ABSTRACTS

DAVIS, CALIFORNIA. Several studies have shown that dietary polyphenols help reduce mortality from coronary heart disease. It is not entirely clear why this is, but it is possible that it is, at least partly, due to the fact that polyphenols reduce the risk of ischemic stroke. Chocolate and cocoa are rich sources of polyphenols, so researchers at the University of California recently set out to investigate if cocoa would be beneficial in preventing stroke. Their experiment included 30 healthy, non-smoking adults with no history of heart disease. The participants were randomly assigned to consume 300 mL of a procyanidin-fortified cocoa beverage (containing 17 mg of caffeine and 897 mg of procyanidins), 300 mL of plain water or 300 mL of a beverage containing 17 mg of caffeine.

Adenosine diphosphate (ADP) and epinephrine-stimulated platelet activation and platelet microparticle formation were measured in blood samples drawn before beverage consumption and 2 and 6 hours after. There was a clear reduction in epinephrine-stimulated platelet activation in the cocoa group (9.6% before beverage consumption, 6.8% after 2 hours, and 3.3% after 6 hours). No changes were observed in the water-consuming group, but a significant increase was noted in the group consuming the caffeine-containing drink. This would indicate that it is not the caffeine in the cocoa that is responsible for the decrease in epinephrine-stimulated platelet activation. Cocoa consumption also reduced ADP- stimulated platelet activation whereas water and the caffeine-containing drink did not. The formation of platelet microparticles was reduced by about 2 thirds in the cocoa group (after 6 hours), but increased by 85% and 50% respectively in the water and caffeine drink groups. The researchers conclude that the regular intake of cocoa or its active components (epicatechin and procyanidins) may help prevent thrombosis (blood clot formation) and thus reduce the risk of ischemic stroke.
Rein, D, et al. Cocoa inhibits platelet activation and function. American Journal of Clinical Nutrition, Vol. 72, July 2000, pp. 30-35

OXFORD, UNITED KINGDOM. It is estimated that about 15% of ischemic strokes are preceded by a TIA (transient ischemic attack) or a minor stroke. A TIA may produce symptoms similar to that of a stroke, but lasts only a few minutes. It is important that TIAs and minor strokes be diagnosed quickly and preventive treatment initiated as soon as possible after the event. North American guidelines recommend that assessment and investigation be completed within one week of the event while British guidelines allow two weeks for assessment to take place.

Researchers at the Radcliffe Infirmary now report that the risk of another stroke during the first weeks after a TIA is much higher than previously assumed (1-2% at 7 days and 4% at 1 month). Their study included 87 patients who had experienced a TIA and 87 who had suffered a minor stroke. Forty-one per cent of the TIA patients had already experienced a previous TIA or stroke, 55% were being treated for hypertension, and 32% had high cholesterol levels – so these patients were by no means healthy. It is of interest to note that 51% of them had taken aspirin or other antiplatelet agents prior to suffering the TIA indicating that these agents provide limited protection.

The researchers found that 8% of patients suffered a minor or major stroke within 7 days of the first event, 11.5% experienced another stroke within the first month, and 17.3% did so within 3 months. Of the 15 strokes suffered by TIA patients within the 3-month follow-up period 10 were minor strokes and 2 were fatal. Of the 16 strokes suffered by patients with minor stroke as the baseline event 4 were fatal and 2 resulted in increased disability at 3 months. The researchers conclude that the 2-week guideline for assessment after a TIA or minor stroke is unacceptable and that patients need to be examined as soon as possible after the event.
Coull, AJ, et al. Population based study of early risk of stroke after transient ischemic attack or minor stroke: implications for public education and organization of services. British Medical Journal, Vol. 328, January 26, 2004

LEUVEN, BELGIUM. Radiofrequency ablation in atrial fibrillation (AF) has evolved from locating and ablating the specific areas that produce the ectopy (focal points) to routinely isolating the 4 pulmonary veins from which the vast majority of ectopy emanates. The focal point ablation is quicker, carries a reduced risk of stenosis, and involves substantially less radiation exposure (fluoroscopy time) to both patient and physician. However, there are indications that the focal point procedure may be less effective than total pulmonary vein isolation (PVI).

Researchers at the University of Leuven report on a recent study aimed at evaluating the relative merits of the two procedures. The study involved 47 patients (32 men and 15 women with an average age of 47 years) 25% of whom had underlying heart disease or hypertension and 5 (11%) of whom had persistent rather than paroxysmal AF. A subgroup of 19 patients (selective group) was found to have significantly more PACs (premature atrial beats) and runs of atrial tachycardia than did the remaining 28 patients (extensive group). The patients in the selective group were focally ablated; that is, the ablation was directed at isolating the foci for the afib-originating ectopy or just the vein from which the ectopy originated (most often the right superior pulmonary vein). In the extensive group all 4 pulmonary veins were isolated in 57% of cases, 3 veins in 36%, and 2 veins in the remaining 7% of patients. A vein was not targeted if it was too small, inaccessible or showed no sign of ectopic activity.

The acute procedural success was 81% in the selective group and 83% in the extensive group. However, 45% of all patients experienced another afib episode in the 6 months following the ablation while 55% did so within the first year. There was no difference in recurrence rate between the two groups. The average time to first recurrence was 22 days in the selective group and 30 days in the extensive group – a non-significant difference. The risk of recurring AF was higher in patients with underlying heart disease, hypertension, enlarged left atrium, and in those of the extensive group in whom not all 4 pulmonary veins were isolated. The procedure time was 3.4 hours in the selective group versus 4.5 hours in the extensive group and the fluoroscopy time (radiation exposure) was 49 minutes in the selective group versus 85 minutes in the extensive group. Two cases of stenosis (vein narrowing in excess of 50%) were observed in the extensive group versus none in the selective group. Sixty-eight per cent of patients in the selective group and 75% of those in the extensive group reported significant symptomatic improvement.

The researchers conclude that selective ablation may be appropriate in younger patients (especially women) with no structural changes to the left atrium and no persistent AF. Total PVI may be more appropriate in older patients with persistent AF, enlarged atria or underlying heart disease.
Dilling-Boer, D, et al. Ablation of focally induced atrial fibrillation: selective or extensive? Journal of Cardiovascular Electrophysiology, Vol. 15, February 2004, pp. 200-05

SEOUL, KOREA. Hypertension (high blood pressure) is a potent risk factor for stroke. It is, however, not clear whether the risk increases more with rising blood pressure in the case of ischemic stroke (stroke caused by a blood clot) or in the case of hemorrhagic stroke (stroke caused by a burst blood vessel). Researchers at the Seoul National University have just released a report which throws considerable light on this question. Their study involved 955,000 public servants and teachers who were followed through biennial health examinations for 10 years. During the 9.5 million person-years of observation 14,057 strokes occurred. Of these, 10,716 had complete diagnostic information; 2695 strokes were classified as hemorrhagic, 5326 as ischemic, 964 as subarachnoid hemorrhage (bleeding into the space surrounding the brain and spinal cord), and 1731 were of undetermined origin.

The researchers noted that the increase in stroke incidence with increasing blood pressure was much steeper for hemorrhagic stroke than for ischemic stroke. Participants with stage 1 hypertension (140-159/90-99 mm Hg) were 2.76 times more likely to suffer an ischemic stroke than were participants with normal blood pressure (less than 140/90 mm Hg). However, participants with stage 1 hypertension were 4.9 times more likely to suffer a hemorrhagic stroke than were those with normal blood pressure. Participants with stage 3 hypertension (greater than 180/110 mm Hg) were 9.56 times more likely to suffer an ischemic stroke, but 28.83 times more likely to suffer a hemorrhagic stroke than were participants with normal blood pressure.
Song, YM, et al. Blood pressure, hemorrhagic stroke, and ischemic stroke: the Korean national prospective occupational cohort study. British Medical Journal, Vol. 328, February 7, 2004, pp. 324-25

Editor's comment: The finding that the risk of hemorrhagic stroke increases much more sharply with an increase in blood pressure (above normal) than does the risk of ischemic stroke is of considerable interest when considering the use of warfarin in stroke prevention. The use of warfarin in patients with stage 2 (160- 179/100-109 mm Hg) or stage 3 hypertension may be counterproductive because warfarin therapy markedly increases the risk of hemorrhagic stroke, which is already high in this group of patients.

ZURICH, SWITZERLAND. Phytic acid (myo-inositol hexakisphosphate) is found in cereals, legumes, and oil seeds and is the major storage form of phosphorous in these foods. Phytic acid is a powerful antioxidant, but does, unfortunately, also strongly inhibits the absorption of calcium, zinc, and iron. Swiss researchers now report that phytic acid (phytates) also strongly inhibits the absorption of magnesium from the intestines. Their study involved 20 healthy men and women (10 men and 10 women). The participants were fed test meals of phytic acid-free white bread (200 grams/day divided between breakfast and lunch) and the same white bread to which either 1.49 mmol or 0.75 mmol of phytic acid had been added. All meals also contained 3.6 mmol of isotope-labeled magnesium that was added to the bread in the form of magnesium chloride. The 1.49 mmol of phytic acid corresponds to the phytate content of whole-meal bread while the 0.75 mmol corresponds to the content of brown bread. The absorption of magnesium was measured as the difference between intake and amount excreted in the stool.

The researchers found that the absorption of magnesium was reduced from 32.5% in phytic acid-free bread to 13% in bread containing 1.49 mmol of phytic acid, and from 32.2% to 24.0% in the bread containing 0.75 mmol of phytic acid. They conclude that magnesium absorption is significantly inhibited by phytic acid, in a dose- dependent manner, and at amounts similar to those found in bread.
Bohn, T, et al. Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans. American Journal of Clinical Nutrition, Vol. 79, March 2004, pp. 418-23

Editor's comment: The fact that phytic acid inhibits magnesium absorption is highly significant for afibbers. I often have oatmeal porridge for breakfast. Oatmeal is quite high in phytates so certainly my morning magnesium supplement is doing me no good at all. Adhering to a paleo diet (without grains, nuts, and legumes) would clearly improve magnesium absorption considerably and this may well be one of the reasons why many afibbers have found this diet to be beneficial. It is also of interest that phytic acid strongly inhibits the absorption of calcium, zinc and iron. Fruits and tubers are low in phytic acid even though they are good sources of dietary fiber.

SAINT-ETIENNE, FRANCE. Stress can be physical, emotional, chemical or biological. The body's response to any kind of stress is the release of stress hormones. Epinephrine (adrenalin) is released from the medulla of the adrenal glands in response to acute stress while cortisol is released from the cortex of the adrenal glands in response to long-term stress. High cortisol levels are associated with Cushing's syndrome, irritable bowel syndrome (IBS), anorexia, osteoporosis, and depression. Prolonged exposure to stress and elevated cortisol levels can lead to adrenal exhaustion. There is clinical evidence that cortisol levels are abnormally high during an afib episode and I am personally convinced that high cortisol levels also play a significant role in the initiation and maintenance of AF. If this is indeed true, then avoidance of high cortisol levels is clearly important for afibbers, whether adrenergic, vagal or mixed.

Cortisol levels are kept in check by conversion to inactive cortisone through the action of the enzyme 11-beta- hydroysteroid dehydrogenase (11beta-HSD). A good approximation of the activity of this crucial enzyme can be obtained by measuring the ratio of cortisol to cortisone (C/Cn ratio) in a 24-hour urine sample.

French sports medicine researchers have just released a most interesting report that examines the relationship between intensity of training in elite swimmers and free cortisol levels and C/Cn ratio. The study involved 14 elite swimmers (5 female and 9 male) who trained 6 days a week. The swimmers went through 3 periods of training - 4 weeks of intensive training (IT), 3 weeks of reduced training (RT), and 4 weeks of moderate training (MT). Their cortisol and cortisone levels were measured at the end of each training period and at this time they also answered an 8-item questionnaire on fatigue, sleep, infections, irritability, perceived stress level, etc.

The swimmers also participated in an official competition on the final day of the individual training periods and their performance was compared to that achieved in similar competitions over the previous year. The researchers found clear evidence that the C/Cn ratio increased markedly with the intensity of training. The baseline value was 0.65, the value after the IT period was 1.10, after the RT period 0.64, and after the MT period 0.57. The differences were mainly due to an increase in cortisone levels when tapering off the training intensity. The researchers interpret this finding to mean hat high intensity training inhibits the action of 11 beta-HSD. They also found that a decrease in C/Cn ratio was significantly associated with an increase in performance during competition as well as with a decrease in fatigue, sleep difficulties, perceived stress level, etc. They conclude that the C/Cn ratio and cortisone levels in 24-hour urine samples are useful markers of overtraining in elite athletes.
Atlaoui, D, et al. The 24-hour urinary cortisol/cortisone ratio for monitoring training in elite swimmers. Medicine & Science in Sports & Exercise, Vol. 36, February 2004, pp. 218-24

Editor's comment: So what does this all mean for afibbers? If my hypothesis is correct, then excessive exercise would be detrimental to all afibbers as it would inhibit the action of 11 beta-HSD and thereby increase the level of free circulating cortisol. The excessive training effect would be particularly bad for vagal afibbers as intensive exercise also increases the vagal component of the autonomic nervous system.

PITTSBURG, PENNSYLVANIA. Hyponatremia is defined as an inappropriately low blood concentration of sodium. It is associated with nausea, fatigue, lethargy and confusion as well as with the development of bradycardia (excessively slow heart beat). The normal plasma sodium level is between 135 and 145 mmol/L and a level below 135 mmol/L indicates hyponatremia. There is some evidence that certain selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) and venlafaxine (Effexor) can cause hyponatremia in elderly depressed patients. A group of American researchers now report that paroxetine (Paxil) can have a similar effect. Their study involved 75 clinically depressed men and women between the ages of 63 and 90 years. The participants had their plasma sodium level measured before commencing paroxetine therapy and after 1, 2, 4, 6 and 12 weeks of treatment. The researchers found that 9 (12%) of the 75 participants developed hyponatremia within an average of 9 days of starting therapy. Lower body mass index (BMI) and a plasma sodium level below 138 mmol/L at baseline were clearly associated with an elevated risk of hyponatremia and there was also a trend for women to be more at risk. The dosage of paroxetine was not related to risk of hyponatremia; 8 out of the 9 hyponatremic patients were on a dose of 10 mg/day.

The researchers speculate that inappropriate secretion or enhanced action of antidiuretic hormone (ADH) as a result of paroxetine-induced enhanced serotonin levels may contribute to SSRI-induced hyponatremia in older patients having an excess fluid intake. They suggest that limiting daily fluid intake to 800-1000 mL may help prevent hyponatremia in cases where continued SSRI therapy is deemed essential. They also recommend that sodium levels be checked before SSRI therapy is commenced and that caution be exercised if the initial level is below 138 mmol/L.
Fabian, TJ, et al. Paroxetine-induced hyponatremia in older adults. Archives of Internal Medicine, Vol. 164, February 9, 2004, pp. 327-32

Editor's comment: So how is this related to afib? Some afibbers, myself included, have found paroxetine or other SSRIs useful in lengthening the period between episodes. I now believe that the underlying reason for this is that paroxetine helps reduce sodium levels and in doing so creates a sodium/potassium ratio that is less prone to initiate an afib episode. My own plasma levels of sodium and potassium are highly unfavourable with sodium being at the high end of normal (144 mmol/L) and potassium at the low end (3.6 mmol/L). Thus the 2-month respite in episodes produced by my paroxetine therapy may well have been caused by a temporary normalization of my Na/K ratio. Unfortunately, my experiment terminated abruptly when I experienced a very frightening 58-hour bradycardia episode.

American College of Cardiology Conference

Younger afibbers may require different ablation technique
Pulmonary vein isolation (PVI) is effective in preventing future episodes in most afibbers. However, for some, it is not curative. Researchers at the University of Pennsylvania report that trigger points outside the pulmonary vein area may be more common among younger afibbers and that additional focal point ablation may be required in afibbers who developed AF before the age of 35 years. They found that atrial tachycardia and atrioventricular reentrant tachycardia are important triggers in this group.
Abstract #1014-207, p. 105A

Sleep apnea associated with AF
Studies have shown that the presence of obstructive sleep apnea is associated with an increased risk of afib recurrence after electrical cardioversion. Now Mayo Clinic cardiologists report that sleep apnea is as much as two times more prevalent among older afibbers than among patients with hypertension. They suggest that treating sleep apnea may reduce the risk of afib recurrence.
Abstract #1014-209, p. 105A

Fibrosis not necessary for AF
Atrial fibrosis (thickening and scarring of atrial tissue) is widely believed to be an important contributor to atrial fibrillation. This belief has been challenged by Cleveland Clinic researchers. They compared the extent of pulmonary vein and atrial fibrosis in 9 afibbers and 21 afib-free controls. They found no difference in the extent of fibrosis and conclude that fibrosis in the atrial chambers and pulmonary veins do not seem to be required for the development and maintenance of AF.
Abstract #1014-212, p. 106A

Asymptomatic recurrence of afib after ablation
Researchers at the University of Michigan have completed a study to determine the incidence of asymptomatic AF episodes in afibbers who have undergone a successful catheter ablation. Forty-seven patients were randomly selected to wear an event recorder for 30 days at least 6 months after a successful ablation. Nine patients (20%) experienced an average of 2 very short episodes (1-10 minutes in duration) during the monitoring period. Prior to the ablation they had experienced an average of 17 significantly longer episodes per month.
Abstract #1071-221, p. 118A

Inflammation and atrial fibrillation
Researchers at the Cleveland Clinic have postulated that inflammation contributes to structural remodelling of the atria which, in turn, increases the persistence of AF. They recently tested their hypothesis by comparing left atrial appendage (LAA) tissue from 11 patients with persistent AF with tissue from 4 patients in normal sinus rhythm undergoing mitral valve repair. They found a significantly higher extent of interstitial fibrosis (a result of inflammation) in the tissue from AF patients (47%) than in controls (29%). They conclude that low level inflammation and the resulting fibrosis have a prominent role in the structural remodelling that promotes AF persistence.
Abstract #1034-211, p. 110A
Editor's comment: The researchers' conclusion can also be interpreted to mean that an abnormal extent of fibrosis was NOT observed in 53% of the afib patients involved. This conclusion supports that reached by other Cleveland Clinic researchers who found that fibrosis in the atrial chambers and pulmonary veins is not required for the development and maintenance of afib. This could well mean that inflammation is not an underlying cause of AF in the majority of afibbers and probably even less so in the case of lone afibbers.

I am a 54-year-old dental surgeon, partially retired because of a chronic back condition, living in a rural area on the beautiful island of Tasmania, Australia. I was born and grew up in southern England, moving here in 1991.

Fifteen months ago I was suffering badly from LAF – experiencing 15/18-hour sessions every other day. I could not drink red wine, coffee or cold fizzy drinks. My diet was free of gluten, dairy products and artificial ingredients (as far as possible). I was reluctant to go out at all as I inevitably got an attack. I did not take any medication apart from aspirin - it either made the AF worse or made me feel ill. I had tried supplements of all types - some improved it for a while, but the effect always wore off. The AF had started when I was 48 years old and gradually got worse - several other members of my family, all male, have it. Tests had shown there was nothing wrong with my heart and there was no angina. I had a fairly slow HR, around 50 bpm, but this would very often sink to 40 at night. In bed I would be very aware of the heart thumping away slowly. I've always had postural hypotension, but that had got very much worse (it would take several minutes to clear after an afternoon rest). My BP was normal - 120/80. When in AF, my HR was 80/90 bpm, and felt like a washing machine in my chest. I could carry on with whatever I was doing, but I felt awful and just wanted to lie down.

Now, I'm a different person. I can eat and drink what I like. The postural hypotension has disappeared. I can no longer hear my heart thumping away at night. And, most important of all, I am no longer bothered by AF and I no longer take aspirin.

In October 2002, things had got so bad that I went to the cardiologist and asked about a pacemaker. In Australia, we do not have anyone doing pulmonary vein ablations with any success and my health insurance only covers treatment in Australia. The cardio thought that because my HR was slow and the rate in AF was also fairly slow, it would be worth trying a pacemaker. My first visit to the hospital was a disaster. First of all, I got gastroenteritis. Then a blood test revealed a high INR - had I been taking warfarin? No - I refused to touch the stuff after reading about it on this Bulletin Board! Aspirin does not affect the INR. More blood tests - my fibrinogen level was 25% of normal and I had bilirubin in the blood! "You should be bleeding like a pig", said my surgeon encouragingly! Had I had any bleeding problems? No - and I had a hernia repaired in '97 without any ill- effects. Off to a haematologist (by now I was convinced I had only months to live!). A liver CT scan and further extensive blood tests followed. The verdict - I had hypofibrinogenaemia and Gilbert's disease. Both genetic and neither serious. My bleeding time was raised, but it still clotted. Aspirin was no longer necessary and warfarin definitely contra-indicated. I was re-booked a week later.

On December 17th 2002 I was re-admitted and my pacemaker fitted under a local anaesthetic. I was aware of the whole procedure, which took about 90 minutes, but there was no pain. There was no abnormal bleeding. The pacemaker was set to 5 volts at 60 bpm. I was kept under observation overnight in an ICU. I slept well. Next morning the technician checked that the pacemaker was working properly and I was discharged. Apart from pain for a week when lifting my arm I had no problems. Unfortunately, the AF continued as before which was disappointing, but I wasn't too upset as I knew that the pacemaker had capabilities that had not been enabled yet. It is a Medtronic AT501 DDDRP with two leads, one to the atria and the other to the ventricles. It has dual pacing, a monitor function which can be downloaded onto a computer for analysis, and an ability to detect fibrillation starting and to take counter measures.

After a week I saw the cardio. He looked very disappointed that there hadn't been an improvement and muttered that it hadn't worked and that we would have to try something else. I said that there was some fine-tuning to be done with the pacemaker settings and that might produce an improvement. He did not look optimistic. I saw the technician a few minutes later and he downloaded the weeks AF sessions and printed them out. He said that he'd had some success out-pacing AF, so he turned up the pacemaker to 80 bpm. I had no AF for the next couple of days, but the combination of 5 volts and 80 bpm caused my diaphragm to spasm at night and it was very painful. It was the same pain that I got with long sessions of AF - a nasty ache under the breastbone - only worse. It was the technician who told me this was caused by spasm of the diaphragm. I went in to see the technician again.

I had not been aware of any AF during this time, but when the technician looked at my printout, he took it straight into the cardio. The cardio came straight back in and gave me the once over. He said that I may have had a couple of sessions of ventricular tachycardia - he wasn't certain, as the pacemaker monitor isn't as detailed as a Holter monitor. He arranged for me to have a Holter Monitor to check this out. Meanwhile he prescribed verapamil, a calcium channel blocker, slow-release once a day, to reduce the likelihood of VT. The technician reduced the rate to 70 bpm, atrial pacing only, and the voltage to 3 volts. It takes about 3 months for the pacing leads to become embedded so a relatively high voltage is needed at first. After this visit the AF stopped. I had the Holter two weeks later and there was no AF, no VT. Having hit upon a solution more by accident than design, things were kept as they were. At the 3-month visit the voltage was dropped from 3 to 1 volt - the usual is 2, but I felt I was still getting some irritation of the diaphragm and 1 volt worked. For several months I noticed my BP had gone up to 140/100, but it is now back to 120/80.

Since that time I've had a few attacks of AF, but it is all very different. The AF never happens during the day, always sitting down in the evening or in bed. It doesn't last. Usually I can stop it by just changing position. Although I'm aware that I have AF the ventricular beat remains steady. As time goes by I am getting less and less. I have re-introduced into my diet all the items I cut out with no ill effect. It doesn't affect my life anymore in any way.

So what is happening? In my humble opinion, I feel the Veramil has reduced the electrical activity in the heart and the pacemaker is pacing the atria at 70 bpm - much faster and with a far greater signal than my natural system, even without the verapamil. Perhaps new electrical pathways have been formed? The atria probably ignore any errant signals unless they get very strong. When the AF does start the atrial pacemaker will cut out as the rate goes above 70. But the pacemaker is programmed to pace the ventricles if the ventricular pace goes below 70, so it switches from atrial to ventricular pacing. The verapamil must stop the chaotic signals passing through the AV node at more than 70 bpm so the ventricles stay regular. It is interesting to note that just stopping my HR dropping too low did not work at all.