Friday, June 24, 2016

Premature ventricular contractions: everything you wanted to know and more

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.

Thursday, June 23, 2016

Vagal atrial fibrillation

This entity has long been known. It represents one group of mechanisms accounting for the increased risk of atrial fib with athletic conditioning. Review here.

Wednesday, June 22, 2016

How should we define valvular and non-valvular atrial fibrillation?

When the NOACs were first introduced atrial fibrillation associated with any hemodynamically significant valvular disease was considered valvular AF, excluding patients for treatment with a NOAC. Subsequently NOAC indications with respect to type of valve have been liberalized somewhat. The present consensus seems to be that patients considered to have valvular AF are those with rheumatic mitral disease, a valvular prosthesis (either tissue or mechanical) and possibly those with MV repair. Here is a recent review.

Tuesday, June 21, 2016

Walking speed, walking distance and mortality

From a recent review:

Although treadmill exercise testing can provide an assessment of cardiorespiratory fitness, which serves as an independent prognostic indicator, numerous studies now suggest that usual gait speed, time, or distance covered during walk performance tests and weekly walking distance/time are powerful predictors of mortality and future cardiovascular events in selected patients. This review summarizes the relation between these variables and their association with cardiovascular and all-cause mortality, with specific reference to potential underlying mechanisms and implications for the clinician. Contemporary health care providers have escalating opportunities to promote lifestyle physical activity using pedometers, accelerometers, and smartphone-based health and wellness applications. In conclusion, fitness and/or ambulatory indexes should be considered a “vital sign” in middle-aged and older adults.

Monday, June 20, 2016

Giving vasoactive drugs through a peripheral IV

Controversy exists as to whether vasopressors can be given through a peripheral IV and practices vary from institution to institution. Here is a systematic review. Although the review was beset with significant methodologic issues some conclusions were drawn. From the review:

The available data do allow the conclusion that administration of vasopressors through the peripheral intravenous line appears to be associated with more local tissue and extravasation events compared with that through central venous catheters, although the events occur with both types of venous access. Additionally, when peripheral intravenous lines are used, local tissue and extravasation events seem to increase when vasopressors are administered through distal sites for an extended period. Therefore, peripheral catheters should be viewed as a bridge to central access, given the apparent higher rate of adverse events with prolonged peripheral administration of vasopressors.

Sunday, June 19, 2016

Weight reduction, pericardial adipose tissue and cardiac structure in patients with atrial fibrillation

From a recent study:


We prospectively performed cardiac magnetic resonance imaging on 87 participants with AF undergoing either structured weight management (intervention) or general lifestyle advice (control). We measured pericardial adipose tissue, atrial and ventricular volumes, and myocardial mass at baseline and 12 months.


In total, 69 participants underwent baseline and 12-month follow-up cardiac magnetic resonance imaging (intervention n = 36 and controls n = 33). From baseline to 12 months, weight loss (kg, mean [95% CI]) was greater in the intervention group from 101.5 kg (97.2-105.8 kg) to 86.5 kg (81.2-91.9 kg) as compared with controls from 102.6 kg (97.2-108.1 kg) to 98.7 kg (91.0-106.3 kg) (time-group interaction P less than .001). The intervention group showed a reduction in left atrial volumes (mL) from 105.0 mL (98.9-111.1 mL) to 96.4 mL (91.6-101.1 mL), whereas the change in the control group was from 108.8 mL (99.6-117.9 mL) to 108.9 mL (99.8-118.0 mL) (time-group interaction P less than .001). There was a decline in pericardial adipose tissue (cm3) from 140.9 cm3 (129.3-152.4 cm3) to 118.8 cm3 (108.1-129.6 cm3) and myocardial mass (g) from 137.6 g (128.1-147.2 g) to 123.1 g (114.5-131.7 g) in the intervention group, whereas the change in the control group was from 143.2 cm3 (124.6-161.7 cm3) to 147.2 cm3 (128.9-165.4 cm3) for pericardial adipose tissue and 138.3 g (124.8-151.8 g) to 140.7 g (127.4-154.1 g) for myocardial mass (both variables, time-group interaction P less than .001).


Weight reduction results in favorable structural remodeling and a reduction in pericardial adipose tissue burden.

Saturday, June 18, 2016

Measles and pertussis risk related to vaccine refusal

From a JAMA report:

Conclusions and Relevance A substantial proportion of the US measles cases in the era after elimination were intentionally unvaccinated. The phenomenon of vaccine refusal was associated with an increased risk for measles among people who refuse vaccines and among fully vaccinated individuals. Although pertussis resurgence has been attributed to waning immunity and other factors, vaccine refusal was still associated with an increased risk for pertussis in some populations.