Archief Roodbont

High Risk of Coronary Ischemic Events Seen After First Atrial Fibrillation

Reuters Health Information 2007. © 2007 Reuters Ltd.
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NEW YORK (Reuters Health) May 17 - The risk of coronary ischemic events is high after first atrial fibrillation, according to findings published in the April issue of the American Journal of Medicine.
"Atrial fibrillation (AF) is a growing public health problem that has reached epidemic proportions," Dr. Teresa S. M. Tsang, of the Mayo Clinic, Rochester, Minnesota, and colleagues write. "Although studies have shown that the risk of acute coronary ischemic events at the time of first AF is low, there are no published longer term data."
The researchers examined the long-term, gender-specific incidence and mortality risk of coronary ischemic events after first AF in a community-based, longitudinal study involving 2768 residents of Olmsted County, Minnesota, with AF first documented in 1980 to 2000. The subjects did not have prior coronary heart disease, and were followed to 2004.
During a mean follow-up of 6 years, 463 (17%) of the participants had a first coronary ischemic event. The risk of coronary ischemic events was greatest during the first year.
The unadjusted incidence of coronary ischemic events after AF was 3.1 per 1000 person-years, with no difference between men and women. However, an association was observed between male sex and an increased risk of coronary ischemic events after adjusting for age (hazard ratio 1.32, p = 0.004).
"Restricting the analysis to the subgroup aged 30 to 74 years (n = 1403), the same age range for which the Framingham coronary risk equation was developed, the estimations of coronary event rates at 10 years were 22% for men and 19% for women by Kaplan-Meier analyses, versus 21% for men and 11% for women by Framingham risk equation," Dr. Tsang's team explains.
That is, atrial fibrillation conferred additional risk for coronary events "beyond conventional risk prediction in women only," the investigators point out. Furthermore, they found, the excess mortality risk associated with coronary events after the occurrence of AF was greater in women.
Am J Med 2007;120:357-363.

DIT IS EEN GOEDE SAMENVATTING VAN HET ARTIKEL.


Future Developments/Research

While the overall technique of cardioversion has changed little over the past 40 years, there have been a number of technical developments which have improved acute success rates. These include the rigorous attention to technical detail, biphasic cardioversion, and the use of adjuvant drugs for almost all from the start, including anti-arrhythmics and others. For those who remain resistant to this approach, internal cardioversion remains a potential option. The major challenge however is the prevention of recurrence; this can certainly be improved with conventional adjuvant anti-arrhythmics, probably with angiotensin converting enzyme (ACE) inhibition, and possibly with calcium antagonists in addition. A large trial examining the combination of all of these would be of great interest. It should of course be emphasized that a single recurrence on one anti-arrhythmic does not necessarily mean that the option has failed; for some patients infrequent periodic cardioversion, perhaps once a year, may be a very satisfactory result. In spite of the negative findings from ACUTE, it seems reasonable to cardiovert as early as practicable. In the future, the continued development of AF ablation will change the role of cardioversion; the return of sinus rhythm is only the start of the process. It is likely that the technique will further develop with new shock waveforms,[111] new anti-coagulants,[112] and novel atrial-selective anti-arrhythmics.[113] Cardioversion should therefore not be considered a strategy in itself, more part of a number of anti-arrhythmic strategies which can be selected for patients on an individual basis involving medication, ablation, and device therapies.

Maintenance of Sinus Rhythm Following Cardioversion

Even if the patient is cardioverted successfully, AF can recur. In the long-term, this will relate to the underlying pathology, that is, the combination of substrate and triggers which initiated the process in the first place. As discussed above, AF itself induces further electrophysiological and structural changes perpetuating the arrhythmia. A proportion of these are reversible in the face of the continued maintenance of sinus rhythm. These changes contribute additionally to the risks of immediate and early post-cardioversion failure. In the absence of anti-arrhythmic medication, the risk of recurrent AF following cardioversion in unselected patients is approximately 65%.[86] This can be reduced to approximately 50% using conventional drugs, such as quinidine, sotalol, flecainide, propafenone, and to approximately 35% with amiodarone.[87-90] The wisdom of considering cardioversion without concomitant anti-arrhythmic medication must be questionable other than in specific cases where the risk of recurrence is deemed to be low; for instance where AF occurs in the context of a transient medical condition, such as intoxication, thoracic surgery, or pneumonia.

Numerous studies over the last four decades investigating the effectiveness of anti-arrhythmic medication in this respect have been comprehensively reviewed in the ACC/AHA/ESC guidance on AF management[1] and by McNamara et al.[2] Drugs may themselves occasionally induce cardioversion in AF of short duration, that is, less than 7 days. Pharmacological attempts at cardioversion can be tried, particularly if electrical cardioversion is acutely contraindicated for anesthetic reasons. Furthermore, in selected patients it may be safe for these medications to be initiated on an outpatient basis in order to prevent hospital admission. This is the so-called "pill-in-the-pocket" approach and can be both clinically effective and cost-effective.[90]

The choice of anti-arrhythmic medication depends largely on patient factors. Class Ic drugs tend to be well-tolerated in young patients and are generally safe in patients with structurally normal hearts. Sotalol may be less well-tolerated by the young but may be preferable in those with coronary disease; its potential for proarrhythmia is shared by class Ia agents. Medication that has some intrinsic rate-slowing action (e.g., sotalol, propafenone) is often better tolerated should AF recur. Amiodarone is clearly the most effective agent with the lowest risk of proarrhythmia but its long-term extracardiac side effects are a significant limitation.

Recent advances in our understanding of the pathophysiology of AF have suggested two new strategies to improve long-term outcomes following cardioversion. Firstly, it is possible that drugs not conventionally thought to affect atrial electrophysiology may be of benefit, partly by reversing the effects of AF-induced remodeling. Secondly, early cardioversion may attenuate adverse atrial remodeling which may in turn promote the long-term maintenance of sinus rhythm.
Calcium Channel Blockade

Intracellular calcium overload appears to be an important step in the induction of AF-induced electrical remodeling. It has therefore been postulated that the use of calcium channel blockers may prevent or help to reverse this change. This hypothesis has led a number of groups to investigate the use of this medication in the prevention of AF recurrence. These studies are summarized in Table 4 . A proportion had positive outcomes, perhaps suggesting some role in the first week post-cardioversion. Not all of the studies were positive, however, and the use of this medication routinely for anything other than rate control remains controversial and is not formally recommended in current guidance.
Renin-Angiotensin System

As discussed earlier, the renin-angiotensin system appears important in atrial remodeling and may therefore contribute to the perpetuation of AF. Several studies, which have been published examining the effects of inhibitors of this system, are summarized in Table 4 . Although there are limited data, these medications may well affect recurrence, at least in the medium term. This impression is also suggested by the results of two recent meta-analyses[102,103] which examined the effects of these classes of drugs on AF in major, multi-center trials of hypertension, heart failure, and post-myocardial infarction patients. More studies are needed to prove this conclusively and whether this will lead to long-term improvements in sinus rhythm maintenance is uncertain.
HMG CoA Reductase Inhibitors

There is some evidence of the importance of oxidative stress and inflammation in the atria of AF patients. It has been the hypothesis in a couple of studies that treatment with the HMG CoA reductase inhibitors, the statins, may affect AF. A retrospective study of 62 patients strongly suggested a benefit from statin use[104] but this was not confirmed in the prospective randomized study of Tveit et al. in 114 patients.[105] Statin use cannot therefore be recommended at this stage for the prevention of recurrent AF following cardioversion.
Early Cardioversion as a Strategy to Prevent Remodeling

As remodeling is clearly important in the perpetuation of AF, at least a proportion of which is reversible, the concept of early and repeated cardioversion developed; the theory being that as the remodeling reversed, the time between AF recurrences would gradually lengthen, eventually producing long-term sinus rhythm maintenance. This has been examined in small studies[106]; although atrial electrophysiology appeared to improve, the effect on clinical outcome was disappointing. In order to simplify the process, an implantable atrial defibrillator was developed[107]; however, again the results were unsatisfactory in the long-term in a significant proportion of patients.[108] Clearly AF triggers and at least a part of the AF substrate remained; in a proportion the repeated shocks, even at low energy, were a significant disadvantage. The standalone atrial defibrillator never found widespread use although the capability to cardiovert AF, automatically or on command, remains a feature of certain ICDs.

Cardioversion of sustained AF traditionally requires a period of prior anti-coagulation (a month, following current guidelines) to minimize the thromboembolic risk. In theory this delay should increase atrial remodeling and thus the risk of AF recurrence after cardioversion. The ACUTE study[109,110] compared the strategy of early cardioversion guided by trans-esophageal echocardiography (TEE; to exclude pre-existing left atrial thrombus) to the conventional approach. One thousand two hundred and twenty-two patients with AF of more than 48 hours duration were randomized to either a conventional approach or a TEE-guided approach. Those in the TEE group were cardioverted sooner (TEE: 3.0 ± 5.6 days vs conventional: 30.6 ± 10.6 days; P < 0.001) and suffered fewer major and minor hemorrhagic events (TEE: 2.9% vs conventional: 5.5%; P = 0.03). Embolic events were equally infrequent, however (TEE: 0.8% vs conventional: 0.5%; P = 0.5). Acute cardioversion success was not different (TEE: 80.3% vs conventional: 79.9%; P = 0.9) as was maintenance of sinus rhythm at 8 weeks (TEE: 52.7% vs conventional: 50.4%; P = 0.43). Although this important study confirmed the safety of the echo-guided approach, it was disappointing in that the accelerated cardioversion strategy failed to have any impact on AF recurrence.

In conclusion, while this approach is safe, the shortening of the period before cardioversion may be insufficient to have a significant impact on atrial remodeling, and thus to improve the maintenance of sinus rhythm.
Future Developments/Research

While the overall technique of cardioversion has changed little over the past 40 years, there have been a number of technical developments which have improved acute success rates. These include the rigorous attention to technical detail, biphasic cardioversion, and the use of adjuvant drugs for almost all from the start, including anti-arrhythmics and others. For those who remain resistant to this approach, internal cardioversion remains a potential option. The major challenge however is the prevention of recurrence; this can certainly be improved with conventional adjuvant anti-arrhythmics, probably with angiotensin converting enzyme (ACE) inhibition, and possibly with calcium antagonists in addition. A large trial examining the combination of all of these would be of great interest. It should of course be emphasized that a single recurrence on one anti-arrhythmic does not necessarily mean that the option has failed; for some patients infrequent periodic cardioversion, perhaps once a year, may be a very satisfactory result. In spite of the negative findings from ACUTE, it seems reasonable to cardiovert as early as practicable. In the future, the continued development of AF ablation will change the role of cardioversion; the return of sinus rhythm is only the start of the process. It is likely that the technique will further develop with new shock waveforms,[111] new anti-coagulants,[112] and novel atrial-selective anti-arrhythmics.[113] Cardioversion should therefore not be considered a strategy in itself, more part of a number of anti-arrhythmic strategies which can be selected for patients on an individual basis involving medication, ablation, and device therapies.

Internal Cardioversion/Atrial Defibrillators (Uit hetzelfde artikel zie hieronder)

Internal (catheter-based) cardioversion, using micro-joule internal shocks, is ineffective for AF.[43] Conversely, high-energy internal shocks, delivered between a conventional diagnostic electrophysiology catheter and an indifferent plate, were found by Levy et al. to be effective in cases resistant to external cardioversion.[44] However, the high energies required led to safety concerns.[45] Subsequent developments have lead to the use of biphasic shocks given between electrodes positioned in the right atrium and either the coronary sinus or the pulmonary artery. These efficient configurations allow cardioversion of short-lived AF with less than 5 J and are also generally effective in longstanding AF even if resistant to conventional cardioversion.[46-49] Two comprehensive reviews of internal cardioversion have been published recently.[50,51]

Alt et al.[52] compared the two modalities in 187 patients. They found higher success with internal cardioversion (internal -- 93% vs external -- 79%; P < 0.01) and also found that internal cardioversion could find success where external failed. Others[53] have also confirmed this in latter findings.

Internal cardioversion has found widespread use in the last decade for patients resistant to external shocks, although it is likely that this group will dwindle considerably in the era of biphasic defibrillators (see below). Nevertheless, the technique will probably retain a place for patients with very large thoracic cages, the obese, and those for whom general anesthesia poses a risk. Additionally, it is a very useful technique for AF occurring in the electrophysiology laboratory. The extraordinary efficiency of biphasic internal shocks led to the development of atrial cardioversion by ICDs and to that of a standalone atrial defibrillator. This technology found favor among certain groups[54]; however, as success rates with ablation have significantly improved the limitations of this device (with respect to patient tolerability and its limited effect on the underlying pathophysiology), have led to its withdrawal from the market.
Biphasic Versus Monophasic Shocks

Undoubtedly, the greatest advance in cardioversion efficacy has been the advent of biphasic shocks. A biphasic shock waveform is known to reduce the ventricular DFT.[55] The same was seen in early studies of atrial DFTs in sheep.[56] This effect appears to relate to the differing effects of the two phases of the shock.[57] The initial phase appears to hyperpolarize the myocardium, allowing some recovery of sodium channels. The second depolarizing phase is subsequently more effective at producing depolarization in sufficient myocardium to terminate the arrhythmia. In addition, biphasic shocks appear less likely to reinitiate fibrillation. There has been considerable interest therefore in the use of biphasic shocks for the cardioversion of AF and a number of these studies are summarized in Table 2 .

These studies differ in the energy delivery protocols, electrode configurations, and waveform characteristics but uniformly have found that biphasic shocks are more effective than monophasic. This advantage is present whatever the precise waveform; indeed two recent studies have directly compared biphasic shock waveforms and found no difference in efficacy.[72,73] Biphasic shocks have a higher success rate than monophasic, with lower energy, lower current, and less skin and muscle damage. Biphasic shocks also appear less sensitive to TTI, which in other studies is a major determinant of cardioversion success. Devices used for biphasic shocks compensate for this impedance but even with impedance-compensation monophasic shocks remain inferior.[68]
Adjuvant Anti-arrhythmic Medication

A number of studies have examined the effects of anti-arrhythmic medication on acute cardioversion success. These are summarized in Table 3 and can be divided into observational retrospective studies, randomized trials investigating specific anti-arrhythmic agents, and acute studies formally examining the effects of medication on the atrial DFT by reinitiating AF before a further test.

From these studies, it is evident that several anti-arrhythmic medications may lower the atrial DFT and improve the immediate likelihood of cardioversion; ibutilide has found particular favor particularly in the United States.[81] Certainly no agent has been found to reduce success. Although it is not clear whether anti-arrhythmic medication is routinely advisable as an adjunct to cardioversion, its use is recommended in the event of initial failure.[1] It has been proposed that the use of adjuvant medication in association with biphasic cardioversion may increase success rates sufficiently to make internal cardioversion obsolete except during electrophysiological procedures. Data are awaited in this area.

Internal Cardioversion/Atrial Defibrillators

Internal (catheter-based) cardioversion, using micro-joule internal shocks, is ineffective for AF.[43] Conversely, high-energy internal shocks, delivered between a conventional diagnostic electrophysiology catheter and an indifferent plate, were found by Levy et al. to be effective in cases resistant to external cardioversion.[44] However, the high energies required led to safety concerns.[45] Subsequent developments have lead to the use of biphasic shocks given between electrodes positioned in the right atrium and either the coronary sinus or the pulmonary artery. These efficient configurations allow cardioversion of short-lived AF with less than 5 J and are also generally effective in longstanding AF even if resistant to conventional cardioversion.[46-49] Two comprehensive reviews of internal cardioversion have been published recently.[50,51]

Alt et al.[52] compared the two modalities in 187 patients. They found higher success with internal cardioversion (internal -- 93% vs external -- 79%; P < 0.01) and also found that internal cardioversion could find success where external failed. Others[53] have also confirmed this in latter findings.

Internal cardioversion has found widespread use in the last decade for patients resistant to external shocks, although it is likely that this group will dwindle considerably in the era of biphasic defibrillators (see below). Nevertheless, the technique will probably retain a place for patients with very large thoracic cages, the obese, and those for whom general anesthesia poses a risk. Additionally, it is a very useful technique for AF occurring in the electrophysiology laboratory. The extraordinary efficiency of biphasic internal shocks led to the development of atrial cardioversion by ICDs and to that of a standalone atrial defibrillator. This technology found favor among certain groups[54]; however, as success rates with ablation have significantly improved the limitations of this device (with respect to patient tolerability and its limited effect on the underlying pathophysiology), have led to its withdrawal from the market.
Biphasic Versus Monophasic Shocks

Undoubtedly, the greatest advance in cardioversion efficacy has been the advent of biphasic shocks. A biphasic shock waveform is known to reduce the ventricular DFT.[55] The same was seen in early studies of atrial DFTs in sheep.[56] This effect appears to relate to the differing effects of the two phases of the shock.[57] The initial phase appears to hyperpolarize the myocardium, allowing some recovery of sodium channels. The second depolarizing phase is subsequently more effective at producing depolarization in sufficient myocardium to terminate the arrhythmia. In addition, biphasic shocks appear less likely to reinitiate fibrillation. There has been considerable interest therefore in the use of biphasic shocks for the cardioversion of AF and a number of these studies are summarized in Table 2 .

These studies differ in the energy delivery protocols, electrode configurations, and waveform characteristics but uniformly have found that biphasic shocks are more effective than monophasic. This advantage is present whatever the precise waveform; indeed two recent studies have directly compared biphasic shock waveforms and found no difference in efficacy.[72,73] Biphasic shocks have a higher success rate than monophasic, with lower energy, lower current, and less skin and muscle damage. Biphasic shocks also appear less sensitive to TTI, which in other studies is a major determinant of cardioversion success. Devices used for biphasic shocks compensate for this impedance but even with impedance-compensation monophasic shocks remain inferior.[68]
Adjuvant Anti-arrhythmic Medication

A number of studies have examined the effects of anti-arrhythmic medication on acute cardioversion success. These are summarized in Table 3 and can be divided into observational retrospective studies, randomized trials investigating specific anti-arrhythmic agents, and acute studies formally examining the effects of medication on the atrial DFT by reinitiating AF before a further test.

From these studies, it is evident that several anti-arrhythmic medications may lower the atrial DFT and improve the immediate likelihood of cardioversion; ibutilide has found particular favor particularly in the United States.[81] Certainly no agent has been found to reduce success. Although it is not clear whether anti-arrhythmic medication is routinely advisable as an adjunct to cardioversion, its use is recommended in the event of initial failure.[1] It has been proposed that the use of adjuvant medication in association with biphasic cardioversion may increase success rates sufficiently to make internal cardioversion obsolete except during electrophysiological procedures. Data are awaited in this area.

Uit electrical cardioversion for AF--The state of the art

Biphasic Versus Monophasic Shocks

Undoubtedly, the greatest advance in cardioversion efficacy has been the advent of biphasic shocks. A biphasic shock waveform is known to reduce the ventricular DFT.[55] The same was seen in early studies of atrial DFTs in sheep.[56] This effect appears to relate to the differing effects of the two phases of the shock.[57] The initial phase appears to hyperpolarize the myocardium, allowing some recovery of sodium channels. The second depolarizing phase is subsequently more effective at producing depolarization in sufficient myocardium to terminate the arrhythmia. In addition, biphasic shocks appear less likely to reinitiate fibrillation. There has been considerable interest therefore in the use of biphasic shocks for the cardioversion of AF and a number of these studies are summarized in Table 2 .

These studies differ in the energy delivery protocols, electrode configurations, and waveform characteristics but uniformly have found that biphasic shocks are more effective than monophasic. This advantage is present whatever the precise waveform; indeed two recent studies have directly compared biphasic shock waveforms and found no difference in efficacy.[72,73] Biphasic shocks have a higher success rate than monophasic, with lower energy, lower current, and less skin and muscle damage. Biphasic shocks also appear less sensitive to TTI, which in other studies is a major determinant of cardioversion success. Devices used for biphasic shocks compensate for this impedance but even with impedance-compensation monophasic shocks remain inferior.[68]

Hello:

The intent of the article is not to invoke fear, but to insist on better blood pressure control and minimize the use of concomitant aspirin. Unfortunately, only coumadin-like drugs have been shown to greatly minimize the risk of ischemic stroke. Aspirin alone will also increase the risk of intracerebral hemorrhage. Your risk of ischemic stroke with atrial fibrillation is still considerably higher than the risk of a bleed. Ischemic stroke is associated with a 24% 30-day mortality. If it were me, I would definitely stay on marcoumar. There hopefully will be newer agents in the next few years with a more predictable level of "blood thinning."

Hope this has been helpful. I would hardly consider any veterinary surgeon "simple"!!

Best wishes,
Elaine Hylek

________________________________

From: Jan Goossens [mailto:roodbont@zonnet.nl]
Sent: Tue 5/22/2007 7:42 AM
To: Hylek, Elaine
Subject: atrial fibrillation

Dear doctor Hylec

My medical doctor diagnosed atrium fibrillation 23 November 2006, and
prescribed me Marcoumar. By blood control the INR has to be between 2
and 3. It varies until now between 1,75 and 3,5.
I am a simple veterinary surgeon, 82 years old and have to use now and
than a couple of celebrex pills, when gout comes up. Moreover I use
omeprazole to keep my stomach quiet. To keep my blood pressure adequate
I use 4mg perindopril and since my atrium fibrilation 50 mg atenolol.
I had not to much troubles with my atrium fibrillation, except now and
than heart palpations.
Reading an article in Neurology 2007; 68: 116-121 by M.L. Flaherty et
al.: The increasing incidence of anticoagulant-associated intra cerebral
hemorrhage and your article in Circulation, May 2007 I think maybe it is
better to use 80 mg aspirin with or
without persantin (pirydamole) to avoid anticoagulant-associated
intra cerebral hemorrhage.
In the meantime I got a cardioversion at 18 May 2007 and my heart is
working normally again.
I would be much obliged to you, if you let me know if you can agree with
my supposition and I can discus it with my doctor.
sincerely yours Jan Goossens.

This electronic transmission may contain information that is privileged, confidential and exempt from disclosure under applicable law. If you are not the intended recipient, please notify me immediately as use of this information is strictly prohibited.

Published online before print May 21, 2007
(Circulation 2007, doi:10.1161/CIRCULATIONAHA.106.653048)
Submitted on July 21, 2006
Accepted on March 13, 2007

Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation
Elaine M. Hylek MD, MPH*, Carmella Evans-Molina MD, Carol Shea RN, Lori E. Henault MPH, and Susan Regan PhD
From the Department of Medicine (E.M.H., L.E.H.), Section of General Internal Medicine-Research Unit, Boston University School of Medicine, Boston Medical Center, and Department of Medicine (C.S., S.R.), General Medicine Division, Massachusetts General Hospital, Boston, Mass; and Department of Medicine (C.E.-M.), University of Virginia, Charlottesville, Va.
* To whom correspondence should be addressed. E-mail: ehylek@bu.edu.

Background--Warfarin is effective in the prevention of stroke in atrial fibrillation but is under used in clinical care. Concerns exist that published rates of hemorrhage may not reflect real-world practice. Few patients 80 years of age were enrolled in trials, and studies of prevalent use largely reflect a warfarin-tolerant subset. We sought to define the tolerability of warfarin among an elderly inception cohort with atrial fibrillation.
Methods and Results--Consecutive patients who started warfarin were identified from January 2001 to June 2003 and followed for 1 year. Patients had to be 65 years of age, have established care at the study institution, and have their warfarin managed on-site. Outcomes included major hemorrhage, time to termination of warfarin, and reason for discontinuation. Of 472 patients, 32% were 80 years of age, and 91% had 1 stroke risk factor. The cumulative incidence of major hemorrhage for patients 80 years of age was 13.1 per 100 person-years and 4.7 for those <80 years of age (P=0.009). The first 90 days of warfarin, age 80 years, and international normalized ratio (INR) 4.0 were associated with increased risk despite trial-level anticoagulation control. Within the first year, 26% of patients 80 years of age stopped taking warfarin. Perceived safety issues accounted for 81% of them. Rates of major hemorrhage and warfarin termination were highest among patients with CHADS2 scores (an acronym for congestive heart failure, hypertension, age 75, diabetes mellitus, and prior stroke or transient ischemic attack) of 3.
Conclusions--Rates of hemorrhage derived from younger noninception cohorts underestimate the bleeding that occurs in practice. This finding coupled with the short-term tolerability of warfarin likely contributes to its underutilization. Stroke prevention among elderly patients with atrial fibrillation remains a challenging and pressing health concern.

Key words: anticoagulants • atrial fibrillation • hemorrhage • stroke

Mihale O'Riordan
Heartwire 2007 Medscape

After adjustment for multiple cofounders, those who drank daily had a 2.6 times greater risk of being in the atrial-fibrillation and atrial-flutter cohort. After researchers controlled for the same confounders, the increased risk remained significant in subjects <60 years of age when they compared atrial-fibrillation and -flutter subjects without arrhythmia but only trended toward significance when compared with SVT patients alone.

When investigators examined the progressive risk of atrial fibrillation and flutter with different amounts of alcohol consumed, there was a trend toward greater risk with more alcohol consumed. Drinking more and more alcohol, on the other hand, was significantly associated with an increased risk of atrial flutter.

"Even at the recommended one to two drinks per day," Marcus told heartwire, "there was an increased and significant risk for atrial flutter."

While alcohol in limited amounts is known to be cardioprotective, many patients with atrial fibrillation might be under the impression that they should be drinking one or two drinks per day, said Marcus. "But I think we need to study this further, especially in atrial-fibrillation patients." he said. "My message would be that they should try to avoid alcohol, and not just binge drinking but also daily consumption, until we know better."

R

The dose-response relationship was seen across age, race, weight, baseline fitness, and hormone therapy subgroups.

Participants’ systolic and diastolic blood pressure levels, weight, and most other cardiovascular risk factors were not significantly altered with any level of exercise.

However, waist circumference, which was similar in each group at baseline, was significantly reduced at the end of the study in all 3 exercise groups compared with the control group (p<0.05 for each). This was a significant finding given the importance of increased risk of insulin resistance, diabetes, and metabolic syndrome, and mortality associated with abdominal obesity, Church and team emphasize.

“Perhaps the most striking finding of our study is that even activity at the 4-kcal/kg per week level (approximately 72 min per week) was associated with a significant improvement in fitness compared with women in the nonexercise control group,” the team comments.

JAMA 2007; 297: 2081-2091

Waist-to-hip ratio
The waist-to-hip ratio measurement can be used to help determine obesity. The distribution of fat is evaluated by dividing waist size by hip size. A person with a 30-inch waist and 40-inch hips would have a ratio of .75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The higher the ratio, the higher the risk of heart disease and other obesity-related disorders.

COX-2 Inhibitor plus PPI Reduces Bleeding in High-Risk Patients

Adding a proton-pump inhibitor to celecoxib treatment in patients at very high risk for ulcer bleeds greatly reduces the incidence of bleeding, according to a Lancet report.

Some 270 patients taking nonselective NSAIDS for arthritis and presenting with upper-GI bleeding underwent randomization — after their ulcers had healed — to treatment with either celecoxib (200 mg twice daily) plus esomeprazole (20 mg twice daily), or celecoxib alone, for a year. The 13-month incidence of recurrent ulcer bleeding was 0% in the combination-therapy group and 8.9% in the controls.

Commentators write that "the finding provides clear guidance for those individuals at greatest gastrointestinal risk who require an NSAID." They add that the new gastrointestinal data should not be interpreted "without careful consideration of competing risks from the cardiovascular perspective."

L

New guidelines on catheter and surgical ablation for AF unveiled

10 May 2007

MedWire News: The first international consensus statement on catheter and surgical ablation techniques to treat atrial fibrillation (AF) has been released at the 28th annual meeting of the US Heart Rhythm Society (HRS) in Denver, Colorado.

The statement aims to improve patient care by providing physicians with a comprehensive review of the techniques in AF. Studies have shown that three-quarters of patients with AF receive inappropriate care.

“These guidelines are a major step toward helping physicians provide better, safer, and more consistent care for heart patients worldwide,” said chair of the HRS scientific and clinical guidelines committee Hugh Calkins, from Johns Hopkins University in Baltimore, Maryland, USA.

The statement was developed by a Task Force convened by the HRS that includes international heart rhythm specialists representing the American Heart Association, the European Heart Rhythm Association, the European Cardiac Arrhythmia Society, and the Society of Thoracic Surgeons HRS.

It stresses that, since ablation of AF is more complicated than other ablation procedures, training should encompass six fundamental principles: appropriate selection of patients; knowledge of the anatomy of the atria and adjacent structures; conceptual knowledge of strategies to ablate AF; technical competence; recognition, prevention, and management complications; and appropriate follow-up and long-term management.

Of note, the primary indication for catheter ablation of AF is the presence of symptomatic AF refractory or intolerant to at least one Class 1 or Class 3 anti-arrhythmic medication. It may rarely be considered as first-line therapy.

The Task Force states that catheter ablation of AF is also appropriate in selected symptomatic patients with heart failure and/or reduced ejection fraction. In contrast, catheter ablation as an alternative to long-term anticoagulation is not appropriate, and left atrial thrombus is a contraindication, it says.

Meanwhile, surgical AF ablation is indicated for symptomatic AF patients undergoing other cardiac surgery; selected asymptomatic patients undergoing cardiac surgery in whom the ablation carries minimal risk; and stand-alone surgery in symptomatic AF patients who prefer a surgical approach, have failed previous catheter ablation attempts, or are not candidates for catheter ablation.

“We felt it was important to develop these guidelines so that patients in every corner of the world can receive the highest quality of care available,” commented Task Force member and president-elect of the EHRA Josep Brugada, from the University of Barcelona, Spain.

Heart Rhythm Society Annual Scientific Sessions; Denver, Colorado: 9-12 May 2007

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Vorhofflimmern und Vorhofflattern sind Störungen der Reizbildung im Herzen. Sie müssen behandelt werden, da sonst schwere Komplikationen drohen.



Ursache:
Die elektrische Erregung des Herzens erfolgt normalerweise vom Sinusknoten aus und wird von dort über den rechten und den linken Vorhof zum AV – Knoten und dann über das His`sche Bündel zur Herzkammer geleitet. Die Leistung des Vorhofes trägt zu etwa 20 % zur Herzleistung bei. Beim Vorhofflimmern kommt es zu einer ungeordneten Reizbildung im Vorhof mit einer Frequenz von etwa 350 – 400 Erregungen pro Minute. Ursächlich diskutiert wird hierfür eine Erregung, die so langsam im Vorhof kreist, dass sie immer wieder auf Gewebe trifft, das erneut erregbar ist und dadurch die hohen Frequenzen entstehen. Treffen diese ungeordneten Erregungen auf den AV – Knoten, werden sie unregelmäßig an die Kammer weiter geleitet und erreichen dann aufgrund der Verzögerung im AV – Knoten Frequenzen von 40 – 180 Schlägen pro Minute. Für das Zustandekommen dieser ungeordneten Bewegungen sind überwiegend Herzkrankheiten verantwortlich, daher kommt die Erkrankung im Alter auch häufiger vor und beträgt mit 80 Jahren 6 %. Neben Herzkrankheiten wie KHK, Herzinfarkt, Herzmuskelentzündungen und vor allem Mitralklappenfehler können auch das Syndrom des kranken Sinusknotens (sick sinus), eine Überfunktion der Schilddrüse, ein schwerer akuter Blutdruckanstieg (hypertone Krise) oder eine chronische Lungenerkrankung (COPD) zu Vorhofflimmern oder Vorhofflattern führen. Es kommen jedoch auch Fälle ohne jede Ursache vor und auch familiäre Häufungen sind beschrieben. Beim Vorhofflattern sind dieselben Ursachen verantwortlich wie beim Vorhofflimmern. Es entstehen hierbei nur Flatterwellen mit einer Frequenz von ca. 250 – 350 pro Minute. Meist wird die Überleitung durch einen AV – Block gebremst, so dass die Kammern dann in einer Frequenz von 125 – 150 schlagen. Wird die Erregung vollständig übergeleitet, was bei Vorhofflattern wegen der geringeren Frequenz geschehen kann, kommt es zu lebensbedrohlichem Herzrasen. Vorhofflattern ist viel seltener als Vorhofflimmern.



Feststellen der Erkrankung:
Manchmal spürt der Betroffene den unregelmäßigen Herzschlag. Beim Tasten des Pulses kann er festgestellt werden. Die endgültige Diagnose wird dann mit Hilfe des EKG und Rhythmusstreifen (längere Aufzeichnung des EKG) gestellt.



Beschwerden:
Es müssen keine Beschwerden vorliegen. Vorhofflimmern wird manchmal auch zufällig vom Arzt entdeckt. Häufig bemerkt jedoch der Patient Herzrasen oder eine Beklemmung in der Brust bzw. eine Leistungsminderung oder Müdigkeit. Schlafstörungen kommen ebenso vor wie Atemnot. Es kann jedoch auch eine schwere Herzschwäche auftreten.



Behandlung:
Die größte Gefahr besteht darin, dass sich durch die unregelmäßigen, schnellen Bewegungen und den fehlenden Blutausstoß Blutgerinnsel im Bereich der Vorhofwand bilden und mit dem Blutstrom fortgeschwemmt werden. Dadurch kann es zu sehr gefährlichen Embolien in den Blutgefäßen kommen. Bei Verstopfung einer Arterie fällt das Gebiet, das von ihr versorgt wird, aus und es kommt zum Absterben des betroffenen Bezirks. Dies kann z. B. zu einem Schlaganfall führen (25 % aller Schlaganfälle werden durch eine vom Herzen stammende Embolie ausgelöst, ca. 15 % der schweren Schlaganfälle entstehen durch Vorhofflimmern). Daher wird heute immer eine Blutverdünnung durchgeführt, wenn nicht ein ernsthafter Grund dagegen spricht. Außerdem versucht man, die Herzschlagfolge wieder zu normalisieren, um das Herz nicht zu überlasten und einen ausreichenden Blutausstoß zu erreichen. Meistens wird hierzu heute ein Betablocker eingesetzt. Je früher eine Behandlung einsetzt, desto größer ist die Chance, die Störung wieder beseitigen zu können. Daher ist eine frühzeitige Behandlung so wichtig. Dies kann nur versucht werden, wenn kein sick sinus Syndrom vorliegt und kein schwerer Mitralfehler besteht (schwerer als Stadium II). Die Beseitigung versucht man zunächst medikamentös mit einem Mittel gegen Rhythmusstörungen. Erreicht man hiermit keinen Erfolg, kann eine Elektrokardioversion (Elektroschock) versucht werden, wenn von medizinischer Seite nichts dagegen spricht. Dabei versetzt man den Patienten in Schlaf und dem Herzen von außen einen massiven Stromstoß von 10 – 100 Wsec, um für eine kurze Zeit alle Erregungen anzuhalten. Normalerweise erholt sich hiervon der Sinusknoten am schnellsten, so dass er seine normale Funktion wieder aufnimmt. Besteht das Vorhofflimmern schon länger, muss mit dem Vorhandensein von Blutpfröpfen in den Vorhöfen gerechnet werden und man verdünnt deshalb zunächst das Blut des Betroffenen, bevor man die Elektrokardioversion durchführt.
Als Rhythmus stabilisierendes Medikament ist Amiadoron zunächst in hoher Dosierung (1500 mg in 24 Stunden), dann zum Aufrechterhalten des normalen Herzrhythmus in einer Dosierung von etwa 200 mg pro Tag das Medikament erster Wahl.



Nach den neuen Leitlinien sollen Patienten unter 75 Jahre mit Vorhofflimmern und Gefäßrisiken wie Bluthochdruck und koronare Herzerkrankung eine Blutverdünnung(Antikoagulation mit Phenprocoumon) erhalten und auf einen INR von 2,0 – 3,0 eingestellt werden, Patienten über 75 auf einen INR von 2.0. Patienten unter 65 Jahren, die nur Vorhofflimmern haben und keine anderen Gefäßrisiken, können ASS 300 mg einnehmen, Patienten über 65 ohne weitere Risiken oder bei Unverträglichkeit von Antikoagulantien sollen ASS einnehmen.

Physician's First Watch for May 7, 2007

David G. Fairchild, MD, MPH, Editor-in-Chief

Arrow BMJ Reviews Beta-Blockers in Hypertension and Cardiovascular Disease
BMJ Reviews Beta-Blockers in Hypertension and Cardiovascular Disease

A clinical review article in this week's BMJ addresses the use of beta-blockers in patients with hypertension and cardiovascular disease. The author discusses, among other studies, recent research that suggests that beta-blockers may be inferior to other classes of antihypertensive drugs at preventing cardiovascular outcomes in hypertensive patients.

The author makes the following points:

— Not all beta-blockers are the same: Some are more effective in reducing post-MI mortality (acebutolol, metoprolol, propranolol, and timolol), others improve prognosis in heart failure (bisoprolol, carvedilol, and metoprolol), and a couple may improve prognosis in patients with coronary artery disease (metoprolol and bisoprolol).

— Atenolol may be inferior to other antihypertensive drugs in reducing cardiovascular disease in hypertensive patients.

— Age makes a difference. In patients under 60, beta-blockers are equivalent to other antihypertensive drugs in reducing cardiovascular outcomes; in older patients, they appear to be less effective.

BMJ article (Free abstract; full text requires subscription)

Joint National Committee hypertension guidelines (Free)

AF prevalence lower in poorest people

1 May 2007

MedWire News: Research highlighting the growing burden of atrial fibrillation (AF) suggests that the chronic arrhythmia is less common among patients with the poorest socioeconomic status.

The study authors say that this probably reflects poorer detection, prognosis, or both in more deprived individuals.

The study, carried out in Scotland, also reveals that women and older people – who are at high risk of stroke - often do not receive recommended AF therapies.

Noting a lack of information on the epidemiology, primary care burden, and treatment of AF in the community, John McMurray (Western Infirmary, Glasgow, UK) and colleagues studied trends in AF prevalence, incidence, referrals, and treatment using cross-sectional data from primary care practices participating in the Scottish Continuous Morbidity Recording scheme between April 2001 and March 2002.

The study included a total of 362,155 patients, 3135 with AF, at 55 primary care practices.

The overall prevalence of AF was 8.7/1000 people and was higher in men than women, at 9.4/1000 versus 7.9/1000 (p<0.001), McMurray and team report in the journal Heart.

The prevalence increased with age, from 0.3/1000 in the <45-years age group to 30.5/1000 in the age range 65-74 years, and more than doubled to 70.7/1000 in those >85 years.

Age- and gender-standardized prevalence of AF decreased with increasing socioeconomic deprivation, from 9.2/1000 in the least deprived to 7.5/1000 in the most deprived category (p for trend=0.02). Deprived individuals had an 18% lower relative rate of AF.

Women and older individuals were less likely to be prescribed warfarin than men and younger individuals and older patients were less likely to be prescribed rate-controlling treatment with a calcium channel blocker of beta blocker.

The authors conclude: “AF is a common condition, more so in men than women. Deprived individuals are less likely to have AF, a finding raising concerns about socioeconomic gradients in detection and prognosis.”

In an accompanying editorial, Gregory Lip (City Hospital Birmingham, UK) and colleagues agreed that the low rate of AF in the lowest socioeconomic group could reflect a poorer rate of detection in this group.

“Indeed, the lowest socioeconomic group had the least contact with their general practitioner,” they noted.

Heart 2007; 93: 606-612

Study Highlights

* Classic symptoms of ICH include the sudden onset of a focal neurologic deficit, which progresses over minutes to hours. Vomiting is more common with ICH than with ischemic stroke or subarachnoid hemorrhage.
* Either CT or MRI may be used for initial neuroimaging of patients suspected of having ICH, but MRI may be more difficult to perform because of impaired consciousness, vomiting, or agitation.
* Recombinant factor VIIa has demonstrated promise in early trials in terms of reducing hematoma size, mortality, and 90-day disability among patients with ICH, but further testing is necessary to assess this therapy.
* If systolic blood pressure exceeds 200 mm Hg in a patient with ICH, continuous intravenous antihypertensive therapy should be considered. A target blood pressure of 160/90 mm Hg is reasonable.
* Treatment of elevated ICP should begin with conservative measures, such as elevation of the head of the bed, analgesia, and sedation. Further steps can include osmotic therapy with mannitol or hyperventilation, which can be associated with hypovolemia and decreased cerebral blood flow, respectively.
* Serum glucose levels should be lowered to at least less than 300 mg/dL after ICH.
* Patients with hemiparesis or hemiplegia following ICH should receive prophylaxis with intermittent pneumatic compression stockings. These patients may receive low-molecular-weight heparin after 3 to 4 days following cessation of bleeding.
* Patients with ICH who develop acute proximal venous thrombosis should be considered for acute placement of a vena cava filter.
* Patients who develop ICH while receiving warfarin should receive intravenous vitamin K. Prothrombin complex concentrate, factor IX complex concentrate, and recombinant activated factor VII can reduce patients' international normalized ratio very rapidly and with less fluid infusion vs fresh frozen plasma, but these newer therapies are associated with a higher risk for thromboembolism.
* The decision of whether to reinitiate warfarin therapy following ICH should be individualized based on the patient's risk for repeat ICH and thromboembolism. Warfarin may be restarted 7 to 10 days following ICH among patients at high risk for thromboembolism.
* Surgical intervention should be considered for patients with cerebellar hemorrhage of 3 cm or greater who are deteriorating neurologically. Patients with brainstem compression or ventricular obstruction resulting from hemorrhage may also be considered for surgical intervention. Patients with lobar clots within 1 cm of the surface may be considered for evacuation of ICH with craniotomy.

Pearls for Practice

* ICH accounts for up to 15% of first-time strokes and associated mortality rates can exceed 50%. Half of patients with ICH who die do so in the first 2 days following hemorrhage.
* The current guidelines for patients with ICH recommend initial conservative measures to reduce ICP and prophylaxis against deep venous thrombosis for all ICH patients with limited mobility. Warfarin therapy may be restarted among patients with ICH who are at high risk for thromboembolism.

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High Calcium, Vitamin D Intake in the Elderly May Have a Down Side

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# Rozerem™ (ramelteon) 8-mg tabletsView indications, efficacy data, and safety data. Full Prescribing Information.


By Megan Rauscher

NEW YORK (Reuters Health) May 01 - In one of the first studies to examine the relationship between diet and brain lesions, researchers observed a significant positive correlation between higher calcium and vitamin D intakes and total brain lesion volume on MRI in a group of elderly adults.

"Our finding of a relationship between brain lesions and consumption of both calcium and vitamin D raises the question about a possible downside to high intakes of these nutrients," Dr. Martha E. Payne of Duke University, Durham, North Carolina, told Reuters Health.

"Since our study was cross-sectional, we cannot conclude that calcium or vitamin D caused the brain lesions that we found. However, we hypothesize that our findings may be due to vascular calcification, whereby calcium is taken up into the blood vessel walls," Dr. Payne said.

She and colleagues assessed calcium and vitamin D intakes by food frequency questionnaires and MRI scans in 232 elderly men and women (average age, 71 years).

All of the subjects displayed some brain lesions of varying sizes but those reporting the highest intakes of calcium and vitamin D were significantly more likely to have higher total volume of brain lesions as measured across several MRI scans.

These positive associations remained significant in two separate multivariable models controlling for age, hypertension, diabetes, heart disease, and depression. In a multivariable model containing both calcium and vitamin D, only vitamin D remained significantly positively associated with lesion volume.

Dr. Payne noted that "higher intakes of calcium and vitamin D have been promoted in recent years as a way to prevent bone loss with aging. We are concerned that some of this extra calcium may end up in the blood vessel walls rather than the bone. This may be a particular problem for individuals with renal disease since calcium excretion may be impaired," she said.

"A longitudinal study," Dr. Payne concludes, "is urgently needed in order to determine if calcium and vitamin D lead to vascular calcification and brain lesions in the long term."

She reported the study findings at a meeting of the American Society for Nutrition, part of Experimental Biology 2007 underway in Washington, DC.