Wishing you lots of sinus rhythm,
Hans Larsen

General Health

The low prevalence of diabetes among afibbers is a welcome surprise. I don't know whether having afib in itself or a genetic abnormality underlying afib prevents the development of diabetes, but this is clearly an area where more in-depth research may prove fruitful. Afibbers though, in an attempt to avoid frequent episodes, tend to take many of the measures that have been proven effective in the prevention of diabetes and glucose intolerance. Among these are:

• Regular exercise
• Healthy diet
• Decreased fat intake (total and saturated)
• Avoidance of trans-fatty acids
• Increased fiber intake
• Maintenance of ideal weight
• Vitamin and mineral supplementation (particularly vitamin E)

The prevalence of hypoglycemia (idiopathic postprandial syndrome) among afibbers is probably somewhat high at 26% although I have not been able to find any official prevalence figures. The prevalence among adrenergic afibbers (42%) is almost certainly abnormally high. Postprandial hypoglycemia involves epinephrine (adrenaline) release (adrenergic stimulation) which is known to cause palpitations and full-blown AF.

It is also possible that a glutamate/MSG sensitivity could explain the absence of diabetes and the prevalence of hypoglycemia as glutamate stimulates insulin release. The high prevalence of hypoglycemia and low prevalence of diabetes could, of course, both point to an oversensitive insulin response. This can be attenuated by emphasizing foods with a low glycemic load and by ensuring that each meal and snack contains some protein.

There was a slight, but statistically highly significant association between having hypoglycemia and having been diagnosed with atrial flutter. There was also a moderate, but statistically significant correlation between having hypoglycemia and having a high maximum heart rate during an episode.

Leg Cramps
Leg cramps during the night or after exercise is a fairly common complaint among afibbers. A survey of 166 afibbers showed that 35 (21%) experienced leg cramps mostly (9%) occurring at night.

Leg cramps sometimes involve a magnesium deficiency, but the survey did not find any correlation between magnesium intake from supplements and the presence of leg cramps. Leg cramps, particularly at night, are quite common among elderly people. A British study involving 365 people aged 65 years or older found that 50% of them experienced leg cramps regularly. The researchers point out that the risk of leg cramps increases with the presence of arthritis and peripheral vascular disease[2].

Premenstrual Syndrome (PMS)
Only 30 respondents answered the question about experiencing PMS (2 adrenergic, 13 mixed, 12 vagal and 3 permanent). Five of the 30 (17%) reported suffering from PMS (1 adrenergic, 3 mixed, 1 vagal). The number of data points was too small to draw any conclusions regarding possible correlations with other variables.

Asthma
The current prevalence of asthma among adults in the United States is 7.2%[3]. We found a prevalence of 8.0% among 162 respondents to the 5th LAF survey. Thus there is no indication that asthma rates among afibbers are significantly different from that in the general population and no reason to suspect a connection between asthma and AF.

The difference in prevalence among adrenergic and vagal afibbers is not statistically significant.

Common Cold/Runny Nose
The average number of colds experienced by 165 respondents was 1.2/year. The National Institutes of Health estimates the average incidence of colds among adults in the United States to be 3/year[4]. Thus there is no reason to suspect that afibbers have a weakened immune system, perhaps rather the opposite.

There was a moderate, but extremely statistically significant inverse correlation between present age of respondents and the number of colds per year with older people tending to have fewer colds. There was no correlation between the number of colds and episode frequency or duration.

A total of 40% of 162 respondents answered "yes" to the question "Do you often suffer from a runny nose without having a cold?" I have not been able to find an official estimate of the prevalence of runny noses in the general population, but 40% does seem rather high. A non-cold related runny nose could be a sign of an allergy, excessive vagal domination or a glutamate/MSG sensitivity. Adrenergic afibbers had a slightly lower prevalence than did mixed, vagal and permanent afibbers, but these differences were not statistically significant. There was no correlation between a tendency to runny nose and self-reported MSG sensitivity or between a tendency to runny nose and episode frequency or duration. It is possible that the high prevalence of runny noses among afibbers is an important clue, but clearly more research would be required to ascertain this.

Environmental & Dietary Factors

Solvent & Pesticide Exposure
A total of 33 afibbers (20%) reported exposure to volatile industrial solvents, pesticides, crop-dusting chemicals or Agent Orange prior to their LAF diagnosis.

There was a very significant correlation between prior solvent/pesticide exposure and duration of afib episodes among paroxysmal afibbers. Those who had been exposed to solvents/pesticides had significantly longer episodes (23 hours versus 9 hours mean; 6 hours versus 15 hours median). There was no correlation between present age and solvent exposure or between gender and incidence of solvent exposure. There was, however, a significant association between solvent exposure and self-reported MSG sensitivity with afibbers exposed to solvents being more likely to report MSG sensitivity. There was a slight, but statistically not quite significant (P=0.07) trend for solvent-exposed afibbers to have hypoglycemia. Solvent-exposed afibbers were more likely to take magnesium supplements, perhaps reflecting the more serious nature of their LAF (longer episode duration).

Sensitivity to Gasoline Smell
Only 5 out of 140 respondents (3 mixed, 2 vagal) reported that exposure to the smell of gasoline (petrol) was likely to precipitate an episode. Four of these 5 had prior exposure to solvents or pesticides and 3 had MSG sensitivity as well. There were not enough data points to establish the statistical significance of this or other possible correlations.

Sensitivity to MSG
Twenty-one of 120 respondents (17.5%) reported that exposure to MSG (monosodium glutamate) was likely to trigger an episode.

The fact that only 17.5% of respondents reported that MSG exposure would set off an afib episode does not mean that only 17.5% are actually sensitive to MSG or glutamate exposure. It could well be that many more have a "subclinical" sensitivity that requires an accumulation of MSG exposure rather than just a single exposure to initiate an episode. Afibbers with acute MSG sensitivity were significantly more likely to have been exposed to solvents and pesticides prior to their diagnosis of LAF. Perhaps prior solvent/pesticide exposure sensitizes one to later MSG exposure. There was a trend (P=0.06) for afibbers taking bulk-forming laxatives (psyllium, Metamucil) to be more likely to report MSG sensitivity.

Regular Use of Bulk-Forming Laxatives
Bulk-forming laxatives, such as psyllium and Metamucil, were used regularly by 22 out of 163 respondents (13.5%). The difference in usage between adrenergic, mixed and vagal afibbers is not statistically significant.

There was no correlation between the use of bulk-forming laxatives and episode frequency or duration; however, there was a trend for laxative users to be sensitive to MSG.

Consumption of Licorice
Only 3 out of 164 respondents (1.8%) reported regular consumption of licorice or licorice root. Thus there is no reason to suspect a connection between licorice consumption and LAF. Licorice contains a component, glycyrrhizic acid, which is known to inhibit 11-beta-hydroxysteroid dehydrogenase type 2, the enzyme responsible for the conversion of cortisol to its inactive form (cortisone). A high licorice consumption has been linked to hypertension.

Lifestyle Factors

Daily Water Consumption
The average daily drinking water consumption among 160 respondents was five 8-oz glasses.

There was no correlation between episode frequency and duration and daily water consumption. There was a statistically significant slight trend for heavy water drinkers to have vagally induced episodes. There was a moderate statistically significant association between a high daily water intake and a high intake of calcium from supplements. There was also a slight trend for heavy water drinkers to report frequent emotional or work-related stress or, equally plausible, for emotionally stressed afibbers to drink more water.

Sleep Pattern
There were no significant differences in the average sleep pattern of adrenergic, mixed, vagal and permanent afibbers. Most (77%) slept in a completely dark room (important for proper melatonin synthesis), went to bed around 11 pm, and got a little more than 7 hours of sleep every night.

There were no associations between episode frequency or duration and bedtime, hours of sleep or sleeping in a dark room. However, there was a slight to moderate statistically highly significant association between hours of sleep and leading a routine life with afibbers leading a routine life tending to sleep longer. Those who slept longer were also more likely to be able to terminate their episodes with rest.

Level of Physical Activity
The majority of 201 respondents (62%) considered themselves somewhat physically active, 28% considered themselves very physically active, and only 10% considered themselves to be sedentary.

There was no association between physical activity level and episode frequency, duration or intensity. There was an extremely significant correlation between gender and physical activity level with women tending to be less physically active than men. There was also a significant correlation between the regular use of beta- blockers and physical activity with afibbers on beta-blockers tending to be les physically active. Not surprisingly, there was an extremely significant correlation between physical activity level and resting heart rate with more physically active afibbers having significantly lower resting heart rates.

Stress Level
The majority (58%) of 165 respondents reported frequent exposure to emotional or work-related stress again underscoring the major role played by psychological stress in the etiology of afib.

It is tempting to speculate that permanent afibbers are less stressed then paroxysmal afibbers because they are not always anxiously awaiting the next episode; however, the observed difference in perceived stress exposure is not significantly different.

There was no correlation between episode frequency and level of stress exposure; however, there was a statistically significant trend for stressed afibbers to have longer lasting and more intensely felt episodes. There was also a significant inverse correlation between leading a routine life and feeling stressed. Afibbers who lead a routine life were less likely to report emotional or work-related stress.

There was a highly significant correlation between stress level and systolic blood pressure. Afibbers who reported frequent exposure to stress had an average systolic blood pressure of 125 mm Hg while unstressed afibbers averaged 120 mm Hg. There was also a significant trend for stressed afibbers to drink more water during the day.

Conclusions

• Afibbers have a very low prevalence of diabetes and perhaps a higher than normal prevalence of hypoglycemia (idiopathic postprandial syndrome). It is possible that afibbers have a heightened insulin response perhaps stimulated by glutamate or high glycemic index foods.

• Afibbers are no more likely to have asthma than is the general population and tend to have significantly fewer colds than observed in the general population.

• Experiencing a runny nose without having a cold was quite common among afibbers and could indicate the presence of an allergy, excessive vagal domination or a glutamate/MSG sensitivity.

• Twenty per cent of all afibbers (out of 162) reported exposure to solvents, pesticides, crop-dusting chemicals or Agent Orange prior to their diagnosis of LAF. These afibbers had significantly longer episodes and were more likely to report a sensitivity to MSG.

• There were no significant differences in sleep patterns between adrenergic, mixed, vagal, and permanent afibbers and no indication that sleep pattern (bedtime, hours of sleep, sleeping in a dark room) had any association with episode frequency and duration. However, afibbers with longer hours of sleep were more likely to lead a routine life and to be more likely to be able to terminate their episodes with rest.

• Most afibbers considered themselves physically active or very physically active. There was no correlation between physical activity level and episode frequency, duration or intensity. Women and afibbers on beta- blockers tended to be less physically active and not surprisingly, there was an extremely significant correlation between physical activity level and resting heart rate with more physically active afibbers having significantly lower resting heart rates.

• Emotional or work-related stress was regularly experienced by 58% of all afibbers underscoring the major role played by psychological stress in the etiology of afib. There was no correlation between episode frequency and stress level, but stressed afibbers did tend to have longer lasting and more intensely felt episodes. Stressed afibbers were also less likely to lead a routine life and tended to have significantly higher systolic blood pressure than did non-stressed afibbers.

1. www.diabetes.org
2. Abdulla, AJ, et al. Leg cramps in the elderly: prevalence, drug and disease associations. International Journal of Clinical Practice, Vol. 53, No. 7, October/November 1999, pp. 494-96
3. www.cdc.gov/mmwr/preview/mmwrhtml/ mm5217a2.htm
4. www.nlm.nih.gov/medlineplus/ency/article /000678.htm

AFIB News

HAMBURG, GERMANY. The recommended dosage of propafenone (Rythmol) for the prevention of paroxysmal atrial fibrillation (AF) episodes is 150 to 300 mg three times daily. Propafenone has a relatively short half-life of between 5 and 7 hours so taking it 3 times a day still leaves room for large variations in blood plasma concentrations and a subsequent risk of breakthrough episodes of AF. A clinical trial of a slow release formulation of propafenone has just been completed in Europe. The trial involved 293 AF patients of which about 40% had underlying structural heart disease. The patients were randomized to receive a placebo or 325 or 425 mg of slow-release propafenone twice daily. After a 5-day stabilization period the participants were monitored for AF episodes during the following 91 days. The median time to the first AF episode was 9 days in the placebo group, 35 days in the 325 mg propafenone group, and 44 days in the 425 mg (twice daily) group. However, when the median treatment failure time (AF episode, adverse event or withdrawal from trial) was considered the results were somewhat less spectacular, 8 days in the placebo group, 19 days in the 325 mg group, and 24 days in the 425 mg group. Adverse events were frequent with over 50% of patients reporting at least one adverse event in the propafenone groups versus 28% in the placebo group. Life-threatening or fatal adverse events were reported in 9.9% of the patients in the 325 mg group, 11.2% in the 425 mg group, and 1.1% in the placebo group. The researchers noted a significant reduction (10 beats/minute) in heart rate during episodes in the 325 mg twice daily group. The researchers reporting on the trial conclude that the time-release propafenone is "superior to placebo, well-tolerated, and prevents symptoms of paroxysmal AF."
Meinertz, Thomas, et al. Efficacy and safety of propafenone sustained release in the prophylaxis of symptomatic paroxysmal atrial fibrillation (The European Rythmol/Rytmonorm Atrial Fibrillation Trial [ERAFT] Study). American Journal of Cardiology, Vol. 90, December 15, 2002, pp. 1300-06

Editor's comment: From my perspective as a veteran afibber I would conclude that the new formulations are not terribly effective and certainly not safe (over 50% of patients taking them experienced adverse events and 2 died).

MUNICH, GERMANY. Researchers at the German Heart Center subjected 200 patients with conventional pacemakers and 148 patients with implanted cardioverter-defibrillators (ICDs) to the electromagnetic field emitted by an airport metal detector gate in use worldwide. They found no interference and conclude that clinically relevant interactions between airport metal detector gates and pacemakers or ICDs are unlikely.
Kolb, C, et al. Do airport metal detectors interfere with implantable pacemakers or cardioverter-defibrillators? Journal of the American College of Cardiology, Vol. 41, June 4, 2003, pp: 2054-59

BERLIN, GERMANY. It is estimated that about 26% of Americans with normal blood pressure and 58% of those with high blood pressure (hypertension) are salt-sensitive. Salt-sensitive persons show a drastic variation in blood pressure depending on the salt content of their diet while salt-insensitive (salt-resistant) people can consume as much or as little salt as they like with no effect on their blood pressure. Research has shown that salt-sensitive people are more likely to develop hypertension later in life, have a higher overall mortality rate, and are more likely to develop kidney problems and left ventricular dysfunction. Salt-sensitive people can reduce their risk of developing hypertension and other illnesses by reducing their salt intake to 2400 mg or even better, 1500 mg per day.

German researchers now report that salt-sensitive people experience a pronounced shift in autonomic nervous system balance when exposed to mental stress. Their experiment included 17 salt-sensitive subjects and 56 salt-resistant controls. All participants had normal blood pressure. The study participants were exposed to a stressful computer job while their heart rate, heart rate variability (HRV), and blood pressure were measured continuously. The researchers observed that salt-sensitive subjects experienced a considerably higher increase in heart rate and diastolic blood pressure during the stressful computer job (as compared to their resting heart rate and blood pressure) than did salt-resistant subjects. They also noted a lower HRV both at rest and during stress in salt-sensitive individuals as compared to controls; they conclude that salt-sensitive individuals experience a decrease in vagal (parasympathetic) activity and an increase in adrenergic (sympathetic) activity during mental stress.
Buchholz, K, et al. Reduced vagal activity in salt-sensitive subjects during mental challenge. American Journal of Hypertension, Vol. 16, July 2003, pp. 531-36

Editor's comment: This research points to the possibility that salt-sensitive adrenergic and perhaps mixed afibbers may be adversely affected by mental stress or more specifically, challenging computer work. Vagal afibbers, whether salt-sensitive or not, would not be affected or may even benefit from challenging computer work.

VALENCIA, SPAIN. Spanish researchers report that l-carnitine prevents glutamate from destroying neurons (glutamate neurotoxicity) and also prevents acute ammonia toxicity in animals. Carnitine contains a trimethylamine group and other compounds (notably carbachol and betaine), which also contain this group, have likewise been found effective in preventing glutamate-induced neuronal death.
Llansola, M, et al. Prevention of ammonia and glutamate neurotoxicity by carnitine: molecular mechanisms. Metab Brain Dis, Vol. 17, No. 4, December 2002, pp. 389-97

Editor's comment: There is growing evidence that glutamate neurotoxicity could be involved in afib. There is also some evidence that carnitine helps protect against afib. Perhaps it does so, at least partly, by preventing glutamate-induced neurotoxicity.

ATLANTA, GEORGIA and ROCHESTER, MINNESOTA. Researchers at the Centers for Disease Control and Prevention report that hospital admissions for atrial fibrillation increased from 787,750 in 1985 to 2,283,673 in 1999 corresponding to a 3-fold (300%) increase over 14 years. Essential hypertension, ischemic heart disease, congestive heart failure, and diabetes often accompanied the atrial fibrillation. The researchers conclude that, "The public health burden of atrial fibrillation is enormous and expected to continue to increase over the next decades. Primary prevention of atrial fibrillation must be recognized and pursued as a complementary management strategy for reducing cardiovascular morbidity and mortality".

Researchers at the Mayo Clinic support these findings. They determined the age-adjusted prevalence of atrial fibrillation in stroke victims and their gender and age-matched controls in the periods 1960-1969 and 1980-1989. The prevalence among controls increased from 5% to 12% among men and from 4% to 8% among women. The prevalence among stroke patients increased from 11% to 16% among men and from 13% to 20% among women.
Wattigney, WA, et al. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention. Circulation, July 28, 2003
Tsang, TS, et al. The prevalence of atrial fibrillation in incident stroke cases and matched population controls in Rochester, Minnesota: changes over three decades. Journal of the American College of Cardiology, Vol. 42, July 2, 2003, pp. 93- 100

Editor's comment: These disturbing finding will hopefully lead to a greater effort to find the causes and effective treatments for afib.

MILAN, ITALY. Cardiologists at the San Raffaele University Hospital have just released the results of a clinical trial designed to compare the effectiveness of pulmonary vein ablation versus pharmaceutical drugs in the treatment of atrial fibrillation (AF). Their study involved 1171 consecutive patients with symptomatic AF who were referred to the hospital between January 1998 and March 2001. About 35% of the patients had lone AF (no underlying cardiovascular disease) and 70% had paroxysmal (intermittent AF) while the remaining 30% were in permanent AF. Circumferential pulmonary vein ablation was performed on 589 of the patients while 582 were treated with antiarrhythmics (33% on amiodarone, 17% on propafenone, 15% on flecainide, 13% on sotalol, 9% on quinidine, 6% on disopyramide, and 7% on more than one antiarrhythmic). All patients were followed up for a median of 900 days with interviews every 3 months and Holter monitoring every 3 months for the first year and every 6 months after that.

The decision to undergo ablation or be treated with drugs was left to the individual patient or to the judgment of the attending electrophysiologist. Criteria for ablation used by the electrophysiologist was 2 or more previous ineffective trials with antiarrhythmic drugs, 2 or more years of antiarrhythmic drug treatment or more than 2 AF- related hospital admissions during the 2 years prior to entering the study.

At the end of the follow-up period 38 of the ablation patients (6%) and 83 (14%) of the medically treated patients had died. Cardiovascular disease (heart attack, stroke, sudden death, and congestive heart failure) was the cause of death for 71% of the medically treated patients who died as compared to 47% among the ablation patients. One hundred and twenty (20%) of the ablated patients had recurrence of AF after their ablation while 58% of the drug treated patients had 1 or more AF episodes after their initial discharge from hospital. The protective effect of ablation increased over time with total cure experienced if patients did not lapse back into AF within 10 months of their ablation. The ablation procedure was found to be equally effective for paroxysmal and permanent afibbers. The percentage of ablated patients who were afib-free was 84%, 79% and 78% respectively 1, 2 and 3 years after the ablation. Among the drug treated patients the corresponding percentages were 61%, 47% and 37%.

The researchers found a direct, statistically significant relationship between the amount of time a patient stayed in normal sinus rhythm (NSR) and the patient's risk of dying or having an adverse event. Patients who maintained sinus rhythm had a lower risk of dying. This finding clearly contradicts the findings of the AFFIRM, RACE, and PIAF trials which concluded that simple rate control is as protective as rhythm control. The researchers also observed that the quality of life (QoL) among ablated patients reached the level of non-AF persons within 6 months of the ablation while the QoL of the medically treated patients remained well below that found in the general population.

The researchers also noted that 90% of the drug treated patients were on warfarin (Coumadin) when they died. Among the 19 patients (in the total group of 1171 patients) who had an ischemic stroke 74% were on warfarin at the time of their stroke and among the 9 patients who had a hemorrhagic stroke 8 (89%) were on warfarin at the time of their stroke. There were a total of 35 transient ischemic attacks (TIAs) among the 1171 patients, of these, 74% were on warfarin when their TIA occurred. It is interesting to note that the total incidence of ischemic stroke among this group of symptomatic AF patients was 1.6% over a 900-day period or about 0.7% per year. Anticoagulation was used in accordance with published guidelines. The incidence of both ischemic and hemorrhagic stroke was considerably higher among drug treated patients (1.0% and 0.5% per year respectively) than among ablated patients (0.3% and 0.1% per year respectively).
Pappone, Carlo, et al. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation. Journal of the American College of Cardiology, Vol. 42, July 16, 2003, pp. 185-97

HRADEC KRALOVE, CZECH REPUBLIC. Atrial fibrillation most often originates around the junction between the left atrium and the pulmonary veins. Czech researchers at the Charles University Medical School have performed autopsies on 43 human hearts to determine the extent to which the left atrial myocardium extends into the pulmonary veins. They found that myocardial fibers extended into the veins in 68% of the 172 pulmonary veins examined. The fibers were most often arranged in a circular pattern and extended an average (mean) 7.7 to 10 mm into the vein reaching a maximum of 48 mm. The maximum thickness of the myocardial sleeve was 5 mm. The researchers noted that hearts from patients with a history of atrial fibrillation had longer and thicker myocardial extensions into the upper pulmonary veins than did normal hearts. They conclude that there is a significant variability in the presence, arrangement, and thickness of atrial myocardial sleeves into the pulmonary veins and that this finding may have implications for the pulmonary vein ablation technique.
Kholova, I. and Kautzner, J. Anatomic characteristics of extensions of atrial myocardium into the pulmonary veins in subjects with and without atrial fibrillation. Pacing and Clinical Electrophysiology, Vol. 26, June 2003, pp. 1348-55

MAASTRICHT, THE NETHERLANDS. Conventional radio frequency ablation (RFA) of type I atrial flutter has a high success rate (96%) and a low rate of recurrence (6-9%). However, the procedure can be painful. Dutch cardiologists recently completed a study of cryoablation in the treatment of atrial flutter. Cryoablation is a catheter-based technique that is somewhat similar to RFA except that the ablation probe is cooled by liquid nitrogen to freeze and thus ablate the target tissue while RFA uses electrical energy to heat and thereby ablate the tissue. Cryoablation has been highly successful in the treatment of prostate cancer, but its use to treat afib and flutter is relatively new. The small clinical trial involved 11 men and 3 women (average age of 55 years) with atrial flutter randomized to receive ablation of the cavotricuspid isthmus either by RFA or by cryoablation. The RFA was performed with an 8 mm catheter tip heated to 55 degrees C while the cryoablation was performed with a 6 mm tip cooled to –82 degrees C. All patients except for 1 in the RFA group were successfully ablated and no recurrences of atrial flutter took place during the 6-month follow-up period. The patients undergoing cryoablation experienced significantly less pain than the patients undergoing conventional RFA.
Timmermans, C, et al. Randomized study comparing radiofrequency ablation with cryoablation for the treatment of atrial flutter with emphasis on pain perception. Circulation, Vol. 107, March 11, 2003, pp. 1250-52