ABSTRACTS

NEWCASTLE-UPON-TYNE, UNITED KINGDOM. British researchers report that pretreatment with angiotensin- converting enzyme inhibitors (ACE inhibitors) may help persistent afibbers stay in sinus rhythm after electrical cardioversion. Their study involved 47 patients with persistent atrial fibrillation (AF lasting longer than 48 hours, but less than 6 months) who were scheduled for cardioversion. Patients with left ventricular dysfunction (low left ventricular ejection fraction), valvular heart disease or permanent AF were excluded from the study.

Twenty-four of the patients had been taking ACE inhibitors [enalapril (11), lisinopril (8), and captopril (5)] for at least 6 months before inclusion and continued to do so for the 1-year follow-up. The researchers observed that the patients taking ACE inhibitors required significantly less energy to effect electrical cardioversion (203 joules versus 271 joules on average) than did the controls. There was also a clear difference between ACE inhibitor- treated patients and controls in regard to P-wave duration 1 year after cardioversion (135 ms versus 150 ms). P- wave duration is prolonged in AF patients.

Finally, there was a trend for patients on ACE inhibitors to have fewer hospital admissions for repeat cardioversion during the follow-up period. The researchers noted that the use of beta-blockers was substantially higher in the control group than in the ACE inhibitor group (83% versus 4%). Both groups had similar left atrial size (48 mm and 49 mm). The researchers conclude that ACE inhibitor therapy may be useful in patients with persistent atrial fibrillation.

Other researchers have observed substantial decreases in afib recurrence in patients with left ventricular dysfunction who were treated with enalapril (78% risk reduction) and trandolapril (47% risk reduction).
Zaman, AG, et al. Angiotensin-converting enzyme inhibitors as adjunctive therapy in patients with persistent atrial fibrillation. American Heart Journal, Vol. 147, May 2004, pp. 823-27
Al-Khatib, SM. Angiotensin-converting enzyme inhibitors: A new therapy for atrial fibrillation? American Heart Journal, Vol. 147, May 2004, pp. 751-52

Editor's comment: The results of this study look intriguing, but certainly should be interpreted with caution. The majority of members of the control group (84%) were on beta-blockers, while only 1 patient (4%) in the ACE inhibitor group was taking beta-blockers. It is well established that beta-blockers can increase afib frequency in vagal afibbers. Presumably, there would have been some vagal afibbers in the control group and these would likely have experienced more episodes than those not on beta-blockers. Thus the lower incidence in hospital readmissions seen in the ACE inhibitor group could equally well stem from the absence of beta- blocker use as from the use of ACE inhibitors. Nevertheless, the findings of less cardioversion energy requirements and a shortening of P-wave duration in ACE inhibitor patients could well be important, but need confirmation in larger trials.

IOANNINA, GREECE. Taiwanese researchers recently reported that pretreatment with the ACE inhibitor enalapril increased long-term maintenance of sinus rhythm in amiodarone-treated patients undergoing electrical cardioversion. The beneficial effect, unfortunately, was most pronounced for the first few weeks and then gradually declined. Greek cardiologists, in commenting on the Taiwanese findings, now suggest that the real culprit in perpetuating afib is aldosterone rather than angiotensin. They point out that

• Aldosterone levels (serum) are elevated in patients with persistent AF.
• Aldosterone levels drop significantly after restoration of sinus rhythm via electrical cardioversion.
• Aldosterone induces cell proliferation and myocardial fibrosis. Myocardial fibrosis has been linked to AF.
• Aldosterone promotes inflammation and oxidative stress and has been implicated in atrial remodeling.
• Aldosterone induces baroreceptor dysfunction and may thus promote an imbalance of the autonomic nervous system.

The Greek cardiologists hypothesize that aldosterone may play a significant role in AF and that treatment with aldosterone antagonists such as spironolactone or eplerenone may help ameliorate its detrimental effects.
Ueng, KC, et al. Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation. European Heart Journal, Vol. 24, 2003, pp. 2090-98
Korantzopoulos, P, et al. Atrial remodeling in persistent atrial fibrillation: the potential role of aldosterone. European Heart Journal, Vol. 25, June 2004, pp. 1086-87

Editor's comment: The comments made by the Greek cardiologists fully support my aldosterone hypothesis published in the March 2003 issue of The AFIB Report. It is indeed encouraging that aldosterone may now receive the attention it clearly deserves as a major player (villain) in the afib drama. My own test results clearly show an elevated aldosterone level just prior to an episode as opposed to a normal level just after the end of an episode. I am currently trying 25 mg/day of spironolactone to see if this will reduce the frequency of my AF episodes.

PERTH, AUSTRALIA. Ischemic stroke (stroke caused by a blood clot) is an important concern in atrial fibrillation patients with one or more additional risk factors for stroke. There are an estimated 150,000 patients in Australia with AF and this number is growing at a rapid rate. Every year 6,000 (4%) of these AF patients suffer an ischemic stroke. Australian researchers have closely evaluated the results of two recent clinical trials (SPORTIF III and V) designed to compare warfarin and ximelagatran. They conclude that the two drugs are equally effective in preventing stroke and systemic embolism, but that ximelagatran is less likely to produce major bleeding (annual risk with warfarin is 3.4% and with ximelagatran it is 2.5%). They also point out that the dose requirement for ximelagatran is independent of the patient's age, gender, weight, ethnicity or diet. Ximelagatran does not interact with other drugs and does not need constant laboratory monitoring, as does warfarin. There is, however, a need to monitor liver function for the first 6 months as ximelagatran has been found to increase the level of alanine aminotransferase enzymes. The Australian researchers predict that ximelagatran will gain substantial market share at the expense of warfarin even though the monthly cost of administration is likely to be about $100.
Eikelboom, JW and Hankey, GJ. The beginning of the end of warfarin? Medical Journal of Australia, Vol. 180, June 7, 2004, pp. 549-51

VIENNA, AUSTRIA. Austrian medical researchers have confirmed a strong connection between GERD (gastroesophageal reflux disease) and lone atrial fibrillation (LAF). Their pilot study involved 89 patients (93% men) between the ages of 39 and 69 years who had been diagnosed with GERD. Eighteen of the patients had also been diagnosed with paroxysmal LAF at least 3 months prior to undergoing gastroscopy to check for the presence of GERD. Immediately upon diagnosis the GERD-positive patients were prescribed proton pump inhibitors (lansoprazole, omeprazole, pantoprazole).

After at least 2 months on their medications, the 18 patients were invited for a follow-up visit to review and compare the severity of LAF and GERD symptoms before and after beginning the medication. The LAF symptoms evaluated were frequency and duration of palpitations, presence of dizziness or weakness, and breathing difficulties upon exertion. An astounding 14 out of the 18 (78%) patients reported a decrease or complete disappearance of one or more LAF symptoms. Fewer episodes (palpitations) were reported by 55% and shorter episodes by 39%. Twenty-two per cent reported no change in episode frequency, while 2 patients (11%) reported an increase in episode frequency. An impressive 28% of all patients were able to discontinue their antiarrhythmic drugs and no patients had to increase their dosage of antiarrhythmic drugs or be prescribed new ones. An electrocardiogram recorded at the time of the follow-up visit showed all patients to be in normal sinus rhythm.

GERD involves a local inflammatory process that manifests itself as heartburn, regurgitation and difficult or painful swallowing. The researchers believe that it is the inflammation that affects LAF severity. They suggest several possible mechanisms:

• The local inflammation penetrates the esophageal wall and affects adjacent vagal nerves making them overly sensitive.
• The inflammatory process results in feedback to the brain leading to over-stimulation of the parasympathetic (vagal) branch of the autonomic nervous system. Vagal over-stimulation may lead to bradycardia and subsequent AF.
• The local inflammatory process penetrates the esophageal wall and spreads to the heart resulting in atrial myocarditis (inflammation of the wall of the atria). Biopsies in LAF patients have revealed that 66% of them suffer from myocarditis.
• GERD may lead to the release of inflammatory mediators such as C-reactive protein (CRP). Many LAF patients reportedly have high CRP levels.
• GERD may induce an autoimmune response that contributes to LAF.

It is interesting that the researchers make a clear distinction between vagal, adrenergic and mixed afibbers. They define vagal afibbers as those whose episodes begin during rest, at night or after a meal. Adrenergic afibbers are defined as those whose episodes occur during the day, during exercise or while under stress. Mixed afibbers experience episodes that can be either vagally or adrenergically initiated. According to these definitions, 4 of the patients were purely vagal, 1 was purely adrenergic, and the remaining 13 were mixed (4 mostly adrenergic and 4 mostly vagal). There was a definite trend for proton pump inhibitor therapy to be more effective in vagal or primarily vagal afibbers. The researchers conclude that LAF patients should be checked for GERD and, if positive, should be treated with proton pump inhibitors.
Weigl, M, et al. Reflux esophagitis in the pathogenesis of paroxysmal atrial fibrillation. Southern Medical Journal, Vol. 96, November 2003, pp. 1128-32

Editor's comment: The 3rd LAF survey in August 2002 revealed that about a third of the 100 respondents experienced GERD episodes on a daily (10%), weekly (14%) or monthly (10%) basis. This incidence rate is no different from the rate found in the general population. However, 69% of afibbers with GERD had noticed a strong correlation between a flare-up of GERD symptoms and the initiation of an AF episode or a worsening of permanent symptoms. The survey concluded that, "GERD could be an important trigger for LAF and its elimination could materially improve the condition of some afibbers." It is indeed gratifying to see the Austrian researchers confirm this conclusion.

CHIETI, ITALY. Current medical practice specifies treatment with warfarin (Coumadin) for 3 weeks prior to and for 4 weeks after electrical cardioversion of AF. Warfarin has many drawbacks such as a high risk of internal bleeding and hemorrhagic stroke and the need to undergo frequent testing in order to determine the correct dosage for maintaining the desired INR. Italian researchers now report that a combination of aspirin and clopidogrel (Plavix) may be just as effective as warfarin in preventing thrombosis and stroke related to cardioversion.

Their clinical trial involved 30 patients (11 women), 18 of whom had persistent AF and 12 of whom had low-risk permanent AF. Patients with a prior stroke or TIA, left ventricular dysfunction (ejection fraction less than 50%), mitral valve disease, prosthetic heart valves, coronary artery disease or untreated diabetes or hypertension were not included in the trial. After a thorough medical examination, including measurement of bleeding time, INR and thromboxane B2 (an important indicator of platelet aggregability), the patients underwent transesophageal echocardiography (TEE) to check for blood clots in the atrium and left atrial appendage (LAA). No clots or dense spontaneous echo-contrast (SEC) were observed in any of the patients. The study participants were then randomly assigned to receive warfarin (to an INR of 2.0-3.0) for 3 weeks or a 1-week course of 100 mg/day of aspirin followed by a 3-week course of 100 mg/day of aspirin plus 75 mg/day of clopidogrel.

At the end of the treatment period, the TEE and blood tests were repeated. The INR had not changed in the aspirin/clopidogrel group, but had increased in the warfarin group. However, aspirin by itself decreased thromboxane B2 levels by 98% (no further change with clopidogrel) and the aspirin/clopidogrel combination increased bleeding time by an astonishing 144%. The repeat TEE showed no clots or dense SEC and there were no strokes, TIAs or bleeding incidents in either group during the treatment period nor in the 4-week period following attempted cardioversion. The researchers conclude that aspirin + clopidogrel may be a safe alternative to warfarin in the pre and post electrical cardioversion period. NOTE: This study was funded by Bristol-Myers Squibb, Italy).
Lorenzoni, R, et al. Short-term prevention of thromboembolic complications in patients with atrial fibrillation with aspirin plus clopidogrel: the CLAAF pilot study. American Heart Journal, Vol. 148, July 2004

MANNHEIM, GERMANY. The goal of radiofrequency ablation is to create strategically-placed scar tissue in the atrial wall so that aberrant electrical impulses can no longer cause atrial fibrillation. The scar tissue is formed by burning the surface of the atrium through the use of special, heated catheters. Clearly, a RF ablation is a traumatic experience for the heart and could have lingering after-effects. German cardiologists recently set out to determine just how much damage is done to the heart during an ablation and how long it takes before complete healing has been achieved. They used markers usually employed to determine the seriousness of a heart attack and compared the rise in these markers for simple and more complicated RF procedures. The markers used were troponin I, a very sensitive indicator of necrosis (death of cells), interleukin-6 (IL-6), a sensitive marker for inflammation, and matrix metalloproteinase-9 (MMP-9), a marker for myocardial healing and repair.

A total of 13 patients participated in the study – 5 had AV nodal reentrant tachycardia, 3 had Wolff-Parkinson- White syndrome, and 5 had atrial flutter. Blood samples for marker analysis were taken before the ablation and on day 1 and day 120 after the ablation. The level of troponin was highly elevated on day 1, particularly in the atrial flutter patients who had received a linear lesion rather than the fairly small focal lesions used in the other two groups of patients. The troponin level in the atrial flutter patients on day 1 after the ablation averaged 0.83 ng/mL, which is just about twice the level observed after a major heart attack. The level of the inflammation marker IL-6 also increased substantially on day 1 from 1.8 pg/mL to 12.4 pg/mL in the atrial flutter group. Both troponin and IL-6 levels had returned to baseline by day 120.

The level of MMP-9, the healing indicator, also increased substantially on day 1 rising from an average baseline value of 6.0 ng/mL to 49.9 ng/mL in the 3 groups combined. Again, the increase in the linear ablation group (patients with atrial flutter) was substantially higher than in the focal ablation groups (102 ng/mL versus 32 ng/mL). MMP-9 values were still elevated on day 120 (24.8 ng/mL compared to baseline at 6.0 ng/mL) indicating that complete healing and return to normalcy can take more than 4 months following the ablation. The researchers conclude that RF ablation induces substantial heart tissue damage and that the healing process can be monitored by observing MMP-9 levels.
Brueckmann, M, et al. Markers of myocardial damage, tissue healing, and inflammation after radiofrequency catheter ablation of atrial tachyarrhythmias. Journal of Cardiovascular Electrophysiology, Vol. 15, June 2004, pp. 686-91

Editor's comment: It is interesting that the focal ablation procedures only required the creation of an average of 3 lesions whereas the atrial flutter procedure required an average of 11 lesions. This explains why the damage markers were so much higher in the atrial flutter patients. It is a sobering thought that an atrial fibrillation procedure can require 50 lesions or more and that the new circumferential procedure makes use of two very large linear lesions. It is not surprising then that AF ablations cause greater trauma to the heart and recovery periods can be long.

MUNICH, GERMANY. PVCs (premature ventricular complexes) is a very annoying heart rhythm abnormality that affects many people, mostly men. PVCs are usually harmless, but are of concern if heart disease, especially ventricular dysfunction, is also present. German researchers now report that fish oil supplementation is quite effective in reducing the frequency of PVCs. Their clinical trial included 68 patients with an average 6600 PVCs over a 24-hour period. The patients were randomized to receive fish oil (providing 900 mg eicosapentaenoic acid [EPA] and 1500 mg docosahexaenoic acid [DHA]) or sunflower seed oil (providing 5000 mg of linoleic acid) daily for a 16-week period. Twenty-four-hour Holter monitoring was performed at baseline and at the end of the trial period.

At the end of the trial, the average number of PVCs in the fish oil group had decreased by 48% as compared to a 25% reduction in the placebo group. Overall, 44% of the patients in the fish oil group achieved a 70% or greater reduction in PVCs (15% in the placebo group achieved the same reduction). The frequency of couplet and triplet beats decreased by 80% and 90% in 52% of the fish oil consumers.
Sellmayer, A, et al. Effects of dietary fish oil on ventricular premature complexes. American Journal of Cardiology, Vol. 76, November 1, 1995, pp. 974-76

Editor's comment: Supplementation with magnesium and potassium is quite effective in reducing PVCs. It would seem that fish oil can be added to our arsenal of natural PVC "busters".

BIRMINGHAM, UNITED KINGDOM. A blood clot formed in the left atrium or the left atrial appendage (LAA) is a significant source of ischemic stroke in afibbers with underlying heart disease or heart failure. The presence of clots in the atrium or LAA can be determined through transesophageal echocardiography (TEE). TEE differs from the normal transthoracic echocardiography in that the ultrasound probe is positioned in the esophagus rather than on the outside of the chest wall. TEE cannot only pick up clots, but can also be used to give an indication of the extent of dense spontaneous echo contrast (SEC). Dense SEC, in turn, is considered an indication of the likelihood that a clot will form. TEE is increasingly used in preparation for cardioversion and pulmonary vein ablation.

British researchers recently set out to determine the factors influencing the presence of dense SEC and actual clots in patients with permanent (chronic) atrial fibrillation and risk factors such as heart disease, heart failure, diabetes, prior stroke, or hypertension. All the patients had been on warfarin (INR=2.0-3.0) for at least 3 weeks prior to the study. The researchers found that 3 out of 37 patients had a blood clot in the LAA and 22 had dense SEC. The patients all had significantly elevated levels of C-reactive protein (CRP) and tissue factor when compared to healthy controls. CRP, soluble P-selectin, and hematocrit levels were higher among AF patients with dense SEC than in those without. Twenty-eight patients (76%) had one or more risk factors for thromboembolism (dense SEC, plaque in the descending aorta, LAA thrombus or slow emptying velocity of the LAA).

Upon considering all their findings, the researchers concluded that an elevated hematocrit level was the only variable which was significantly related to the presence of one or more risk factors and to the presence of dense SEC. The risk of dense SEC increased by 40% for each 1% increase in hematocrit. Hematocrit or packed cell volume is determined as the volume of red cells (erythrocytes) in the blood expressed as a percent of total blood volume. The researchers speculate that increased hematocrit may increase dense SEC directly due to increased concentration of erythrocytes or indirectly by promoting blood stagnation.
Conway, DSG, et al. Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation. American Journal of Cardiology, Vol. 93, June 1, 2004, pp. 1368-73

Editor's comment: The fact that over two-thirds of the patients had blood clots or dense SEC after at least 3 weeks of warfarin treatment does not speak highly of warfarin's efficacy in protecting against embolism in the left atrium. It is quite likely that nattokinase would be equally or more effective. There is no evidence that lone afibbers with no other risk factors for stroke have an elevated risk of clot formation in the left atrium or LAA. Nevertheless, the findings concerning CRP and hematocrit levels are intriguing. Low levels of these factors would seem to be protective against embolism (and possibly stroke). It is likely that CRP levels can be reduced by the use of natural anti-inflammatories and high hematocrit levels may respond to increased water intake.

BOSTON, MASSACHUSETTS. Pulmonary vein isolation (PVI) by radiofrequency ablation is now the most common invasive procedure for treating atrial fibrillation (AF). Electrophysiology studies have shown that the pulmonary veins are the most likely sources of the ectopic beats that initiate AF. By isolating these veins from the left atrium propagation of the aberrant impulses can be stopped before fibrillation develops. Early versions of the procedure involved ablation inside the pulmonary veins and this could lead to subsequent obstruction of the veins by scar tissue resulting in stenosis. Nowadays the ablation scars are placed in the atrium itself in the form of a ring surrounding, but not entering the vein; this procedure is known as segmental ostial PVI. Fairly recently Italian cardiologists (Pappone, et al.) further refined the PVI procedure by creating the ablation scar in one large ring encompassing both left pulmonary veins and another encircling the right pulmonary veins. The new procedure is known as circumferential extra-ostial PVI and reportedly almost totally eliminates the risk of stenosis.

Electrophysiologists at the Massachusetts General Hospital have now compared the efficacy of the two procedures and conclude that the circumferential extra-ostial PVI is at least as safe and effective as the segmental ostial PVI. Their study included 40 consecutive AF patients (33% with lone AF) who underwent the segmental procedure and 40 consecutive patients (35% with lone AF) who underwent the circumferential procedure. The total time during which radiofrequency energy was applied was 44 minutes in the segmental group and 71 minutes in the circumferential group. Total fluoroscopy time was 16.4 and 14.4 minutes respectively. Bleeding into the pericardium (tamponade) occurred in two patients in the segmental group and in one patient in the circumferential group. One patient in each group (2.5%) experienced an ischemic stroke after the procedure, but experienced 90% recovery after one month. After a follow-up of 21 months, 24 patients (60%) in the segmental group were still in sinus rhythm as compared to 30 patients (75%) in the circumferential group after 11 months of follow-up.
Mansour, M, et al. Efficacy and safety of segmental ostial versus circumferential extra-ostial pulmonary vein isolation for atrial fibrillation. Journal of Cardiovascular Electrophysiology, Vol. 15, May 2004, pp. 532-37

MILAN, ITALY. Italian researchers report that ablation of vagal nerve endings (vagal denervation) during pulmonary vein isolation (PVI) may improve the outcome of the procedure. Their study involved 297 patients undergoing circumferential pulmonary vein ablation (CPVA) for paroxysmal AF. The majority of the patients had lone AF (AF with no underlying heart disease). During the procedure the electrophysiologist kept an eye out for vagal reflexes (sinus bradycardia, dropped beats (asystole), atrioventricular block or hypotension) occurring shortly after the initial application of radiofrequency energy (RF) to create scar tissue. If a reflex was observed RF was applied for up to 30 seconds to ensure that the reflex stopped. One hundred and two of the patients exhibited vagal reflexes during the procedure while 195 did not. After 12 months of follow-up only one patient in the vagal reflex group had experienced a recurrence of AF (1%) as opposed to a recurrence rate of 15% in the group exhibiting no vagal reflexes during the procedure.

Twenty-four per cent of the patients in the vagal denervation group did, however, develop inappropriate sinus tachycardia that disappeared within the month following the procedure. It is also of interest to note that the average heart rate among all the patients went from 72.4 bpm prior to the procedure to 81.4 bpm one month after the procedure. However, after 6 months the average heart rate had returned to 72.5 bpm. The researchers conclude that vagal denervation performed during PVI markedly improves the success rate in the approximately one third of afibbers showing clear vagal reflexes during the procedure.
Pappone, C, et al. Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation. Circulation, Vol. 109, January 27, 2004, pp. 327-34

Editor's comment: It is interesting to note that the average heart rate had increased by about 10 bpm one month after the procedure, but returned to normal within 6 months. Several ablated afibbers have experienced and worried about this change; this study indicates that it is common and temporary. It is also of interest that 24% of the vagally-denervated patients experienced episodes of tachycardia (rapid heartbeat) after the procedure. Several afibbers have also experienced episodes of tachycardia after their PVI. These episodes may well have been caused by inadvertent vagal denervation and again, would appear to be just a temporary phenomenon.

NEWSBRIEFS

Obituary – Philippe Coumel.
Professor Philippe Coumel MD passed away in Paris on March 18, 2004. Dr. Coumel is rightly considered one of the founding fathers of modern arrhythmology. He developed the concept of the triangle of arrhythmogenesis:

"There are always three main ingredients required for the production of a clinical arrhythmia, the arrhythmogenic substrate, the trigger factor and the modulation factors of which the most common is the autonomic nervous system."

Dr. Coumel authored almost 400 scientific papers and more than 200 book chapters. He will be remembered by cardiologists worldwide, not only because of his originality leading to important new findings, but also because of his support and friendship.
European Heart Journal, Vol. 25, June 2004, pp. 1083-84

Editor's comment: Dr. Coumel will be sadly missed. He was one of the few cardiologists who showed an interest in and commented on our research. He was kind enough to write the foreword to my book "Lone Atrial Fibrillation: Towards A Cure".

Generic propafenone equivalent to brand name product.
Israeli researchers have compared the performance of brand name propafenone (Rythmol) with that of a generic equivalent (Profex) – both products manufactured in Germany. The researchers followed a group of 114 patients with paroxysmal AF who had been treated with Rythmol for at least 18 months. As a cost containment measure, the brand name drug was replaced with the generic version and the patients followed for another 18 months or until discontinuation of the drug. The researchers observed that study participants had significantly fewer visits to the emergency department (79 versus 45) after switching to the generic product, especially for arrhythmia symptoms (22 versus 9) and chest pain (30 versus 10). They conclude that the generic version of propafenone is just as effective as the original brand name version and point out that other researchers have found that the generic version (warfarin) of the anticoagulant Coumadin has also been found to be as effective as the brand name product.
American Journal of Cardiology, Vol. 93, June 15, 2004, pp. 1558-60

Heart rate variability (HRV) and biofeedback.
Heart rate variability (a measure of the variability in the time interval between consecutive heart beats) is becoming increasingly important as an indicator of heart health. Numerous studies have shown that coronary artery disease (CAD) patients with diminished heart rate variability have a greater mortality and more rapid progression of their disease than do people with normal heart rate variability. American researchers recently reported that 18 weeks of biofeedback training (abdominal breath training, heart and respiratory physiologic feedback and daily breathing practice) significantly reduced HRV in a group of 63 patients with established CAD. They conclude that biofeedback may prove to be an integral tool in the treatment of CAD.
American Heart Journal, Vol. 147, March 2004, p. 545

BNP increases during atrial fibrillation.
There is ample evidence that the blood level of atrial natriuretic peptide (ANP) is elevated in patients with atrial fibrillation and returns to a value close to normal upon conversion to sinus rhythm. ANP is a natural diuretic that is formed in the atria during rapid, chaotic beating. Polish researchers recently reported that the level of brain natriuretic peptide (BNP) also tends to be elevated during afib with a return to near normal once sinus rhythm is restored. The decline in BNP level was quite significant with a drop from 95 pg/mL to 28 pg/mL in paroxysmal afibbers and a drop from 75 pg/mL to 41 pg/mL in persistent afibbers. It is known that BNP levels are elevated in heart failure patients; however, all study participants had normal left ventricular function. The researchers conclude that the presence of AF should be taken into account when interpreting BNP levels in patients with heart disease. In other words, a high BNP level does not necessarily indicate heart failure, but could be due to atrial fibrillation.
American Journal of Cardiology, Vol. 93, June 15, 2004, pp. 1555-58

Hyperthyroidism and LAF.
It is generally accepted that hyperthyroidism (excessive thyroid hormone level) is a significant risk factor for atrial fibrillation. It is not clear though, just how significant. Brazilian researchers now report that the incidence of clinical hyperthyroidism and hypothyroidism (abnormally low thyroid levels) among AF patients presenting at an emergency department is quite high. They checked 72 afibbers for thyroid hormones (T3, T4 and TSH [high sensitivity]) and observed that 6.9% of them had hyperthyroidism, 5.6% had hypothyroidism, and 4.2% had increased T4 levels associated with the use of amiodarone (Cordarone). They conclude that the incidence of hyperthyroidism observed in AF patients is substantially higher than the incidence in the general population (0.7-2.7%).
Sao Paulo Medical Journal, Vol. 121, 2003, pp. 159-62

Folic acid reduces stroke risk.
Researchers at Harvard Medical School report that men with a high intake of folic acid and vitamin B12 have a significantly reduced risk of stroke. The study involved 43,732 male physicians whose medical records were available for the 14-year period 1986-2000. The physicians all completed dietary questionnaires every 4 years from 1986 on. During the observation period, a total of 725 strokes (455 ischemic, 125 hemorrhagic, and 145 strokes of unknown type) occurred in the group. This corresponds to an annual stroke incidence of 0.1% - significantly lower than the oft-quoted 1% for the US population as a whole. The researchers observed that participants with a folic acid intake of about 800 micrograms/day had a 30% lower incidence of ischemic stroke than did those with a daily intake of about 200 micrograms/day. They also noted that physicians with a vitamin B12 intake of about 20 micrograms/day had a 25% lower incidence of ischemic stroke than did those with an intake of about 5 micrograms/day. The incidence of hemorrhagic stroke was not affected by intake of vitamin B12 or folic acid. It is interesting that 93% of physicians with the highest folate intake were taking a daily multivitamin as compared to only 14% in the lowest intake group.
Stroke, Vol. 35, January 2004, pp. 169-74

BOOK REVIEW

The Magnesium Factor
by M.S. Seelig, MD, MPH and A. Rosanoff, PhD
Avery (Penguin Group, Inc), New York, 2003 ISBN 1583331565

The front cover of the paperback edition expands on the title as follows: "How one simple nutrient can prevent, treat and reverse high blood pressure, heart disease, diabetes, and other chronic conditions." A bold claim indeed! Dr. Seelig has been studying the role of magnesium in health and disease for over 35 years. She is chair of the Magnesium Advisory Board which oversees the New York Weill Cornell Medical Center's Magnesium Information Center. Dr. Rosanoff has been involved in the study of magnesium nutrition for the past 17 years. The authors' thesis is as follows; (a) Magnesium deficiency is widespread and aggravated in part by its removal from many foods during processing. (b) Magnesium is involved in innumerable human biochemical processes and is directly involved in the action of more than 350 enzymes and indirectly implicated in many more. (c) Magnesium deficiency is involved in many disease states, including heart disease, hypertension, Syndrome X and diabetes. (d) Deficiency is easily corrected with rather low levels of supplementation (up to 700 mg/d) or attention to diet or both. Supplements are inexpensive, safe for almost everyone, and normally very well tolerated.

The following list of chapters provides a good indication of the scope of this book and the relevance of magnesium to health and disease:

• Magnesium: the mineral that combats heart disease and keeps blood vessels healthy.
• Metabolic Syndrome X, diabetes and magnesium.
• High blood pressure, salt and magnesium.
• Obesity, physical activity and magnesium.
• Fat, cholesterol and magnesium.
• Magnesium, stress and the Type A personality.
• Magnesium and genetics; family history and sex differences.
• Magnesium and other heart disease risk factors.
• Are we really low in magnesium?
• Do you need more magnesium?
• Making sure you have enough magnesium.
• Magnesium, the silent guardian of our hearts and arteries.

In the chapter "Making Sure You Have Enough Magnesium," guidance is provided on maximizing magnesium from food and water, and on selecting supplements. Guidance is also given on the appropriate ratio of magnesium to calcium intake. Many readers will find the discussion of magnesium and hypertension of particular interest, and as well, the chapter titled "Fat, Cholesterol and Magnesium" contains a modern discussion of this subject which is currently very relevant. Included is a section on the HMG-CoA reductase inhibitory action of magnesium which includes a discussion of the similarities and differences in its action compared to the statin class of drugs which inhibits the same enzyme.

Ten appendices include a magnesium questionnaire which is provided for self-assessment of status, tables of common foods classified by magnesium content and a list of common medications that influence magnesium status. The book also contains some interesting case histories describing the almost magical effects of correcting a magnesium deficiency.

This appears to be an authoritative treatment of a very important subject, both for the layman and the health- care professional. It is up-to-date and comprehensive. The authors make a strong case that magnesium is clearly an important and often overlooked factor in some of the most serious and prevalent disorders that are encountered in the practice of medicine, in fact, frequently on a daily basis. It is probably true that not nearly enough attention is given to this essential mineral nor is there sufficient awareness of the potential role magnesium plays in a number of disease states or the need in some cases for aggressive supplementation. This book should provide a wake-up call.

Published in 2003, The Magnesium Factor includes very recent research and an extensive set of references. Unfortunately, while the references are listed by chapter, they are not cited in the text.

Reviewed by William R. Ware