Fish oil prevents atrial fibrillation
KUOPIO, FINLAND. The three most important components of fish oil are eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA). Extensive research has established that EPA and DHA play a vital role in the prevention of Alzheimer�s disease, atherosclerosis, heart attack, angina, stroke, congestive heart failure, depression and cancer. Clinical trials have also shown that fish oil supplementation is effective in the treatment of many disorders including high blood pressure, rheumatoid arthritis, diabetes, ulcerative colitis and Raynaud�s disease.

Now Finnish researchers report that high serum levels of EPA, DHA and DPA are associated with a significantly reduced risk of developing atrial fibrillation (AF). Their study included 2174 men enrolled in the Kuopio Ischemic Heart Disease Risk Factor Study begun in 1984-1989. The men were 42, 48, 54 or 60 years of age at the baseline examination. During 17.7 years of follow-up, 11% of the participants were found to have AF upon admission to hospital (for arrhythmia or other reasons). This corresponds to an incidence rate of 0.6% a year. NOTE: Considering that the study only included men admitted to hospital, it is clear that the population-wide incidence would be significantly higher than 0.6% a year.

At baseline, the mean percentages of EPA, DPA and DHA in serum fatty acids were 1.67%, 0.55% and 2.46% respectively. After adjustment for age and other possible confounders the researchers observed that men in the highest quartile of EPA+DPA+DHA concentration (5.3 � 15.6%) had a 35% reduced risk of developing AF when compared to men in the lowest quartile (1.7 � 3.6%). The absolute risk in the lowest quartile group was 13.4% vs 8.7% in the highest quartile group. Further analysis revealed that DHA accounted for the entire risk reduction and that EPA and DPA levels were not associated with risk of developing AF.

Considering only lone afibbers (no heart disease prior to diagnosis of AF) strengthened the association between serum fatty acid concentration of DHA and AF risk. Men in the lowest quartile had a risk of 10.9%, while those in the highest quartile had a risk of only 5.6% � a relative risk reduction of 49%.

The mean serum fatty acid concentration of alpha-linolenic acid (found in flaxseed and other vegetable oils) was 0.74% and was not related to the risk of developing AF. A hair analysis revealed no correlation between methylmercury level (methylmercury is an increasingly common contaminant of fish) and risk of AF, nor did a high methylmercury level attenuate the beneficial effects of DHA. There was also no evidence that age, hypertension, systolic blood pressure or a history of ischemic heart disease modified the association between DHA level and AF risk.
Virtanen, JK, et al. Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men. Circulation, Vol. 120, December 8, 2009, pp. 2315-21

Fish oils prevent AF recurrence following PVI
AUSTIN, TEXAS. Atrial fibrillation is a common sequel to coronary artery bypass grafting (CABG). In 2005 a team of Italian researchers reported that supplementation with 2 grams/day of fish oil (EPA + DHA) for 5 days prior to CABG reduced the incidence of postoperative AF from 33.3% (control group) to 15.2% (fish oil group). Now a team of researchers from St. David�s Medical Center in Austin, TX, Northeastern College of Medicine in Canton, OH, IKEM in the Czech Republic, and McMaster University in Hamilton, Canada reports that fish oil supplementation before and after a pulmonary vein isolation (PVI) procedure reduces the risk of AF recurrence.

Their retrospective study included 1500 afibbers who underwent a pulmonary vein antrum isolation (PVAI) procedure at St. David�s between 2004 and 2007. Two hundred and eighty-five patients (19%) had supplemented with a minimum of 655 mg of fish oil (in capsules) for at least a month prior to their PVAI and continued to do so during the entire follow-up period. It was possible to closely match 129 of these patients (70% paroxysmal and 30% persistent or permanent) with 129 patients (control group) from the remaining 1215 patients who had not taken fish oil. The two groups were matched for type of afib, age, gender, left atrial size, ejection fraction and the presence of type 2 diabetes, hypertension, coronary artery disease and stroke. The two groups, fish oil group and control group, were scheduled for follow-up (including 48-hr Holter monitoring) 3, 6, 9 and 12 months after the procedure and were equipped with a cardiac event monitor during the first 5 months following their PVAI.

During the blanking period (8 weeks following the procedure) 27% of patients in the fish oil group and 44% in the control group experienced afib recurrence; in other words, fish oil supplementation reduced the risk of early recurrence by 39%. Procedural failure (afib recurring more than 8 weeks from the PVAI) was 23% in the fish oil group and 32% in the control group, or a risk reduction of 28%. The research team also noted that the fish oil group had a significantly lower pre-procedure level of C-reactive protein (CRP) than did the control group (2.1 mg/L vs. 3.0 mg/L). CRP, an important marker of inflammation, measured 48 hours after the procedure was also lower in the fish oil group (14.3 mg/L vs. 18.0 mg/L). Complication rates were similar in the two study groups.

The research team concludes that patients treated with long-chain omega-3 polyunsaturated fatty acids (fish oils) prior to and following a PVAI experienced a lower incidence of early recurrence and procedural failure compared to untreated patients.
Shaheen, PD, et al. Omega-3 polyunsaturated fatty acid supplementation reduced atrial fibrillation recurrence after pulmonary vein antrum isolation. Indian Pacing and Electrophysiology Journal, Vol. 9, No. 6, November 1, 2009, pp. 292-98

Progression of paroxysmal AF
FLORENCE, ITALY. Paroxysmal (intermittent, self-terminating) atrial fibrillation may over time progress to persistent or permanent afib (episodes lasting 7 days or longer). It is not clear why some paroxysmal afibbers progress to the persistent variety, while other remain paroxysmal for decades. A group of American and Italian researchers now provide at least a partial answer to this question.

Their study involved 330 patients with a history of paroxysmal AF (mean age of 70 years, 61% male) who had had a pacemaker implanted to deal with bradycardia (slow heart beat). Most study participants had underlying heart disease, but 21% were lone afibbers. The pacemaker (Medtronic AT501) automatically recorded the daily burden (duration) of afib and tachycardia for an average of 400 days. After a mean interval of 147 days, 24% of the patients progressed to persistent afib. The researchers made the following interesting observations.

• The prevalence of lone atrial fibrillation (LAF) did not differ between the group that remained in paroxysmal afib and the one that progressed to persistent afib.
• Patients with congestive heart failure were significantly more likely to progress to persistent AF.
• Patients destined to progress to persistent AF experienced a higher daily afib burden and a higher probability of experiencing afib on any given day than those in the paroxysmal group.
• The mean daily afib burden in the group destined for progression to persistent AF increased by about 14 seconds/day, while it stayed relatively constant in the group that remained paroxysmal.
• Lone afibbers experienced significantly more PACs (premature atrial beats, ectopics) than did patients with CVD. However, the incidence of these ectopics decreased over time.
• The conversion to persistent afib occurred suddenly and was often preceded by a period of normal sinus rhythm.
• It is possible that treatment with ACE inhibitors or angiotensin receptor blockers (ARBs) may slow down the remodeling that underlies progression to persistent AF.

The researchers conclude that, �Our results suggest that functional electrical remodeling may not impact all patients or inevitably lead to increasing AT/AF burden and persistent AF. In fact, a large proportion of patients may not increase their AT/AF burden, particularly in the absence of CVD.�
Saksena, S, et al. Progression of paroxysmal atrial fibrillation to persistent atrial fibrillation in patients with bradyarrhythmias. American Heart Journal, Vol. 154, November 2007, pp. 884-92

Is lone AF recurrence inevitable?
BARCELONA, SPAIN. Lone atrial fibrillation (LAF) is defined as AF occurring in the absence of structural heart disease. Idiopathic AF is defined as lone AF of no known cause; ie. thyroid disorders, hemochromatosis, alcoholism, and electrolyte disturbances have been ruled out. Although LAF patients, in most cases idiopathic, constitute between 10 and 30% of all afib patients, comparatively few studies have been done dealing specifically with this condition. A recently released study by researchers at the University of Barcelona is, hopefully, a harbinger of a trend to focus greater efforts on determining the causes and likely progression of LAF.

The study involved 98 patients (71% men with an average age of 48 years) who were admitted to the University hospital�s emergency room with AF of no known cause (idiopathic). Most (64.3%) had experienced previous episodes, while the remaining 35.7% showed up with their first episode. Half the patients reverted spontaneously to normal sinus rhythm (NSR) or did so after oral flecainide administration (classified as paroxysmal afibbers), while the other half required electrical cardioversion to convert (classified as persistent afibbers). First-occurrence patients were discharged with no medication, while recurrent patients were discharged on whatever medications they had used prior to the index episode (the episode at which they first were admitted to the ER), or on a class 1C antiarrhythmic (mostly flecainide). Patients for whom class 1C drugs had clearly not worked were recommended to try amiodarone. None of the patients were discharged with a prescription for anticoagulants (warfarin).

During the following 6 months, 57% of the entire patient group experienced at least one subsequent afib episode. Recurrent afib was more common among those with prior episodes before the index episode (65.1%) than among �first-onset� patients (34.9%); this despite the fact that 70% of the �veteran� afibbers were taking antiarrhythmics. As a matter of fact, taking amiodarone or a class 1C antiarrhythmic did not significantly influence the risk of recurrence in this group. The researchers also observed that an enlarged left atrium (dilated anteroposterior LA diameter) was associated with a 30% increased risk of AF recurrence. However, they found no association between recurrence risk and afib type (paroxysmal or persistent).

They conclude that for lone (idiopathic) afibbers who have a recurrent episode and an enlarged left atrium (indexed for body surface area), the probability of another episode is about 90% despite the use of antiarrhythmics. On the other hand, the probability of another episode is only 30% in a patient with normal LA diameter who has just experienced one episode.
Arriagada, G, et al. Predictors of arrhythmia recurrence in patients with lone atrial fibrillation. Europace, Vol. 10, 2008, pp. 9-14

Role of fibrosis in atrial fibrillation
MONTREAL, CANADA. According to the late Professor Philippe Coumel, three conditions must be met in order for atrial fibrillation to occur:

1. The myocardium (heart tissue) must be capable of being triggered into and sustaining an episode. In other words, it must provide an electrophysiological substrate that is suitable for AF initiation and maintenance.
2. The autonomic nervous system must be out of balance.
3. A trigger or precipitating event capable of initiating an episode must be present.

Researchers at the Montreal Heart Institute believe that cardiac fibrosis (formation of scar tissue in response to injury) is an important feature in the development of an �afib friendly� substrate. Tissue fibrosis results from an accumulation of fibrillar collagen deposits which themselves are formed in a repair process aimed at replacing degenerating myocardial tissue. Fibrosis is associated with aging, dilated cardiomyopathy, mitral valve disease, and possibly myocardial ischemia (angina).

However, fibrosis and increased collagen deposition have also been observed in lone afibbers. Fibrosis interferes with the normal progression of the sine wave from the sinoatrial node to the atrioventricular node by impairing the transfer of the impulse from myocyte (heart muscle cell) to myocyte. The researchers point out that the renin-angiotensin-aldosterone system (RAAS) is involved in the formation of myocardial fibrosis and that patients with primary hyperaldosteronism (Conn�s syndrome) have a significantly increased incidence of atrial fibrillation. They also point out that locally produced angiotensin II is associated with the formation of collagen deposits and fibrosis.

Mechanical stretch of cardiac muscle fibers induces collagen synthesis and increased angiotensin II production, thus creating structural remodeling that further promotes afib (AF begets AF). The researchers reason that, if the production of collagen deposits and fibrosis could be slowed or even reversed, then it may be possible to eliminate or at least control AF. They suggest that ACE inhibitors (lisinopril, enalapril, ramipril), angiotensin II type 1 receptor blockers (valsartan, irbesartan, losartan), and aldosterone antagonists (spironolactone, eplerenone, canrenone) may be useful in preventing fibrosis and thus denying the atria the electrophysiological substrate necessary for initiating and sustaining an AF episode.
Burstein, B and Nattel, S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. Journal of the American College of Cardiology, Vol. 51, No. 8, February 26, 2008, pp. 802-09

Afib begets afib � Or does it?
WARREN, NEW JERSEY. Animal experiments have shown that continued pacing of the heart makes paroxysmal (intermittent, self-converting) atrial fibrillation (AF) progress to persistent (episodes lasting longer than 7 days needing cardioversion) and permanent AF. Hence the expression �afib begets afib�. The question is, �Do these findings apply to humans�? After all, patients with paroxysmal AF do not have their heart constantly paced and do spend often long periods in normal sinus rhythm. A group of electrophysiologists at the University of Florence, Italy, the Robert Wood Johnson School of Medicine, and Medtronic Inc. (a major manufacturer of pacemakers and implantable cardioverter/defibrillators) now provides at least a partial answer to this question.

Their study involved 330 patients with a history of paroxysmal AF and bradycardia (mean age of 70 years, 61% male). All suffered from heart failure to varying degrees and had had a pacemaker (Medtronic Model AT501) installed prior to the study. Most patients (79%) experienced some form of cardiovascular disease with 61% having hypertension; thus, the proportion of lone afibbers was insignificant and the results of the study may not apply to lone afibbers. After an average follow-up of one year and 3 months, 24% of the study participants had converted to persistent afib with the median time to conversion being 9 months (103 days). The researchers noted the following important differences between the patients who remained in paroxysmal AF (Group 1) and those who progressed to persistent AF (Group 2).

• Prior to conversion to persistent afib, patients in Group 2 were more likely to experience afib on any given day and had a higher average afib burden (no. of episodes x duration) than did those in Group 1.
• Prior to conversion to persistent afib, there was a significant linear increase in daily afib burden (mean increase of 14 sec/day) in Group 2, but no increase (on average) in Group 1.
• The transition from paroxysmal to persistent afib in Group 2 was quite abrupt and was preceded by a few days of normal sinus rhythm.
• The increase in afib burden over time was substantially higher among patients with cardiovascular disease (average 0.18 min/day) than among those with no cardiovascular disease (CVD) where the burden actually declined slightly over time (average �0.06 min/day). Patients with CVD were also more likely to progress to persistent AF.
• Atrial premature beats (PACs) were more frequent in patients without CVD, but decreased with time in all patients.

The researchers conclude that structural remodeling (substrate modification) is critical to the transition to persistent afib. The changes to the substrate may involve fibrosis, apoptosis (cell death), and altered cellular junction proteins. In an accompanying editorial, electrophysiologists at the Tufts-New England Medical Center suggest that the renin angiotensin aldosterone system (RAAS) may play a significant role in the substrate modification and that ACE inhibitors and/or angiotensin receptor blockers may help slow down the structural remodeling. They also suggest that targeting just the pulmonary veins during an ablation (pulmonary vein isolation) is unlikely to suffice in the case of persistent or permanent AF.
Saksena, S, et al. Progression of paroxysmal atrial fibrillation to persistent atrial fibrillation in patients with bradyarrhythmias. American Heart Journal, Vol. 154, No. 5, November 2007, pp.884-92
Homoud, MK and Estes, M. Shedding new light on the pathophysiology of conversion of paroxysmal atrial fibrillation into persistent atrial fibrillation. American Heart Journal, Vol. 154, No. 5, November 2007, pp.801-04

Gender differences in arrhythmia
TAMPA, FLORIDA. Surveys of lone afibbers generally find that the ratio of men to women is about 80:20. It is by no means clear why this is indeed the case, but the proportion of afib induced by sustained, vigorous endurance exercise would likely be higher among men. If all cases of atrial fibrillation (AF) are considered, including those involving heart disease, men have a 50% higher risk of developing AF than do women. The overall prevalence of AF is, however, higher among women because they tend to outlive men.

Other significant differences between men and women when it comes to arrhythmias and the heart in general were summarized in a recent study carried out by cardiologists at the University of South Florida. Among the highlights are:

• The average resting heart rate in women is about 3-5 bpm faster than in men. This may be due to an intrinsic difference in the sinus node.
• Women have longer QT (corrected) intervals than men. NOTE: The QT interval is the duration of the activation (contraction) and recovery of the ventricular myocardium. A prolonged QT interval is associated with ventricular arrhythmias.
• Women are more likely to suffer from supraventricular tachycardia (SVT). Research has shown that SVT episodes are more common during the luteal phase of the menstrual cycle when progesterone levels are elevated.
• Inappropriate sinus tachycardia (inappropriately high heart rate at rest [over 100 bpm] and during stress) is also more common among women and is thought to involve abnormal autonomic regulation of the sinus node. Editor�s comment: Inappropriate sinus tachycardia is also fairly common after an ablation, perhaps indicating that an ablation can result in a temporary, abnormal regulation of the sinus node.
• Women with AF are more likely than men to suffer an embolic stroke; however, they are also more likely to experience a major bleeding event if taking warfarin, so stroke prevention in women is particularly challenging. Women with paroxysmal AF tend to have longer episodes and a higher average heart rate during an episode.
• Pulmonary vein isolation (ablation) procedures are equally effective in men and women.
• Women are more likely to experience Torsades de Pointes (a distinctive form of ventricular tachycardia associated with a prolonged QT interval). This means that class 1C antiarrhythmics (flecainide and propafenone) are the preferred antiarrhythmics for women since they do not increase the QT interval. Amiodarone, sotalol, dofetilide and disopyramide may, on the other hand, increase the QT interval and should be used with caution in women.
• In the United States sudden cardiac death (SCD) claims between 300,000 and 400,000 victims every year. The incidence among women is only half of that among men and occurs 10-20 years later in life.
• The risk of SVT increases during pregnancy and during the post-partum period.

The Florida researchers conclude that there are important differences in the presentation and clinical course �of many cardiovascular disorders in men and women. It is important for health care providers to be aware of these differences to provide optimal care for their patients�.
Yarnoz, MJ and Curtis, AB. More reasons why men and women are not the same (gender differences in electrophysiology and arrhythmias). American Journal of Cardiology, Vol. 101, 2008, pp. 1291-96

Seasonal variation in AF episodes
LUBLIN, POLAND. It has been known since the time of Hippocrates that the weather (atmospheric conditions) influences people�s mood and health. As far back as the first half of the 19th century, Polish researchers reported an association between short-term weather changes and a worsening of angina, increased incidence of heart attacks, and more pronounced fluctuations in blood pressure. More recent research has shown that levels of the stress hormone cortisol are lower at high barometric pressures and that lower levels are associated with a lessening of depression. So, conceivably, a person with elevated cortisol levels would feel better on a sunny day.

Now Polish researchers report that weather conditions also affect the incidence of paroxysmal afib episodes. Their study involved 739 patients (52% females, average age of 65 years, range of 18-91 years) who were admitted to hospital because of an AF episode during the period 2005-2006. Patients with acute coronary syndrome, myocarditis, pericarditis, thyrotoxicosis, and respiratory problems were excluded from the study, as were those who had recently suffered a heart attack.

The researchers correlated the number of patients admitted each day with air temperature, atmospheric pressure, wind speed and cloudiness, and also investigated the effect of approaching cold fronts and warm fronts. On average, there was one admission per day related to afib episodes. However, there were 9 days on which 4 patients were admitted and 4 days on which 5 patients were admitted. There was a seasonal effect with more cases (2.4/day) reported in the winter (December to February) than in the spring and summer (1.7 cases/day during the period May to August).

The most interesting correlation though was between the approach of a cold front and the number of afib-related hospital admissions. All the high admission days (4-5 cases/day) occurred 24-36 hours prior to the arrival of a cold front. The researchers speculate that the effect may be due to the electromagnetic waves created in deep low-pressure systems and storm centers. These waves travel at the speed of light, whereas the front itself moves at 10-50 km/hr, thus explaining why the effect of an approaching cold front would be felt 24-36 hours in advance. The researchers found no relationship between afib incidence and the approach of a warm front. However, they did notice that periods of constant high atmospheric pressure were associated with a significant decline in hospital admissions for AF.
Gluszak, A, et al. Episodes of atrial fibrillation and meteorological conditions. Kardiologia Polska, Vol. 66, September 2008, pp. 958-63

Long-term progression of lone AF
ROCHESTER, MINNESOTA. More than 50 years ago cardiologists at the Mayo Clinic began following a group of lone afibbers in order to determine their long-term prognosis and survival. The group consisted of 34 participants with the paroxysmal variety, 37 with persistent afib, and 5 with permanent afib at entry to the study. Lone AF was defined as atrial fibrillation without underlying structural heart disease or hypertension (no age limitation). Atrial fibrillation was defined as paroxysmal if it terminated on its own, as persistent if cardioversion (electrical or drug-assisted) was required to terminate episodes, and as permanent if sinus rhythm could not be restored or maintained despite intervention. The average age at diagnosis was 44 years and 78% of the group was male. Thirty-four percent of study participants were prescribed digoxin within 30 days of their first episode. The number of �digoxin users� had increased to 75% at the latest follow-up.

After an average follow-up of 30 years, 29% of paroxysmal and persistent afibbers had progressed to permanent AF. It is interesting to note that 68% of persistent afibbers became paroxysmal and 22% became permanent during follow-up. Only 6% of paroxysmal afibbers became persistent, while 41% became permanent. In most cases the progression to permanent AF occurred within the first 15 years after diagnosis. Survival in the study group at 92% at 15 years and 68% at 30 years was similar to or even slightly better than expected for an age- and sex-matched group of Minnesotans (86% and 57% at 15 and 30 years respectively). Twelve of the reported deaths were due to cardiovascular causes, while the remaining 15 deaths were due to other causes. The development of congestive heart failure (19% of group at 30 years follow-up) was not significantly higher than expected (15%). During the follow-up, 5 strokes (0.2%/person-year) and 12 transient ischemic attacks (0.5%/person-year) occurred in the group � mostly among permanent afibbers. All strokes and TIAs occurred in participants who had developed one or more risk factors for stroke during follow-up (hypertension in 12 patients, heart failure in 4, and diabetes in 3). Not a single stroke or TIA occurred among lone afibbers with no risk factors for stroke. This prompted the following remark from the researchers:

Our long-term data suggest that the increased risk of stroke in atrial fibrillation is due to �the company it keeps�.

In other words, lone atrial fibrillation as such is not a risk factor for ischemic stroke. The overall conclusion of the study is highly reassuring to lone afibbers,

After >30 years of follow-up of our rigorously defined cohort, findings confirm that overall survival is not affected adversely by lone atrial fibrillation.

In an accompanying editorial, Dr. Lars Frost of the Aarhus University Hospital in Denmark makes the following interesting comment, Cardiologists with strong political influence have suggested that a diagnosis of lone atrial fibrillation should be restricted to patients <60 years of age, although there is not evidence of any threshold values by age regarding the risk of stroke in patients with atrial fibrillation � or in any other medical condition for that matter.
Jahangir, A, et al. Long-term progression and outcomes with aging in patients with lone atrial fibrillation. Circulation, Vol. 115, June 19, 2007, pp. 3050-56
Frost, L. Lone atrial fibrillation: Good, bad, or ugly? Circulation, Vol. 115, June 19, 2007, pp. 3040-41

Magnesium infusions in AF control
TORONTO, CANADA. Magnesium is effective in prolonging the atrial and atrioventricular nodal refractory periods. As afib cannot be initiated during refractory periods, this is clearly a good thing and may explain why many afibbers have experienced substantial benefit from magnesium supplementation. Unfortunately, several studies have shown that 50% or more of patients with atrial fibrillation suffer from hypomagnesemia � that is, a lower than normal blood serum magnesium concentration (less than about 0.8 mmol/L). Serum magnesium concentration is a fairly poor indicator of magnesium status since only about 2% of the body�s total magnesium stores are found in the blood. It is thus likely that substantially more than 50% of afibbers are magnesium deficient if intracellular levels are measured.

Researchers at the University of Toronto have just released the results of a meta-analysis of 8 clinical trials involving patients presenting with rapid atrial fibrillation. The trials compared the effect of magnesium infusions with placebo controls and patients given intravenous diltiazem or amiodarone. In the trials 1,200 to 10,000 mg of magnesium (as magnesium sulfate) was infused over a period of 1 to 30 minutes. In four of the studies magnesium infusion was continued for an additional 2 to 6 hours. Adequate rate control (ventricular rate below 100 bpm) was achieved in 61% of patients with magnesium as compared to 35% among controls. Magnesium was found to be as effective as diltiazem and amiodarone in achieving adequate rate control during the first hour. Magnesium was also found to be twice as effective as diltiazem or placebo in restoring sinus rhythm. Overall, the average time to conversion to sinus rhythm was 4 hours for magnesium as compared to 15 hours for placebo. The researchers conclude that magnesium infusions are safe and effective in achieving both rate and rhythm control in patients presenting with rapid atrial fibrillation.
Onalan, O, et al. Meta-analysis of magnesium therapy for the acute management of rapid atrial fibrillation. American Journal of Cardiology, Vol. 99, June 15, 2007, pp. 1726-32

New scale for measuring AF severity
TORONTO, CANADA. �Because of its high incidence and the considerable disability that it may generate, atrial fibrillation (AF) is increasingly recognized as an important clinical problem in medical practice� and �the primary purpose of any therapy in AF is to improve patient well-being�. These two statements do, in my opinion, signal a quantum shift in medical thinking about afib. Not only do they recognize that afib can generate considerable disability � ie. cannot be dismissed as a mere �nuisance�, but also that patient well-being, not stroke prevention, should be the attending physician�s primary concern, especially in regard to lone afibbers. The above statements are contained in a report prepared by a group of Canadian EPs and cardiologists describing the development of a new scale for gauging the severity of afib. The scale is called the �Canadian Cardiovascular Society Severity of Atrial Fibrillation Scale� or CCS-SAF Scale for short.

Afib is classified as first documented episode, recurrent paroxysmal, recurrent persistent, or permanent where paroxysmal episodes are defined as being self-terminating, persistent episodes as requiring medical intervention for termination, and permanent afib as not being convertible to normal sinus rhythm. Rating an afibber on the Scale begins by determining the symptoms � palpitations, dyspnea (shortness of breath), dizziness, syncope (light-headedness or fainting), chest pain, weakness, or fatigue, accompanying documented AF. The severity of these symptoms is then assigned to one of five classes. Class 0 indicates that the afib is asymptomatic. Class 3 indicates a moderate effect on the patient�s quality-of-life such as moderate awareness of symptoms on most days in patients with persistent/permanent AF, or more common episodes (eg. more than every few months), or more severe symptoms, or both, in patients with paroxysmal afib. Class 5 indicates a severe effect on quality-of-life and would include frequent and highly symptomatic episodes in patients with paroxysmal afib or episodes accompanied by syncope. The Scale is now in the process of being tested. Preliminary results indicate that it is valid and reliable in providing an estimate of the effect of AF on a patient�s quality-of-life.
Dorian, P, et al. A novel, simple scale for assessing the symptoms severity of atrial fibrillation at the bedside. Canadian Journal of Cardiology, Vol. 22, No. 5, April 2006, pp. 383-86

Magnesium helps control afib
Canadian researchers have done a meta-analysis of studies dealing with the benefits of intravenous administration of magnesium in the acute treatment of atrial fibrillation. They found that effective rate control (reduction in heart rate to below 100 bpm) and/or conversion to normal sinus rhythm was achieved in 84% of patients given magnesium as compared to 53% given a placebo. Seven trials used calcium channel blockers or placebo as controls. In these trials 69% of patients in the magnesium group experienced relief as compared to 53% in the control group. The researchers conclude that intravenous magnesium is an effective and safe strategy for the acute treatment of afib.
PACE, Vol. 29, April 2006, Suppl 1, Abstract #36, p. S19 (European Cardiac Arrhythmia Society, 2nd Annual Congress)

AF prevalence higher than expected
ROCHESTER, MINNESOTA. A 2001 study by Kaiser Permanente researchers estimated the number of afibbers in the United States at 2.3 million rising to 5.6 million in 2050. Mayo Clinic researchers now report that these estimates are likely to be low by a factor of two to three. The Mayo study determined the incidence (first AF episode documented by an electrocardiogram) of atrial fibrillation in Olmsted County, MN. They found that the number of new afib cases in 1980 was 4.09 per 1000 person-years for men and 2.36 per 1000 person-years for women. By the year 2000, the incidence had increased to 4.89 per 1000 person-years for men and 2.80 per 1000 person-years for women. This corresponds to an overall increase of 12.6% over 21 years. Applying their data to the entire US population, the researchers estimate that 5.1 million Americans were suffering from AF in 2000. The prevalence in 2006 would be about 6 million and by 2050 it would be 15.9 million assuming the growth rate observed over the period 1980-2000 continues. The Mayo researchers point out that the prevalence of obesity (BMI of 30 or more) increased from 10% in 1980 to 25% in 2000 and suggest that about 60% of the observed increase in AF cases could be due to the increase in obesity.
Miyasaka, Y, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation, Vol. 114, July 11, 2006, pp. 119-25

Prevalence and incidence of AF
ROTTERDAM, THE NETHERLANDS. It is becoming increasingly clear that atrial fibrillation is reaching epidemic proportions and that the incidence (new cases per 1000 person-years) and prevalence (percent of a given population having the disorder at any given point in time) of the condition continue to rise. A team of Dutch and British researchers has just reported the results of a 7-year study involving 6400 inhabitants (aged 55 years or older in 1990) of a suburb of Rotterdam. At the start of the study 5.5% of the participants had been diagnosed with afib for an average prevalence among men of 6.0% and a prevalence of 5.1% among women. The prevalence increased significantly with age, with the prevalence being only 0.7% in the 55-60 year age group versus 17.8% in the over 85 year age group. By January 2000, the overall prevalence had increased to 8.3%. The incidence (new cases) over an average of 7 years was 9.9/1000 person-years or about 1% a year. The incidence was highly dependent on age with the group aged 55-60 having an incidence of 0.1% a year and the age group 80-85 having an incidence of 2.1% a year. The incidence was higher in men than in women across all age groups. The results of the study also showed that a 55-year-old man has a 25% chance of developing afib during his remaining life. The average lifetime risk for a 55-year-old woman was found to be 23%. Lifetime risk remained pretty well constant until age 75 when it began to decline. This means that about a quarter of the population between the ages of 55 and 75 years can expect to develop afib at some point in their lives � a sobering thought indeed!
Heeringa, J, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. European Heart Journal, Vol. 27, 2006, pp. 949-53
Boriani, G, et al. The epidemiological burden of atrial fibrillation: a challenge for clinicians and health care systems. European Heart Journal, Vol. 27, 2006, pp. 893-94 (editorial)

Treating hypertension helps prevent atrial fibrillation
GENEVA, SWITZERLAND. There is increasing evidence that essential hypertension (high blood pressure) is an important risk factor in the development of atrial fibrillation. What is less clear is whether treating the hypertension lessens the risk of afib. Swiss researchers now report that appropriate treatment does indeed reduce the risk and that the risk reduction is independent of the type of blood pressure reducing agent used. The study involved a group of 597 patients who, after having been diagnosed with hypertension (systolic blood pressure equal to or greater than 140 mm Hg and/or diastolic pressure equal to or greater than 90 mm Hg), were placed on antihypertensive therapy using ACE inhibitors (46%), angiotensin II receptor blockers (23%), calcium channel blockers (52%), and beta-blockers (21%) either alone or in combination.

After a 7-year follow-up the researchers found that the risk of developing atrial fibrillation decreased by 24% with a 12 mm Hg drop in systolic pressure after adjusting for age, gender, body mass, and pulse pressure (systolic blood pressure minus diastolic pressure). All blood pressure measurements were averages of 24-hour ambulatory measurements. Those of the patients who did develop atrial fibrillation were slightly older than those who did not, were more likely to be men, and to be overweight or obese. A decrease in pulse pressure also correlated with a decrease in AF risk, but this trend was not statistically significant. There was no indication that one class of blood pressure medications was superior in preventing the development of AF. The researchers conclude that an increased systolic pressure and pulse pressure may promote the onset of atrial fibrillation by modification of left ventricular diastolic function.
Ciaroni, S, et al. Prognostic value of 24-hour ambulatory blood pressure measurement for the onset of atrial fibrillation in treated patients with essential hypertension. American Journal of Cardiology, Vol. 94, December 15, 2004, pp. 1566-69

Differences between AF and atrial flutter
VANCOUVER, CANADA. Canadian researchers have compared stroke incidence and mortality between a group of 781 patients with newly-diagnosed AF and 96 patients with newly-diagnosed atrial flutter. Most of the patients had underlying heart disease or hypertension, but 19% were classified as having lone AF, while 17% were classified as having lone atrial flutter. The patients were followed for an average (median) of 6.9 years during which time 65 ischemic strokes (10 fatal) and 7 hemorrhagic strokes (5 fatal) occurred. This corresponds to an annual stroke rate of 1.33% a year among afibbers and 1.24% a year in patients with atrial flutter. Not a significant difference, but certainly well below the 5-fold increase in stroke risk often quoted for patients with AF. It is of interest that 57% of afibbers and 43% of atrial flutter patients were on warfarin at the time of their stroke. The estimated overall mortality rate in the group was about 3% a year with no significant difference between afibbers and atrial flutter patients. There were no strokes in the lone atrial flutter group (no mention is made in the report of strokes in the lone AF group) and patients with lone atrial fibrillation or flutter were found to have significantly smaller left atria than those with hypertension or underlying heart disease. The researchers also observed that 28% of patients originally presenting with atrial flutter later converted to AF. They question the hypothesis that the main cause of ischemic stroke in atrial fibrillation and flutter is the formation of clots in the left atrial appendage and point out that high-risk patients with AF have been found to have a 63% incidence of aortic plaque. Thus, ischemic strokes in atrial fibrillation and atrial flutter patients are more likely related to comorbid conditions than to the fibrillation or flutter as such.
Lelorier, P, et al. Prognostic differences between atrial fibrillation and atrial flutter. American Journal of Cardiology, Vol. 93, March 1, 2004, pp. 647-49

Digoxin may worsen atrial fibrillation
ANN ARBOR, MICHIGAN. A recent study of coronary artery bypass surgery patients reached the surprising conclusion that patients treated with digoxin (digitalis, Lanoxin) were almost three times more likely to develop atrial fibrillation after their operation than were patients given a placebo. Researchers at the University of Michigan Medical Center now confirm the deleterious effects of digoxin. Their study involved 38 patients who were to undergo radiofrequency catheter ablation of paroxysmal supraventricular tachycardia. Nineteen of the patients had been taking 0.25 mg/day of digoxin for at least 14 days prior to the surgery while the remaining 19 (control group) had not taken any anti-arrhythmic medicine.
After the operation a short episode of atrial fibrillation was induced in all patients through electrical pacing of the atrium. The researchers noted a significant shortening in the effective refractory period (ERP) in both groups after the induced atrial fibrillation episode, but the shortening was significantly greater in the digoxin group. NOTE: The refractory period is the time of recovery needed for a nerve cell that has just transmitted a nerve impulse or for a muscle fiber that has just contracted.
The researchers conclude that digoxin exacerbates the shortening of atrial ERP and predisposes patients to further atrial fibrillation attacks subsequent to an initial attack. They point out that digoxin has already been found to be deleterious to patients who suffer from the vagal type of atrial fibrillation. This new study would indicate that digoxin might promote atrial fibrillation not only in vagal type patients, but indeed among the general population of atrial fibrillation patients.
Sticherling, Christian, et al. Effects of digoxin on acute, atrial fibrillation � induced changes in atrial refractoriness. Circulation, Vol. 102, November 14, 2000, pp. 2503-08

Spontaneous conversion of lone atrial fibrillation
MODENA, ITALY. Lone atrial fibrillation, that is atrial fibrillation (heart palpitations) without underlying heart disease, is becoming an increasingly common disorder. It manifests itself by irregular, rapid heartbeat and is often accompanied by dizziness or breathlessness. It is most often intermittent (paroxysmal) lasting anywhere from a few minutes to several days. Patients with lone atrial fibrillation (LAF) who are hospitalized are often exposed to drug infusions or direct current shock (cardioversion) in order to stop the fibrillation and bring the heart rhythm back to normal.
Researchers at the University of Modena now report that the use of potentially dangerous, time- consuming, and expensive treatments to normalize heart rhythm in LAF patients may not be necessary in most cases. Their study involved 140 patients who were admitted to the University Hospital with LAF of recent onset. The researchers found that 108 (77 per cent) of the patients reverted to normal heart rhythm within 48 hours without any treatment at all. The average duration of the LAF episodes was four hours. Extensive clinical examination of all patients revealed that people whose LAF attack occurred during sleep had a seven-fold higher probability of spontaneous conversion during the first 24 hours than did those whose attacks occurred during the day. Patients with a high blood level of ANP (atrial natriuretic peptide) were 3.2 times more likely to experience a spontaneous conversion than were patients with lower levels. The researchers found no correlation between age, gender, duration of LAF or left atrial dimension and the propensity for spontaneous conversion.
Mattioli, Anna Vittoria, et al. Clinical, echocardiographic, and hormonal factors influencing spontaneous conversion of recent-onset atrial fibrillation to sinus rhythm. American Journal of Cardiology, Vol. 86, August 1, 2000, pp. 351-52

Valsalva maneuver in atrial fibrillation
ISTANBUL, TURKEY. Paroxysmal (intermittent) atrial fibrillation is an increasingly common heart arrhythmia. The condition may be associated with heart disease or it may have no known cause in which case it is classified as lone, primary or idiopathic atrial fibrillation (AF). It is believed that the arrhythmia is initiated by irregularities in autonomic tone (imbalances between the sympathetic and parasympathetic nervous systems) which causes a slowed and nonuniform progression of the atrial impulse. This progression is represented by the so-called P-wave dispersion on a standard 12-lead electrocardiogram.

Researchers at the Istanbul Faculty of Medicine now report that the P-wave dispersion during an atrial fibrillation attack is much longer than in normal controls (60 milliseconds vs. 37 milliseconds). Their clinical study involved 27 patients with AF and 27 controls with no history of heart problems. Almost half (48 per cent) of the patients suffered from lone atrial fibrillation. All participants had their electrocardiograms taken before, during, and after performing the Valsalva maneuver (exhaling into a mercury manometer with enough force to reach 35 mm Hg pressure and sustaining this pressure for 20 seconds). The AF patients were evaluated during an attack.

The researchers noted that the P-wave dispersion increased markedly in the controls after performing the Valsalva maneuver (from 37 ms to 47 ms). On the other hand, in the patients the P-wave dispersion declined from 60 to 45 ms indicating a pronounced decrease in sympathetic activity. They conclude that the Valsalva maneuver normalizes the P-wave duration and dispersion in AF patients and suggest that medications that decrease sympathetic tone may be beneficial in converting AF to sinus rhythm.
Tukek, Tufan, et al. Effect of Valsalva maneuver on surface electrocardiographic P-wave dispersion in paroxysmal atrial fibrillation. American Journal of Cardiology, Vol. 85, April 1, 2000, pp. 896- 99

Magnesium and heart surgery in children
CHARLESTON, SOUTH CAROLINA. Administration of magnesium has been shown to reduce the incidence of heart surgery related arrhythmias in adults. It has also been observed that the magnesium level in the right atrial tissue is lower in adult patients with postoperative cardiac arrhythmias compared to patients without arrhythmias after heart surgery. Researchers at the Department of Pediatric Cardiology at the Medical University of South Carolina now report that children undergoing surgery for congenital heart defects develop a severe magnesium deficiency immediately after surgery. This deficiency is associated with a greater incidence of a serious arrhythmia (junctional ectopic tachycardia) and can be prevented by an infusion of magnesium sulfate immediately after completion of the surgery.
The study involved 28 pediatric patients (average age of five years) who were scheduled to undergo heart surgery with cardiopulmonary bypass (CPB). The patients were randomly assigned to receive an infusion of magnesium (30 mg/kg body weight of a five per cent saline solution administered over a period of 10 minutes) or an infusion of saline solution immediately after cessation of CPB. Blood levels of magnesium were measured in all patients before surgery, before CPB, after CPB, upon arrival in the intensive care unit (ICU), and then every four hours for 24 hours. Each patient was also monitored for arrhythmias for 24 hours with a Holter monitor.
Comparison of the results for the two treatment groups revealed that the magnesium level was significantly below normal in patients who had received saline solution (placebo) when they arrived in the ICU and for the following 20 hours. Patients who had received the magnesium infusion, on the other hand, had magnesium levels that were well within the normal range (1.6 to 2.3 mg/dL) when tested in the ICU and for the following 20 hours. There were no incidences of junctional ectopic tachycardia in the magnesium group, but four (27 per cent) of the patients in the placebo group experienced this serious arrhythmia. It stopped after a magnesium infusion. The researchers "recommend routine measurement of magnesium levels after CPB in children undergoing heart surgery, with timely magnesium supplementation in the postoperative period." [49 references]
Dorman, B. Hugh, et al. Magnesium supplementation in the prevention of arrhythmias in pediatric patients undergoing surgery for congenital heart defects. American Heart Journal, Vol. 139, No. 3, 2000, pp. 522- 28

Fish oils help prevent sudden cardiac death
AALBORG, DENMARK. Sudden cardiac death (SCD) is now the most common cause of death in the Western world. SCD is often caused by ventricular arrhythmias in patients with heart disease, but may also occur among previously healthy people. The risks of arrhythmias and SCD are closely tied in with heart rate variability (HRV) with a high variability index corresponding to a lower risk. It would also appear that the risk of SCD can be substantially reduced by an increased consumption of fish. Some very recent research has shown that survivors of a first heart attack can avoid having a second one by supplementing with fish oils. An obvious question is whether there is a connection between heart rate variability and fish oil intake.

Danish researchers at the Aalborg Hospital are convinced that there is indeed a very close connection - at least in men. Their recently released study involved 25 women and 35 men who were generally healthy and took no medications. The participants were randomized into three groups. Group 1 was given 10 fish oil capsules daily providing a total of 6.6 grams of n-3 polyunsaturated fatty acids (3.0 g eicosapentaenoic acid [EPA] and 2.9 g docosahexaenoic acid [DHA]); group 2 was given three fish oil capsules (0.9 g EPA and 0.8 g DHA) plus seven olive oil capsules daily, and group 3, the control group, was given 10 olive oil capsules daily. The study participants gave fasting blood samples and had their HRV measured with a Holter recorder for 24 hours at the start of the study and after 12 weeks of supplementation.

The researchers found that fish oil supplementation significantly increased the concentration of EPA and DHA in both blood platelets and granulocytes and that this increase was highly dose-dependent. They also found a significant, dose-dependent reduction in triacylglycerols, but no significant changes in total, LDL or HDL cholesterol levels. The 24-hour Holter recordings showed a correlation between heart rate (pulse rate) and blood level of EPA and DHA with a higher level corresponding to a lower pulse rate in both men and women. There was also a very significant association between DHA level in men and SDNN. SDNN (the standard deviation of all normal R-R intervals during the 24-hr Holter recording) is an important index of HRV with higher values indicating greater heart rate variability. The researchers conclude that supplementation with fish oils, especially DHA, may help prevent arrhythmias and sudden cardiac death in healthy men. They found no association between EPA/DHA levels in women and HRV, but urge further studies to confirm this seeming lack of effect.
Christensen, Jeppe Hagstrup, et al. Heart rate variability and fatty acid content of blood cell membranes: a dose-response study with n-3 fatty acids. American Journal of Clinical Nutrition, Vol. 70, September 1999, pp. 331-37

Omega-3 fatty acids: the missing link?
BERLIN, GERMANY. Dr. Emanuel Severus of the Berlin University points out that major depression is characterized by a deficiency of omega-3 fatty acids and that these acids possess powerful antiarrhythmic properties. He suggests that the missing link in the recently established association between major depression and sudden cardiac death may be the omega-3 fatty acid deficiency which characterizes both conditions.
Severus, W. Emanuel, et al. Omega-3 fatty acids: the missing link? Archives of General Psychiatry, Vol. 56, April 1999, pp. 380-81 (letter to the editor)

Shock stops arrhythmia
OSSEO, WISCONSIN. Thomas Screnock, a family doctor in Wisconsin, reports an interesting case where a persistent atrial fibrillation was stopped and sinus rhythm restored through exposure to static elecricity. Dr. Screnock's patient was a 51-year-old, otherwise healthy man, who had suddenly developed atrial fibrillation. Treatment with oral verapamil, digitalis, and quinidine did not stop the fibrillation so the patient was put on warfarin in preparation for cardioversion. Just near the end of the four-week anticoagulation period the man went shopping. As he reached for a bottle of steak sauce placed on a steel shelf he received a powerful shock caused by a build-up of static electricity. Later that evening he noticed that his pulse was regular and an electrocardiogram confirmed that his heart rhythm was back to normal. Dr. Screnock ascribes the termination of the fibrillation attack to the static electricity shock and closes his letter to the editor with the comment "Please don't alert your managed care CEO of this rather surprising resolution of a recalcitrant dysrhythmia."
Screnock, Thomas. Static electricity stops a recalcitrant arrhythmia. Annals of Internal Medicine, Vol. 130, January 5, 1999, p. 78 (letter to the editor)

Atrial fibrillation and anticoagulation
GREENVILLE, NORTH CAROLINA. Atrial fibrillation (AF) is the most common cardiac arrythmia and affects more than 1.5 million Americans. Its primary characteristic is a rapid and irregular heartbeat. The incidence of AF shows a significant increase beyond the age of 50 years and the condition is considerably more common among men than among women. Atrial fibrillation may be chronic or intermittent (paroxysmal) and may be triggered by an underlying heart disease such as mitral valve prolapse or stenosis, coronary artery disease, hypertensive heart disease, a heart attack or an inflammation of the membrane surrounding the heart (pericarditis). Atrial fibrillation is also a common complication of heart surgery. AF not caused by underlying heart disease is referred to as primary or lone atrial fibrillation.

Several studies have shown that the risk of thromboembolic stroke is significantly higher in people with AF than in the general population. This has led to the widespread use of anticoagulation drugs, notably warfarin (Coumadin) as a preventive measure. Unfortunately, warfarin is a potent risk factor for internal bleeding. Most doctors agree that the benefits of warfarin therapy outweigh the risk for AF patients with underlying heart disease but no consensus exists as far as the use of warfarin in patients with lone AF is concerned.

Medical doctors at the East Carolina University School of Medicine now present guidelines for the use of warfarin in AF patients. These guidelines are based on the results of five major trials involving the use of anticoagulants in AF patients. The indications for anticoagulation depend on two major factors - the patient's age and the presence of specific risk factors such as rheumatic heart disease, poor left ventricular function, enlarged left atrium, and a history of diabetes, hypertension, angina pectoris, heart attack, congestive heart failure or stroke. For patients less than 65 years of age with none of the specific risk factors (other than AF) anticoagulant therapy is not needed, but some doctors do recommend "an aspirin (325 mg) a day". For patients aged 65 to 75 years and no other risk factors than AF, aspirin or warfarin may be prescribed and for patients older than 75 years with no other risk factors warfarin is recommended. All patients who have risk factors for stroke other than AF should receive warfarin standardized to a target INR (International Normalized Ratio) of 2 to 3. The cardiologists caution that warfarin therapy must always be weighed against the risk of internal bleeding and may be contraindicated in some cases. NOTE: Recent research has shown that patients on warfarin who also take acetaminophen (Tylenol, Paracetemol) can elevate their INR to dangerously high levels thereby increasing the risk of internal bleeding.
Akhtar, Waheed, et al. Indications for anticoagulation in atrial fibrillation. American Family Physician, Vol. 58, July 1998, pp. 130-36

Vigorous exercise linked to atrial fibrillation
HELSINKI, FINLAND. There is ample evidence that regular physical exercise reduces the risk of cardiovascular disease. It is therefore somewhat surprising that researchers at the Central Military Hospital and the University of Helsinki have found that men who engage in long term vigorous exercise have a five times greater risk of developing lone atrial fibrillation than do less active men. The researchers studied 300 top ranked orienteers aged 35 to 59 years and compared their incidence of atrial fibrillation to the incidence of among 495 healthy controls of the same age group. The orienteers, as expected, had lower overall mortality (1.7 per cent) than controls (8.5 per cent), fewer cases of coronary heart disease since 1985 (2.7 per cent vs. 7.5 per cent), and fewer risk factors for atrial fibrillation. Nevertheless, lone atrial fibrillation was diagnosed in 12 out of 228 orienteers as compared to two out of 212 controls. As a matter of fact, it was later determined that the two controls with atrial fibrillation also were regular participants in vigorous exercise. The first attack of lone atrial fibrillation in the orienteers was at a mean age of 52 years. The researchers conclude that vigorous long term exercise is associated with an increased risk for atrial fibrillation despite its protective effects against heart disease and premature death. They speculate that enhanced vagal tone and atrial enlargement so often found in endurance athletes may predispose to atrial fibrillation. It is not known whether stopping exercise will prevent recurrence of atrial fibrillation.
Karjalainen, Jouko, et al. Lone atrial fibrillation in vigorously exercising middle aged men: case- control study. British Medical Journal, Vol. 316, June 13, 1998, pp. 1784-85

Adrenaline secretion in panic attacks
MELBOURNE, AUSTRALIA. A connection between abnormalities in the sympathetic nervous system and panic attacks has long been suspected. As early as 1871 "irritable heart", a condition very similar to panic attacks, was attributed to hypersensitivity of the "cardiac nerve centers". Now a team of Australian researchers confirms that the secretion of epinephrine (adrenaline) does indeed increase dramatically during panic attacks (by an average 153 per cent) and may be accompanied by rapid heart beat and atrial fibrillation. The researchers performed a carefully controlled study of 13 patients with panic disorder and 14 healthy controls. They found no difference in sympathetic nervous activity among patients and controls when at rest. They did observe that epinephrine was released from the heart in panic disorder patients during rest. They speculate that this release is a result of the heart's uptake of large amounts of epinephrine during panic attacks. The researchers also found that the heart rate and systolic blood pressure increased significantly in both patients and controls when exposed to simulated mental stress (rapidly subtracting 1- digit numbers from a 3-digit number for 10 minutes). They conclude that there may be a selective increase in cardiac sympathetic activity during panic attacks and that release of epinephrine from the sympathetic nerves of the heart could trigger cardiac arrhythmias.

Dr. George Heninger, MD of Yale University School of Medicine concludes in an accompanying commentary that panic attacks originate in the brain and that the excessive epinephrine discharge is a secondary effect. He suggests that abnormalities in the body's GABA (gamma-aminobutyric acid) system could be the main trigger for panic attacks.
Wilkinson, Dominic J.C., et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks. Archives of General Psychiatry, Vol. 55, June 1998, pp. 511- 20
Heninger, George R. Catecholamines and pathogenesis of panic disorder. Archives of General Psychiatry, Vol. 55, June 1998, pp. 522-23 (commentary)

Inappropriate prescription of digoxin is rampant
NEW YORK, NY. Digoxin (digitalis) is widely prescribed for a variety of heart conditions. Several studies have found that this drug is often inappropriately prescribed, that it may cause arrhythmias, that it is highly toxic and its use responsible for many hospital admissions, that it can cause severe visual problems and that it can, in many cases, be safely withdrawn. Now Wilbert Aronow, a medical doctor at the Mount Sinai School of Medicine, confirms that digoxin is indeed widely misused. Dr. Aronow's study involved 500 patients with an average age of 81 years who were admitted to a nursing home on consecutive days. He found that 96 of the patients (19 per cent) were receiving digoxin at the time of their admission. A thorough medical examination and evaluation concluded that 47 per cent of these patients should not be taking digoxin at all. Dr. Aronow believes that digoxin is appropriate in the treatment of atrial fibrillation with or without accompanying congestive heart failure and in congestive heart failure with sinus rhythm and abnormal left ventricular ejection fraction; he questions the use of digoxin in the treatment of many other forms of heart disease especially for patients suffering from paroxysmal (intermittent) atrial fibrillation. Dr. Aronow also noted that 18 per cent of the patients receiving digoxin had been misdiagnosed as having congestive heart failure when, in fact, they were suffering from edema or dyspnea (labored breathing). Digoxin therapy was discontinued in the 47 per cent of patients for whom it had been inappropriately prescribed.
Aronow, Wilbert S. Prevalence of appropriate and inappropriate indications for use of digoxin in older patients at the time of admission to a nursing home. Journal of the American Geriatrics Society, Vol. 44, No. 5, May 1996, pp. 588-90

Fish oils protect against arrhythmias
AALBORG, DENMARK. Research has shown that heart attack survivors who increase their intake of oily fish considerably improve their chance of long-term survival. Now Danish researchers report that daily supplementation with fish oil capsules may have a similar effect. Their experiment involved 49 patients who had been discharged from hospital after suffering a heart attack. The study participants were randomly allocated to receive 5 grams per day of fish oil as a mixture of eicosapentaenoic acid and docosahexaenoic acid or a similar amount of olive oil as a placebo for a 12-week period. A 24-hour recording (Holter) of their heart rate was obtained at the start and end of the study. At the end of the experiment the patients in the fish oil group exhibited a marked increase in the variability of their heart rate as compared to the controls. It is believed that greater heart rate variability is desirable in heart attack patients as it protects the heart against often fatal ventricular arrhythmias. The researchers conclude that fish oils may have an antiarrhythmic effect which could account for the better survival among heart attack patients who increase their intake of them.
Christensen, Jeppe Hagstrup, et al. Effect of fish oil on heart rate variability in survivors of myocardial infarction. British Medical Journal, Vol. 312, March 16, 1996, pp. 677-78

Digitalis linked to visual problems
NEW YORK, NY. A team of neuro-ophthalmologists from the Columbia-Presbyterian Medical Center reports that digitalis (digoxin) intoxication can lead to visual problems. Their investigation involved five patients with photopsia (the subjective sensation of seeing lights not present in the environment) and one patient with a significant decline in visual acuity. All the patients (aged 66 to 85 years) were taking digitalis medication (0.25 to 0.75 mg/day), but had no other indication of digitalis intoxication. The concentration of digitalis in their blood serum was found to be within or below the range expected during therapy. The researchers concluded that the digitalis therapy could safely be stopped in five of the six patients. Upon doing so, the photopsia problem resolved gradually witin days and disappeared completely within one to two weeks in all patients. The researchers then put one of the patients back on digitalis and the photopsia came back; it disappeared again when the therapy was stopped. The researchers conclude that digitalis can cause visual problems even at dosages normally considered safe. They also reiterate earlier warnings that digitalis can cause arrhythmias and cardiac conduction disturbances even in patients whose blood serum levels are within the accepted therapeutic range.
Butler, Vincent P., et al. Digitalis-induced visual disturbances with therapeutic serum digitalis concentrations. Annals of Internal Medicine, Vol. 123, No. 9, November 1, 1995, pp. 676-80

Fish oils help prevent cardiac arrest
SEATTLE, WASHINGTON. Cardiac arrest is a serious, usually fatal condition in which the heart stops pumping. Cardiac arrest most commonly occurs in connection with ventricular fibrillation and its primary cause is a heart attack. Researchers at the University of Washington now report that the risk of cardiac arrest can be significantly lowered by an increased intake of seafood rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Their study involved 334 patients who had suffered cardiac arrest during the period 1988 to 1994 and 493 controls matched for age and sex. None of the study participants had had any indication of heart disease prior to the beginning of the study. Interviews with survivors or their spouses were used to determine the participant's fish intake in the month preceding the cardiac arrest. The researchers found that the intake of just one portion of fatty fish per week lowered the risk of cardiac arrest by an impressive 50 per cent after adjusting for age, smoking, family history of heart attacks, hypertension, diabetes, obesity, physical activity, education, and cholesterol level.

The researchers believe that consumption of fish increases the level of EPA and DHA in the membranes of the red blood cells which in turn reduces platelet aggregation and coronary spasm. This belief was confirmed by finding that blood samples taken from 95 cardiac arrest patients and 133 controls showed that a high blood content of EPA and DHA (five per cent of total fatty acids) corresponded to a 70 per cent reduction in the risk of cardiac arrest when compared to study participants with a low EPA and DHA content in their blood (3.3 per cent of total fatty acids). Other studies have shown that patients who have already suffered a heart attack can reduce their risk of future life-threatening arrhythmias and sudden cardiac death by increasing their intake of fish, fish oils or linolenic acid (flax seed oil). The researchers conclude that a modest intake of EPA and DHA from seafood may reduce the risk of ventricular fibrillation and death from coronary heart disease. NOTE: Fresh salmon is one of the best sources of fish oils; it contains twice as much per serving as does albacore tuna and six times more EPA and DHA than a serving of cod.
Siscovick, David S., et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. Journal of the American Medical Association, Vol. 274, No. 17, November 1, 1995, pp. 1363-67

Use of antiarrhythmic drugs drops sharply in Italy
MILAN, ITALY. Recent trials have shown that heart attack patients who are treated with some antiarrhythmic drugs are more likely to die than patients who are not treated. The Italian medical community has taken this lesson to heart. During the period 1984 to 1985, 11.9 per cent of all patients were prescribed a class I or class III antiarrythmic drug at discharge and 14.4 per cent were prescribed one at their follow-up visit (six months after their heart attack). During the period 1991 to 1994 only 5.8 per cent of all patients were prescribed an antiarrhythmic drug either at discharge or at follow-up. The most widely prescribed drug was amiodarone followed by mexiletine hydrochloride. The number of prescriptions for amiodarone dropped by about 45 per cent while the number of prescriptions for mexiletine hydrochloride dropped by about 60 per cent over the period studied. Flecainide acetate (Tambocor) was used in Italy as an antiarrythmic drug until 1989 when it was banned because it was found to significantly increase the mortality among heart attack patients who took it. Note: Flecainide acetate is still available in the United States and Canada.
Avanzini, Fausto, et al. Antiarrhythmic drug prescription in patients after myocardial infarction in the last decade. Archives of Internal Medicine, Vol. 155, May 22, 1995, pp. 1041-45

Niacin effective in the treatment of atrial fibrillation
VICTORIA, CANADA. Dr. Abram Hoffer, a world-renowned psychiatrist in Victoria, reports on the successful treatment of six patients with atrial fibrillation. One 76 year old physician who suffered from atrial fibrillation was completely cured after starting a vitamin supplementation program which included megadoses of niacin and folic acid. Other patients report complete disappearance of their irregular heart beat symptoms after supplementing with high doses of niacin, folic acid, and vitamin B-12. Dr. Hoffer believes that one of the main causes of atrial fibrillation is excessive stress. High levels of stress release large amounts of adrenalin which in turn is oxidized to adrenochrome. Adrenochrome is known to cause fibrillation and other cardiac dysfunctions. Adrenochrome is a natural free radical and is primarily produced in the heart tissue, but circulates in the blood throughout the body. It can cross the blood-brain barrier and excessive amounts of it are believed to be a main cause of schizophrenia. Antioxidants protect against the formation of excessive amounts of adrenochrome and schizophrenics have been successfully treated with large amounts of niacin and ascorbic acid. Penicillamine has also been successfully used in the treatment of schizophrenia. Dr. Hoffer points out that adrenochrome is not all bad. He believes that the leucocytes use adrenochrome to destroy abnormal cells like cancer cells and that we therefore need a certain amount of adrenochrome in order to control cancer. The fact that schizophrenics rarely develop cancer supports this hypothesis. Dr. Hoffer concludes that we need a certain amount of stress in order to produce enough adrenochrome to enable our leucocytes to kill bacteria and tumor cells. However, we also need an adequate supply of natural antioxidants such as vitamins C and E and beta-carotene in order to neutralize an excess of adrenochrome after its work is done. (51 references)
Hoffer, A. Schizophrenia: an evolutionary defence against severe stress. Journal of Orthomolecular Medicine, Vol. 9, No. 4, Fourth Quarter, 1994, pp. 205-21

Digitalis is a dangerous drug
BALTIMORE, MARYLAND. Digitalis (digoxin, Lanoxin) is one of the most commonly dispensed prescription drugs in the United States. It is estimated that about 13 per cent of people over 65 years of age took this drug for heart problems in 1987. Among Medicare beneficiaries alone, about 3.3 million elderly people were treated with digitalis in 1987. Researchers at the Health Care Department in Maryland have just completed a study to determine the extent of adverse effects connected with this therapy. Their findings are very disturbing. In the period 1985 through 1991 over 200,000 of the 3.3 million digitalis users were hospitalized because of digitalis intoxication. The risk of being hospitalized because of the adverse effects of digitalis increases with age; women were found to have a 33 per cent greater risk of hospitalization than men and black people a 37 per cent greater risk than whites. It is ironic that digitalis is often prescribed for people who suffer from atrial fibrillation and yet, the most common manifestation of digitalis intoxication is also atrial fibrillation. Other symptoms of digitalis poisoning are nausea, vomiting, diarrhea, psychoses, and fatigue. Perhaps the most disturbing finding in the study is that in 73 per cent of all cases the reason for prescribing the digitalis in the first place was unclear or weak. The researchers also point out that the high level of hospitalization for adverse effects of digitalis is, to a large extent, due to inadequate monitoring of patients taking the drug. It is also of concern that for the period in which the researchers uncovered data for 200,000 hospitalizations only 577 adverse events involving digitalis were reported directly to the FDA (the drug watchdog) by doctors or hospitals.
Warren, Joan L., et al. Hospitalizations with adverse events caused by digitalis therapy among elderly Medicare beneficiaries. Archives of Internal Medicine, Vol. 154, July 11, 1994, pp. 1482-87