Copenhagen holter study, 15 years tracking of PAC, AF and strokes

The cohorts in this study were healthy volunteers with no apparent heart disease at the start. They were tracked over the long term to understand the relationship between PACs development, AF development and stroke risks. The results show that strokes are often the first presentation of PACs before the onset of AF. Study raises a lot of questions and more work needs to be done to understand the role of PACs in strokes. The most important conclusion from the study is that PACs are not benign if they cluster together. There was an accompanying editorial titled "PACs, Wolf in Sheep's Clothing" that sort of sums up the sentiment from looking at the results.

[content.onlinejacc.org]

My vote is that the strokes are due to undiagnosed afib, rather than the PAC's per se.

I have and do track PAC rate/hr with my Polar strap/program/iPhone app combination (formerly with a Polar S810 HRM watch). 11 1/3 years ago it was 2/hr on a Holter. Yesterday 2/hr, today 3/hr. Sometimes more. Reduction of PAC rates was an early target of mine when I was developing my supplement strategy for afib remission.

From 10 years ago, I recall people like Hans and George Eby having counts in the thousands to tens of thousands of PAC's/day.

George

Yes, George, I agree as well. The PACs or even PVCs aren't typically thought of as significant when the results of formal heart monitorings are reviewed although clusters are definitely attention-getting and very annoying. The shortening of the refractory period that can promote that type activity is often due to low potassium levels which may not have been compared by testing during that study. Managing that factor definitely helps and should also help to offset worry about stroke-related issues once the activity is diminished or, better, eliminated by proper electrolyte balance.

Jackie



PS - from long ago there was this finding in a report by George Eby:

Reminder of this 2006 publication regarding the use of taurine to eliminate arrhythmia by George Eby, MS and William Halcomb, DO

Elimination of cardiac arrhythmias using oral taurine with L-arginine with case histories: hypothesis for nitric oxide stabilization of the sinus node

Abstract
We searched for nutrient deficiencies that could cause cardiac arrhythmias [premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation, and related sinus pauses], and found literature support for deficiencies of taurine and L-arginine.

Case histories of people with very frequent arrhythmias are presented showing 10 to 20 grams taurine per day reduced PACs by 50 percent and prevented all PVCs but did not prevent pauses. Adding 4 to 6 grams of L-arginine immediately terminated essentially remaining pauses and PACs, maintaining normal cardiac rhythm with continued treatment.
Effects of taurine useful in preventing arrhythmias include regulating potassium, calcium and sodium levels in the blood and tissues, regulating excitability of the myocardium, and protecting against free radicals damage. Taurine restored energy and endurance in one of the cases from a debilitated status to normal.

Arrhythmias may also respond to taurine because it dampens activity of the sympathetic nervous system and dampens epinephrine release. L-arginine may have anti-arrhythmic properties resulting from its role as a nitric oxide (NO) precursor and from its ability to restore sinus rhythm spontaneously.

Endogenous production of taurine and L-arginine may decline in aging perturbing cardiac rhythm, and these "conditional" essential nutrients therefore become "essential" and require supplementation to prevent morbidity and mortality. L-arginine is hypothesized to prevent cardiac arrhythmias by NO stabilization of the sinus node.

Cardiac arrhythmias having no known cause in otherwise healthy people are hypothesized to be symptoms of deficiencies of taurine and arginine.

Introduction
Premature atrial contractions (PACs) and premature ventricular contractions (PVCs) [ectopic heartbeats] are common disorders of cardiac rhythm particularly in healthy older people. These arrhythmias are beats that occur early in either the atria or the ventricle, causing the heart to beat out of synchronization before the next regular heartbeat. In both cases the heart seems to pause or hesitate until the next beat. Neither are usually considered to be serious cardiac events, and patients may have experienced them for many years with little cardiac distress, although they can be discomforting and annoying. Sinus pauses occur when the sinus node fails to generate an impulse for a few seconds, and long pauses require pacemakers.

Normally, the pacemaking activity of the sinus node suppresses impulse production by other cardiac cells, but if conductance to some other part of the heart muscle is blocked, or if the heart is over stimulated, islands of cells may express their latent impulse-production ability, resulting in extra or early beats.
Continue: [www.george-eby-research.com]



Edited 1 time(s). Last edit at 10/21/2015 09:14PM by Jackie.

Hi reseearcher.

I too had reviewed this study when looking for AFIB Report candidates, but it had too many holes and as with many of these population-based studies their determination of when or if a person has been in AFIB is rather spotty and questionable.

Just read 'excess ectopy' in this regard as an 'association' with stroke but it's NOT necessarily the ectopy that is the 'causal' agent for such strokes. I'd bet my bottom dollar it's the loads of undiagnosed paroxysmal AFIB, often silent, that is the real cryptogenic stroke culprit here.

A finding that is being underscored in other recent, and better done, prospective studies using implantable HR recorders like LINQ and other similar methods of more consistent 24/7/365 HR monitoring with the end point of searching for the real cryptogenic culprits. These studies almost uniformly have all shown a far higher degree of both incident AFIB and overall AFIB burden than anyone previously thought was likely from studies just like the one referenced above, and other similar retrospective look back population studies.

This is why I have to read so many articles ... more than 35 to 45 for each newsletter issue ... most of which initially look interesting, but just to find 5 to 6 that after careful review I I can report on in the AFIB Report that are both relevant to lay afibbers, and reasonably solid evidence-wise overall.

I bounced this study off of three different top tier EPs who kindly help me with such vetting processes as well, and got a unanimous verdict that my take on it was definitely the right one, in that the undiagnosed AFIB that is also often 'associated' with periods of higher degree of atrial ectopy is the real smoking gun here as George noted too.

There is little question that the real culprit for the stroke increase observation in such a group was largely due to the added, and usually unrecognized, added AFIB burden behind the scene. Just looking at how 'incident AFIB' was determined in such a population-based study leaves some big holes to fill and as the authors duly noted in their study lLimitations section, that indeed is a core limitation inherent in most studies of these kind. However there are some interesting and valuable things to learn from these studies as well.


Thanks again researcher for ferreting out another good topic to review.

Cheers!
Shannon



Edited 1 time(s). Last edit at 10/26/2015 12:53AM by Shannon.

Shannon and George, Yes what you say is consistent with what the authors are also saying and also the editorial. The difficulty of identifying subclinical AF is a big issue that requires more work. For practical purposes, the study reflect the difficulty faced by patients and EPs in how to deal with runs of PACs and whether they mean anything in terms of heart function and circulation. Reading the editorial along with the paper is really helpful. Below is the meat of the editorial by Greg Marcus of UCSF and completely consistent with your thoughts regarding the results.

PACs Wolf in Sheep's Clothing - editorial

excerpt ….. >>>

In 2010, Binici et al. (6) used 48-hour ambulatory monitoring data from the Copenhagen Holter Study to assess the association between PACs and the outcomes of incident AF, stroke, and death. In this earlier investigation, excessive atrial ectopy was defined as either 30 or more PACs per hour or an episode of 20 or more consecutive PACs (these defi- nitions were derived from the upper decile cutpoints from the overall cohort). Importantly, over a median follow-up of 6.3 years, this study found that excessive atrial ectopy conferred a nearly 3-fold increased risk of AF hospitalization. These investigators also demonstrated that a high PAC burden was associated with a combined endpoint of stroke or death, a finding that persisted in a sensitivity analysis that censored patients at the time of an AF diagnosis. This last observation hinted at the intriguing notion that PACs could be associated with adverse clinical outcomes independent of AF.

In this issue of the Journal, Larsen et al. (8) take a second look at the Copenhagen Holter Study data to understand the relationship between atrial ectopy and stroke more clearly. The duration of follow-uphas lengthened (median follow-up is now 14.4 years) and is accompanied by an increase in clinical events, including stroke diagnoses. Using definitions and methodology similar to those of the previous investigation, excessive atrial ectopy was associated with a doubling in the adjusted risk of stroke (hazard ratio: 2.02; 95% confidence interval: 1.17 to 3.49). Notably, only a minority of the patients with excessive ectopy and stroke (14.3%) had a clinical diagnosis of AF before their cerebrovascular accident. Further- more, the association between PACs and stroke per- sisted in sensitivity analyses that censored patients at the time of AF diagnosis or treated AF as a time-varying exposure.

The present investigation has several strengths that should be emphasized. Holter data were ob- tained in an ambulatory, population-based cohort of participants who were well characterized at baseline. The investigators carefully considered and accounted for potential confounders in their analysis, and they applied appropriate statistical methodology to sub- stantiate their findings. Participants were followed for nearly 15 years, and, impressively, no patients were lost to follow-up. In addition, the primary stroke outcome used a specific definition that included only ischemic events and required computed tomog- raphy or magnetic resonance imaging for diagnostic confirmation.

We must also consider limitations that may affect our interpretation of the results. As in all obser- vational studies, residual confounding caused by unmeasured or incompletely characterized covariates could potentially result in bias. In addition, the con- clusions of the present study may be less applicable to U.S. patients, who may suffer medical comorbid- ities at a frequency or severity different from that of their Danish counterparts. As acknowledged by the investigators, the present findings do not establish causality, nor do they definitively implicate atrial ectopy as the primary driver of increased risk of stroke or death. The identification of asymptomatic or paroxysmal AF is difficult and is an important limita- tion shared by nearly all clinical AF investigations. As such, we cannot exclude that some patients with frequent PACs also had AF before they were enrolled in the study, nor can we be completely assured that pa- tients who experienced stroke or death did not have intervening AF.

<<<< end excerpt

Shannon - thanks and good points. How about the hyperviscosity issue in these cases? I know a couple of long-standing, permanent afibbers who are still functionally living with the afib who are managing with anticoagulants but one is not. I'd think the tendency for strokes lies with the viscosity (thick, sticky blood) issue.

Jackie