Total Left Ventricular Stroke Volume Research Articles

Quantitation of mitral regurgitation using positron emission tomography

BackgroundCardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR).ResultsTwenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p < 0.001). A systematic underestimation (bias) was found for PET (RegVol: 15O-water − 11 ± 13 mL, p = 0.002, 11C-acetate − 28 ± 16 mL, p < 0.001 and RegF: 15O-water − 4 ± 6%, p = 0.01, 11C-acetate − 10 ± 7%, p < 0.001). PET measurements in patients were compared to healthy volunteers (n = 18). Mean RegVol and RegF was significantly lower in healthy volunteers compared to patients for both tracers. The accuracy of diagnosing moderately elevated regurgitant volume (> 30mL) was 95% for 15O-water and 92% for 11C-acetate.ConclusionsLV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers.

Functional Diagnostics by Rational Echocardiography

Functional diagnostics by rational echocardiography are the base of a verifiable and reliable analysis of ventricular and valvular function. The most important functional parameters in echocardiography are cardiac volumes - especially total and effective left ventricular stroke volume -, global longitudinal strain, effective orifica areas in valvular stenoses and effective regurgitant volumes, regurgitant fraction and regurgitant orifice areas in valvular regurgitations. Standardized documentation and correct measurements are the prerequisites for accurate echocardiographic estimations. In addition, optimization of image quality supports the correctness of measurements to ensure plausibility of hemodynamics in each individual patient. However, measurements of cardiac volumes by planimetry are error-prone. In addition, calculation of the effective orifice areas using the continuity equation needs methodological accuracy and standardization. Finally, assessment of regurgitant volumes, regurgitant fraction, and regurgitant orifice is often inconsistent with stable hemodynamic conditions - especially by functional assessment the 2D-PISA method. Thus, functional diagnostics by echocardiography in valvular heart diseases should focus on a plausible hemodynamic assessment.

Long-term outcome after transcatheter mitral annuloplasty for secondary mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background The long-term effects of transcatheter mitral valve annuloplasty (TMVA) for secondary mitral regurgitation is unknown. Purpose We studied the clinical outcome and the effects on left ventricular (LV) function and remodeling and on mitral regurgitation (MR) severity after TMVA using the Carillon annuloplasty device. Methods We analyzed 33 consecutive patients with symptomatic MR who were treated with TMVA at Leipzig University Hospital between 2012 and 2018. Echocardiography was performed before TMVA and at follow-up. MR severity was quantitatively assessed by regurgitant volume (calculated as LV total stroke volume – LV forward stroke volume) and regurgitant fraction (calculated as regurgitant volume / LV total stroke volume). Results Mean age was 80 ± 10 years, 19 patients were women. A Society of Thoracic Surgeons (STS) score of 8.1 ± 7.2% indicated high risk status for mitral valve surgery. In 26 patients, mitral regurgitation resulted from LV remodeling and LV dysfunction, 7 suffered from left atrial dilatation. LV ejection fraction at baseline was 38% (30-49%; median, interquartile range). During a mean follow-up time of 45 ± 20 months, 17 patients died, 2 patients withdraw consent, and 4 patients were lost. Of the remaining patients, 4 were hospitalized for decompensated heart failure, and 2 underwent additional transcatheter edge-to-edge mitral valve repair. At follow-up, NYHA functional class improved from 95% in class III/IV at baseline to 70% in class I/II with no patients in NYHA class IV (p &amp;lt; 0.0001). Mitral regurgitant volume was reduced from 27mL (25-42mL) to 8mL (3-17mL) (p = 0.035) and regurgitant fraction from 43% (32-54%) to 11% (8-24%) (p = 0.020). LV end-diastolic volume index (92mL/m2 (71-107mL/m2) vs. 67mL/m2 (46-101mL/m2), p = 0.084) and end-systolic volumes index (51mL/m2 (44-69mL/m2) vs. 32mL/m2 (20-53mL/m2), p = 0.037) decreased. Thus, total stroke volume remained similar (38mL/m2 (33-43mL/m2) vs. 33mL/m2 (26-44mL/m2), p = 0.695) while LV ejection fraction increased (43% (31-49%) vs. 54% (46-57%), p = 0.032). Forward stroke volume, heart rate and forward cardiac output remained unchanged. Blood pressure was similar at baseline and at follow-up. Conclusion. Among high risk patients undergoing transcatheter mitral valve annuloplasty for symptomatic secondary MR, mortality was about 50% at 4 years. In the surviving patients, reduced MR severity was associated with fewer heart failure symptoms, reverse LV remodeling and improved LV function.

Disproportionate mitral regurgitation: new entity or reflection of measurment errors?

Abstract Funding Acknowledgements Type of funding sources: None. Background The results of recent studies of transcatheter mitral valve repair proposed a new conceptual framework that categorized mitral regurgitation (MR) into proportionate (propMR) or disproportionate (dispropMR) according to the relationship between effective regurgitant orifice area (EROA) and left ventricular (LV) end-diastolic volume (EDV). Purpose To determine the prevalence of dispropMR in consecutive heart failure patients with reduced ejection fraction (HFrEF) undergoing clinically indicated echocardiography over one year period and to examine characteristics of this new entity. Methods We retrospectively identified 179 patients(age:69 ± 12 years, male:132[74%]) with HFrEF who were classified more than mild MR by performing echocardiographer. Following parameters of MR severity were analysed: regurgitant volume(PISA-based regurgitant volume[RVol-PISA] and RVol calculated by the difference of total LV stroke volume by LV planimetry and Doppler-estimated effective LV stroke volume[RVol-SV]), PISA-based EROA and regurgitant fraction (RF). Grading of MR severity based on RVol was performed (mild:&amp;lt;30 ml, mild-moderate:30-44ml, moderate-severe:45-59 ml, severe:≥60 ml). The distinction between propMR and dispropMR was determined by using a proportionality scheme by Grayburn, considering ratio EROA/LVEDV. DispropMR was identified by the ratio greater than 0.14, while the others were classified as propMR. Results In our cohort, 49(27.4%)patients had dispropMR. Both MR groups were comparable in age and gender. DispropMR group had significantly smaller LV dimensions(LV end-diastolic diameter:59 ± 9mm vs. 65 ± 8mm,p &amp;lt; 0.001; LVEDV:164 ± 54ml vs. 222 ± 60ml,p &amp;lt; 0.001) and higher EF(41 ± 11% vs. 34 ± 9%, p &amp;lt; 0.001). Higher proportion of primary MR was noted in dispropMR group(15[31%] vs. 4[3.3%] patients, p &amp;lt; 0.001). Significant differences were observed in PISA-based quantification of MR between both groups (p &amp;lt; 0.001, for all), whereas RVol-SV was comparable(p = 0.667;Figure A). Discrepant grading in MR severity between RVol-PISA and RVol-SV methods was observed(p &amp;lt; 0.001), with significant high discordance in dispropMR(p &amp;lt; 0.001) and no significant differences in propMR(p = 0.187;Figure B). Additionally, difference in RVol assessed by PISA method and SV method were more prominent in dispropMR (RVol difference: dispropMR:27 ml[17-46] vs. propMR:13 ml[-4 to 24],p &amp;lt; 0.001). MR severity would be reclassified in a substantial proportion of dispropMR when considering RVol-SV. Conclusion Our results suggest that dispropMR may be found in roughly one fourth of echocardiographic studies in patients with HFrEF. DispropMR patients have less extensive LV remodelling and more severe MR based on PISA parameters compared to propMR. However, inconsistencies between parameters of MR severity in dispropMR might suggest echocardiographic limitations of quantitative grading of the MR severity or/and LV volume assessment rather than a new pathophysiological concept of disproportionate MR. Abstract Figure A, B

Quantitative assessment of primary mitral regurgitation using left ventricular volumes obtained with new automated three-dimensional transthoracic echocardiographic software: A comparison with 3-Tesla cardiac magnetic resonance

Quantitative assessment of primary mitral regurgitation (MR) using left ventricular (LV) volumes obtained with three-dimensional transthoracic echocardiography (3D TTE) recently showed encouraging results. Nevertheless, 3D TTE is not incorporated into everyday practice, as current LV chamber quantification software products are time consuming. To investigate the accuracy and reproducibility of new automated fast 3D TTE software (HeartModelA.I.; Philips Healthcare, Andover, MA, USA) for the quantification of LV volumes and MR severity in patients with isolated degenerative primary MR; and to compare regurgitant volume (RV) obtained with 3D TTE with a cardiac magnetic resonance (CMR) reference. Fifty-three patients (37 men; mean age 64±12 years) with at least mild primary isolated MR, and having comprehensive 3D TTE and CMR studies within 24h, were eligible for inclusion. MR RV was calculated using the proximal isovelocity surface area (PISA) method and the volumetric method (total LV stroke volume minus aortic stroke volume) with either CMR or 3D TTE. Inter- and intraobserver reproducibility of 3D TTE was excellent (coefficient of variation≤10%) for LV volumes. MR RV was similar using CMR and 3D TTE (57±23mL vs 56±28mL; P=0.22), but was significantly higher using the PISA method (69±30mL; P<0.05 compared with CMR and 3D TTE). The PISA method consistently overestimated MR RV compared with CMR (bias 12±21mL), while no significant bias was found between 3D TTE and CMR (bias 2±14mL). Concordance between echocardiography and CMR was higher using 3D TTE MR grading (intraclass correlation coefficient [ICC]=0.89) than with PISA MR grading (ICC=0.78). Complete agreement with CMR grading was more frequent with 3D TTE than with the PISA method (76% vs 63%). 3D TTE RV assessment using the new generation of automated software correlates well with CMR in patients with isolated degenerative primary MR.

Quantitative Evaluation of Mitral Regurgitation Secondary to Mitral Valve Prolapse by Magnetic Resonance Imaging and Echocardiography

The present prospective study was designed to evaluate the accuracy of quantitative assessment of mitral regurgitant fraction (MRF) by echocardiography and cardiac magnetic resonance imaging (cMRI) in the modern era using as reference method the blinded multiparametric integrative assessment of mitral regurgitation (MR) severity. 2-Dimensional (2D) and 3-dimensional (3D) MRF by echocardiography (2D echo MRF and 3D echo MRF) were obtained by measuring the difference in left ventricular (LV) total stroke volume (obtained from either 2D or 3D acquisition) and aortic forward stroke volume normalized to LV total stroke volume. MRF was calculated by cMRI using either (1) (LVstroke volume- systolic aortic outflow volume by phase contrast)/LV stroke volume (cMRI MRF [volumetric]) or (2) (mitral inflow volume- systolic aortic outflow volume)/mitral inflow volume (cMRI MRF [phase contrast]). Six patients had 1+ MR, 6 patients had 2+ MR, 12 patients had 3+ MR, and 10 had 4+ MR. A significant correlation was observed between MR grading and 2D echo MRF (r= 0.60, p <0.0001) and 3D echo MRF (r= 0.79, p <0.0001), cMRI MRF (volumetric) (r= 0.87, p <0.0001), and cMRI MRF (phase contrast r= 0.72, p <0.001). The accuracy of MRF for the diagnosis of MR ≥3+ or 4+ was the highest with cMRI MRF (volumetric) (area under the receiver-operating characteristic curve [AUC]= 0.98), followed by 3D echo MRF (AUC= 0.96), 2D echo MRF (AUC= 0.90), and cMRI MRF (phase contrast; AUC= 0.83). In conclusion, MRF by cMRI (volumetric method) and 3D echo MRF had the highest diagnostic value to detect significant MR, whereas the diagnostic value of 2D echo MRF and cMRI MRF (phase contrast) was lower. Hence, the present study suggests that both cMRI (volumetric method) and 3D echo represent best approaches for calculating MRF.

0123: Quantitative assessment of primary mitral regurgitation using left ventricular volumes: a three-dimensional transthoracic echocardiographic pilot study

Aims: To investigate the value of assessment of mitral regurgitant fraction (RF) using left ventricular (LV) volumes obtained by 3 dimensional echocardiography (3DE) to quantify primary mitral regurgitation (MR). Fifty-one patients with primary MR in sinus rhythm were prospectively enrolled. RF was calculated using either 2DE or 3DE LV volumes obtained as follows: (LV total stroke volume - LV forward stroke volume by Doppler) / LV total stroke volume. Severity of MR was graded independently using an integrative approach, as recommended by current guidelines. The 3D method had a feasibility of 89%. A significant correlation was observed between grade of MR severity and 3D RF(r=0.84, P<0.0001) and 2D RF (r=0.74, P<0.0001). The area under the ROC curves for ≥3+ or 4+ MR was 0.99 for 3DRF and 0.94 (0.83 to 0.99) for 2D RF. All patients with 3DRF ≥40% had ≥3+ or 4+ MR and all patients with 3DRF ≤30% had 1+ or 2+ MR with a “grey” overlap zone between 30 and 40%. RF can be routinely determined using 3D LV volumes with a high feasibility in patients with primary MR and is reliable for identification of severe MR. This 3D method should be included in the currently recommended multiparametric integrative approach.

Imaging Challenges in Secondary Mitral Regurgitation

Chronic secondary mitral regurgitation (SMR) is a complex entity that is often clinically underappreciated.1 It complicates either ischemic heart disease or dilated cardiomyopathy; its prevalence varies among series but may reach ≤50% in patients with heart failure.2 When present, SMR may exhibit a broad range of severity and confers an adverse prognosis, which is worse with increasing severity of mitral regurgitation (MR).3,4 The management of SMR poses a unique set of challenges, based partly on the complexity of the valve disorder and the still-evolving adoption of the optimal therapeutic approach.5 Noninvasive imaging and, in particular, echocardiography, plays a critical role for the initial and longitudinal assessment, for individual risk stratification and outcome prediction, and for guiding intervention in patients with chronic SMR.6 SMR develops because of a combination of mitral leaflet tethering secondary to left ventricular (LV) dilatation/deformation with papillary displacement/discoordination, annular dilatation/dysfunction, insufficient LV-generated closing forces attributable to reduction of LV contractility, and global LV/papillary muscle dyssynchrony.1,5 Tethering of the mitral leaflets is the principal lesion of SMR and results in restriction of systolic leaflet motion, namely type IIIb of Carpentier’s classification. SMR does not typically occur in global LV dysfunction without tethering. However, once tethering occurs, leaflet closure is further impaired by LV dysfunction because there is decreased force opposing tethering.6–9 The key event in the pathogenesis of SMR is the distortion of normal LV geometry—regional and global LV remodeling—with subsequent apical and lateral displacement of papillary muscles, which, in turn, draws the chordae tendineae away from the line of coaptation.7,8 The extent of LV systolic dysfunction and dilatation is weakly correlated to the degree of SMR unless accompanied by geometric distortion in the region of the papillary muscles.1,9 …

Quantitative assessment of primary mitral regurgitation using left ventricular volumes: a three-dimensional transthoracic echocardiographic pilot study.

To investigate the value of assessment of mitral regurgitant fraction (RF) using left ventricular (LV) volumes obtained by three-dimensional echocardiography (3DE) to quantify primary mitral regurgitation (MR). Sixty patients with primary MR in sinus rhythm were prospectively enrolled. RF was calculated using either 2DE or 3DE LV volumes obtained as follows: (LV total stroke volume - LV forward stroke volume by Doppler)/LV total stroke volume. Severity of MR was graded independently by two cardiologists blinded to LV volumetric data using an integrative approach, as recommended by current guidelines. Sixty patients with LV ejection fraction >50% and no MR were also studied. In patients without MR, 3D total LV stroke volume was more strongly correlated with LV forward stroke volume than 2D total LV stroke volume (r = 0.75, P < 0.0001 vs. r = 0.62, P < 0.0001, respectively). The 3D method had a feasibility of 90% in patients with MR. Inter-reader concordance for MR grading (four grades) was excellent with a Kappa-value of 0.90, P < 0.0001. A significant correlation was observed between grade of MR severity and 3D RF (r = 0.83, P < 0.0001) and 2D RF (r = 0.74, P < 0.0001). Comparisons between individual grades for 3D RF were significant (P < 0.05) except for 3+ vs. 4+ MR (P = 0.213). All patients with 3D RF ≥40% had ≥3+ or 4+ MR and those with 3D RF ≤30% had 1+ or 2+ MR with a 'grey' overlap zone between 30 and 40%. RF can be routinely determined using 3D LV volumes with a high feasibility in patients with primary MR and is reliable for identification of Grade 3+ or Grade 4+ MR. The incorporation of this parameter into the currently recommended multiparametric integrative approach might be helpful to discriminate significant MR.

Prospective Comparison of Valve Regurgitation Quantitation by Cardiac Magnetic Resonance Imaging and Transthoracic Echocardiography

Both transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging allow quantification of chronic aortic regurgitation (AR) and mitral regurgitation (MR). We hypothesized that CMR measurement of regurgitant volume (RVol) is more reproducible than TTE. TTE and CMR performed on the same day in 57 prospectively enrolled adults (31 with AR, 26 with MR) were measured by 2 independent physicians. TTE RVol(AR) was calculated as Doppler left ventricular outflow minus inflow stroke volume. RVol(MR) was calculated by both the proximal isovelocity surface area method and Doppler volume flow at 2 sites. CMR RVol(AR) was calculated by phase-contrast velocity mapping at the aortic sinuses and RVol(MR) as total left ventricular minus forward stroke volume. Intraobserver and interobserver variabilities were similar. For AR, the Bland-Altman mean interobserver difference in RVol was -0.7 mL (95% confidence interval [CI], -5 to 4) for CMR and -9 mL (95% CI, -53 to -36) for TTE. The Pearson correlation was higher (P=0.001) between CMR (0.99) than TTE readers (0.89). For MR, the Bland-Altman mean difference in RVol between observers was -4 mL (95% CI, -21 to 13) for CMR compared with 0.7 mL (95% CI, -30 to 32) for the proximal isovelocity surface area and -10 mL (95% CI, -76 to 56) for TTE volume flow at 2 sites. Correlation was similar for CMR (0.94) versus TTE readers (0.90 for the proximal isovelocity surface area). Compared with TTE, CMR has lower intraobserver and interobserver variabilities for RVol(AR), suggesting CMR may be superior for serial measurements. Although RVol(MR) is similar by TTE and CMR, variability in measured RVol by both approaches suggests that caution is needed in clinical practice.

Equal stroke volumes, different costs: left ventricular 4D flow in normal and failing hearts

Summary Although total left ventricular (LV) stroke volume (SV) is equal in healthy subjects and heart failure patients with mild LV remodeling, the SV’s transventricular flow paths to ejection and diastolic energetics are different. These flow-specific markers of inefficiency of the failing heart are detectable prior to clinical decompensation, and might be predictors of progressive adverse cardiac remodeling. Background Heart failure is a common disorder with a dismal prognosis. Cardiac remodeling is a key component of heart failure that progresses from adaptive to maladaptive as the disease worsens, and is associated with increased risks of symptoms and mortality. In earlier stages of heart failure with adaptive remodeling, patients may remain clinically compensated and the failing heart’ sl eft ventricular (LV) stroke volume (SV) remains the same as in the normal heart. Recently, time-varying and complex three-dimensional flow patterns and energetics within the normal LV have been demonstrated. Based on such 4D flow-specific measures, we hypothesized that while the SV of normal and failing LVs may be equal, the SV’s diastolic kinetic energy (KE) and transventricular routes to ejection are different in the two states. Methods In ten patients with dilated cardiomyopathy (DCM) (6 females, 49±14 years [mean±SD]) and ten healthy subjects (4 female, 44±17 years), 4D phase-contrast CMR velocity data and morphological data were acquired at 1.5T (Philips Achieva). A previously validated method was used for the analysis: The LV endocardium was segmented from the morphological images at end-diastole (ED) and end-systole. Pathlines were emitted from the ED blood volume and traced forward and backward in time until end-systole, allowing separation of the Total SV into two flow components (figure 1): 1) Blood that enters and leaves the LV during the analyzed cardiac cycle (Direct SV), and 2) Blood that leaves but does not enter the LV during the analyzed cardiac cycle (Delayed SV). The KE was calculated over the cardiac cycle for these flow components based on the volume occupied by each pathline, its velocity, and blood density. Results The LV ED volume was larger and LV ejection fraction was smaller in DCM compared to healthy (179±33 vs 147±22 ml, p=0.021, and 42±5 vs 54±6 %, p<0.001, respectively). While the Total SV was equal in the two groups (77±19 vs 79±16 ml, p=0.8), the Direct SV represented a significantly smaller part of the Total SV in DCM compared to healthy (45±11 vs 69±5 %, p<0.001) (figure 2). At ED, the “KE of the Direct SV” / “KE of the Total SV”-ratio was lower in DCM compared to healthy (47±15 vs 76±7 %, p<0.001) (figure 2). Conclusions Although total LV stroke volume is equal in healthy subjects and in clinically compensated heart failure patients with mild LV remodeling, the diastolic routes through the LV and pre-systolic energetics of the SV are significantly different in the two states. Inefficient flow may augment the chronic stress on the failing heart’s reserve, promoting progressive maladaptive cardiac remodeling.

Three-Dimensional Echocardiography in Paravalvular Aortic Regurgitation Assessment after Transcatheter Aortic Valve Implantation

Paravalvular aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) is common, but the evaluation of its severity by two-dimensional (2D) transthoracic echocardiography (TTE) presents several constrains. The aim of this study was to assess the usefulness of a new methodology, using three-dimensional (3D) TTE, for better assessment of paravalvular AR after TAVI. Two-dimensional and 3D TTE was performed in 72 patients, 5 months after TAVI, using the X5-1 PureWave microbeamforming xMATRIX probe. The position and severity of the paravalvular AR jets were described using 2D and 3D TTE, and a model was designed for paravalvular AR systematic location description. Vena contracta width was measured using 2D transthoracic echocardiographic views, and the planimetry of the vena contracta was assessed after the perfect alignment plane was obtained using the multiplanar 3D transthoracic echocardiographic reconstruction tool. AR volume was calculated as the difference between 3D TTE-derived total left ventricular stroke volume and right ventricular stroke volume estimated using 2D TTE. Diagnostic efficiency for moderate AR was assessed using receiver operating characteristic curve analysis. Forty-three patients (57.4%) presented with AR; 10 (13.3%) had central AR, and 33 (44.0%) had paravalvular AR jets. Vena contracta widths were similar between patients with moderate and mild AR (2.1 ± 0.53 vs 1.9 ± 0.16 mm, P = .16), but vena contracta planimetry was larger in patients with moderate AR than in those with mild AR (0.30 ± 0.12 vs 0.09 ± 0.07 cm(2), P = .001). Vena contracta planimetry on 3D TTE was better correlated with AR volume than vena contracta width on 2D TTE (Kendall's τ = 0.82 [P < .001] vs 0.66 [P < .001]). The areas under the receiver operating characteristic curves were 0.96 for vena contracta planimetry and 0.35 for vena contracta width. This study proposes an alternative methodology for paravalvular AR assessment after TAVI. Using vena contracta planimetry on 3D TTE, an accurate methodology for paravalvular AR jet evaluation and moderate AR classification is described.

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Misinterpretation About the Contribution of the Left Ventricular Long-Axis Shortening to the Stroke Volume

Misinterpretation about the contribution of the left ventricular long-axis shortening to the stroke volume

Contribution of mitral annular excursion and shape dynamics to total left ventricular volume change.

The mitral annulus (MA) has a complex shape and motion, and its excursion has been correlated to left ventricular (LV) function. During the cardiac cycle the annulus' excursion encompasses a volume that is part of the total LV volume change during both filling and emptying. Our objective was to evaluate the contribution of MA excursion and shape variation to total LV volume change. Nine healthy subjects aged 56 +/- 11 (means +/- SD) years underwent transesophageal echocardiography (TEE). The MA was outlined in all time frames, and a four-dimensional (4-D) Fourier series was fitted to the MA coordinates (3-D+time) and divided into segments. The annular excursion volume (AEV) was calculated based on the temporally integrated product of the segments' area and their incremental excursion. The 3-D LV volumes were calculated by tracing the endocardial border in six coaxial planes. The AEV (10 +/- 2 ml) represented 19 +/- 3% of the total LV stroke volume (52 +/- 12 ml). The AEV correlated strongly with LV stroke volume (r = 0.73; P < 0.05). Peak MA area occurred during middiastole, and 91 +/- 7% of reduction in area from peak to minimum occurred before the onset of LV systole. The excursion of the MA accounts for an important portion of the total LV filling and emptying in humans. These data suggest an atriogenic influence on MA physiology and also a sphincter-like action of the MA that may facilitate ventricular filling and aid competent valve closure. This 4-D TEE method is the first to allow noninvasive measurement of AEV and may be used to investigate the impact of physiological and pathological conditions on this important aspect of LV performance.

Accurate determination of mitral regurgitation by assessing its influence on the combined diastolic mitral and pulmonary venous flow: just 'looking twice'.

To assess the diagnostic accuracy of combined transmitral E wave velocity and reversed systolic pulmonary venous flow for the quantification of mitral regurgitation severity. Measuring forward and total left ventricular stroke volume, mitral regurgitation severity was assessed quantitatively by calculating the regurgitant fraction in 106 consecutive patients with pure mitral regurgitation. According to the regurgitant fraction, the optimal E wave velocity for accurate distinction of mild to moderate and more than moderate mitral regurgitation was chosen by calculating the receiver-operating characteristic plot. Severe mitral regurgitation was defined by reversed systolic pulmonary venous flow. Combining transmitral E wave velocity and reversed systolic pulmonary venous flow had an overall accuracy of 78% (95% CI 70--86%) for classification of mitral regurgitation severity. E wave velocity >1.0ms(-1) predicted more than moderate mitral regurgitation with 78% sensitivity (95% CI 69-86%) and 90% specificity (95% CI 82--95%), resulting in a positive likelihood ratio of 8.1 (95% CI 5--15) and negative likelihood ratio of 0.25 (95% CI 0.18--0.35). For reversed systolic pulmonary venous flow in the presence of increased E wave velocity, the sensitivity and specificity to detect severe mitral regurgitation was 78% (95% CI 69--86%) and 97% (95% CI 92--99%) with the corresponding positive and negative likelihood ratio of 29 (95% CI 11--96) and 0.22 (95% CI 0.14--0.31). Test accuracy was independent of systolic function in a multivariate regression analysis. 'Looking twice', once at the transmitral E wave velocity and once at pulmonary venous flow in patients with mitral regurgitation, allows accurate determination of moderately severe and severe mitral regurgitation.

Quantitation of mitral regurgitation using the systolic/diastolic pulmonary venous flow velocity ratio.

The purpose of this study was to test the hypothesis that pulmonary venous flow velocity ratios during systole and diastole in patients with mitral regurgitation (MR) correctly predict the quantitative degree of MR. Pulmonary venous flow velocity measurements have thus far been used only for the qualitative assessment of MR. Recent studies have evaluated this method using transesophageal echocardiography against semiquantitative references. In 100 patients without aortic regurgitation or atrial fibrillation and with left ventricular (LV) ejection fraction >45%, MR was assessed by quantitative echocardiographic Doppler and color Doppler, providing forward and total LV stroke volume for the calculation of the mitral regurgitant fraction (RFstandard), the reference parameter, and also supplying mitral regurgitant orifice area (ROA) values and the RF by the flow convergence method (RFPISA [proximal isovelocity surface area]). Measurements of pulmonary venous flow velocity time integral values during systole to diastole (VTIs/VTId) were obtained and tested for their predictibility of ROA, RFstandard and RFPISA. There was an inverse and significant correlation between VTIs/VTId and ROA, RFPISA and RFstandard, respectively: RFstandard=49 - 20 VTIs/VTId, r=0.77, p=0.0001. A principal source of variability in the relation between VTIs/VTId and RFstandard was the presence of mitral valve prolapse as the cause of MR. Pulmonary venous flow reversal (VTIs/VTId <0) correctly identified severe MR with 52% sensitivity, 96% specificity and 80% positive and 87% negative predictive accuracy. The VTIs/VTId ratio allows a moderately accurate assessment of the severity of MR.

Effects of Dobutamine Infusion on Mitral Regurgitation.

Both intensity of mitral regurgitant murmur and color-coded Doppler regurgitant signal area have been reported to correlate with the degree of regurgitation. To evaluate the relationship between the intensity of regurgitant murmur and severity of mitral regurgitation, phonocardiography, echocardiography, and Doppler ultrasound were performed in 18 patients with mitral regurgitation before and during dobutamine infusion. Mitral regurgitation was due to mitral valve prolapse with ruptured chordae tendineae in 8 patients, rheumatic change in 5 patients, and dilated cardiomyopathy in 5 patients. With intravenous dobutamine infusion, heart rate (77-103 beats/min), systolic blood pressure (119-144 mmHg), peak mitral regurgitant jet velocity (4.5-5.4 m/sec), intensity of mitral regurgitant murmur (to 201% of that before infusion in early systole) increased, while left ventricular end-diastolic volume (124-102 mm), left ventricular end-systolic volume (57-42 mm), mitral anular diameter (33-28 mm), and color Doppler mitral regurgitant signal area (704-416 mm(2)) decreased (P < 0.05). Total (forward + backward) left ventricular stroke volume (66-61 mL/beat) showed no change. Dobutamine decreased mitral regurgitant flow/beat, regardless of etiology of mitral regurgitation, which was probably due to the decrease of left ventricular size and mitral annular diameter. Although total (forward + backward) left ventricular stroke volume was unchanged, dobutamine effectively increased forward left ventricular stroke volume by decreasing backward regurgitation. Mitral regurgitant murmur became louder despite the decrease of mitral regurgation, indicating the uselessness of auscultation in the grading of the severity of mitral regurgitation.

An Improved Noninvasive Method for Measurement of Cardiac Output and Evaluation of Left-Sided Cardiac Valve Incompetence

A time-saving method was developed to label red blood cells in vitro with 99mTc while avoiding centrifugation. After tin incubation, extracellular tin was oxidized by sodium hypochlorite, and EDTA was added for stabilizing the complex prior to 99mTc incubation. Labeling yields were 95%, and in vivo decay showed a high stability with a mean biologic half-life of eleven hours. The first-passage radionuclide technique for determination of cardiac output using the above-mentioned tracer was evaluated by using the left ventricle as area-of-interest with individual background correction after complete mixing of the tracer. This technique showed a high level of agreement with invasive methods. By combining this method for measurement of the forward stroke volume with the multigated equilibrium principle for determination of the total left ventricular stroke volume using similar background corrections, an exact evaluation of regurgitation fractions was obtained. In patients with aortic and mitral valve disease the noninvasive radionuclide technique gave similar but probably more accurate results as compared with contrast aortography and ventriculography. The radionuclide technique may be suitable for monitoring and selecting patients for surgical treatment.

124: HEMODYNAMIC EFFECTS OF SUBMAXIMAL TREADMILL EXERCISE IN LAMBS WITH AN AORTOPULMONARY SHUNT (S)

We showed that S lambs at rest could maintain their systemic blood flow (SBF) at the expense of an increased heart rate (HR). Therefore we wondered whether a diminished reserve in HR would limit the S lambs to perform strenuous exercise. We studied 6 7-week-old lambs (12±1 kg; mean±SD) with a Goretex O graft between aorta (ao) and pulmonary artery (pa) (PBF: SBF ratio =3). Six lambs without graft served as controls (C). Variables were recorded at the end of a 10 min. treadmill run at 75% of predetermined VO2max. During exercise HR increased more in C (108±23 to 239±31 bpm) than in S lambs (169±32 to 238±32). Total left ventricular stroke volume (SVlv) did not change in both groups (S: 2.0±0.3 to 2. 0±0.3; d 1.1±0.3 to 1.1±0.1 ml/kg), but the fraction of total SVlV through the shunt decreased per heart beat so that the fraction contributing to SBF (effective SVlv) increased significantly (S: 0.7±0.2 to 0.9±0.3). This enabled S lambs to increase SBF (118±20 to 216±40 ml/min/kg) to such an extent that it was not significantly different from SBF in C lambs (116±10 to 260±20). We conclude that S lambs adapt well to exercise by increasing their effective SVlV.