Pathophysiologic determinants of third heart sounds: A prospective clinical and Doppler echocardiographic study

PURPOSE: We sought to determine the importance of a third heart sound (S₃) and its relation to hemodynamic and valvular dysfunction. SUBJECTS AND 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 S₃ (as noted in routine clinical practice by internal medicine physicians) and hemodynamic alterations measured by comprehensive quantitative Doppler echocardiography. RESULTS: S₃ 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 S₃ were more likely to have class III-IV symptoms (55% [74 of 137] vs. 18% [80 of 443] of those without an S₃, P <0.001) and had a higher mean [± SD] pulmonary pressure (55 ± 15 vs. 41 ± 11 mm Hg, P <0.001). An S₃ was also related to a higher early filling velocity due to a greater filling volume, restrictive filling, or both. An S₃ was a marker of severe regurgitation (regurgitant fraction ≥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 S₃ 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). CONCLUSION: An audible S₃ is an important clinical finding, indicating severe hemodynamic alterations, and should lead to a comprehensive assessment and consideration of vigorous medical or surgical treatment.