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EDITORIAL
Hans Larsen |
Evaluation of Survey Results
Fifty-five per cent of 326 afibbers surveyed used pharmaceutical drugs in the management of their condition.
Twenty-six per cent used antiarrhythmics on a continuous basis to prevent afib episodes (rhythm control) while
19 per cent used beta or calcium channel blockers on a continuous basis to control their heart rate. Eleven per
cent used both antiarrhythmics and blockers.
Women were slightly more likely to be using pharmaceutical drugs than were men, however, the difference in usage was not statistically significant. There was no statistical difference in age between users and non-users of drugs. Adrenergic afibbers were significantly more likely to be using beta or calcium channel blockers than were vagal afibbers. Other differences in observed drug use among the various afib types were not statistically significant. The most widely used antiarrhythmic drug was flecainide while atenolol was the most used beta-blocker and diltiazem was the most used calcium channel blocker.
The most notable finding from this tabulation is that 36% of the drugs used to treat vagal afibbers were beta- blockers (20%) or drugs with beta-blocking properties (16%). These drugs are not recommended for vagally mediated afib. These findings support those of our first drug survey in which 50% of all vagal afibbers had been prescribed drugs contraindicated for their condition. About half of the vagal afibbers who were on beta-blocking drugs also took an antiarrhythmic, which may have ameliorated somewhat the negative effects of the beta- blocking drug. Nevertheless, it is possible that a sizeable proportion of vagal afibbers could significantly improve their situation by optimizing their drug regimen. It is encouraging that the current use of digoxin, a drug contraindicated for all afibbers, is only 4% - a level well below that observed in our first drug survey. Nevertheless, 30% of 180 respondents reported that they had been taking digoxin for an extended period (3 months or longer) at some point during their afib "career". It is puzzling that 28% of permanent afibbers were taking an antiarrhythmic drug, as there is no indication that this would be helpful except in preparation for electrical cardioversion. There was a slight trend for afibbers with a regular pattern to their episodes to be less likely to use drugs, however, the correlation was not statistically significant (p=0.06).
The average median number of afib episodes during a 6-month period among 223 paroxysmal afibbers was 5
for non-drug users and 4 for drug users. This difference was not statistically significant.
The average median duration of episodes among 223 paroxysmal afibbers was 6 hours for non-drug users and
6 hours for drug users.
The average median time spent in afib over a 6-month period among 223 paroxysmal afibbers was 30 hours for
non-drug users and 37 hours for drug users. This difference was not statistically significant.
(1) median number of episodes over a 6-month period There were no statistically significant differences in episode frequency or duration or in total time spent in afib over a 6-month period among non-drug users and drug users when viewed by afib category (adrenergic, mixed, vagal). There was a slight, statistically non-significant trend (p=0.06) for non-drug treated adrenergic afibbers to spend less time in afib than did non-drug treated vagal afibbers.
Drug therapy aimed at preventing or shortening afib episodes was generally found not to be effective.
Disopyramide (Norpace) showed a trend towards fewer episodes, but this trend was not quite statistically
significant (p=0.08). Sotalol (Betapace), on the other hand, confirmed its reputation as possibly the worst drug
for afibbers. All differences observed between individual drugs and no drugs were not statistically significant.
*including Toprol XL The use of beta or calcium channel blockers on their own on a continuous basis did not shorten episode duration, did not decrease intensity of episodes nor did it, somewhat surprisingly, reduce the maximum reported heart rate during an episode. There was no indication that amiodarone, as prescribed among these survey respondents, was effective in preventing or shortening episodes.
The problem of finding the appropriate drug for an individual afibber is particularly difficult in the case of vagally-
mediated afibbers where beta-blocking drugs should be avoided. An evaluation of drugs used in the treatment
of vagal afibbers shows this.
Flecainide significantly shortens episode duration and time spent in a fib for vagal afibbers. Disopyramide would
also appear to shorten both frequency and duration, but these observations did not reach statistical significance
due to the small sample size. Sotalol and amiodarone did not appear to be effective for vagal afibbers and may
actually increase the number of episodes, possibly due to their weak beta-blocking effect.
(1) median number of episodes over a 6-month period
Considering that ablation therapy is now achieving success rates of 80-90% and results in a complete cure, it
would probably not be too much to expect that an effective pharmaceutical drug properly prescribed should be
able to keep an afibber in normal sinus rhythm for at least 6 months. Even if the drug was able to achieve this
goal for just 50% of its users it might be worthwhile. According to this latest survey a total of 21 drug treated
afibbers out of 125 (17%) had achieved the enviable goal of staying in sinus rhythm for 6 months. Among
afibbers not on drugs 12 out of 105 or 11% had achieved an afib-free 6-month period - hardly an impressive
difference.
In conclusion, there is no evidence that pharmaceutical drugs, as currently prescribed, are generally effective in
preventing or shortening afib episodes for the vast majority of afibbers. A notable exception is flecainide and
disopyramide, which would appear to shorten episodes among vagal afibbers.
Twenty-six afibbers out of 138 respondents (19%) had tried the on-demand approach (1 adrenergic, 9 mixed
and 16 vagal). Nineteen or 73% of the on-demand users had found the approach beneficial, 4 or 15% believed
the approach worked sometimes while the remainder was not sure. Only 10% had found that the effectiveness
decreased over time. The average conversion time was 5 hours for both mixed and vagal afibbers and never
exceeded 36 hours.
The most commonly used on-demand drug was flecainide which was used by 62% in dosages between 100 and
400 mg with 200 mg being the most common dosage. Propafenone was used by 19% in dosages of 150 to 600
mg (average of 250 mg).
Surprisingly, there was no indication that the on-demand users on average actually experienced shorter
episodes than experienced by afibbers who used no drugs or used drugs on a continuous preventive basis. This
is a bit of a puzzle and can perhaps be explained by the possibility that afibbers who used to have very long
episodes preferentially used the on-demand approach and that the approach just brought them back to a more
"normal" level. I know this is the case for myself. I have experienced episodes as long as 223 hours, but have
been able to shorten several of my more recent episodes to 2-4 hours and never longer than 36 hours. So if you
have very long episodes the on-demand approach may well be worth trying. If your episodes, on the other hand,
are relatively short (less than 6 hours) you may not gain much by using this approach. Most effective dosages
would seem to be 200 mg of flecainide or 300 mg of propafenone perhaps combined with 12.5 mg of atenolol or
80 mg of verapamil.
Beta and calcium channel blockers
Please note that percentages do not add up to 100% due to the fact that many afibbers combined stroke prevention regimen, particularly aspirin and natural approaches. Only 25 respondents answered the question regarding the use of aspirin on-demand. Six out of these 25 (2 adrenergic, 1 mixed and 3 vagal) used the stroke prevention technique of taking an aspirin at the onset of an episode. The median age (61 years) of warfarin users was significantly higher than that of both aspirin users (56 years) and natural remedy users (57 years). There was no significant difference in gender distribution between users of warfarin, aspirin and natural remedies. Warfarin users had significantly longer episodes (median duration = 12 hours) than did non-users of warfarin (median duration = 5 hours). It is not possible to deduce whether this is because warfarin prolongs the episodes or because afibbers with long lasting episodes are more likely to use warfarin. There was no difference in episode duration among users and non-users of aspirin.
References
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Calcium & Magnesium Supplementation
According to the most recent and past LAF surveys combined 65% of 249 respondents supplement regularly
with magnesium and 23% supplement with calcium.
There is no indication that supplementation with magnesium as such has any effect on episode frequency,
duration or time spent in afib. The observed lack of effect is almost certainly due to the fact that the amount of
elemental magnesium actually provided by the supplements is quite small.
In LAFS-V 83 of 151 participants specified the type of magnesium supplement they were taking and 62 also
specified the amount taken. Again there was no overall difference in episode frequency or duration between
those supplementing with magnesium and those who were not in this subset of afibbers. An analysis limited to
the 62 for whom dosage and type of magnesium was known revealed the following:
* Bioavailability is the % of the available elemental magnesium that is actually absorbed by the body. It is about 4% for magnesium oxide and is estimated to be 50% for all other forms. It is clear that the average content of bioavailable elemental magnesium in most supplements is very small except in the case of chelated magnesium and Waller water. Thus it is not surprising that no correlation was found between episode frequency and daily intake of elemental magnesium or bioavailable magnesium, nor between episode duration and daily intake of elemental or bioavailable magnesium. The recent experience of several afibbers, myself included, indicates that a threshold level of somewhere between 600 and 900 mg of elemental magnesium per day must be reached in order to achieve a noticeable effect on the frequency of premature beats and afib episodes. Our benchmark diet (Fran's diet) provides 931 mg/day of elemental magnesium and the diet used to reduce PACs by 50% in the USDA clinical trial contains 411 mg of elemental magnesium[1]. In contrast, the average content of elemental magnesium in the diet of 65 paroxysmal afibbers participating in our October 2001 diet survey was 250 mg. The average intake from supplements was 181 mg giving a total of 431 mg or well below what is now believed to be the minimum required to obtain a beneficial effect. Taking magnesium glycinate or chelated magnesium (Albion Process) is the most effective way of achieving a daily intake of 600-900 mg of elemental magnesium. Acceptable brands of chelated magnesium are Solgar and Metagenics in the USA and Trophic in Canada. It is best to begin slowly with 1 tablet containing 100 mg of elemental magnesium with each meal working up to 2 or 3 tablets with each meal as needed. If loose stools or diarrhea occurs back off until things are normal again. Drinking 2 liters a day of neutralized Waller water will provide 250 mg of highly bioavailable elemental magnesium. Thus taking 2 tablets of chelated magnesium or magnesium glycinate with each main meal plus drinking 2 liters of Waller water throughout the day would provide a total daily intake of elemental magnesium of 850 mg and would, at the same time, provide adequate hydration. It is important to note that while magnesium glycinate is highly bioavailable it only contains 14 mg of elemental magnesium in 100 mg of glycinate. So it is important that the label of the product you purchase states the Mg content in elemental magnesium and not in magnesium glycinate as such. It is also essential to ensure that magnesium intake from supplements is balanced with an appropriate intake of calcium.
There is no indication that supplementation with calcium as such has any effect on episode frequency, duration
or time spent in afib. There was a slight trend for vagal afibbers who supplemented with calcium to have longer
lasting episodes, but this trend was not statistically significant (p=0.07). This finding contradicts findings from
previous smaller surveys that vagal afibbers who take calcium tend to have statistically significant longer lasting
episodes[2].
In LAFS-V 25 of 123 respondents specified the type of calcium supplement they were taking and 20 also
specified the amount taken. Again there was no overall difference in episode frequency or duration between
those supplementing and those not supplementing in this subset of afibbers. An analysis limited to only the 20
supplementers for whom dosage and type was known revealed the following:
The average intake of elemental calcium from supplements was 236 mg/day ranging from 8-800 mg/day. There were no indications of a correlation between the daily intake of elemental calcium and episode frequency or duration nor was there any indication that the Ca:Mg ratio played a role as far as episode severity is concerned. Our benchmark diet (Fran's diet) provides 1521 mg of calcium per day. Thus the average daily Ca intake from supplements of 236 mg combined with the average dietary intake of 600 mg/day estimated from the analysis of the diet of 65 afibber provides only a total of 836 mg/day or about 55% of the amount of elemental calcium contained in the benchmark diet. The estimated 836 mg/day average Ca intake is also well below the RDA of 1200 mg/day.
Although both the 2001 diet survey and the later supplement survey point to a possible calcium and magnesium
deficiency among afibbers, it should very much be kept in mind that both of these surveys lacked considerably in
power due to the relatively small number of participants, and the simplified design of the diet survey. It would be
highly desirable to repeat these surveys at some future date. Nevertheless, the findings of deficiency are, to
some extent, corroborated by studies carried out in the general population. A recent survey found an average
daily calcium intake of only 761 mg/day among over 17,000 participants in the NHANES III survey[3]. Another
study concluded that the average magnesium intake from a normal diet is about 271 mg/day[4].
Although our surveys have found no significant correlation between calcium and magnesium intake and episode
severity it is likely that approaching the Ca and Mg intakes in Fran's diet may be beneficial. This would apply
particularly to magnesium where a daily intake of 600 to 900 mg of elemental magnesium in chelated or
glycinate form would appear to be potentially highly beneficial. The total supplementary intake of elemental
magnesium should be balanced with the intake of elemental calcium so as to maintain a ratio of between 1:1
and 2:1. Closer to 1:1 if the diet contains a fair amount of dairy products and closer to 2:1 if it does not. The
benchmark diet had a Ca:Mg ratio of 1.6.
An earlier survey indicated that vagal afibbers who supplemented with large amounts of calcium tended to have
longer lasting episodes than those not supplementing. This finding was not supported by this much larger
survey. Thus there would appear to be no reason for vagal afibbers to shun calcium unless they find it is indeed
detrimental in their own particular case.
References
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Other Minerals
The detailed analysis of our benchmark diet (Fran's diet) provided measures of the daily dietary intake of iron,
calcium, magnesium, potassium, sodium, copper, zinc, and selenium. Comparing these benchmark intakes to
the average intakes of the 65 afibbers participating in our 2001 diet survey makes sobering reading indeed.
(1) survey in % of benchmark diet It is perhaps not surprising that the average afibber's diet shows a significant shortfall in potassium, calcium and magnesium when compared to the benchmark diet. However, the difference in daily copper intake is startling. Even if the diet survey is off by a factor of two the difference is still remarkable. Could a relative copper deficiency play a role in the etiology of lone atrial fibrillation?
Copper deficiency is widespread in the western world. A daily intake of between 0.65 and 1.02 mg (based on
analyses of actual food consumed) has been found to lead to deficiency symptoms and it is estimated that
approximately one third of the populations of Belgium, Canada, the UK, and the United States have daily intakes
in this range[1[. A copper deficiency has been linked to osteoporosis, high cholesterol levels, hypertension,
cardiac rhythm abnormalities, increased tendency to blood clotting (thrombosis), an increase in the oxidative
stress on the heart tissue and the development of fibrosis[1,2,3,4,5].
Of particular interest to afibbers is the finding of an association between a copper deficiency and fibrosis of the
heart muscle (a suspected important player in afib), cardiac arrhythmias, and in particular, a tendency to
experience an increased level of premature ventricular complexes (PVCs)[1,6,7]. While PVCs have not been
linked directly to the initiation of atrial fibrillation it is possible that they could be involved indirectly. PVCs do
cause anxiety, particularly when they come in runs and may also disturb the mechanical, if not electrical, balance
of the heart. Both could lead to increased anxiety and thus provoke an afib episode.
A copper deficiency also reduces the level of superoxide dismutase (copper-zinc superoxide
dismutase)[1,4,5,8,9,10]. Superoxide dismutase is one of the body's most effective antioxidants and is
particularly adept at neutralizing the superoxide radical, a potent free radical generator and initiator of oxidative
stress. It is likely that the superoxide radical would be particularly plentiful in the blood entering the left atrium
through the pulmonary veins and thus could be involved in the etiology of afib episode initiation[11].
Blood (erythrocyte) levels of superoxide dismutase can be increased by copper supplementation, but
commensurate high intakes of zinc or ascorbic acid (vitamin C) reduce the effectiveness of the
supplementation[12,13].
Several experiments have shown that the frequency of PVCs can be markedly reduced by supplementation with
copper. As early as 1979 it was observed that daily supplementation with as little as 4 mg of elemental copper
(from copper gluconate) completely eliminated PVCs in less than 2 weeks in three individuals suffering from
PVCs[6]. Again it was pointed out that a high zinc intake would be detrimental because it interferes with copper
absorption.
The average copper intake among the 65 afibbers participating in the 2001 diet survey was 1.3 mg/day.
However, this is a value calculated from the USDA nutrition database. According to research yet to be published
calculated values are at least 52% higher than the values obtained by actually analyzing meals consumed[2].
So the calculated 1.3 mg/day would actually correspond to an analyzed value of about 0.86 mg/day. This is well
within the deficient range; considerably below the official "Adequate and Safe Intake" of 1.5 to 3.0 mg/day, and
even below the recently established RDA of 0.9 mg/day (many scientists feel that this value is way too low)[3].
So not only could many afibbers be deficient in copper, but it would also seem that the average Zn:Cu ratio in
the afibbers diet is undesirably high at 7.8:1 compared to 3.1:1 in the benchmark diet (Fran's diet) and the RDA
of 6:1. Many researchers consider the Zn:Cu ratio in human milk to be ideal[2]. This ratio is 3:1, very close to
the benchmark diet, but substantially lower than the RDA and the average ratio found in the afibbers diet survey.
Considering that many men take zinc supplements for prostate health without a commensurate intake in copper
would further push the Zn:Cu ratio in an undesirable direction.
Nuts, legumes, and dark chocolate are excellent dietary sources of copper and chelated copper and copper
gluconate are effective supplements[14,15,16]. Copper intakes up to 10 mg/day are considered safe, but
intakes of 6 mg and more may produce stomach upsets[2].
References
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The AFIB Report is published 10 times a year by Hans R. Larsen MSc ChE 1320 Point Street, Victoria, BC, Canada V8S 1A5 Phone: (250) 384-2524 E-mail: [email protected] URL: http://www.afibbers.org Copyright © 2003 by Hans R. Larsen The AFIB Report does not provide medical advice. Do not attempt self- diagnosis or self-medication based on our reports. Please consult your health-care provider if you wish to follow up on the information presented. |