title: Prognostic Importance of Exercise Brain Natriuretic Peptide in Asymptomatic Chronic Organic Severe Mitral Regurgitation: An Observational Study.
abstract: BACKGROUND
  The optimal timing of surgery in patients with chronic organic severe mitral regurgitation (MR) continues to be debated, especially for those who are asymptomatic. The aim of the study was to determine independent and additive prognostic value of exercise brain natriuretic peptide (eBNP) in patients with severe asymptomatic MR and normal left ventricular ejection fraction (LVEF).
  
  
  METHODS
  Two hundred twenty-three consecutive patients with severe MR defined by effective regurgitant orifice (ERO) area ≥ 40 mm2and/or residual volume ≥ 60 mL, LVEF > 60%, and normal LV end-systolic diameter < 40 mm underwent symptom limited exercise treadmill test (TMT). Echocardiography was done immediately after exercise. Data were obtained within 3 minutes of peak exercise. BNP levels were assessed before echo (after 30 minutes of supine rest) and at exercise (i.e., within the 3 minutes of the end of effort). Patients were followed up every 3 months up to 15 months for major adverse cardiac events (MACEs) (cardiovascular death, need for mitral valve surgery and hospitalization for acute pulmonary edema or heart failure).
  
  
  RESULTS
  Mean age was 31.2 ± 9 years (range: 18 - 40) with majority being male (n = 153; 68%). Etiologies were rheumatic (n = 201; 90%), mitral valve prolapse (n = 17; 7.6%) and hypertrophic cardiomyopathy (n = 5; 2.4%). BNP level significantly increased from rest (65.24 ± 43.92 pg/mL; median: 43.5 pg/mL) to exercise (100.24 ± 98.24 pg/mL; median: 66.5 pg/mL; P < 0.001). Patients were divided into three tertiles according to eBNP levels (T1= 15 - 44; T2= 45 - 104; T3= 105 - 400). There was trend for significantly lower exercise time in T3. During TMT, 66 (29.5%) stopped exercise due to dyspnea. They had similar resting BNP level compared with others but had significantly higher eBNP level (136 ± 109.7 pg/mL vs. 84.88 ± 90.2 pg/mL; P < 0.001). During follow-up (15 months), MACE occurred in 83 patients (37.2%): mitral valve replacement (MVR) in 59 patients (symptomatic: 43; LV dilatation or dysfunction: 9; both symptoms and dilatation/dysfunction: 7), 17 hospitalizations for congestive heart failure, five patients developing acute pulmonary edema and atrial fibrillation in remaining two patients. This was 7.6%, 35% and 69% in T1, T2and T3, respectively and had significantly higher eBNP level than without any event (165 ± 119 pg/mL vs. 57 ± 48 pg/mL; P < 0.001). Using receiver operating characteristic curve analysis, the best cut-off value of eBNP level to predict cardiac events was 90 pg/mL (sensitivity: 75%; specificity: 88.6%; positive predictive value: 79%; negative predictive value: 83.9%).
  
  
  CONCLUSIONS
  In asymptomatic patients, eBNP level provides incremental prognostic value beyond echocardiographic data and those with elevated eBNP should be considered at high risk for reduced event-free survival and might be considered for early MVR.
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Sinha
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Garg
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Thakur
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Krishna
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Karandeep
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Sachan
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Goel
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Mahamdula
authors.initials: M
authors.lastname: Razi
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Umeshwar
authors.initials: U
authors.lastname: Pandey
authors.affiliation: Department of Cardiology, LPS Institute of Cardiology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh 208002, India.
authors.forename: Chandra Mohan
authors.initials: CM
authors.lastname: Varma
keywords: Dilatation; Dysfunction; Effective regurgitant orifice area; Exercise brain natriuretic peptide; MACE; Mitral regurgitation; Mitral valve replacement; Receiver operating characteristic curve; Tertiles