Latent Left Ventricular Research Articles

Prognostic implications of cardiac magnetic resonance feature tracking derived multidirectional strain in patients with chronic aortic regurgitation.

Speckle-tracking echocardiography (STE) deformation parameters detect latent LV dysfunction in chronic aortic regurgitation (AR) and are associated with outcomes. The aim of the study was to evaluate cardiac magnetic resonance (CMR) feature tracking (FT) deformation parameters in asymptomatic patients with AR and implications in outcomes. Fifty-five patients with AR and 54 controls were included. Conventional functional CMR parameters, aortic regurgitant volume, and fraction were assessed. CMR-FT analysis was performed with a dedicated software. Clinical data was obtained from hospital records. A combined endpoint included all-cause mortality, cardiovascular mortality, aortic valve surgery, or cardiovascular hospital admission due to heart failure. Left ventricular (LV) mechanics is impaired in patients with significant AR. Significant differences were noted in global longitudinal strain (GLS) between controls and AR patients (- 19.1 ± 2.9% vs - 16.5 ± 3.2%, p < 0.001) and among AR severity groups (- 18.3 ± 3.1% vs - 16.2 ± 1.6% vs - 15 ± 3.5%; p = 0.02 for AR grades I-II, III, and IV). In univariate and multivariate analyses, circumferential strain (GCS) and global radial strain (GRS) but not GLS were associated with and increased risk of the end point with a HR of 1.26 (p = 0.016, 1.04-1.52) per 1% worsening for GCS and 0.90 (p = 0.012, 0.83-0.98) per 1% worsening for GRS. CMR-FT myocardial deformation parameters are impaired in patients with AR not meeting surgical criteria. GLS decreases early in the course of the disease and is a marker of AR severity while GCS and GRS worsen later but predict a bad prognosis, mainly the need of aortic valve surgery. • CMR feature tracking LV mechanic parameters may be reduced in significant chronic AR with normal EF. • LV mechanics, mainly global longitudinal strain, worsens as AR severity increases. • LV mechanics, specially global radial and circumferential strain, is associated with a worse prognosis in AR patients.

Preclinical and clinical assessment of immune checkpoint inhibitor-associated left ventricular dysfunction

Abstract Background Immune checkpoint inhibitor (ICI) therapy has improved treatment of advanced cancers but is associated with yet incompletely characterized cardiotoxic side effects. While inflammatory cardiac complications were initially described as a rare phenomenon, emerging evidence indicates frequent cardiotoxicity, particularly latent left ventricular (LV) dysfunction. Distinct clinical characteristics and potential pathomechanisms are so far unknown. Purpose This study aims to investigate incidence and frequency of LV dysfunction in patients receiving ICI therapy for malignant melanoma. Using a suitable melanoma mouse model, ICI-related cardiotoxicity will be reenacted to identify potential underlying pathomechanisms. Methods Patients receiving ICI therapy for stage IV melanoma that presented in our cardio-oncology unit were evaluated at baseline and four weeks after initiation of therapy including echocardiography, cardiac biomarkers, and dobutamine stress echocardiography in the absence of contraindications. Patients with decreased LV ejection fraction (LVEF) were further evaluated by 18-fludeoxyglucose PET-MRI to assess manifest myocarditis. To elucidate underlying pathomechanisms, we established a melanoma mouse model that showed profound response to anti-programmed death 1 (PD1) ICI therapy. Immune cell infiltration was assessed by flow cytometry and light sheet fluorescence microscopy. Myocardial biochemical function was analyzed using a multi-omics mass spectrometry-based approach. Results Seven patients were included to the analysis. Six patients received a combination ICI therapy with ipilimumab and nivolumab, and one patient received nivolumab monotherapy. Echocardiography revealed significantly decreased 3D-LVEF after 4 weeks of therapy in treated patients (p=0.021). A reduced global longitudinal strain was found in six of seven patients. Remarkably, dobutamine stress echocardiography revealed a more pronounced LVEF-decrease (p=0.009) as a sign for impaired myocardial contractility with a mean decrease of 5 percentage points. Using the melanoma mouse model, we were able to recapitulate the disease phenotype as indicated by decreased LVEF and impaired response to inotropic stress during mouse pressure/volume catheterization. Increased concentrations of intramyocardial CD4+ and CD8+ T cells were found in mice treated with anti-PD1 ICI therapy compared to controls (p=0.01). Mass spectrometry revealed disrupted energy metabolism and calcium homeostasis as a putative underlying pathomechanism for impaired myocardial function. Conclusions ICI-related left ventricular dysfunction may affect a large proportion of patients and potentially increase cardiac morbidity and mortality. Preclinical data proposes myocardial lymphocyte infiltration and disruption of cardiomyocyte metabolism as the underlying pathomechanism. Prospective studies are now needed for a further characterization of this novel form of ICI-related cardiotoxicity. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): IFORES research grant, Medical Faculty, University Duisburg-Essen, Germany

Parameters of tissue iron overload and cardiac function in patients with thalassemia major and intermedia

AbstractBackgroundNoninvasive T2* magnetic resonance imaging (MRI) assessment can stratify the risk of subsequent cardiac dysfunction in β-thalassemia major (TM) and β-thalassemia intermedia (TI) patients. The normal level of N-terminal pro B-type natriuretic peptides (NT-proBNP) can rule out acute heart failure.AimWe aim to investigate the relation of NT-proBNP level, T2* MRI, and echocardiographic findings in TM and TI patients.Materials and methodsIn this cross-sectional study, 41 TM patients, 41 TI patients, and 41 healthy individuals (HI) were enrolled. NT-proBNP level, T2* MRI, and two-dimensional echocardiography were assessed for all patients and controls.ResultsThere was statistically significant correlation between NT-proBNP levels and mitral inflow late diastolic velocity (r = −0.538; p = 0.006) in TM group. There was statistically significant correlation between NT-proBNP levels and tricuspid annulus systolic velocity (r = −0.438; p = 0.028), systolic velocity of septum (r = −0.472; p = 0.020), and mitral inflow early-to-late diastolic wave ratio (r = 0.592; p = 0.002) in TM group.ConclusionEarly diagnosis and treatment of myocardial iron overload are likely to prevent the mortality in patients with established ventricular dysfunction. Since NT-proBNP levels were not significantly increased in documented left ventricular (LV) diastolic dysfunction, this factor may not be sensitive for the detection of latent LV diastolic dysfunction in the early stages of disease progression.

Phenotyping Left Ventricular Obstruction With Postprandial Re-Test Echocardiography in Hypertrophic Cardiomyopathy

Dynamic left ventricular (LV) obstruction has important clinical and therapeutic implications in patients with hypertrophic cardiomyopathy (HC). Although absent at rest, LV obstruction may be elicited using varying stressors. Meal-related hemodynamic changes may favor LV obstruction and support postprandial (PP) symptoms in HC patients. The aim of this study was to evaluate PP-LV obstruction inducibility in HC patients in comparison with fasting Valsalva maneuver and exercise test. Ninety-two HC patients without LV obstruction underwent at-rest Transthoracic Echocardiography (TTE) during Valsalva maneuver and exercise test under fasting condition followed by at-rest re-test PP-TTE 30 to 60 minutes after a standardized midday meal. LV obstruction was noted and classified as being related to systolic anterior motion (SAM) of the mitral valve (SAM-related) and/or non-SAM-related (mid-cavity or apical), and intraventricular gradient was measured. At-rest re-test PP-TTE showed significant intraventricular gradient (>30 mm Hg) in 68 patients (60 SAM-related, 8 non-SAM related, 30 combined) with a higher prevalence (74%) of HC phenotype re-classified as obstructive compared with the fasting Valsalva maneuver (23%) or exercise test (33%) (p < 0.001). At multivariate analysis, a clinical history of PP symptoms and mitral anterior leaflet length and/or LV outflow ratio >2 were independently correlated with PP-TTE obstruction. In conclusion, PP TTE re-test is a simple and effective approach to unmask latent LV dynamic obstruction in daily clinical practice over fasting Valsalva maneuver or exercise test. PP clinical phenotype refinement may be relevant in targeting and evaluating HC therapy.

Left ventricular systolic dysfunction in asymptomatic Marfan syndrome patients is related to the severity of gene mutation: insights from the novel three dimensional speckle tracking echocardiography.

BackgroundIn asymptomatic Marfan syndrome (MFS) patients we evaluated the relationship between the types of fibrillin-1 (FBN1) gene mutation and possible altered left ventricular (LV) function as assessed by three-dimensional speckle tracking echocardiography (3D-STE).Methods and ResultsForty-five MFS patients (mean age 24±15 years) and 40 age-matched healthy controls were studied. Genetic evaluation for the FBN1 gene was carried on 32 MFS patients. Gene mutation (n = 15, 47%) was classified as mild when the mutation resulted in nearly normally functioning protein, while mutations resulting in abnormally function protein were considered to be severe (n = 17, 53%). All patients and controls underwent 3D-STE for evaluation of LV function by an echocardiographer blinded to the results of the genetic testing. Compared to controls, MFS patients had significantly lower 3D-STE derived LV ejection fraction (EF, 57.43±7.51 vs. 62.69±4.76%, p = 0.0001), global LV longitudinal strain (LS, 14.85±2.89 vs. 17.90±2.01%, p = 0.0001), global LV circumferential strain (CS, 13.93±2.81 vs. 16.82±2.17%, p = 0.0001) and global LV area strain (AS, 25.76±4.43 vs. 30.51±2.61%, p = 0.0001). Apart from the global LV LS all these parameters were significantly lower in patients with severe gene mutation than in those with mild mutation (p<0.05). In the multivariate linear regression analysis only the type of mutation had a significant influence on the 3D-STE derived LVEF (p = 0.017), global CS (p = 0.005) and global AS (p = 0.03).ConclusionsIn asymptomatic MFS patients latent LV dysfunction can be detected using 3D STE. The LV dysfunction is mainly related to the severity of gene mutation, suggesting possible primary cardiomyopathy in MFS patients.

Plasma brain natriuretic peptide concentration in β-thalassemia patients

Objectives The aim of this study was to investigate the diagnostic and predictive value of plasma brain natriuretic peptide (BNP) levels in detecting diastolic dysfunction in β-thalassemic patients in comparison with conventional and new Doppler echocardiography indices. Background β-Thalassemia major is a unique disease characterized by early diastolic dysfunction related exclusively to iron myocardial deposition. BNP is a sensitive biomarker for the detection of asymptomatic left ventricular (LV) dysfunction and has important diagnostic and prognostic implications. Materials and methods This study enrolled 25 b-thalassemic major patients with normal systolic function and 10 age-matched and sex-matched individuals. All participants were studied thoroughly by tissue Doppler echocardiography and blood samples were taken for determination of BNP, ferritin, total iron, and complete blood count. Patients were divided into two groups according to the E mitral/E mitral annulus ratio (E/E') at cutoff point 8. Results BNP levels were higher in thalassemic patients compared with the control group. BNP and serum ferritin levels showed a statistically significant increase in group I (E/E' >8) in comparison with group II (E/E' P = 0.003) in ruling out diastolic dysfunction (E/E' Conclusion BNP level is significantly increased in LV diastolic dysfunction and has a predictive value in detecting latent LV diastolic dysfunction in β-thalassemia major.

Stress Echocardiography in Regurgitant Valve Disease

Because of its wide availability, low cost, versatility, and clinical use, stress echocardiography has become increasingly recognized as a valuable tool in the assessment of patients with regurgitant valvular heart disease. Exercise testing is favored compared with pharmacological stress testing for risk stratification in asymptomatic patients and can identify what might otherwise be considered as a moderate valve disease. It has been shown to provide insights into exertional symptoms disproportionate to resting hemodynamics in these patients and to facilitate individual risk stratification. Aggravation of valvular regurgitation severity, exercise-induced pulmonary hypertension (PHT), impaired left ventricular (LV) contractile reserve, inducible ischemia, dynamic LV dyssynchrony, and altered exercise capacity, together with the development of symptoms during exercise echocardiography, provide the clinician with straightforward prognostic information, therefore enabling a more accurate definition of the optimal timing of intervention in patients with valvular regurgitation.1,2 In contrast, dobutamine stress echocardiography has little value in cases of valvular regurgitation. Dobutamine infusion is almost systematically associated with a decrease in the severity of regurgitation; however, it might be of interest in the detection of LV contractile reserve and inducible ischemia. The most common form of exercise used in conjunction with echocardiography is immediate postexercise imaging on a treadmill or upright bicycle ergometer. However, semisupine exercise testing on an appropriate tilted table allows continuous echocardiographic monitoring, which represents an advantageous tool for quantifying changes in valvular regurgitation severity, LV function, and pulmonary pressure (Table). This exercise stress echocardiography modality (ie, per-exercise echocardiography) is the most used in Europe, and we strongly suggest this approach in the setting of valvular heart disease to detect evanescent changes. A symptom-limited graded exercise test is recommended, and ≥80% of the age-predicted upper heart rate should be reached in the absence of symptoms. The test is adapted to the clinical conditions …

Global longitudinal strain predicts left ventricular dysfunction after mitral valve repair

Despite a successful surgical procedure and adherence to current recommendations, postoperative left ventricular (LV) dysfunction after mitral valve repair (MVr) for organic mitral regurgitation (MR) may still occur. New approaches are therefore needed to detect subclinical preoperative LV dysfunction. LV global longitudinal strain (GLS), assessed with speckle-tracking echocardiographic analysis, has been proposed as a novel measure to better depict latent LV dysfunction. The aim of this study was to investigate the value of GLS to predict long-term LV dysfunction after MVr. A total of 233 patients (61% men, 61 ± 12 years) with moderate-severe organic MR who underwent successful MVr between 2000 and 2009 were included. Echocardiography was performed at baseline and long-term follow-up (34 ± 20 months) after MVr. LV dysfunction at follow-up was defined as LV ejection fraction (EF) <50% and was present in 29 (12%) patients. A cut-off value of -19.9% of GLS showed a sensitivity and specificity of 90 and 79% to predict long-term LV dysfunction. By univariate logistic regression analysis, baseline LVEF ≤60%, LV end-systolic diameter (ESD) ≥40 mm, atrial fibrillation, presence of symptoms, and GLS >-19.9% were predictors of long-term LV dysfunction. By multivariate analysis, GLS remained an independent predictor of LV dysfunction (odds ratio 23.16, 95% confidence interval: 6.53-82.10, P < 0.001), together with LVESD. In a large series of patients operated within the last decade, MVr resulted in a low incidence of long-term LV dysfunction. A GLS of >-19.9% demonstrated to be a major independent predictor of long-term LV dysfunction after adjustment for parameters currently implemented into guidelines.

Endothelial‐Mediated Coronary Flow Reserve and Its Relation to Mitral Annular Tissue Doppler Velocities in Offspring of Hypertensive Parents

Although coronary flow reserve (CFR) is reduced in hypertensive patients, data regarding the endothelial response of coronary vasomotion and its relation to left ventricular (LV) function in their offspring is limited. To investigate the endothelial response of coronary flow, using cold pressor test (CPT), in offspring of hypertensive parents and its impact on LV diastolic function. The study population consisted of 32 healthy young offspring (mean age 23.5 ± 7.1 years) of hypertensive parents and 26 aged matched volunteers (healthy offspring of normotensive parents) as controls. Coronary blood flow velocities were recorded in all subjects at rest and after CPT; a stimulus that can be considered totally endothelium-dependent. CFR was calculated as the ratio of hyperemic-to-resting diastolic peak velocities. Doppler echocardiographic assessment was performed using both conventional and tissue Doppler assessment. Coronary diastolic peak velocities at rest was comparable between the two groups (27.1 ± 6.2 vs 26.4 ± 5.8; P > 0.05); but the velocities were significantly lower after CPT in offspring of hypertensive parents (P < 0.02), with highly significant lower CFR (P < 0.0001). Conventional echo-Doppler variables were comparable in both groups, whereas tissue Doppler assessment demonstrated significant LV diastolic dysfunction among offspring of hypertensive parents. The CPT-CFR was significantly correlated to tissue Doppler diastolic dysfunction in this group (For Em, Am and Em/Am, r was 0.65, 0.59 and 0.61, respectively, and P < 0.001). Offspring of hypertensive parents have coronary endothelial dysfunction that appears in response to physiological stimuli (CPT). The coronary endothelial dysfunction is associated with latent LV diastolic dysfunction.

PREDICTION OF INCIPIENT LEFT VENTRICULAR DYSFUNCTION IN PATIENTS WITH CHRONIC PRIMARY MITRAL REGURGITATION: A VELOCITY VECTOR IMAGING STUDY

Aims Progressive left ventricular (LV) dilatation and irreversible myocardial damage are important causes of morbidity and mortality in patients with chronic primary mitral regurgitation (MR) due to myxomatous mitral valve disease. We assessed the hypothesis that early subclinical LV dysfunction secondary to chronic primary MR could be signalled by abnormal LV rotation mechanics, utilizing velocity vector imaging (VVI). Methods and results Forty-three with chronic primary MR and 41 normal subjects were evaluated. All had normal LV systolic function. Peak endocardial and epicardial rotations in systole were measured in apical and basal short-axis images. LV twist was defined as the net difference between apical and basal angles of rotation while LV torsion was calculated as LV twist divided by LV diastolic longitudinal length. To explore the effects of MR severity on LV rotation, patients were divided into three groups: mild, moderate, and severe MR. The peak twist and torsion of the LV endocardium displayed significant differences across the study groups ( P = 0.005 and 0.015, respectively). Subjects with moderate MR revealed the highest LV rotation profile (2.26 ± 0.66°/cm and 17.83 ± 5.2° for torsion and twist, respectively), implicating hyperdynamic LV function. However, severe MR group showed the lowest LV rotation profile (1.39 ± 0.8°/cm and 11.43 ± 6.09° for torsion and twist, respectively), suggesting incipient LV dysfunction. There were no significant differences in epicardial LV rotations. Conclusion Evaluation of global LV function by VVI is a novel reproducible index for detecting subnormal latent LV dysfunction in chronic MR patients, which may aid in the optimal timing of surgery.

Prediction of incipient left ventricular dysfunction in patients with chronic primary mitral regurgitation: a velocity vector imaging study

Progressive left ventricular (LV) dilatation and irreversible myocardial damage are important causes of morbidity and mortality in patients with chronic primary mitral regurgitation (MR) due to myxomatous mitral valve disease. We assessed the hypothesis that early subclinical LV dysfunction secondary to chronic primary MR could be signalled by abnormal LV rotation mechanics, utilizing velocity vector imaging (VVI). Forty-three with chronic primary MR and 41 normal subjects were evaluated. All had normal LV systolic function. Peak endocardial and epicardial rotations in systole were measured in apical and basal short-axis images. LV twist was defined as the net difference between apical and basal angles of rotation while LV torsion was calculated as LV twist divided by LV diastolic longitudinal length. To explore the effects of MR severity on LV rotation, patients were divided into three groups: mild, moderate, and severe MR. The peak twist and torsion of the LV endocardium displayed significant differences across the study groups (P = 0.005 and 0.015, respectively). Subjects with moderate MR revealed the highest LV rotation profile (2.26 ± 0.66°/cm and 17.83 ± 5.2° for torsion and twist, respectively), implicating hyperdynamic LV function. However, severe MR group showed the lowest LV rotation profile (1.39 ± 0.8°/cm and 11.43 ± 6.09° for torsion and twist, respectively), suggesting incipient LV dysfunction. There were no significant differences in epicardial LV rotations. Evaluation of global LV function by VVI is a novel reproducible index for detecting subnormal latent LV dysfunction in chronic MR patients, which may aid in the optimal timing of surgery.

How to Identify Latent Systolic Dysfunction and Post Operative Risk in Patients with Mitral Incompetence and Normal Ejection Fraction?

Purpose: To study the significance of impaired positive peak rate of left ventricular (LV) pressure development (MR + dp/dt) and global systolic strain (GLPSS) values in patients presented with significant mitral incompetence (MR) in coronary artery disease (CAD) and early dilated cardiomyopathy (DCM) with normal ejection fraction (EF). Methods: A description of LV contractile behavior requires measurement of the ability of the ventricle to develop force (pressure) and to shorten. Hence, performance of the ventricle as a pump assessed in the present study by measuring the pressure developed by the ventricle (Left ventricular +dP/dt is estimated from MR jet as the rate of pressure rise from 1 to 3 m/sec) and shortening assessed by GLPSS (this Doppler technology allowed measurement of LV systolic strain for the entire length of LV myocardium). GLPSS and MR + dp/dt were calculated in 30 consecutive patients (mean age was 55 ± 12 years) characterized by echocardiographic evidence of moderate or severe MR (in CAD and DCM patients) and normal EF (mean LV Ejection Fraction of 50.9% ± 5.9%) and compared with those obtained in 35 consecutive controls (age 54.7 ± 11.4 years) with normal echocardiographic study of the heart. Results: The mean values of MR +dp/dt and GLPSS averaged from the 3 apical views, differed significantly in DCM and CAD patients (characterized by significant MR with normal EF) compared with control group, (MR + dp/dt = 733 ± 170 mmhg/s and GLPSS –13% ± 1.3%) versus (1420 ± 210 mmhg/s and -19.5% ± 3.3%) for patients versus control, respectively, p < 0.001. A depressed values of MR + dp/dt were highly correlated with GLPSS values in patients with CAD and DCM, r = 0.78. The combined use of 2D Strain (<-13%) and MR dp/dt (<900 mmhg/s) in the presence of MR (grade II or more) had 89% sensitivity and 92% specificity for detection of patients at risk of post-operative major cardiac events after MR and coronary artery bypass surgery. Conclusions: Latent LV systolic dysfunction could be defined noninvasively by depressed peak MR + dp/dt and GLPSS in the echocardiography laboratories.

Detection of Left Ventricular Dysfunction With Tei Index in Normal Ejection Fraction Patients With Mitral Regurgitation Before Mitral Valve Surgery

Ejection fraction (EF) was not considered a reliable parameter of left ventricular (LV) function and was normal in most patients with chronic mitral regurgitation (MR), whereas LV dysfunction expressed as decreased EF was often shown after mitral valve surgery. This study sought the ability of the Tei index to detect latent LV dysfunction in patients with MR and apparently normal EF. One hundred eight patients with apparently normal EF (EF > or =50%) and chronic severe MR who underwent mitral valve repair were investigated. EF was significantly decreased after surgery and LV dysfunction (EF <50%) was shown in 37 patients (34% of all patients). The preoperative Tei index significantly correlated with postoperative EF in all patients (r = -0.64, p <0.0001) and asymptomatic patients (n = 44; r = -0.57, p <0.0001). By setting the preoperative Tei index >0.5 to predict postoperative EF <50%, this index had sensitivity, specificity, and accuracy of 89%, 85%, and 86% in all patients and 80%, 85%, and 84% in asymptomatic patients, respectively. In conclusion, a preoperative Tei index >0.5 allowed prediction of postoperative LV dysfunction in patients with MR with apparently normal EF. Thus, earlier surgery is recommended in asymptomatic patients with MR with normal EF, but Tei index >0.5.

Abstract 3383: Assessment Of The Left Ventricular Long-axis And Short-axis Function Using Strain Rate Imaging In Chronic Severe Mitral Regurgitation: A Comparative Echocardiography-catheterization Study

Background Assessment of the left ventricular (LV) contractile function is critical for deciding optimal timing of surgery in patients with chronic severe mitral regurgitation (MR). We investigated the LV long-axis and short-axis function in MR. Methods We studied 30 patients (16 men, age: 51 ± 14 years) who had 3+ or 4+ MR with LV ejection fraction (EF) greater than 50%. Comprehensive 2D and Doppler echocardiography was performed. Peak systolic radial (SR R ), circumferential (SR C ), and longitudinal strain rate (SR L ) were measured using speckle tracking imaging. In all patients, peak dP/dt was measured using micromanometer-tipped catheter. Results Mean LVEF was 63.1% and regurgitation fraction was 61.8%. LV end-systolic volume was 78.3 ml. Peak dP/dt ranged from 1019 to 2049 mmHg/sec with the mean value of 1583 mmHg/sec. 16 patients (53.3%) showed latent systolic dysfunction defined by peak dP/dt less than 1300 mmHg/s. SR R and SR C correlated well with peak dP/dt (Fig. A , r=0.74, p&lt; 0.01, r=− 0.54, p&lt;0.01, respectively). However, SR L did not correlate with peak dP/dt (r=− 0.58, p=0.76). SR R &gt; 1.94 S −1 showed a sensitivity of 86 % and a specificity of 75 % for predicting latent LV systolic function (Fig. B , AUC=0.87, CI=0.732– 0.991). SR R also correlated with LV end-diastolic and end-systolic sphericity index (r=− 0.54, p&lt;0.01, r=− 0.66, p&lt; 0.01, respectively). Conclusion SR R and SR C , not SR L , correlated well with peak LV dP/dt. These results imply the importance of short-axis function in the presence of chronic severe MR, probably due to the geometrical change in response to chronic volume overload.

Evaluation of Left Ventricular Contractile Function Using Noninvasively Determined Single-beat End-systolic Elastance in Mitral Regurgitation: Experimental Validation and Clinical Application

We performed this study to validate the single-beat estimation of end-systolic elastance (E(es)) in an animal model of chronic mitral regurgitation (MR) and to use E(es) to predict postoperative left ventricular (LV) systolic function with the noninvasively derived single-beat E(es) (E(es-s)) in patients with MR. Eight sheep with MR were studied under 4 different loading conditions. E(es) was measured as the slope of the end-systolic pressure-volume relationship with a conductance catheter during inferior vena cava occlusion. E(es-s) was calculated using a bilinearly approximated time-varying elastance curve. We also studied 105 patients with MR who had undergone mitral valve repair. All measurements in these patients were performed before surgery and repeated at about 1 week after surgery. In the animals in a total of 23 different stages, E(es-s) showed a good correlation and agreement with invasively determined E(es) (y = 0.84 x + 0.38; r = 0.8; P < .01, mean difference = 0.1 +/- 0.6 mm Hg/mL). In the clinical study, preoperative E(es-s) (r = 0.77; P < .001) and end-systolic volume index correlated well with postoperative ejection fraction (r = -0.69; P < .001). Multivariate analyses revealed that only E(es-s) was an independent predictor of postoperative LV function. Preoperative E(es-s) less than or equal to 1.0 mm Hg/mL was most predictive for identifying patients with LV dysfunction after surgery (sensitivity 87%; specificity 76%). LV end-systolic elastance can be estimated noninvasively and is useful to detect latent LV dysfunction in patients with MR before surgery.

977 Quantitative assessment of myocardial contractile reserve during exercise in patients with mitral valve prolapse

Background: Although the actual trends is toward early surgery in patients with asymptomatic severe organic mitral regurgitation (MR), some of them might already have latent left ventricular (LV) dysfunction. This study sought to examine whether tissue Doppler imaging measurement of longitudinal function could be used to identify contractile reserve (CR) during exercise in NYHA I-II patients with MR due to mitral valve prolapse. Methods: Forty-seven patients underwent quantitative off-line assessment of longitudinal function by averaging peak mitral annular velocities (PSv) obtained at rest and during semi-supine exercise test. Results: During test, CR defined by 34% improvement in ejection fraction was present in 25 patients. As compared to patients with CR, the degree of MR at rest (effective regurgitant orifice (ERO): 43±18 vs 24±14 mm2, p=0.0048) and at peak exercise (ERO 46±22 vs 23±19 mm2, p=0.0049) was greater in the absence of CR whereas ejection fraction was similar (69±6 vs 66±6%, p=ns). The increase in PSv (11±1.9 vs 8±2.5 cm/s, p=0.00029) and changes in LV end-systolic volume (-14±7 vs 4.4±12 ml p=0.0029) during exercise were higher in the CR group. In multivariate analysis, exercise-induced changes in LV end-systolic volume and in PSv independently predicted the presence of CR. An increase in PSv by 32 cm/s yielded a sensitivity of 88% and a specificity of 82% to identify positive CR. Conclusions: Latent LV dysfunction in patients with mitral valve prolapse could be reliably identified using tissue Doppler imaging.

The use of stress echocardiography in the assessment of mitral valvular disease.

Stress echocardiography plays an important role in evaluating asymptomatic patients with significant mitral stenosis and symptomatic patients with only mild disease at rest, as it correlates the exercise-induced symptoms with changes in transmitral gradients, pulmonary pressures, and mitral valve area. In patients with mitral regurgitation (MR), exercise or dobutamine protocols assess for the change in the degree of regurgitation and the pulmonary artery pressure (PAP) in response to high flow states, and detect underlying left ventricular (LV) dysfunction prior to valvular surgery. Exercise echocardiography also helps in the prognostic assessment of patients with mitral valve prolapse as new MR, or latent LV dysfunction may be provoked to identify a group of high risk individuals with normal resting echocardiographic parameters. Finally, it evaluates the proper functioning of prosthetic mitral valves and helps on the monitoring of transmitral gradients and PAPs after mitral valve surgery.

Relationship of ventricular longitudinal function to contractile reserve in patients with mitral regurgitation

Background Latent left ventricular (LV) dysfunction in patients with valvular or myocardial disease may be identified by loss of contractile reserve (CR) at exercise echocardiography. Contraction in the LV longitudinal axis may be more sensitive than radial contraction to minor disturbances of LV function. We sought to determine whether tissue Doppler measurement of longitudinal function could be used to identify CR. Methods Exercise echocardiography was performed in 86 patients (20 women, age 53 ± 18 years), 72 with asymptomatic or minimally symptomatic mitral regurgitation, and 14 normal controls. Pulsed-wave tissue Doppler imaging (DTI) was used to measure maximum annular systolic velocity at rest and stress. Inducible ischemia was excluded by analysis of wall motion by an experienced observer. CR was defined by ≥5% improvement of stress compared with rest ejection fraction (EF). Exercise capacity was assessed from expired gas analysis. Results CR was present in 34 patients with mitral regurgitation (47%); peak EF in patients with and without CR was 74% ± 11% versus 54% ± 15% ( P < .0001). CR could not be predicted by resting EF, volumes or sphericity, and DTI measurement of base-apex function was the only resting echocardiographic parameter to distinguish between patients with and without CR (10 ± 2 vs 8 ± 2 cm/s, P < .03). This parameter showed greater differences after stress (14 ± 4 vs 11 ± 3 cm/s, P < .001). Patients with CR showed lower peak DTI than controls, as well as lower exercise capacity and EF response to exercise. In a multiple linear regression model, rest DTI ( P = .03) was an independent correlate of contractile reserve. The other correlates were age ( P < .0001), resting ( P < .0001) and peak end-systolic volume ( P = .01), and resting ( P < .0001) and peak end-diastolic volume ( P < .0001); the model r 2 was 0.93 ( P < .001). Conclusion In the absence of regional LV dysfunction, measurement of longitudinal axis function by DTI may be a marker of CR.

Evaluation by contrast-enhanced electron beam computed tomography of myocardial perfusion and tissue characteristics in congenital aortic stenosis.

The evaluation of myocardial perfusion and tissue characteristics gives useful information regarding the indication for surgery. In the present study, two-phase contrast enhanced electron beam computed tomography (EBT) was used to quantitatively examine myocardial perfusion and the tissue characteristics of the left ventricular (LV) myocardium in congenital aortic stenosis (AS). The AS group comprised 15 patients and the control group had 14 non-AS patients. Myocardial ischemia and tissue characteristics were evaluated by the ratio of the incremental CT number of the myocardium (M) and the lumen (L) of the LV (M/L) in, the early phase with and without dipyridamole (Dp) loading and in the late phase after enhancement (respectively). In a comparison between the AS group and the controls, mean early M/Ls were significantly lower in the AS group than in the controls (20+/-5% vs 37+/-10%, p<0.01) and mean late M/Ls in the AS group were also significantly lower (47+/-11% vs 62+/-13%, p<0.01). In the AS patients, early M/Ls in the subendocardial and apical regions were especially lower than those of other segments, but the late M/Ls in these segments were inversely higher than those of other segments. These results suggest 2 things: (1) the existence of latent LV myocardial ischemia in AS patients, which is probably because of a hypertrophied LV wall, in turn caused by afterload, and (2) the presence of more myocardial ischemia and interstitial fibrosis in the subendocardial and apical regions of the AS heart. Using Dp loading for the AS patients increased the clarity of the contrast images. Contrast-enhanced EBT is useful for evaluating myocardial characteristics and perfusion in AS, and gives new insight into the LV wall characteristics in AS, as well as an indication for surgical correction of congenital AS.

Latent left ventricular dysfunction in patients with mitral regurgitation: Feasibility of measuring diminished contractile reserve from a simplified model of noninvasively derived left ventricular pressure-volume loops

Background Assessment of left ventricular (LV) contractility in mitral regurgitation is difficult, and latent systolic dysfunction may be present despite conventional indexes being in the “normal” range. We sought to demonstrate the presence of latent LV dysfunction in mitral regurgitation by showing diminished contractile reserve with the use of simplified pressure-volume loops from noninvasively derived parameters. Methods and Results We performed exercise echocardiography in 72 patients with isolated mitral regurgitation, minimal or no symptoms, normal resting LV function, and no coronary disease who subsequently underwent uncomplicated valve repair and in 15 healthy subjects. Simplified pressure-volume loops were constructed and LV stroke work was estimated at rest and immediately after exercise. As pressures were estimated, the findings were confirmed with a validated numerical model to estimate stroke work in patients and control subjects. Patients had a higher stroke work than did control subjects at rest (1.45 ± 0.39 vs 0.92 ± 0.21 J, P < .001). Eighteen patients had LV dysfunction develop after surgery. Patients with postrepair dysfunction had a significantly lower exercise stroke work (1.79 ± 0.69) than did patients without (2.28 ± 0.84 J, P = .02), but there was no difference in resting stroke work (1.48 ± 0.39 vs 1.44 ± 0.4, P = not significant). Change in stroke work with exercise was higher in patients with normal postoperative function (0.84 ± 0.59 J) and control subjects (0.59 ± 0.36 J) than patients with postoperative dysfunction (0.31 ± 0.55 J, P = .001). The numerical model confirmed the lower exercise stroke work and change in stroke work in patients with postoperative dysfunction. Conclusions The clinical study and numerical model confirmed diminished contractile reserve in patients who had LV dysfunction develop after uncomplicated mitral valve repair. Diminished contractile reserve may be a preoperative marker of latent contractile dysfunction. (Am Heart J 1999;137:427-34.)