Enriquez‐Sarano, Maurice

Background— To assess the prevalence, determinants, and prognosis value of right ventricular (RV) ejection fraction (EF) impairment in organic mitral regurgitation. Methods and Results— Two hundred eight patients (62±12 years, 138 males) with chronic organic mitral regurgitation referred to surgery underwent an echocardiography and biventricular radionuclide angiography with regional function assessment. Mean RV EF was 40.4±10.2%, ranging from 10% to 65%. RV EF was severely impaired (≤35%) in 63 patients (30%), and biventricular impairment (left ventricular EF<60% and RV EF≤35%) was found in 34 patients (16%). Pathophysiologic correlates of RV EF were left ventricular septal function (β=0.42, P <0.0001), left ventricular end-diastolic diameter index (β=−0.22, P =0.002), and pulmonary artery systolic pressure (β=−0.14, P =0.047). Mitral effective regurgitant orifice size (n=84) influenced RV EF (β=−0.28, P =0.012). In 68 patients examined after surgery, RV EF increased strongly (27.5±4.3–37.9±7.3, P <0.0001) in patients with depressed RV EF, whereas it did not change in others ( P =0.91). RV EF ≤35% impaired 10-year cardiovascular survival (71.6±8.4% versus 89.8±3.7%, P =0.037). Biventricular impairment dramatically reduced 10-year cardiovascular survival (51.9±15.3% versus 90.3±3.2%, P <0.0001; hazard ratio, 5.2; P <0.0001) even after adjustment for known predictors (hazard ratio, 4.6; P =0.004). Biventricular impairment reduced also 10-year overall survival (34.8±13.0% versus 72.6±4.5%, P =0.003; hazard ratio, 2.5; P =0.005) even after adjustment for known predictors ( P =0.048). Conclusions— In patients with organic mitral regurgitation referred to surgery, RV function impairment is frequent (30%) and depends weakly on pulmonary artery systolic pressure but mainly on left ventricular remodeling and septal function. RV function is a predictor of postoperative cardiovascular survival, whereas biventricular impairment is a powerful predictor of both cardiovascular and overall survival.

Background— Aortic valve calcification (AVC) is the intrinsic mechanism of valvular obstruction leading to aortic stenosis (AS) and is measurable by multidetector computed tomography. The link between sex and AS is controversial and that with AVC is unknown. Methods and Results— We prospectively performed multidetector computed tomography in 665 patients with AS (aortic valve area, 1.05±0.35 cm 2 ; mean gradient, 39±19 mm Hg) to measure AVC and to assess the impact of sex on the AVC–AS severity link in men and women. AS severity was comparable between women and men (peak aortic jet velocity: 4.05±0.99 versus 3.93±0.91 m/s, P =0.11; aortic valve area index: 0.55±0.20 versus 0.56±0.18 cm 2 /m 2 ; P =0.46). Conversely, AVC load was lower in women versus men (1703±1321 versus 2694±1628 arbitrary units; P <0.0001) even after adjustment for their smaller body surface area or aortic annular area (both P <0.0001). Thus, odds of high-AVC load were much greater in men than in women (odds ratio, 5.07; P <0.0001). Although AVC showed good associations with hemodynamic AS severity in men and women (all r >0.67; P <0.0001), for any level of AS severity measured by peak aortic jet velocity or aortic valve area index, AVC load, absolute or indexed, was higher in men versus women (all P ≤0.01). Conclusions— In this large AS population, women incurred similar AS severity than men for lower AVC loads, even after indexing for their smaller body size. Hence, the relationship between valvular calcification process and AS severity differs in women and men, warranting further pathophysiological inquiry. For AS severity diagnostic purposes, interpretation of AVC load should be different in men and in women.

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.

Background —Functional mitral regurgitation (FMR) occurs with a structurally normal valve as a complication of systolic left ventricular dysfunction (LVD). Determinants of degree of FMR are poorly defined; thus, mechanistic therapeutic approaches to FMR are hindered. Methods and Results —In a prospective study of 21 control subjects and 128 patients with LVD (defined as ejection fraction <50%, mean 31±9%) in sinus rhythm, we quantified simultaneously by echocardiography the effective regurgitant orifice (ERO) of FMR by using 2 methods: mitral deformation (valve and annulus) and left ventricular (LV) global (volumes, stress, function, and sphericity) and local (papillary muscle displacements and regional wall motion index) remodeling. A wide range of ERO (15±14 mm 2 , 0 to 87 mm 2 ) was observed, unrelated to ejection fraction ( P =0.32). The major determinant of ERO was mitral deformation, ie, systolic valvular tenting and annular contraction in univariate ( r =0.74 and r =−0.61, respectively; both P <0.0001) and multivariate (both P <0.0001) analyses, independent of global LV remodeling. Systolic valvular tenting was strongly determined by local LV alterations, particularly apical ( r =0.75) and posterior ( r =0.70) displacement of papillary muscle, with confirmation in multivariate analysis (both P <0.0001), independent of LV volumes, function, and sphericity. Conclusions —The presence and degree of FMR complicating LVD are unrelated to the severity of LVD. Local LV remodeling (apical and posterior displacement of papillary muscles) leads to excess valvular tenting independent of global LV remodeling. In turn, excess tenting and loss of systolic annular contraction are associated with larger EROs. These determinants of FMR warrant consideration for specific approaches to the treatment of FMR complicating LVD.

Background The optimal timing for surgery in patients with mitral regurgitation is disputed. Because of the frequency of left ventricular dysfunction, which is difficult to predict, early surgery has been recommended, but its potential benefits have not been demonstrated. Methods and Results The outcomes of 221 patients (mean age, 65±13 years; 71% males) with flail leaflets diagnosed with two-dimensional echocardiography between 1980 and 1989 who were eligible for operation were analyzed. Group I comprised 63 patients who had early mitral valve surgery (within 1 month after diagnosis). Group II comprised 158 patients initially treated conservatively (80 of whom were operated on later). Group I patients were younger ( P =.009), had more symptoms ( P <.0001), and were more frequently in atrial fibrillation ( P =.023) than group II patients. There was no difference in ejection fraction between the groups. The early surgery strategy was followed by an improved overall survival rate ( P= .028) and a lower incidence of cardiovascular deaths ( P =.025), congestive heart failure ( P =.046), and new chronic atrial fibrillation ( P =.032), as confirmed by multivariate analysis (adjusted risk ratios of 0.31, 0.18, 0.38, and 0.05, respectively; all P< .02). Conclusions In patients with mitral regurgitation due to flail leaflets, the strategy of early surgery versus conservative management is associated with an improved long-term survival rate, decreased cardiac mortality, and decreased morbidity after diagnosis. This outcome advantage suggests that early surgery is a reasonable treatment option to be considered in low-risk candidates with repairable valves and severe mitral regurgitation.

BackgroundQuantitative Doppler echocardiography and proximal flow convergence methods are validated techniques for quantifying mitral regurgitation. However, the clinical interpretation of the values calculated is hindered by the absence of calibration of ranges of severity in large numbers of patients.Methods and ResultsIn 180 consecutive patients (men, 62%; mean age±SD, 66±11 years), the results of Doppler quantification of isolated mitral regurgitation were calibrated by use of left ventricular angiographic grading performed within 3 months in routine practice and without intervening events. The thresholds of the quantitative variables corresponding to the angiographic grades were identified by maximizing the sum of sensitivity and specificity and minimizing their difference. The mitral regurgitation grade by angiography was 2.7±1.3. The mean value and correlation with angiographic grades for effective regurgitant orifice were 43±37 mm andr=.79 (P<.0001); for regurgitant volume, 62±45 mL andr=.80 (P<.0001); and for regurgitant fraction, 45±17% andr=.78 (P<.0001). Despite some overlap, differences between mitral regurgitation grades were all significant (allP<.05). The thresholds for severe mitral regurgitation (grade 4) were 60 mL, 50%, and 40 mm2for regurgitant volume, regurgitant fraction, and orifice, respectively.ConclusionsIn routine practice in large numbers of patients in a clinical laboratory, Doppler echocardiographic quantification of mitral regurgitation shows highly significant correlation with qualitative angiographic grades. Despite an expected overlap between classes, the calibration by angiography of grading ranges for the quantitative variables provides a framework for their interpretation and allows the definition in clinical practice of thresholds for severe mitral regurgitation.

BackgroundIndications for surgical correction of aortic regurgitation have been established mostly in men and have not been validated in women. The outcome of this surgical correction in women is unknown.Methods and ResultsBaseline characteristics and postoperative outcomes were compared between 51 women and 198 men undergoing surgery for isolated aortic regurgitation between 1980 and 1989. Compared with men, women had surgery rarely for severe left ventricular enlargement (systolic diameter ≥55 mm in 11% versus 27%,P=.031; diastolic diameter ≥80 mm in 0% versus 16%,P<.0001) and more often for class III to IV symptoms (59% versus 32%,P<.0001). Operative mortalities were similar in women and men (3.9% and 4.5%, respectively). Among operative survivors, 10-year survival was worse for women than for men (39±9% versus 72±4%,P=.0002) and, in contrast with men, was worse than expected for women (P<.0001). Independent predictors of late survival were different for men (age and ejection fraction) and women (age and concomitant coronary bypass grafting). By multivariate analysis, female sex was an independent predictor of worse late survival (adjusted relative risk, 1.80; 95% CI, 1.04 to 3.11).ConclusionsThe generalization to women of the unadjusted left ventricular diameter surgical criteria established in men results in irrelevant criteria almost never reached in women, who often undergo surgery after developing severe symptoms. After surgery, women exhibit an excess late mortality, suggesting that surgical correction of aortic regurgitation should be considered at an earlier stage in women.

Background In patients with mitral regurgitation, surgical intervention produces immediate improvement in symptoms, but the long-term incidence and significance of postoperative congestive heart failure are unknown. Methods and Results The long-term outcome of 576 operative survivors of surgical correction of pure mitral regurgitation performed between 1980 and 1989 was analyzed. Survival was 77±2% and 56±3% at 5 and 10 years, respectively. Cumulative incidence of congestive heart failure was 23±2%, 33±3%, and 37±3% at 5, 10, and 14 years, respectively. Survival after the first episode of congestive heart failure was dismal, 44±4% at 5 years. Cause of congestive heart failure was left ventricular dysfunction in two thirds of the patients and valvular dysfunction in the other third. With multivariate analysis, the independent predictors of postoperative heart failure were preoperative ejection fraction ( P =.0001), coronary artery disease ( P =.0017), and New York Heart Association functional class ( P =.012), with borderline value for atrial fibrillation ( P =.10). The performance of valve repair was independently predictive of a lower incidence of the combined end point of death and heart failure ( P =.001), compared with valve replacement. Conclusions Congestive heart failure frequently occurs late after surgical correction of mitral regurgitation and portends dismal prognosis. This complication is due most often to left ventricular dysfunction; its main determinant is decreased left ventricular function preoperatively. These data should lead to earlier indication of surgical correction of mitral regurgitation, before left ventricular dysfunction occurs.

BackgroundIn patients with mitral valve prolapse, spontaneous changes of the effective regurgitant orifice during systole are not well documented. Such changes can now be analyzed by use of the proximal isovelocity surface area method, but the changes raise concern about the reliability of this method for assessing overall severity of regurgitation in these patients.Methods and ResultsIn a prospective study of 42 patients with mitral valve prolapse, the effective mitral regurgitant orifice was calculated at four phases of systole (early, mid, mid-late, and late) as the ratio of regurgitant flow to regurgitant velocity by use of the proximal isovelocity surface area method. Throughout systole, the effective regurgitant orifice increased significantly, from 32±27 mm2in early systole to 41±27 in midsystole, 55±30 in mid-late systole, and 107±66 mm2during late systole (P<.0001). Phasic regurgitant volume increased from early to mid-late systole but decreased in late systole. For quantitation of the overall effective regurgitant orifice, four approaches using the proximal isovelocity surface area were compared with simultaneously performed quantitative Doppler echocardiography (54±30 mm2) and quantitative two-dimensional echocardiography (51±29 mm2). All correlations were good (r>.95), but overestimation was considerable when the largest flow convergence was used (70±39 mm2; bothP<.0001), significant when the simple mean of the four phases was used (59±36 mm2;P=.005 andP=.0007, respectively), mild when a weighted mean of the four phases was used (55±33 mm2;P=.41 andP=.01, respectively), and no overestimation was observed when the effective regurgitant orifice calculated at maximum regurgitant velocity was used (54±30 mm2;P=.29 andP=.17, respectively).ConclusionsPhasic changes of mitral regurgitation are observed in patients with mitral valve prolapse. The effective regurgitant orifice increases throughout systole. Regurgitant volume also increases initially but tends to decrease in late systole. These changes can lead to overestimation of the overall degree of regurgitation, but properly timed measurements made by use of the proximal isovelocity surface area method allow an accurate estimation of the overall effective regurgitant orifice.