title: Pathophysiologic determinants of third heart sounds: a prospective clinical and Doppler echocardiographic study.
abstract: OBJECTIVE
  We sought to determine the importance of a third heart sound (S(3)) and its relation to hemodynamic and valvular dysfunction.
  
  
  METHODS
  We prospectively enrolled 580 patients who had isolated valvular regurgitation (mitral, n = 299; aortic, n = 121) or primary left ventricular dysfunction with or without functional mitral regurgitation (n = 160). We analyzed the associations between the clinical finding of an audible S(3) (as noted in routine clinical practice by internal medicine physicians) and hemodynamic alterations measured by comprehensive quantitative Doppler echocardiography.
  
  
  RESULTS
  S(3) was more prevalent in patients with primary left ventricular dysfunction (46%, n = 73) than in organic mitral (16%, n = 47) or aortic (12%, n = 14) regurgitation (P <0.001). Patients with an S(3) were more likely to have class III-IV symptoms (55% [74 of 137] vs. 18% [80 of 443] of those without an S(3), P <0.001) and had a higher mean [+/- SD] pulmonary pressure (55 +/- 15 vs. 41 +/- 11 mm Hg, P <0.001). An S(3) was also related to a higher early filling velocity due to a greater filling volume, restrictive filling, or both. An S(3) was a marker of severe regurgitation (regurgitant fraction > or =40%) in patients with primary left ventricular dysfunction (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.1 to 5.5), mitral regurgitation (OR = 17; 95% CI: 5.8 to 52), and aortic regurgitation (OR = 7.1; 95% CI: 1.8-28). An S(3) was also associated with restrictive filling in primary left ventricular dysfunction (OR = 3.0; 95% CI, 1.6 to 5.9), marked dilatation in mitral regurgitation (OR = 20; 95% CI: 6.8 to 58), and an ejection fraction (<50%) in aortic regurgitation (OR = 19; 95% CI: 6.0 to 62).
  
  
  CONCLUSIONS
  An audible S(3) is an important clinical finding, indicating severe hemodynamic alterations, and should lead to a comprehensive assessment and consideration of vigorous medical or surgical treatment.
authors.affiliation: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Tribouilloy
authors.forename: M
authors.initials: M
authors.lastname: Enriquez-Sarano
authors.forename: D
authors.initials: D
authors.lastname: Mohty
authors.forename: R A
authors.initials: RA
authors.lastname: Horn
authors.forename: K R
authors.initials: KR
authors.lastname: Bailey
authors.forename: J B
authors.initials: JB
authors.lastname: Seward
authors.forename: A M
authors.initials: AM
authors.lastname: Weissler
authors.forename: A J
authors.initials: AJ
authors.lastname: Tajik
mesh_terms: D000368:Aged; D001022:Aortic Valve Insufficiency / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001783:Blood Flow Velocity; D001794:Blood Pressure; D003937:Diagnosis, Differential; D003971:Diastole; D015150:Echocardiography, Doppler; D005260:Female; D006337:Heart Murmurs / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015588:Observer Variation; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure; D013318:Stroke Volume; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology*