherlands, of Primary Care, Maastricht University, the Netherlands, 3Department of Cardiology, Atrium Medical Centre, Heerlen, the Netherlands, and 4Department of Anaesthesiology, Atrium Medical Centre, Heerlen, the Netherlands
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2Department
KEY MESSAGE: • The load of premature ventricular contractions (PVCs) can be detected by Holter or event recording. • More frequent PVCs may lead to fatigue or exertional dyspnoea. • PVCs are only harmless when they occur incidentally, i.e. in less than 1% of heartbeats.
ABSTRACT Introduction: Premature ventricular contractions (PVCs) are among the most prevalent arrhythmias. PVCs lead to haemodynamically insufficient heartbeats. Their presence is considered rather insignificant, but this widespread assumption is not supported by research evidence. Cases: We present three cases of patients commonly seen in daily general practice, with a range of presentations, varying from incidental (harmless) PVCs to frequent and potentially symptomatic PVCs. Discussion: In more frequent PVCs (⬎ 10% heart beats) fatigue and exertional dyspnoea may occur. When ⬎ 20% of heart beats are PVCs, patients may develop cardiomyopathy and heart failure. Incidental PVCs are harmless. Anti-arrhythmic drug treatment should be considered in case of frequent PVCs but also catheter ablation appears an effective treatment option. Conclusion: Altogether, PVCs may not be harmless, depending on their occurrence rate. Research data from primary care settings on epidemiology and natural course is needed. Keywords: premature ventricular contractions, fatigue, exertional dyspnoea
INTRODUCTION A premature ventricular contraction (PVC), also known as a ventricular extra systole, is a common, if not the most common, arrhythmia (1–4). PVCs may cause symptoms such as irregular heartbeats, palpitations or gaps in a, usually regular, pulse rhythm. Repeatedly, this results in fear of a serious heart condition in patients (1). Each PVC is followed by a compensatory electrical pause (Figure 1). This may be felt as palpitation or a gap in the pulse rate. The general assumption among GPs is that PVCs are usually harmless and clinically less relevant. This assumption has been the rule for many years and is postulated in the medical literature, both in books and scientific journals (4–7). Literature reveals no publications in which harmlessness of PVCs is confirmed or explained.
PVCs are quite common. Incidental PVCs are reported as being most frequent in the general population (1,3,4,8). In the age group of 45–65 years prevalence, is roughly 6% and increases with age (9). The prevalence of frequent instead of incidental PVCs in the open population is, however, unknown. Literature often reveals data on selected cases in specific patient groups, resulting in higher prevalence. PVCs often arise from a pre-excitation, mostly in the right ventricle. Such an abnormal excitation may occur in the myocardium of healthy people, even without cardiac abnormalities. Remainders of embryonic tissue may become electrically active and then lead to pre-excitation. PVCs may also be caused by myocardial damage (ischaemia, trauma), valvular disorders, hypertension, thyroid function disorders or drugs (e.g. anti-arrhythmics).
Correspondence: Ron A. G. Winkens, Diagnostic Centre MUMC, Department of Integrated Care, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, the Netherlands. E-mail: [email protected] (Received 1 June 2012; accepted 9 October 2013) ISSN 1381-4788 print/ISSN 1751-1402 online © 2014 Informa Healthcare DOI: 10.3109/13814788.2013.859243
Are PVCs harmless?
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Figure 1. Example of PVCs found in a routine electrocardiography.
These possible causes of PVCs should be considered during history taking, physical examination and ECG, together with risk factors such as a family history of sudden cardiac death or heart disease and the age of the patient. When risk factors or possible causes are present in a patient with PVCs, they could merit referral to a cardiologist. Erroneously, tobacco and coffee are sometimes held accountable (1). An explanation of the possible haemodynamic consequences of PVCs is shown in the following examples.
CASE DESCRIPTIONS Patient A Patient A is a man aged 63 who presented to his GP with symptoms of exertional dyspnoea, fatigue and palpitations. The medical history revealed type 2 diabetes, hypertension and a mild hypercholesterolemia. Drug use: metoprolol, perindopril, metformin and simvastatin. At physical examination, a blood pressure of 125/75 was found and an irregular pulse rate of 54 per minute. Subsequent electrocardiography showed a heart rate of 62 beats per minute, including 12 PVCs per minute. The patient was referred to a cardiologist because, based on the clinical presentation, the GP considered the presence of heart failure. Additional testing revealed no heart failure; the metoprolol dose was reduced and gradually the symptoms disappeared. Comments. The symptoms of patient A and the response to lowering the metoprolol dose can be explained by the haemodynamic consequences of PVCs. The abnormal excitation leads to a premature and inefficient contraction, sometimes even in the opposite direction.
Apart from this, during diastole the ventricles are not filled completely. The electrical pause after the PVC prevents the insufficient heartbeat during the PVC from being followed by a compensational extra heartbeat. Thus, the haemodynamic deficit of the PVC is not compensated by the next heartbeat. The systolic discharge is, therefore, reduced as echocardiographically confirmed by Zaborska et al., (10). They found that stroke volume of a PVC was only 26% of the normal stroke volume during a heartbeat. Therefore, the cardiac output is determined by the pulse rate minus the number of PVCs each minute. The haemodynamic effects of the reduced stroke volume of PVCs can be visualized by a plethysmography. A plethysmograph measures changes in volume (usually resulting from fluctuations in the amount of blood or air it contains) within an organ or vessel. Figure 2 shows a plethysmogram of a 60 year old healthy patient with PVCs. The plethysmogram (lower line in Figure 2) shows the absence of increase in blood flow and artery volume after a PVC, while an increase is visible after a normal contraction. Patient A had a heart rate of 62, but due to the 12 PVCs each minute, the cardiac output of only 50 efficient beats remained causing the same symptoms as in a bradycardia. This is called a mechanical bradycardia (11). By lowering the metoprolol dose, pulse rate and the cardiac output increased thereby reducing the dyspnoea and fatigue. The frequency of PVCs remained unchanged with still one PVC in five heartbeats. Patient B Patient B is a 68 year old woman with symptoms of periodic irregular heartbeats and palpitations; sometimes she gets dizzy. As a result of a family history of
Figure 2. Plethysmography of a patient with frequent PVCs. The arrows show the increase of blood flow in the circulation after each left ventricular contraction. The dotted arrows show the absence of an increased blood flow after a premature ventricular contraction.
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heart attacks, she is worried about these symptoms. At physical examination a pulse rate of 72 was found, a resting electrocardiography showed five PVCs per minute, with duplets. The GP explained the extra systoles and the fact that they are considered harmless to the patient and consequently reassured her. Comments. As stated earlier, it is generally assumed that PVCs are harmless and cause no clinically important symptoms. Taking into account information in the previous case, this indeed seems true for this patient. Here, the patient ’s symptoms can be explained by the irregularity in the heart rhythm. However, the presence of frequent PVCs cannot be excluded solely based on a resting electrocardiography. It requires event recording or a Holter registration as this provides information on the percentage of PVCs occurring in 24 h. In patient B, the palpitations persisted. Ultimately, the GP referred her for a Holter registration, and this revealed only incidental PVCs.
Patient C Patient C is a man aged 57 with no symptoms in whom very frequent PVCs were found on an electrocardiogram, performed during a routine occupational health check. He was advised to seek further cardiological analysis. After referral to a cardiologist, a repeated electrocardiography and subsequent Holter revealed a heart rate of 70 bpm with 20 PVCs (frequently ventricular bigeminy) each minute. After weighing the pros and cons of drug treatment versus invasive treatment, patient C underwent a catheter ablation. As a result, the PVCs disappeared completely. Comments. Despite that patient C is asymptomatic, there is evidence reported in the literature suggesting that frequent PVCs (more than 10% of heartbeats) may result in cardiomyopathy with an impaired left ventricular function and heart failure (6,12–16). There are, however, varying recommendations about when to treat. The threshold in critical PVC load resulting in treatment varies between 10 and 24% (13,15,17–19). Recent echocardiography techniques such as ‘speckle tracking analysis’ suggest that a PVC load of 10% already can lead to cardiomyopathy (12). From a haemodynamic viewpoint, the situation in patient C is quite similar to the situation in patient A. Therefore, one might expect that patient C would also have physical complaints but obviously this is dependent on factors like physical condition, co-morbidity and the level of physical activity the patient has to perform (or has adapted to). Although unlikely, it cannot be excluded that the PVCs in patient A were caused by the metoprolol treatment.
DISCUSSION Are PVCs harmless? While searching the literature for evidence on the potential consequences of PVCs, we found conflicting papers on the definition of frequent PVCs (6,12,13, 15–21). Unfortunately, we found no study that directly compares frequencies of PVCs with the risk of heart problems. Evidence on clinical consequences of PVCs is rather scarce, especially from primary care setting. Studies discussing symptoms due to PVCs are most often based on hospital data. These studies show a relation between frequent PVCs and symptoms such as fatigue and exertional dyspnoea (3,4,6,11–15,17, 18,20,21 ). There is some evidence showing that PVCs are not always harmless (3,4,6,11–15,17,18,20,21). In the ACC guidelines, it is concluded that frequent ventricular ectopic activity predicts an increased risk of sudden cardiac death. This conclusion, however, is based on data from hospital studies among patients with a pre-existing cardiac problem (22). Other studies have reported a correlation with tachycardia related cardiomyopathy (6,11–16,19). A causal relation between PVCs and cardiomyopathy seems likely as two studies report improvement of left ventricular function after treating PVCs through ablation (12,14,15,17–20,23). Should PVCs be treated? Until recently, anti-arrhythmic drugs, predominantly beta-blockers, were considered as the first choice treatment. Unfortunately, they combine effectiveness with a serious risk of side effects (1,24). Bradycardia is considered one of the contraindications to initiate beta blocker treatment (24). Niwano found that PVCs could not produce an effective cardiac output due to the premature excitation resulting in a much lower pulse rate. Patients might lose up to almost a third of the effective cardiac output and might develop similar conditions as in sick sinus syndrome or atrioventricular block (25). Based on evidence reported in the literature, we suggest that there is only an indication for beta-blockers in case of highly frequent PVCs (more than 10%) in combination with a heart rate above 70 beats per minute (11,24–26). An alternative would be catheter ablation, an invasive procedure in which the origin of the PVCs is directly treated. With this technique, the locations in the myocardium that cause the pre-excitation and thus PVCs are searched for and disabled by heating through RFCA (Radio Frequent Catheter Ablation) or by freezing (cryoablation). Effect rates of 70–90% are reported, but long-term prognosis is not yet known (6,12,14, 15,18,20).
Are PVCs harmless?
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Primary care research? Although the treatment options are usually applied by cardiologists, be it drug treatment or ablation, the main presentation of PVCs occurs in primary care setting, and PVCs are often noticed as an incidental finding by GPs. It is in this setting that the initial management decision is made, either to neglect the PVCs and reassure the patient, as some studies seem to suffer from the misapprehension that PVCs are always harmless and, when desired, can be treated best with beta-blockers or to take additional diagnostic actions (10,24). Therefore, the natural course and the consequences of incidence rates should be studied in primary care settings instead of in selected cases in specialist settings. A growing number of GPs has direct access to electrocardiography and/or event recording in primary care without referral (27). These instruments offer a first impression whether PVCs occur and in what frequency.
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with other treatment (e.g. cardiac resynchronization therapy), or suspicion of PVC-mediated cardiomyopathy (28). In our view, pulse rate should also play an important role in this decision. Should PVCs occur more frequently or should they be found together with symptoms such as fatigue or exertional dyspnoea, a 24-h Holter registration is a reliable assessment of the actual PVCload (29). When the PVC-load is more than 10% of all heartbeats or when a PVC-load of 1–10% is accompanied by fatigue or exertional dyspnoea, referral to a cardiologist is recommended (13,15,17,18). The cardiologist could then perform an analysis of the cause(s) of the frequent PVCs and decide on the best treatment option. Further research in primary care setting is needed to assess the clinical consequences of PVCs and the value of various management options. Conclusion
Suggestions for daily practice This paper is concerned with patients in a primary care setting who present with PVCs, irrespective of the presence of cardiovascular risk factors. Awaiting data from studies in primary care settings we suggest GPs should take the information from this paper into account and not assume the presence of PVCs on electrocardiography to be an incidental and meaningless finding. Test facilities such as Holter techniques or event recording can be used by GPs to assess the PVC load when PVCs are found, especially when a patient has symptoms such as exertional dyspnoea or fatigue. In several parts of the Netherlands, both Holter and/or event recording can be ordered by GPs without referral. They are then performed in the hospital, diagnostic centre or private institution, and the GP receives the test result together with an interpretation plus recommendation by a cardiologist. Based on the available literature, we consider the following suggestions for managing PVCs to be helpful in general practice. Items to be checked by the GP in cases with frequent or symptomatic PVCs (1,15): • myocardial damage (ischaemia, trauma), • valvular disorders, hypertension, thyroid function disorders, • side effects of drugs (e.g. anti-arrhythmics), • risk factors: age and a family history of (sudden) heart disease, • unrelated aspects: tobacco or coffee use. Reassurance of the patient is justifiable in case of sporadic and incidental PVCs (less than 1% of heartbeats as suggested in literature) (7,14,28). Decisions to treat PVCs appear mainly based on symptoms, interference
The assumption that PVCs are always harmless is not justified. Further research should try to assess in primary care setting when PVCs may cause harm. Awaiting such evidence, GPs could consider various management options for managing PVCs. The patients whose test results are presented (anonymously) in this paper gave their approval for publication. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. REFERENCES 1. Ng GA. Treating patients with ventricular ectopic beats. Heart 2006;92:1707–12. 2. Zwietering PJ, Knottnerus JA, Gorgels AP, Rinkens PE. Occurrence of arrhythmias in general practice. Scand J Prim Health Care 1996;14:244–50. 3. Cheriyath P, He F, Peters I, Li X, Alagona P Jr, Wu C, et al. Relation of atrial and/or ventricular premature complexes on a twominute rhythm strip to the risk of sudden cardiac death (the Atherosclerosis Risk in Communities [ARIC] study). Am J Cardiol. 2011;107:151–5. 4. Massing MW, Simpson RJ, 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;98:1609–12. 5. Zwietering PJ, Knottnerus JA, Rinkens PE, Kleijne MA, Gorgels AP. Arrhythmias in general practice: Diagnostic value of patient characteristics, medical history and symptoms. Family Practice 1998;15:343–53. 6. Bogun F, Crawford T, Reich S, Koelling TM, Armstrong W, Good E, et al. Radiofrequency ablation of frequent, idiopathic premature ventricular complexes: Comparison with a control group without intervention. Heart Rhythm. 2007;4:868–9.
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7. Kesh Hebbar A, Hueston WJ. Management of common arrhythmias: Part II. Ventricular arrhythmias and arrhythmias in special populations. Am Fam Phys. 2002;65;2491–6. 8. Hinkle LE, Carver ST, Stevens M. The frequency of asymptomatic disturbances of cardiac rhythm and conduction in middle-aged men. Am J Cardiol. 1969;24:629–50. 9. Simpson RJ, Cascio WE, Schreiner PJ, Crow RS, Rautaharju PM, Heiss G. 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;143:535–40. 10. Zaborska B, Stec S, Flasińska K, Piluś A, Kułakowski P. Echocardiography and tissue Doppler imaging in assessment of haemodynamics in patients with idiopathic premature ventricular complexes. Pol Merkur Lekarski. 2006;20:302–4. 11. Satish OS, Yeh KH, Wen MS, Wang CC. Premature ventricular contraction-induced concealed mechanical bradycardia and dilated cardiomyopathy. J Cardiovasc Electrophysiol. 2005; 16:88–91. 12. Wijnmaalen AP, Delgado V, Schalij MJ, van Huls van Taxis CF, Holman ER, Bax JJ, et al. Beneficial effects of catheter ablation on left ventricular and right ventricular function in patients with frequent premature ventricular contractions and preserved ejection fraction. Heart 2010;96:1275–80. 13. Kanei Y, Friedman M, Ogawa N, Hanon S, Lam P, Schweizer P. Frequent premature ventricular complexes originating from the right ventricular outflow tract are associated with left ventricular dysfunction. Ann Noninvasive Electrocardiol. 2008;13:81–85. 14. Blaauw Y, Pison L, Opstal JM van, Dennert RM, Heesen WF, Crijns HJ. Reversal of ventricular premature beat induced cardiomyopathy by radiofrequency catheter ablation. Neth Heart J. 2010;10:493–8. 15. Hasdemir C, Ulucan C, Yavuzgil O, Yuksel A, Kartal Y, Simsek E, et al. Tachycardia-induced cardiomyopathy in patients with idiopathic ventricular arrhythmias: The incidence, clinical and electrophysiologic characteristics, and the predictors. J Cardiovasc Electrophysiol. 2011;22:663–8. 16. Topaloglu S, Aras D, Cagli K, Yildiz A, Cagirci G, Cay S, et al. Evaluation of left ventricular diastolic functions in patients with frequent premature ventricular contractions from right ventricular outflow tract. Heart Vessels 2007;22:328–34. 17. Baman TS, Lange DC, Ilg KJ, Gupta SK, Liu TY, Alguire CTS, et al. Relationship between burden of premature ventricular
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complexes and left ventricular function. Heart Rhythm. 2010; 7:865–9. Yarlagadda RK, Iwai S, Stein KM, Markowitz SM, Shah BK, Cheung JW, et al. Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract. Circulation 2005;112:1092–7. Shanmugam N, Chua TP, Ward D. Frequent ventricular bigeminy. A reversible cause of dilated cardiomyopathy. How frequent is Frequent? Eur J Heart Fail. 2006;8:869–73. Sekiguchi Y, Aonuma K, Yamauchi Y, Obayashi T, Niwa A, Hachiya H, et al. Chronic hemodynamic effects after radiofrequency catheter ablation of frequent monomorphic ventricular premature beats. J Cardiovasc Electrophysiol. 2005;16:1057–63. O’Neill JO, Young JB, Pothier CE, Lauer M. Severe frequent ventricular ectopy after exercise as a predictor of death in patients with heart failure. J Am Coll Cardiol. 2004;4:820–6. Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, et al. ACC/AHA/ESC 2006 Guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation 2006;114:e–385–e484. Taieb JM, Maury P, Shah D, Duparc AM, Galinier M, Delay M, et al. Reversal of dilated cardiomyopathy by the elimination of frequent left or right premature ventricular contractions. J Interv Card Electrophysiol. 2007;20:9–13. Sweetman S. Martindale: The complete drug reference. Pharmaceutical Press. 37th ed. London; 2011. Niwano S, Wakisaka Y, Niwano H, Fukaya H, Kurokawa S, Kiryu M, et al. Prognostic significance of frequent premature ventricular contractions originating from the ventricular outflow tract in patients with normal left ventricular function. Heart 2009;95:1230–7. Lopez-Sendon J, Swedberg K, McMurray J, Tamargo J, Maggioni AP, Dargie H, et al. ESC task force 2004. Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J. 2004;25:1341–62. Adams JC, Komandoor S, Win KS. Advances in management of premature ventricular extrasystoles. J Interv Card Electrophysiol. 2012;35:137. Hoefman E, Van Weert HC, Reitsma JB, Koster RW, Bindels PJ. Diagnostic yield of patient-activated loop recorders for detecting heart rhythm abnormalities in general practice: A randomised clinical trial. Fam Pract. 2005;22:478–84. Van Weert HCPM, Peters RJG. Palpitations (In Dutch). Huisarts Wet. 2003;46:773–8.
Clinical Lesson
Are premature ventricular contractions always harmless?
R. A. G. Winkens1,2, P. F. Höppener2, J. A. Kragten3, M. P. Verburg4 & H. F. J. M. Crebolder2 1Diagnostic
Centre, Department of Integrated Care, Maastricht University Medical Centre, the Netherlands, of Primary Care, Maastricht University, the Netherlands, 3Department of Cardiology, Atrium Medical Centre, Heerlen, the Netherlands, and 4Department of Anaesthesiology, Atrium Medical Centre, Heerlen, the Netherlands
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2Department
KEY MESSAGE: • The load of premature ventricular contractions (PVCs) can be detected by Holter or event recording. • More frequent PVCs may lead to fatigue or exertional dyspnoea. • PVCs are only harmless when they occur incidentally, i.e. in less than 1% of heartbeats.
ABSTRACT Introduction: Premature ventricular contractions (PVCs) are among the most prevalent arrhythmias. PVCs lead to haemodynamically insufficient heartbeats. Their presence is considered rather insignificant, but this widespread assumption is not supported by research evidence. Cases: We present three cases of patients commonly seen in daily general practice, with a range of presentations, varying from incidental (harmless) PVCs to frequent and potentially symptomatic PVCs. Discussion: In more frequent PVCs (⬎ 10% heart beats) fatigue and exertional dyspnoea may occur. When ⬎ 20% of heart beats are PVCs, patients may develop cardiomyopathy and heart failure. Incidental PVCs are harmless. Anti-arrhythmic drug treatment should be considered in case of frequent PVCs but also catheter ablation appears an effective treatment option. Conclusion: Altogether, PVCs may not be harmless, depending on their occurrence rate. Research data from primary care settings on epidemiology and natural course is needed. Keywords: premature ventricular contractions, fatigue, exertional dyspnoea
INTRODUCTION A premature ventricular contraction (PVC), also known as a ventricular extra systole, is a common, if not the most common, arrhythmia (1–4). PVCs may cause symptoms such as irregular heartbeats, palpitations or gaps in a, usually regular, pulse rhythm. Repeatedly, this results in fear of a serious heart condition in patients (1). Each PVC is followed by a compensatory electrical pause (Figure 1). This may be felt as palpitation or a gap in the pulse rate. The general assumption among GPs is that PVCs are usually harmless and clinically less relevant. This assumption has been the rule for many years and is postulated in the medical literature, both in books and scientific journals (4–7). Literature reveals no publications in which harmlessness of PVCs is confirmed or explained.
PVCs are quite common. Incidental PVCs are reported as being most frequent in the general population (1,3,4,8). In the age group of 45–65 years prevalence, is roughly 6% and increases with age (9). The prevalence of frequent instead of incidental PVCs in the open population is, however, unknown. Literature often reveals data on selected cases in specific patient groups, resulting in higher prevalence. PVCs often arise from a pre-excitation, mostly in the right ventricle. Such an abnormal excitation may occur in the myocardium of healthy people, even without cardiac abnormalities. Remainders of embryonic tissue may become electrically active and then lead to pre-excitation. PVCs may also be caused by myocardial damage (ischaemia, trauma), valvular disorders, hypertension, thyroid function disorders or drugs (e.g. anti-arrhythmics).
Correspondence: Ron A. G. Winkens, Diagnostic Centre MUMC, Department of Integrated Care, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, the Netherlands. E-mail: [email protected] (Received 1 June 2012; accepted 9 October 2013) ISSN 1381-4788 print/ISSN 1751-1402 online © 2014 Informa Healthcare DOI: 10.3109/13814788.2013.859243
Are PVCs harmless?
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Figure 1. Example of PVCs found in a routine electrocardiography.
These possible causes of PVCs should be considered during history taking, physical examination and ECG, together with risk factors such as a family history of sudden cardiac death or heart disease and the age of the patient. When risk factors or possible causes are present in a patient with PVCs, they could merit referral to a cardiologist. Erroneously, tobacco and coffee are sometimes held accountable (1). An explanation of the possible haemodynamic consequences of PVCs is shown in the following examples.
CASE DESCRIPTIONS Patient A Patient A is a man aged 63 who presented to his GP with symptoms of exertional dyspnoea, fatigue and palpitations. The medical history revealed type 2 diabetes, hypertension and a mild hypercholesterolemia. Drug use: metoprolol, perindopril, metformin and simvastatin. At physical examination, a blood pressure of 125/75 was found and an irregular pulse rate of 54 per minute. Subsequent electrocardiography showed a heart rate of 62 beats per minute, including 12 PVCs per minute. The patient was referred to a cardiologist because, based on the clinical presentation, the GP considered the presence of heart failure. Additional testing revealed no heart failure; the metoprolol dose was reduced and gradually the symptoms disappeared. Comments. The symptoms of patient A and the response to lowering the metoprolol dose can be explained by the haemodynamic consequences of PVCs. The abnormal excitation leads to a premature and inefficient contraction, sometimes even in the opposite direction.
Apart from this, during diastole the ventricles are not filled completely. The electrical pause after the PVC prevents the insufficient heartbeat during the PVC from being followed by a compensational extra heartbeat. Thus, the haemodynamic deficit of the PVC is not compensated by the next heartbeat. The systolic discharge is, therefore, reduced as echocardiographically confirmed by Zaborska et al., (10). They found that stroke volume of a PVC was only 26% of the normal stroke volume during a heartbeat. Therefore, the cardiac output is determined by the pulse rate minus the number of PVCs each minute. The haemodynamic effects of the reduced stroke volume of PVCs can be visualized by a plethysmography. A plethysmograph measures changes in volume (usually resulting from fluctuations in the amount of blood or air it contains) within an organ or vessel. Figure 2 shows a plethysmogram of a 60 year old healthy patient with PVCs. The plethysmogram (lower line in Figure 2) shows the absence of increase in blood flow and artery volume after a PVC, while an increase is visible after a normal contraction. Patient A had a heart rate of 62, but due to the 12 PVCs each minute, the cardiac output of only 50 efficient beats remained causing the same symptoms as in a bradycardia. This is called a mechanical bradycardia (11). By lowering the metoprolol dose, pulse rate and the cardiac output increased thereby reducing the dyspnoea and fatigue. The frequency of PVCs remained unchanged with still one PVC in five heartbeats. Patient B Patient B is a 68 year old woman with symptoms of periodic irregular heartbeats and palpitations; sometimes she gets dizzy. As a result of a family history of
Figure 2. Plethysmography of a patient with frequent PVCs. The arrows show the increase of blood flow in the circulation after each left ventricular contraction. The dotted arrows show the absence of an increased blood flow after a premature ventricular contraction.
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heart attacks, she is worried about these symptoms. At physical examination a pulse rate of 72 was found, a resting electrocardiography showed five PVCs per minute, with duplets. The GP explained the extra systoles and the fact that they are considered harmless to the patient and consequently reassured her. Comments. As stated earlier, it is generally assumed that PVCs are harmless and cause no clinically important symptoms. Taking into account information in the previous case, this indeed seems true for this patient. Here, the patient ’s symptoms can be explained by the irregularity in the heart rhythm. However, the presence of frequent PVCs cannot be excluded solely based on a resting electrocardiography. It requires event recording or a Holter registration as this provides information on the percentage of PVCs occurring in 24 h. In patient B, the palpitations persisted. Ultimately, the GP referred her for a Holter registration, and this revealed only incidental PVCs.
Patient C Patient C is a man aged 57 with no symptoms in whom very frequent PVCs were found on an electrocardiogram, performed during a routine occupational health check. He was advised to seek further cardiological analysis. After referral to a cardiologist, a repeated electrocardiography and subsequent Holter revealed a heart rate of 70 bpm with 20 PVCs (frequently ventricular bigeminy) each minute. After weighing the pros and cons of drug treatment versus invasive treatment, patient C underwent a catheter ablation. As a result, the PVCs disappeared completely. Comments. Despite that patient C is asymptomatic, there is evidence reported in the literature suggesting that frequent PVCs (more than 10% of heartbeats) may result in cardiomyopathy with an impaired left ventricular function and heart failure (6,12–16). There are, however, varying recommendations about when to treat. The threshold in critical PVC load resulting in treatment varies between 10 and 24% (13,15,17–19). Recent echocardiography techniques such as ‘speckle tracking analysis’ suggest that a PVC load of 10% already can lead to cardiomyopathy (12). From a haemodynamic viewpoint, the situation in patient C is quite similar to the situation in patient A. Therefore, one might expect that patient C would also have physical complaints but obviously this is dependent on factors like physical condition, co-morbidity and the level of physical activity the patient has to perform (or has adapted to). Although unlikely, it cannot be excluded that the PVCs in patient A were caused by the metoprolol treatment.
DISCUSSION Are PVCs harmless? While searching the literature for evidence on the potential consequences of PVCs, we found conflicting papers on the definition of frequent PVCs (6,12,13, 15–21). Unfortunately, we found no study that directly compares frequencies of PVCs with the risk of heart problems. Evidence on clinical consequences of PVCs is rather scarce, especially from primary care setting. Studies discussing symptoms due to PVCs are most often based on hospital data. These studies show a relation between frequent PVCs and symptoms such as fatigue and exertional dyspnoea (3,4,6,11–15,17, 18,20,21 ). There is some evidence showing that PVCs are not always harmless (3,4,6,11–15,17,18,20,21). In the ACC guidelines, it is concluded that frequent ventricular ectopic activity predicts an increased risk of sudden cardiac death. This conclusion, however, is based on data from hospital studies among patients with a pre-existing cardiac problem (22). Other studies have reported a correlation with tachycardia related cardiomyopathy (6,11–16,19). A causal relation between PVCs and cardiomyopathy seems likely as two studies report improvement of left ventricular function after treating PVCs through ablation (12,14,15,17–20,23). Should PVCs be treated? Until recently, anti-arrhythmic drugs, predominantly beta-blockers, were considered as the first choice treatment. Unfortunately, they combine effectiveness with a serious risk of side effects (1,24). Bradycardia is considered one of the contraindications to initiate beta blocker treatment (24). Niwano found that PVCs could not produce an effective cardiac output due to the premature excitation resulting in a much lower pulse rate. Patients might lose up to almost a third of the effective cardiac output and might develop similar conditions as in sick sinus syndrome or atrioventricular block (25). Based on evidence reported in the literature, we suggest that there is only an indication for beta-blockers in case of highly frequent PVCs (more than 10%) in combination with a heart rate above 70 beats per minute (11,24–26). An alternative would be catheter ablation, an invasive procedure in which the origin of the PVCs is directly treated. With this technique, the locations in the myocardium that cause the pre-excitation and thus PVCs are searched for and disabled by heating through RFCA (Radio Frequent Catheter Ablation) or by freezing (cryoablation). Effect rates of 70–90% are reported, but long-term prognosis is not yet known (6,12,14, 15,18,20).
Are PVCs harmless?
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Primary care research? Although the treatment options are usually applied by cardiologists, be it drug treatment or ablation, the main presentation of PVCs occurs in primary care setting, and PVCs are often noticed as an incidental finding by GPs. It is in this setting that the initial management decision is made, either to neglect the PVCs and reassure the patient, as some studies seem to suffer from the misapprehension that PVCs are always harmless and, when desired, can be treated best with beta-blockers or to take additional diagnostic actions (10,24). Therefore, the natural course and the consequences of incidence rates should be studied in primary care settings instead of in selected cases in specialist settings. A growing number of GPs has direct access to electrocardiography and/or event recording in primary care without referral (27). These instruments offer a first impression whether PVCs occur and in what frequency.
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with other treatment (e.g. cardiac resynchronization therapy), or suspicion of PVC-mediated cardiomyopathy (28). In our view, pulse rate should also play an important role in this decision. Should PVCs occur more frequently or should they be found together with symptoms such as fatigue or exertional dyspnoea, a 24-h Holter registration is a reliable assessment of the actual PVCload (29). When the PVC-load is more than 10% of all heartbeats or when a PVC-load of 1–10% is accompanied by fatigue or exertional dyspnoea, referral to a cardiologist is recommended (13,15,17,18). The cardiologist could then perform an analysis of the cause(s) of the frequent PVCs and decide on the best treatment option. Further research in primary care setting is needed to assess the clinical consequences of PVCs and the value of various management options. Conclusion
Suggestions for daily practice This paper is concerned with patients in a primary care setting who present with PVCs, irrespective of the presence of cardiovascular risk factors. Awaiting data from studies in primary care settings we suggest GPs should take the information from this paper into account and not assume the presence of PVCs on electrocardiography to be an incidental and meaningless finding. Test facilities such as Holter techniques or event recording can be used by GPs to assess the PVC load when PVCs are found, especially when a patient has symptoms such as exertional dyspnoea or fatigue. In several parts of the Netherlands, both Holter and/or event recording can be ordered by GPs without referral. They are then performed in the hospital, diagnostic centre or private institution, and the GP receives the test result together with an interpretation plus recommendation by a cardiologist. Based on the available literature, we consider the following suggestions for managing PVCs to be helpful in general practice. Items to be checked by the GP in cases with frequent or symptomatic PVCs (1,15): • myocardial damage (ischaemia, trauma), • valvular disorders, hypertension, thyroid function disorders, • side effects of drugs (e.g. anti-arrhythmics), • risk factors: age and a family history of (sudden) heart disease, • unrelated aspects: tobacco or coffee use. Reassurance of the patient is justifiable in case of sporadic and incidental PVCs (less than 1% of heartbeats as suggested in literature) (7,14,28). Decisions to treat PVCs appear mainly based on symptoms, interference
The assumption that PVCs are always harmless is not justified. Further research should try to assess in primary care setting when PVCs may cause harm. Awaiting such evidence, GPs could consider various management options for managing PVCs. The patients whose test results are presented (anonymously) in this paper gave their approval for publication. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. REFERENCES 1. Ng GA. Treating patients with ventricular ectopic beats. Heart 2006;92:1707–12. 2. Zwietering PJ, Knottnerus JA, Gorgels AP, Rinkens PE. Occurrence of arrhythmias in general practice. Scand J Prim Health Care 1996;14:244–50. 3. Cheriyath P, He F, Peters I, Li X, Alagona P Jr, Wu C, et al. Relation of atrial and/or ventricular premature complexes on a twominute rhythm strip to the risk of sudden cardiac death (the Atherosclerosis Risk in Communities [ARIC] study). Am J Cardiol. 2011;107:151–5. 4. Massing MW, Simpson RJ, 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;98:1609–12. 5. Zwietering PJ, Knottnerus JA, Rinkens PE, Kleijne MA, Gorgels AP. Arrhythmias in general practice: Diagnostic value of patient characteristics, medical history and symptoms. Family Practice 1998;15:343–53. 6. Bogun F, Crawford T, Reich S, Koelling TM, Armstrong W, Good E, et al. Radiofrequency ablation of frequent, idiopathic premature ventricular complexes: Comparison with a control group without intervention. Heart Rhythm. 2007;4:868–9.
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