Atrial

Background: The presence of substantial mitral annular area reduction prior to ventricular systole suggests an atrial influence on annular dynamics. We implanted radiopaque myocardial markers in normal sheep to investigate the effects of acute LV ischemia on atrial contraction, mitral annular area (MAA), and mitral regurgitation. Methods: Six adult sheep had radiopaque markers placed on the left ventricle, mitral annulus, left atrium (LA) and the central edge of both mitral leaflets. After 6-8 days, animals were studied with biplane videofluoroscopy and transesophageal echocardiography before and during sequential balloon occlusion of the LAD, distal LCX, and proximal LCX coronary artery. MAA and LA area were calculated from the corresponding markers. Percent reduction in these parameters was calculated between maximum in late diastole and minimum in early systole. MR (0-4) was assessed by TEE. Results: LAD occlusion did not alter LA area reduction (14.8±8.4% and 14.8±5.8% for preischemia and ischemia, respectively; p=0.9) or pre-systolic MAA reduction (68±25% and 69±14%; p=0.9) whereas dLCX occlusion resulted in a mild decrease in the former (16.4±3.4% and 12.4±6.2%; p=.04) with no change in the latter (79±18% and 70±23%; p=0.3). Neither occlusion resulted in MR. pLCX occlusion, however, significantly decreased LA area reduction (16.5±3.2% and 5.6±4.0%; p=0.005) and pre-systolic MAA reduction (79±16% and 35±23%; p=0.01) and resulted in increased end-diastolic MAA (7.09±1.50cm and 8.46±2.01cm; p=0.006), delayed valve closure from end-diastole (52±26 ms and 92±23 ms; p=0.03) and mitral regurgitation (0.5±0.5 and 2.0±1.1; p=0.007). Conclusion: Atrial contraction is closely coupled to pre-systolic mitral annular area reduction. Decreased atrial contractile function, as observed during acute posterolateral ischemia, is linked to diminished pre-systolic mitral annular reduction, a larger mitral annular size at end-diastole, and mitral regurgitation. Atrial contraction in acute ischemiaFinal Accepted Version H-00149-2002.R1 3

'SUMMARY Atrial fibrillation is relatively common, particularly among the elderly. Management requires identifying and treating the causes. Treatment aims at improving overall cardiac status. A number of patient factors determine whether treatment should focus on establishing sinus rhythm (electrically or with drugs) and maintaining it or on controlling ventricular rate. For most patients, anticoagulants are recommended to prevent pulmonary thromboembolism.
La fibrillation auriculaire est une pathologie relativement frequente, particulierement chez les personnes agees. La  creases with age to about 4% in those older than 60 years. The management ofa condition with this prevalence is important for all physicians.
The first step is the diagnosis, which is based on a history ofpalpitations, and findings on physical examination of an irregularly irregular pulse, the absence of a waves in the jugular venous pressure, and variation in the intensity of the first heart sound. The definitive diagnosis is made from the electrocardiograph, by the absence of P waves, rapid irregular atrial activity (usually at the rate of 350 to 600 cycles per minute), the usual QRS complex, and irregularly irregular ventricular depolarization. The fibrillatory waves in the baseline electrocardiogram are usually best seen in leads II, III, and VI.
The second step in the management of atrial fibrillation is the identification of the cause of the arrhythmia. Causes of atrial fibrillation (Table 1) include thyrotoxicosis, mitral stenosis, sick sinus syndrome, acute myocardial infarction, and alcohol excess. Various acute stress conditions may precipitate atrial fibrillation, including infections-Dr Rabkin is a Prfessor ofMedicine, iirison of Cardiologv, Unwersity Hospital (Shaughnessy Site), at the Universiy ofBitish Colwnbia, Vancouver especially pneumoniapericarditis, and pulmonary embolism. The management of atrial fibrillation involves managing its causes. Heart failure is a common cause of atrial fibrillation. Decreasing left ventricular size and left atrial size can help reestablish sinus rhythm or reduce recurrences once sinus rhythm has been restored. Other causes, such as hyperthyroidism, recent surgely, myocardial infarction, pulmonary embolism, pericarditis, and infection, require separate attention.
The third step in management is deciding on treatment. The clinician must assess whether atrial fibrillation has resulted in clinical and hemodynamic deterioration and determine reasonable time frames for improvement. Treatment goals can include: * reducing or alleviating symptoms ofpalpitations, angina, heart failure, or hypotension; * improving overall cardiac function; * improving exercise tolerance; and * decreasing the risk of embolic complications. The first decision the clinician must make is whether to attempt cardioversion to sinus rhythm or to leave the patient in atrial fibrillation and control the ventricular response.
Restoration of sinus rhythm Electrical cardioversion is necessary after the acute onset of atrial fibrillation when the consequences of the arrhythmia (such as pulmonary edema or hypotension) are threatening. For patients with chronic atrial fibrillation, conversion to sinus rhythm should be considered because of the symptoms of fatigue and palpitations and the risk of thromboembolism.
Electrical conversion is not offered for patients with long-standing atrial fibrillation or large left atrium in whom the probability of conversion to sinus rhythm is low or maintenance ofsinus rhythm is low. Similarly, patients who are not limited by symptoms from their atrial fibrillation, especially the elderly, are not offered cardioversion. However, for younger patients, especially those with normal left ventricular function, cardioversion to sinus rhythm can considerably improve exercise capacity.'

Control of ventricular response
The clinician must decide whether the ventricular rate is too fast or too slow and whether it requires management. Avoid the tendency to treat an arrhythmia just because it exists.
If the ventricular rate is normal, with some degree of impaired conduction across the atrioventricular node, then no drug treatment may be necessary, unless excessive heart rate responses to exercise are noted.
Patients with atrial fibrillation and a slow ventricular response usually have conduction system disease and must be treated differently, because therapy with such drugs as digoxin and verapamil, which prevent conduction across the atrioventricular node, can further slow the ventricular response. Electrical cardioversion of such patients must be done with caution, as sinus arrest or slow nodal escape rhythms can follow electrical cardioversion. Atrial fibrillation with a slow ventricular response is an indication for a pacemaker, if potentially reversible factors are not found.
The most common situation, however, is rapid ventricular response to atrial fibrillation. The treatment response must take into account the patient's hemodynamic stability. If the patient is hemodynamically unstable, then cardioversion may be necessary. If the patient is hemodynamically stable, then the objective is rate control. If the problem is acute, the patient may be digitalized with intravenous digoxin or intravenous verapamil2; the objective is to re-duce the ventricular rate to between 90 and 100 beats per minute.3 In chronic atrial fibrillation, the doses of digitalis, calcium antagonists (verapamil or diltiazem), or n-blockers are adjusted to obtain optimal heart rate. What is the optimal heart rate? There is no definitive answer to the question of the optimal heart rate in patients with atrial fibrillation. Rawles3 has proposed a ventricular rate of 90 beats/min, at rest, based on the need for a slightly faster than normal heart rate to maintain normal cardiac output when atrial contribution to cardiac output is lost in atrial fibrillation. This suggestion was based on data from Doppler-estimated cardiac output in patients with atrial fibrillation. Ventricular rate must also be able to increase to accommodate the increased demands during exercise.
Wolff-Parkinson-White syndrome A special consideration is the patient with Wolff-Parkinson-White syndrome (WPW). Atrial fibrillation can be serious in patients who have WPW (bypass) conduction because atrial impulses may spread to the ventricle, causing a very fast rate. Even worse, the spread of fibrillatory waves can induce ventricular fibrillation. Digitalis can produce adverse effects in WPW if it slows conduction across the atrioventricular node and permits conduction across the accessory pathway.
The therapy ofpatients with atrial fibrillation and WPW is opposite to the usual atrial fibrillation therapy. Such drugs as digoxin and verapamil should be avoided because they slow conduction across the atrioventricular node, can accelerate conduction over the accessory pathway, and can lead to ventricular fibrillation. Quinidine, procainamide, disopyramide, propafenone, and amiodarone all prolong conduction in the accessory pathway and therefore slow the ventricular response. Intravenous procainamide can be useful in treatment ofacute onset ofatrial fibrillation in a patient with WPW.
Preventing recurrence Once sinus rhythm has been restored, recurrent atrial fibrillation is prevented by using one or more of the following drugs to maintain the patient in sinus rhythm.
Antiarrhythmic drugs. Quinidine is the traditional agent used to prevent recurrence of atrial fibrillation. It continues to be used frequently because of its long-standing use and known efficacy and side effects, but there has been concern recently about the dangers of its use in this condition.4 Antiarrhythmic drugs, such as propafenone, which have been classified as type I-C agents, are definitely useful in preventing recurrences of atrial fibrillation. However, the risk of wide QRS tachyarrhythmia in patients receiving these agents, although slight, has led to the suggestion that they be used only after other antiarrhytimic agents have failed.5 n-Blockers. 1 Amiodarone. Amiodarone is effective in preventing recurrent atrial fibrillation, but the complexity of its toxicity and dosage makes it a drug to be reserved for difflcult' cases.
Drug combinations. In a recent study, 109 patients with recurrent episodes of symptomatic atrial fibrillation or flutter who had failed one to five previous antiarrhythmic trials were treated with propafenone and subsequently with sotalol.8 A

Refractory cases
One procedure should be considered for patients with atrial fibrillation that is resistant to drug therapy, including multiple drugs, and whose ventricular rate is too fast or who have frequent episodes of recurrent atrial fibrillation. Electrical ablation of the atrioventricular node and insertion of a permanent pacemaker into the ventricle may benefit some of these patients. Rate-responsive pacemakers, which increase the heart rate with increases in the person's activity, permit patients to have more of an increase in cardiac output with exercise, and excessive responses are eliminated because the patient's own atrioventricular node has been ablated.
Thromboembolism Relative rtisk. Thromboembolism is a significant and important factor for most patients with atrial fibrillation. Longitudinal studies have reported an almost fourfold increase in mortality from stroke.9 Furthermore, patients with chronic atrial fibrillation may suffer cerebral dysfunction that appears to be due to "silent" emboli.' " In a retrospective analysis of 54 patients with symptoms of cerebral ischemia, 13% had computed tomographic evidence of previous clinically silent cerebral infarctions; incidence in a control group was only about 4%. Previous myocardial infarction is a significant risk for the development of thromboembolism in patients with atrial fibrillation.'" The risk of thromboembolic complications in patients with chronic atrial fibrillation increases considerably when atrial fibrillation is due to or associated with rheumatic heart disease. The estimated risk for such patients is more than 15 times the normal. Risk factors for embolism include a large left atrium (although this is debated). However, there is no excess risk of embolic complication associated with paroxysmal atrial fibrillation, a type in which the person goes from sinus rhythm to atrial fibrillation and then back spontaneously. The low risk could reflect the short duration of fibrillation. The risk of stroke is also low for patients younger than 60 with lone atrial fibrillation, a label applied when there is no other evidence ofheart disease.12 Prevention. Drug therapy can be effective in preventing systemic thromboembolism in patients with atrial fibrillation. In a double-blind, randomized Danish trial (the AFASAK study),'3 more than 1000 patients with chronic nonrheumatic atrial fibrillation were followed. One third received anticoagulants with warfarin; one third received acetylsalicylic acid, 75 mg once daily; and one third received a placebo. Each patient was followed for 2 years or until the termination of the trial.
The primary end points were thromboembolic complications, such as stroke, transient ischemic attacks, or embolic complications to the viscera. The secondary end point was death. The incidence of thromboembolic complications in vascular mortality were significantly lower in the warfarin-treated group; the ASA and placebo groups did not differ significantly (Table 21'"4). One hundred twenty-six (38%) patients on warfarin withdrew from the study, 23 because of nonfatal bleeding.'3 In contrast, only 44 (13%) withdrew from ASA treatment.
In a multicenter, randomized, controlled trial in the United States,'4 anticoagulation therapy with warfarin or ASA reduced embolic events by over 50% in patients with atrial fibrillation without valvular heart disease or heart failure. Acetylsalicylic acid was effective prophylaxis in this study, though not in the AFASAK trial. The difference in results may be explained by the higher ASA dose in the American study (325 mg) and the difference in population. The American study excluded patients older than 75 years ofage or with heart failure. No benefit ofanticoagulation therapy was found in patients with atrial fibrillation but without any other kind of heart disease (lone atrial fibrillation). A comparison of ASA and warfarin in this study is still pending.
Thus patients with chronic atrial fibrillation and with other signs of heart disease should receive anticoagulation therapy to prevent systemic emboli. Acetylsalicylic acid is as effective as warfarin for patients younger than 75 years and without heart failure.