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 (S(3)) 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 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). CONCLUSION: 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.

Plasma homocysteine and severity of thoracic aortic atherosclerosis.

STUDY OBJECTIVES: Plasma homocysteine level is a risk factor for coronary events, stroke, and peripheral atherosclerotic disease. However, few data are available concerning the relationship between homocysteine level and severity of thoracic aortic atherosclerosis. We hypothesized in this multiplane transesophageal echocardiography (TEE) study that homocysteine level is a marker of the presence and severity of thoracic aortic atherosclerosis. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENTS: Risk factors, angiographic features, and TEE findings were analyzed prospectively in 82 valvular patients. MEASUREMENTS AND RESULTS: The following risk factors were recorded: age, gender, hypertension, smoking, lipid parameters, diabetes, body mass index, and family history of coronary artery disease. Plasma levels of homocysteine, vitamin B(12), and folic acid were measured for each patient. By univariate analysis, age, diabetes, hypertension, smoking, family history of coronary artery disease, and levels of homocysteine, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significant predictors of the presence of thoracic aortic plaques. There was a positive correlation between the plasma homocysteine levels and the score of severity of thoracic atherosclerosis (r = 0.48; p = 0.0001) as well as between the homocysteine levels and the grades of severity of aortic intimal changes (p = 0.0008). Multivariate regression analysis revealed that homocysteine was an independent predictor of the presence and severity of thoracic aortic atherosclerosis. CONCLUSION: This prospective study indicates that plasma homocysteine level is a marker of severity of thoracic atherosclerosis detected by multiplane TEE. These findings emphasize the role of homocysteine as a marker of atherosclerotic lesions in the major arterial locations.

Quantification of tricuspid regurgitation by measuring the width of the vena contracta with Doppler color flow imaging: a clinical study.

OBJECTIVE: We sought to evaluate the vena contracta width (VCW) measured using color Doppler as an index of severity of tricuspid regurgitation (TR). BACKGROUND: The VCW is a reliable measure of mitral and aortic regurgitation, but its value in measuring TR is uncertain. METHODS: In 71 consecutive patients with TR, the VCW was prospectively measured using color Doppler and compared with the results of the flow convergence method and hepatic venous flow, and its diagnostic value for severe TR was assessed. RESULTS: The VCW was 6.1+/-3.4 mm and was significantly higher in patients with, than those without, severe TR (9.6+/-2.9 vs. 4.2 +/- 1.6 mm, p<0.0001). The VCW correlated well with the effective regurgitant orifice (ERO) by the flow convergence method (r = 0.90, SEE = 0.17 cm2, p<0.0001), even when restricted to patients with eccentric jets (r = 0.93, p < 0.0001). The VCW also showed significant correlations with hepatic venous flow (r = 0.79, p < 0.0001), regurgitant volume (r = 0.77, p<0.0001) and right atrial area (r = 0.46, p< 0.0001). A VCW > or =6.5 mm identified severe TR with 88.5% sensitivity and 93.3% specificity. In comparison with jet area or jet/right atrial area ratio, the VCW showed better correlations with ERO (both p<0.01) and a larger area under the receiver operating characteristic curve (0.98 vs. 0.88 and 0.85, both p<0.02) for the diagnosis of severe TR. CONCLUSIONS: The VCW measured by color Doppler correlates closely with severity of TR. This quantitative method is simple, provides a high diagnostic value (superior to that of jet size) for severe TR and represents a useful tool for comprehensive, noninvasive quantitation of TR.

Assessment of severity of aortic regurgitation using the width of the vena contracta: A clinical color Doppler imaging study.

BACKGROUND: The width of the vena contracta (VC-W), the smallest area of regurgitant flow, reflects the degree of valvular regurgitation and is measurable by color Doppler imaging, but this method has not been validated in aortic regurgitation (AR). METHODS AND RESULTS: We prospectively examined 79 patients with isolated AR and 80 patients without regurgitation. The VC-W was measured from the long-axis parasternal view and compared with 2 simultaneous reference methods (quantitative Doppler and 2D echocardiography). In patients without regurgitation, the agreement between methods was excellent. In patients with AR, good correlations (all P<0.0001) were obtained between VC-W and effective regurgitant orifice (ERO) area and regurgitant volume recorded by quantitative Doppler (r=0.89 and 0.90, respectively) and 2D echocardiographic (r=0.90 and 0.89, respectively) methods. These correlations were similar with eccentric or central jets (all P>0.60). The other methods used showed good correlations of VC-W with aortographic grading of AR (n=8, r=0.82, P=0.01), with the proximal flow convergence method (n=53, r=0.85, P<0.0001), and with left ventricular end-diastolic volume (r=0.81, P<0.0001). Sensitivity and specificity of VC-W >/=6 mm for diagnosing severe AR (ERO >/=30 mm(2)) were 95% and 90%, respectively. CONCLUSIONS: For assessment of the degree of AR, VC-W shows good correlations with simultaneous quantitative measures (regardless of jet direction), shows good correlations with other methods of assessment of AR, and provides a high diagnostic value for severe AR. VC-W is a simple, reliable method that can be used clinically as part of comprehensive Doppler echocardiographic assessment of AR.

Functional anatomy of mitral regurgitation: accuracy and outcome implications of transesophageal echocardiography.

OBJECTIVES: This study was performed to determine the accuracy and outcome implications of mitral regurgitant lesions assessed by echocardiography. BACKGROUND: In patients with mitral regurgitation (MR), valve repair is a major incentive to early surgery and is decided on the basis of the anatomic mitral lesions. These lesions can be observed easily with transesophageal echocardiography (TEE), but the accuracy and implications for outcome and clinical decision-making of these observations are unknown. METHODS: In 248 consecutive patients operated on for MR, the anatomic lesions diagnosed with TEE were compared with those observed by the surgeon and those seen on 216 transthoracic echocardiographic (TTE) studies, and their relationship to postoperative outcome was determined. RESULTS: Compared with surgical diagnosis, the accuracy of TEE was high: 99% for cause and mechanism, presence of vegetations and prolapsed or flail segment, and 88% for ruptured chordae. Diagnostic accuracy was higher for TEE than TTE for all end points (p < 0.001), but the difference was of low magnitude (<10%) except for mediocre TTE imaging or flail leaflets (both p < 0.001). The type of mitral lesions identified by TEE (floppy valve, restricted motion, functional lesion) were determinants of valve repairability and postoperative outcome (operative mortality and long-term survival; all p < 0.001) independent of age, gender, ejection fraction and presence of coronary artery disease. CONCLUSIONS: Transesophageal echocardiography provides a highly accurate anatomic assessment of all types of MR lesions and has incremental diagnostic value if TTE is inconclusive. The functional anatomy of MR defined by TEE is strongly and independently predictive of valve repairability and postoperative outcome. Therefore, the mitral lesions assessed by echocardiography represent essential information for clinical decision making, particularly for the indication of early surgery for MR.

Relation between low-density lipoprotein cholesterol and thoracic aortic atherosclerosis.

This prospective study, which included 320 patients, showed that total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol, and triglycerides correlate with thoracic aortic atherosclerosis. Low-density lipoprotein cholesterol is identified as an independent predictor of thoracic aortic plaque related to the severity of thoracic aortic atherosclerosis.

Determinants of pulmonary venous flow reversal in mitral regurgitation and its usefulness in determining the severity of regurgitation.

Pulmonary venous flow (PVF) reversal is observed in mitral regurgitation (MR) and can be detected by Doppler echocardiography. However, the determinants of PVF alterations in MR have not been analyzed with simultaneous quantitative methods, and the diagnostic accuracy of flow reversal is uncertain. Prospectively, in 128 patients with isolated MR of various degrees (regurgitant fraction 4% to 81%), Doppler echocardiography was used to measure PVF velocity simultaneously to quantify MR by 2 methods and to perform a comprehensive hemodynamic assessment. Systolic PVF velocity was 4 +/- 56 cm/s (systolic flow reversal in 39 patients) and showed the strongest correlations with mitral effective regurgitant orifice (r = -0.56, p <0.0001). In multivariate analysis, larger effective regurgitant orifice (p <0.0001), eccentric jets (p = 0.0023), longer jets (p = 0.0033), and lower mitral regurgitant velocity (p = 0.0015) were independent determinants of decreased systolic PVF velocity. In organic MR, increased filling pressures were associated with systolic PVF reversal. Blunted systolic flow was associated with shorter mitral deceleration time (p <0.0001) and enlarged left atrium (p = 0.0007). For the diagnosis of severe MR (regurgitant orifice > or = 35 mm2, regurgitant fraction > or = 50%), systolic flow reversal sensitivity was 61% and 60%, and specificity was 92% and 85%, respectively. Among 29 patients in whom surgery demonstrated severe mitral lesions, 12 (41%) had no systolic flow reversal preoperatively. In patients with MR, the determinants of systolic PVF are complex and, in addition to the degree of MR, include the hemodynamic consequences of MR, jet characteristics, left ventricular filling, and left atrial volume alterations. Consequently, systolic PVF reversal is a useful sign of severe MR but of relatively low sensitivity, emphasizing the importance of quantifying MR.

Use of echocardiography in the management of congestive heart failure in the community.

OBJECTIVES: We evaluated the use and the impact of echocardiography in patients receiving an initial diagnosis of congestive heart failure in Olmsted County, Minnesota, in 1991. BACKGROUND: The American College of Cardiology/American Heart Association clinical practice guidelines recommend echocardiography in all patients with suspected congestive heart failure. No data are available on use and impact of echocardiography in management of congestive heart failure in a community. METHODS: The medical records linkage system of the Rochester Epidemiology Project was used to identify all 216 patients who satisfied the Framingham criteria for congestive heart failure. Of these, 137 (63%) underwent echocardiography within 3 weeks before or after the episode of congestive heart failure (Echo group), and the other 79 patients constitute the No-Echo group. RESULTS: The No-Echo group patients were older (p=0.022), were more likely to be female (p=0.072), had milder symptoms (p=0.001) and were less often hospitalized at diagnosis (p=0.001). Fewer patients in the No-Echo group were treated with angiotensin-converting enzyme inhibitors (p=0.001). Advanced age (> or = 80 years), lower New York Heart Association functional class, absence of a fourth heart sound on examination, absence of cardiomegaly or signs of congestive heart failure on chest radiography and absence of known valve disease were independently related to the decision not to obtain an echocardiogram. Survival after adjustment for age, functional class and gender was lower in the No-Echo group than the Echo group (risk ratio=0.607, p=0.017). CONCLUSIONS: The underuse of echocardiography appears to be associated with poorer survival and underuse of angiotensin-converting enzyme inhibitor therapy.

Congestive heart failure in the community: trends in incidence and survival in a 10-year period.

OBJECTIVE: To compare the incidence of congestive heart failure and the survival in patients with congestive heart failure in Rochester, Minn, in 1981 with that observed in 1991. METHODS: Population-based, descriptive epidemiological study with ecological and individual level comparisons over time. Olmsted County, Minnesota, where the Rochester Epidemiology Project provides passive surveillance of the population for health outcomes. All 248 patients fulfilled the Framingham criteria, 107 patients presenting with the new onset of congestive heart failure in 1981 and 141 patients in 1991. The community inpatient and outpatient medical records of all incident cases were reviewed to evaluate the presenting characteristics of patients at diagnosis. RESULTS: The incidence of congestive heart failure after adjustment for age and sex to the US population was not significantly different in the 1991 cohort compared with that in 1981 (3.0 per 1000 person-years; 95% confidence interval, 2.5-3.5 vs 2.8 per 1000 person-years; 95% confidence interval, 2.2-3.3; P = .55). The survival of patients with new diagnosis of congestive heart failure was similar in the 2 cohorts (P = .53). Survival adjusted for age, sex, and New York Heart Association functional class was not significantly different in patients with congestive heart failure in 1981 and 1991 (relative risk, 0.907; P = .55). CONCLUSIONS: These data suggest that recent advances in management of cardiovascular disease, as used in the community, had not yet impacted incidence or survival of patients with congestive heart failure in the community during the 10-year study period. This highlights the need to continue efforts to ensure that advances in diagnosis and therapy are incorporated into the care of patients with congestive heart failure in the community.

Impact of preoperative symptoms on survival after surgical correction of organic mitral regurgitation: rationale for optimizing surgical indications.

BACKGROUND: Surgical correction of mitral regurgitation in patients with no or mild symptoms remains controversial, particularly because the impact of preoperative symptoms on postoperative outcome is unknown. METHODS AND RESULTS: The long-term outcome of 478 patients with organic mitral regurgitation (199 in NYHA functional class I/II and 279 in class III/IV before surgery) operated on between 1984 and 1991 was analyzed. In patients in NYHA class I/II before surgery compared with those in class III/IV, postoperative long-term survival was higher (at 10 years, 76+/-5% versus 48+/-4%, P<0.0001), with lower operative mortality (0.5% versus 5.4%, P=0.003) and better late survival (P<0.0001). Comparison of observed and expected survival showed identical curves in patients in class I/II before surgery (P=0.18), whereas excess mortality was observed in patients in class III/IV before surgery (P<0.0001). Excess mortality associated with severe symptoms was also confirmed in all subgroups (all P<0.003) and in multivariate analysis (P=0.0036; adjusted hazard ratio [95% CI], 1.81 [1.21 to 2.70]). CONCLUSIONS: In patients with organic mitral regurgitation, preoperative functional class III/IV symptoms are associated with excess short- and long-term postoperative mortality independently of all baseline characteristics. These data should lead to consideration of surgical correction of severe organic mitral regurgitation when no or minimal symptoms are present in patients at low operative risk, especially if repair is feasible.

Excess mortality due to coronary artery disease after valve surgery. Secular trends in valvular regurgitation and effect of internal mammary artery bypass.

BACKGROUND: During the 1980s, mortality from coronary artery disease (CAD) decreased markedly in the United States. This raises the question of whether a parallel decrease occurred in excess mortality due to CAD in patients undergoing surgical correction of valvular regurgitation. METHODS AND RESULTS: Survival of 752 patients (age, 64 +/- 13 years) with isolated left-sided valvular regurgitation operated on from 1980 to 1991 was analyzed. Of 242 patients with CAD (stenosis > or = 70%), 208 had coronary artery bypass grafting. Multivariate analysis identified CAD as an independent predictor of operative mortality (odds ratio [OR] = 2.35, P = 0.012), overall (hazard ratio [HR] = 1.65, P < 0.0001) and late mortality (HR = 1.57, P = 0.0006), and postoperative congestive heart failure (HR = 2.35, P = 0.0001). Comparison of patients operated on in 1980 to 1985 with those operated on in 1986 to 1991, excess of operative, overall, and late mortality and postoperative congestive heart failure (adjusted for age and gender) related to associated CAD did not decrease significantly (P = 0.23, P = 0.64, P = 0.90, and P = 0.61, respectively). Overall survival was better for patients receiving an internal mammary artery graft than those receiving vein grafts only (HR = 0.57, P = 0.011). CONCLUSIONS: In contrast to the secular trend for decreased mortality from CAD, excess mortality related to associated CAD after surgery for valvular regurgitation has not decreased. Internal mammary artery grafts were associated with improved outcome. In patients with valvular regurgitations, these results support continued active search of associated CAD, wide use of internal mammary artery graft, and vigorous efforts for secondary prevention of complications of CAD.

Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991.

BACKGROUND: Data are limited regarding the classification and prognosis of patients with congestive heart failure (CHF) in the community. METHODS AND RESULTS: Using the resources of the Rochester Epidemiology Project, we evaluated all patients receiving a first diagnosis of CHF in Olmsted County, Minnesota, in 1991 (n=216). Among these patients, 88% were >/=65 years and 49% were >/=80 years of age. The prognosis of patients with a new diagnosis of CHF was poor; survival was 86+/-2% at 3 months, 76+/-3% at 1 year, and 35+/-3% at 5 years. Of the 216 patients, 137 (63%) had an assessment of ejection fraction. In these patients, systolic function was preserved (ejection fraction >/=50%) in 59 (43%) and reduced (ejection fraction <50%) in 78 (57%). Survival adjusted for age, sex, NYHA class, and coronary artery disease was not significantly different between patients with preserved and those with reduced systolic function (relative risk, 0.80; P=0.369). ACE inhibitors were used in only 44% of the total population with CHF. CONCLUSIONS: The present study reports the clinical characteristics and natural history of CHF as it presents in the community in the vasodilator era. CHF is a disease of the "very elderly," frequently occurs in the setting of normal ejection fraction, and has a poor prognosis, regardless of the level of systolic function. Diagnostic and therapeutic methods are underused in the community.

Application of the proximal flow convergence method to calculate the effective regurgitant orifice area in aortic regurgitation.

OBJECTIVES: We sought to determine the reliability of the proximal isovelocity surface area (PISA) method for calculation of effective regurgitant orifice (ERO) of aortic regurgitation (AR). BACKGROUND: The ERO area can be calculated by the PISA method, but this method has not been validated in AR. METHODS: ERO calculation by the PISA method was undertaken prospectively in 71 consecutive patients with isolated AR and achieved in 64 and compared with two simultaneous reference methods (quantitative Doppler and quantitative two-dimensional echocardiography). In addition, this method was compared with angiography in 12 patients, with surgical assessment in 18 patients and with ventricular volumes in all patients. RESULTS: Good correlations between PISA and reference methods were obtained (both r=0.90, both p < 0.0001), but a trend toward underestimation of the ERO by the PISA method was noted (24+/-19 vs. 26+/-22 mm2 and 27+/-23 mm2, respectively, both p=0.04). However, this trend was confined to five patients with an obtuse flow convergence angle (>220 degrees), and on multivariate analysis this variable was the only independent determinant of underestimation of the ERO. In contrast, in 59 patients with a flat flow convergence (< or =220 degrees ), the PISA method, in comparison with reference methods, showed excellent correlations, with a narrow standard error of the estimate (r=0.95, SEE 5.4 mm2, and r=0.95, SEE 5.8 mm2; all p < 0.0001) and no trend toward underestimation (22+/-18 vs. 23+/-16 mm2, p=0.44, and vs. 23+/-18 mm2, p=0.34). CONCLUSIONS: In patients with AR, the PISA method can be used to measure the ERO with reasonable feasibility. Underestimation of the ERO by PISA may occur in patients with an obtuse flow convergence angle. However, in most patients with appropriate flow convergence, PISA provides reliable measurement of the ERO of AR.

Exercise echocardiography: technique and diagnostic value.

Exercise echocardiography has experienced a rapid rise in clinical acceptance because of its recognized ability to detect coronary artery disease in addition to attractive features such as portability, versatility and relatively low cost. To achieve and maintain accuracy and diagnostic yield, adequate training of the sonographer and the cardiologist is essential.

Determinants of the pulmonary artery pressure rise in left ventricular dysfunction.

Pulmonary artery hypertension in patients with left ventricular dysfunction is related to poor outcome but the role of cardiac functional abnormalities in the genesis of pulmonary hypertension remains unknown. The aim of this prospective study was to identify the determinants of pulmonary hypertension in 102 consecutive patients with primary left ventricular dysfunction (ejection fraction < 50%). Systolic pulmonary artery pressure was measured by continuous wave Doppler. Left ventricular systolic and diastolic function, severity of functional mitral regurgitation, cardiac output, and left atrial volume were assessed using Doppler echocardiography. In patients with left ventricular dysfunction, systolic pulmonary artery pressure was increased (51 +/- 14 mmHg, range 23 to 87 mmHg). Mitral deceleration time (r = -0.61; p = 0.0001) and mitral effective regurgitant orifice (r = 0.50; p = 0.0001) were the strongest parameters related to systolic pulmonary artery pressure. Multivariate analysis identified these two variables as the strongest predictors of systolic pulmonary artery pressure in association with the mitral E/A ratio (p = 0.006) and age (p = 0.005). In conclusion, pulmonary hypertension is common and variable in patients with left ventricular dysfunction. It is closely related to diastolic dysfunction and severity of functional mitral regurgitation but not independently to the degree of left ventricular systolic dysfunction. These findings underline the importance of assessing diastolic function and quantifying mitral regurgitation in patients with left ventricular dysfunction.