Risk of Death and AMI in Apparently Healthy Subjects with Ventricular Arrhythmias

Abstract & Commentary

By Harold L. Karpman, MD, FACC, FACP, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.

Synopsis: Apparently healthy, middle-aged and older subjects with frequent PVCs have a poor prognosis and should be considered to be high-risk subjects who require strict risk factor modification and primary prevention.

Source: Sajadieh A, et al. Ventricular arrhythmias and risk of death and acute myocardial infarction in apparently healthy subjects of age >or=55 years. Am J Cardiol. 2006;97:1351-1357.

Ventricular premature beats and even transient complex ventricular arrhythmias are not uncommon findings in patients without apparent heart disease. The clinical relevance of these arrhythmias in otherwise healthy subjects has been extremely difficult to accurately assess because of the lack of appropriate epidemiologic studies utilizing properly acquired electrocardiographic (EKG) monitoring information. The data derived from most large studies of ventricular arrhythmias in healthy subjects have been inadequate to determine prognostic significance because these studies have been based solely on short-term EKG monitoring which has proven to be incapable of determining PVC frequency and usually has also not been able to provide sufficient data to properly evaluate complex arrhythmias.1-5

Sajadieh and associates studied the prevalence and prognostic significance of different ventricular arrhythmias in 678 men and women aged 55 to 75 years without a prior history of heart disease or stroke.6 The study was part of the Copenhagen Holter study which was designed to determine the value of a 48-hour Holter recording in risk assessment in middle-aged and elderly men and women without apparent heart disease. All patients were followed for up to 5 years. Frequent PVCs (> 30 per hour) proved to be a significant predictor of increased all-cause mortality, acute myocardial infarction and/or cardiovascular death. Runs of > 4 PVCs or > 2 episodes of paired PVCs were also associated with a poor prognosis but only in the presence of frequent PVCs. The detection of a single PVC on standard EKG screening was a significant predictor of frequent PVCs and therefore an important independent predictor of cardiovascular events. They concluded that apparently healthy, middle-aged and older subjects with frequent PVCs have a poor prognosis and should be considered to be high-risk subjects who require strict risk factor modification and primary prevention.

Commentary

The Copenhagen Holter study evaluated 48-hour Holter recordings in risk assessment in middle-aged and elderly men and women with no apparent heart disease.7-8 All men age 55 years and older and all men and women aged 60-75 in 2 geographic areas of Copenhagen were studied. The 8% of subjects with an increased frequency of PVCs (ie, > 30 per hour) were found to have an over 2½ times greater risk for death or AMI and this increased risk was noted to occur especially in men but also in all subjects with a Framingham risk score greater than average. Increased ventricular activity was found in 9% of all men and, it is important to note that 25% of all events (ie, all cause mortality, AMI, and/or cardiovascular death) occurred in this select group. The findings of the study confirmed Lown and Wolf's early observations regarding the significance of PVCs occuring at a frequency of > 30 per hour.9

For the practicing cardiologist, the results of this study suggests that the accidental detection of increased ventricular ectopic activity (eg, > 1 PVC on a resting EKG, a run of PVCs or couplets) in middle-aged or elderly patients with no apparent heart disease and/or symptoms should be followed up with a 24-48 hour Holter recording especially in those individuals who have an elevated Framingham risk score. If PVCs are found to be present with a frequency of > 30 PVCs per hour, a careful and complete diagnostic workup for structural and ischemic heart disease should be performed in all of these patients according to current national and international guidelines.10-12 Finally, it should be noted that anti-arrhythmic therapy has not been demonstrated to be of clinical benefit in PVC suppression and, given the negative results of previous anti-arrhythmic studies,10-12 anti-arrhythmic therapy is usually not recommended except in carefully select groups of patients.

References

1. Bikkina M, et al. Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham Heart Study. Ann Intern Med. 1992;117: 990-996.

2. Abdalla IS, et al. Relation between ventricular premature complexes and sudden cardiac death in apparently healthy men. Am J Cardiol. 1997;60:1036-1042.

3. Bjerregaard P, et al. Predictive value of ventricular premature beats for subsequent ischemic heart disease in apparently healthy subjects. Eur Heart J. 1991;12:597-601.

4. Fleg JL, et al. Long-term prognostic significance of ambulatory electrocardiographic findings in apparently healthy subjects greater than or equal to 60 years of age. Am J Cardiol. 1992;70:748-751.

5. Hedblad B, et al. Survival and incidence of myocardial infarction in men with mandatory EKG-detected frequent and complex ventricular arrhythmias. 10 year follow-up of the "Men born 1914" study in Malmo, Sweden. Eur Heart J. 1997;18:1787-1795.

6. Sajadieh A, et al. Ventricular arrhythmias and risk of death and acute myocardial infarction in apparently healthy subjects of age >or=55 years. Am J Cardiol. 2006;97:1351-1357.

7. Sajadieh A, et al. Prevalence and prognostic significance of daily-life silent myocardial ischaemia in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J. 2005;26:1402-1409.

8. Sajadieh A, et al. Increased heart rate and reduced heart rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J. 2004;25:363-370.

9. Lown B, et al. Approaches to sudden death from coronary heart disease. Circulation. 1971;44:130-142.

10. Epstein AE, et al. Mortality following ventricular arrhythmia suppression by encainide, flecainide, and moricizine after myocardial infarction. The original design concept of the cardiac arrhythmia suppression trial (CAST) JAMA. 1993;270:2451-2455.

11. Torp-Pedersen C,, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. N Engl J Med. 1999;341:857-865.

12. Waldo AL, et al. Effect of d-sotolol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. Lancet. 1996;348:7-12. Erratum in: Lancet. 1996;348:416.