title: Effect of Ivabradine on Heart Rate and Duration of Exercise in Patients With Mild-to-Moderate Mitral Stenosis: A Randomized Comparison With Metoprolol.
abstract: BACKGROUND
  Symptoms in mitral stenosis (MS) are heart rate (HR) dependent. Increase in HR reduces diastolic filling period with rise in transmitral gradient. By reducing HR, beta-blockers improve hemodynamics and relieve symptoms, but the use may be limited by side effects. The present randomized crossover study looked at comparative efficacy of ivabradine and metoprolol on symptoms, hemodynamics, and exercise parameters in patients with mild-to-moderate MS (mitral valve area, 1-2 cm) in normal sinus rhythm.
  
  
  METHODS
  Baseline clinical assessment, treadmill stress testing, and an echocardiographic Doppler evaluation were performed to determine resting HR, total exercise duration, mean gradient across mitral valve, and mean pulmonary artery systolic pressure (PASP). Patients were then allocated to either metoprolol or ivabradine to maximal tolerated doses over 6 weeks (metoprolol: 100 mg twice a day, ivabradine: 10 mg twice a day). Reevaluation was done at the end of this period, and all drugs stopped for washout over 2 weeks. Thereafter, the 2 groups were crossed over to the other drug that was continued for another 6 weeks. Assessment was again performed at the end of this period.
  
  
  RESULTS
  Thirty-three patients of 34 completed the protocol. Fifteen were male, mean age was 28.9 ± 6.6 years, all were in New York Heart Association class 2, and mean resting HR was 103.5 ± 7.2/min. Mean mitral valve area was 1.56 ± 0.16 cm, mean PASP was 38.1 ± 5.1 mm Hg, and mean gradient across mitral valve was 10.6 ± 1.6 mm Hg. Significant decrease in baseline and peak exercise HR was observed at the end of follow-up with both drugs. Reduction in mitral valve gradient after ivabradine (42%) and metoprolol (37%) and reduction in PASP after both ivabradine (23%) and metoprolol (27%) were to a similar extent. Significant reduction in total exercise duration after both ivabradine and metoprolol therapy was observed. One patient developed blurring of vision with ivabradine therapy but did not require discontinuation of drug. An improvement in dyspnea of one grade was observed in all the patients by treatment with both ivabradine and metoprolol.
  
  
  CONCLUSIONS
  Both metoprolol and ivabradine reduced symptoms and improved hemodynamics significantly from baseline to a similar extent. Ivabradine thus can be used effectively and safely in patients with MS in normal sinus rhythm who are intolerant or contraindicated for beta-blocker therapy.
authors: *CARE Hospital, Department of Cardiology, The Institute of Medical Sciences, Hyderabad, India; †King George's Medical University, Department of Cardiology, Lucknow, India.
authors: Daljeet K
authors: DK
authors: Saggu
authors: Varun S
authors: VS
authors: Narain
authors: Sudhanshu K
authors: SK
authors: Dwivedi
authors: Rishi
authors: R
authors: Sethi
authors: Sharad
authors: S
authors: Chandra
authors: Aniket
authors: A
authors: Puri
authors: Ram K
authors: RK
authors: Saran
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D015150:Echocardiography, Doppler; D025401:Echocardiography, Stress; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007194:India; D000077550:Ivabradine; D008297:Male; D020714:Maximum Tolerated Dose; D008790:Metoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D008946:Mitral Valve Stenosis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D000077550:Ivabradine; D008790:Metoprolol
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