Samir rafla antiarrhythmic drug therapy in hf and af , what is reasonable


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Antiarrhythmic drug therapy in Heart Failure and Atrial Fibrillation, what is reasonable?
Presented in the 8th International conference of the Egyptian Cardiac Arrhythmia Association (ECRA) on 23 October 2013

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Samir rafla antiarrhythmic drug therapy in hf and af , what is reasonable

  1. 1. Antiarrhythmic drug therapy in HF with AF, what is reasonable Prof. Samir Rafla, FACC, FESC Alexandria Univ. 1
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  3. 3. Recommendations for Use of Dronedarone (Multaq) in Atrial Fibrillation Class IIa 1.Dronedarone is reasonable to decrease the need for hospitalization for cardiovascular events in patients with paroxysmal AF or after conversion of persistent AF. Dronedarone can be initiated during outpatient therapy. (Level of Evidence: B 4
  4. 4. Recommendations for Use of Dronedarone in Atrial Fibrillation Class III–Harm 1. Dronedarone should not be administered to patients with class IV heart failure or patients who have had an episode of decompensated heart failure in the past 4 weeks, especially if they have depressed LV function (EF<35%). (Level of Evidence: B) 5
  5. 5. - The major adverse cardiac effects of dronedarone are bradycardia and QT prolongation. Torsades de pointes has been reported. - Like amiodarone, dronedarone inhibits renal tubular secretion of creatinine, which can increase plasma creatinine levels. However, there is no reduction in GFR. - Dronedarone increases digoxin levels 1.7- to 2.5-fold. 6
  6. 6. - Dronedarone is predominantly metabolized by the liver (CYP3A4). It can be administered with verapamil or diltiazem, but low doses of these agents should be used initially . - Dronedarone does not alter the INR when used with warfarin. - The recommended oral dose of dronedarone is 400 mg twice a day with meals. 7
  7. 7. Dronedarone - Adverse Events VARIABLE DRONEDARONE N=828 PLACEBO N=409 P value Stroke 4 (0.5) 3 (0.7) 0.69 Cough Dyspnea 19 (2.3) 7(1.7) 0.67 Hyperthyroidism Hypothyroidism 67/801 (8.4) 44/801 (5.5 56/396 (14.1) 14/396 (3.5) 0.002 0.15 Abnormal LFTs 100/822 (12.2) 55/404(13.6) 0.52 Elev of Serum Creatinine 20 (2.4) 1 (0.2) 0.004 Bradycardia Heart Failure 22 (2.7) 20 (2.4) 8 (2.2) 4 (1.0) 0.56 0.12
  8. 8. Dronedarone - ATHENA: Summary Dronedarone significantly prolongs time to first CV hospitalization or death in moderate- to high-risk AF patients All-cause mortality was not increased in patients receiving dronedarone CV mortality was lower in the dronedarone compared to the placebo group The reduction in CV hospitalization was mainly due to fewer admissions for AF and acute coronary syndromes The application of Dronedarone may be useful in low risk patients (only in NYHA Class I and II) Hohnloser SH. Heart Rhythm Society 2008 Scientific Sessions; May 15, 2008; San Francisco, CA.
  9. 9. Atrial Fibrillation and Acute Decompensated Heart Failure Although the optimal resting HR during AF is between 60 and 100 bpm, rates below 100 bpm may not be achievable during AHDF until volume overload and hypoxia have been corrected. A more realistic target is to achieve a HR < 120 bpm during the first hours of treatment. Digoxin should be the first rate-control agent considered. If the patient has already been taking digoxin, add doses only if serum digoxin concentration is <0.5 ng/mL. 10
  10. 10. Atrial Fibrillation and Acute Decompensated Heart Failure Cautious addition of small doses of an IV B blocker, usually metoprolol in 2.5- to 5-mg increments or, if systolic function is preserved, diltiazem will often be required. If rate control along with relief of volume overload and dyspnea can be achieved, patients will frequently revert back to SR if the AF episode is of recent onset. If the patient does not improve with these measures, meets anticoagulation criteria for conversion, and if not already on an antiarrhythmic drug, a trial of IV amiodarone may be helpful. 11
  11. 11. Amiodarone can be reloaded in patients already on chronic, moderate doses (<200 mg daily) but should not be added if the patient has been taking another antiarrhythmic drug that prolongs the QT interval, such as sotalol or dofetilide. If this approach fails and heart rates during AF remain elevated, cardioversion after a period of loading with an antiarrhythmic drug, usually amiodarone, is the next step. 12
  12. 12. Pharmacological Cardioversion of AF of up to 7 Days Duration Vernakalant IV or oral I 13
  13. 13. 15
  14. 14. 17
  15. 15. Torsade de Pointes Occurs in 1% of patients taking Amiodarone Predisposing conditions – LVH, congestive heart failure – Bradycardia – Hypokalemia – Hypomagnesemia – Digitalis therapy – Baseline QT prolongation – High drug concentration (except quinidine)
  16. 16. Patient Who Was Treated with Amiodarone for Atrial Fibrillation
  17. 17. Treatment of Torsade de Pointes Remove offending agent Temporary ventricular or atrial pacing Isoproterenol – Increases rate and decreases QT interval Lidocaine Mexiletine Phenytoin Magnesium
  18. 18. Porto-marina Beach - Egypt 24
  19. 19. Flecainide (Tambocor) & propafenone (Rythmol®) Toxicity and Cautions for Class IC Drugs: - They are proarrhythmic drugs causing worsening of a preexisting arrhythmia or de novo occurrence of life-threatening ventricular tachycardia - Notice: Class 1C drugs are particularly of low safety and have shown even to increase mortality when used chronically after MI.
  20. 20. With Sotalol (Betapace) and Dofetilide (Tikosyn), the QT interval should be monitored carefully during drug loading. Serum potassium levels should also be watched carefully; in fact, one should use torsades de pointes producing agents with caution in patients requiring potassium-wasting diuretics. 26
  21. 21. Dofetilide (Tikosyn) had no effect on cardiac output, cardiac index, or systemic vascular resistance in patients with ventricular tachycardia, mild to moderate congestive heart failure . Because increase in QT interval and the risk of ventricular arrhythmias are directly related to plasma concentrations of dofetilide, dosage adjustment based on calculated creatinine clearance is critically important 27
  22. 22. Ras Sidr Beach. Saini. Egypt 28
  23. 23. Atrial Specific AADs Vernakalant is a sodium channel blocker (I Na) and a potassium channel blocker. In ACT study, adverse events were reported in 32% of placebo recipients and 38% of Vernakalant recipients. No deaths or torsade de points were reported. 29
  24. 24. Vernakalant BRINAVESS is contraindicated in patients with severe aortic stenosis, systolic BP<100 mm Hg, and heart failure class III and IV. Vernakalant is contraindicated in patients with prolonged QT at baseline (uncorrected >440 msec), severe bradycardia, sinus node dysfunction, or second-degree or third-degree heart block in the absence of a pacemaker. 30
  25. 25. Vernakalant is also contraindictated in patients who use IV rhythm control antiarrhythmics (class I and class III) within 4 hours prior to administration of Vernakalant and patients with acute coronary syndrome (including myocardial infarction) within the last 30 days. Adverse reactions (>5%) seen in the first 24 hours after receiving Vernakalant were taste disturbance (20.1%), sneezing (14.6%), and paraesthesia (9.7%). 31
  26. 26. Ain Sokhna – Stella di Mare Hotel and Beach - Egypt 36