A detailed review was recently published, which should be read in the original. Below are a few key issues covered.
Known or purported mechanisms include automaticity, triggered activity and re-entry. Automaticity causes ventricular ectopy (VE) by premature depolarization of pacemaker cells. This results from a shortening of the time it takes for phase 4 diastolic depolarization to reach threshold, due to an increased slope of diastolic depolarization or other mechanisms.
So called triggered activity is the result of afterdepolarizations, which could take the form of delayed (DAD) or early afterdepolarizations (EAD). DAD occur in phase 4 and are believed to be related to increased intracellular calcium concentrations due to a variety of mechanisms (eg catecholamine effects) with increased cAMP levels as a final common pathway. This in turn leads to a transient inward depolarizing sodium current generated by the Na/Ca exchanger. DAD is believed to be the mechanism of adenosine sensitive RVOT ectopy.
The mechanisms of EAD are less clear. Because EAD occur in phase 3 they increase repolarization time and appear to be instrumental in causing arrhythmias in the setting of a long QT interval.
Re-entry, once thought to be the primary mechanism of VE, is now in doubt as an important cause of PVCs.
The PVC coupling interval may provide a clue as to the mechanism but this is not entirely clear. A fixed coupling interval implies re-entry (if such exists in man) or triggered activity. Variable coupling intervals imply automaticity. Variable coupling intervals with equal or mathematically related inter-ectopic intervals are designated as parasystole which is usually associated with structural heart disease.
Are PVCs associated with harm?
It is useful to approach this question with respect to the presence or absence of structural heart disease. In both acute ischemia and chronic structural heart disease we know that they are associated with negative outcomes though it is less clear whether as a marker or a cause.
What about patients with no structural heart disease? In such patients VE was traditionally thought to be almost universally benign, based primarily on this paper from 1985 by Harold Kennedy and others. Drawing from a larger database that has accumulated since that time, this notion has been challenged, and there may be risk in some patients. This risk is poorly characterized with the exception of two categories: certain purely electrical heart diseases (channelopathies) and the potential for chronic frequent PVCs to cause a dilated cardiomyopathy (DCM). In purely electrical diseases a single PVC may trigger a life threatening event. From the article:
PVCs can trigger VF or polymorphic VT in patients with or without structural heart disease. 6 30 Some features of PVCs can help to identify “malignant PVCs” that have the potential of triggering VF in some patients. Most often PVCs are not tightly coupled to prior sinus beats; however, in certain conditions, tightly coupled PVCs have been described to trigger VF. This has been described for patients with Brugada syndrome, 31 early repolarization syndromes, 32 idiopathic VF, 33 or in the setting of acute myocardial infarction. 7 In the absence of these conditions, malignant ventricular arrhythmias are rare but have been reported and often have been triggered by tightly coupled PVCs. 6 34 No absolute cutoff value for a tight coupling interval has been defined, although most often the PVC coupling interval was less than 400 ms in these circumstances. 6 Other parameters that need to be assessed include the QT interval and the presence of nonsustained VT, including rate and morphology. More malignant arrhythmias have shorter cycle lengths, 35 and in 1 report, the coupling interval of the second beat of the nonsustained VT was found to be shorter in patients with VF compared with patients without VF. 36
It must be kept in mind that in some conditions (eg LQTS, hereditary and acquired) not all triggering PVCs are short coupled.
Concerning PVC induced DCM recent findings challenge the notion that this is caused chiefly by RVOT ectopy. Though RVOT ectopy is a known cause, DCM can result from VE originating from other foci. Also recently challenged is the idea that 15% of heartbeats is necessarily the ectopic frequency threshold for the development of DCM. The critical frequency is actually quite variable and is likely influenced by other risk factors, one of which is PVC QRS width, which is roughly directly proportional to the risk of DCM. A cutoff of 150 ms has been suggested. Epicardial origin of PVCs is associated with a wider QRS and greater DCM risk. Finally, interpolation of PVCs is also associated with a greater DCM risk. PVC induced DCM was once thought to be a variant of tachycardia mediated DCM but is now believed due to different mechanisms. It should be noted that in patients who already have structural disease for other reasons, frequent PVCs can lead to further deterioration of ventricular function.
Beta blockers are first line despite low efficacy due to their favorable safety profile. I-C antiarrhythmic drugs have stronger efficacy and are considered the next line of treatment provided the patient has no structural heart disease. The concern that these drugs increase the risk of SCD when used to treat PVCs is restricted to patients with structural heart disease. Careful assessment and appropriate expertise are required. Amiodarone is an option for patients who do have structural heart disease. Once DCM ensues due to frequent PVCs therapeutic options become limited for the above stated reasons. Suppression of VE with amiodarone has been reported to reverse DCM in that situation.
Catheter ablation is a preferred option in selected patients and is discussed in detail in the article.