Quantification of diastolic dysfunction via the age dependence of diastolic function - impact of insulin resistance with and without type 2 diabetes.

BACKGROUND: The alarming prevalence of heart failure with preserved ejection fraction requires quantification of diastolic dysfunction (DDF). Myocardial diastolic velocity E' implies that age is the most important determinant. We tested the hypothesis that age allows for quantification of DDF and assessment of the structural and metabolic determinants in patients with and without type 2 diabetes (D). METHODS: This prospective, cross-sectional study assessed cardiovascular, metabolic and ultrasound data in 409 consecutive patients (Diabetes Center, Bogenhausen-Munich) between 20 and 90 years without known cardiac disease and either with (n=204) or without D but with common prevalence of cardiovascular risk factors, including a subgroup of healthy individuals (H, n=94). RESULTS: In H, E' related to age as: E'norm=-0.163∗years+19.69 (R(2)=0.77, p<0.0001). According to this 1% reduction by annual physiologic aging, DDF was quantitated as E'-E' norm. Compared to nondiabetics, D patients were older, had greater BMI, lower E', more cardiovascular risk and greater DDF. In nondiabetics, grading of DDF by E-E'norm correlated with grading by filling pressure E/E'. Determinants of DDF by multivariate analysis included pulse wave velocity, diastolic blood pressure and the triglyceride/HDL ratio (a marker of insulin resistance) in nondiabetics and in D the same risk factors in reverse sequence and heart rate. Neither left atrial size nor left ventricular mass had significant impact. CONCLUSIONS: The physiological impact of age on myocardial function consists of a 1% annual reduction in E' and enables precise quantification of diastolic dysfunction thereby unmasking the importance of metabolic risk for DDF.

Oxidative stress after a carbohydrate meal contributes to the deterioration of diastolic cardiac function in nonhypertensive insulin-treated patients with moderately well controlled type 2 diabetes.

The prevalence and prognostic importance of diastolic dysfunction in type 2 diabetes has only recently been appreciated. We tested the hypothesis that in insulin treated type 2 diabetes (D), carbohydrate consumption induces oxidative stress resulting in further impairment of diastolic function beyond structural myocardial stiffness. The effects of a pure carbohydrate breakfast (48 g) on oxidative stress and cardiac function were studied in the fasting and postmeal states in subjects without hypertension or overt cardiac disease (moderately well controlled D, n=21 and controls without D, n=20). Studied variables included systolic and early diastolic (E') myocardial velocities, traditional metabolic and hemodynamic parameters, serum nitrotyrosine, and sVCAM-1. In D compared to control subjects, the postmeal increase (∆) in glucose (1.44±2.78 vs. 0.11±0.72 mmol/l, p=0.04) and ∆nitrotyrosine (0.34±0.37 vs. -0.23±0.47 nM/l, p<0.001) were significantly higher. sVCAM-1 was higher in fasting and postmeal (p=0.02). E' was significantly lower in postmeal (7.3±1.3 vs. 9.6±1.3 cm/s, p<0.001) and fasting (p<0.001) whereas the rate pressure product was significantly higher (9 420±1 118 vs. 7 705±1 871 mm Hg/min, p<0.001). Multivariable regression models of the pooled data demonstrated that independent predictors for postmeal E' were ∆nitrotyrosine and septal thickness (R² 0.466) and for fasting E' age, ∆nitrotyrosine, and septal thickness (R² 0.400). In insulin requiring type 2 diabetes, carbohydrate consumption may induce oxidative stress that is associated with worsening diastolic function, indicating that this metabolic factor is an important determinant of diastolic dysfunction in the diabetic heart beyond the increase in structural myocardial stiffness.

Diastolic dysfunction in diabetes and the metabolic syndrome: promising potential for diagnosis and prognosis.

Cardiac disease in diabetes mellitus and in the metabolic syndrome consists of both vascular and myocardial abnormalities. The latter are characterised predominantly by diastolic dysfunction, which has been difficult to evaluate in spite of its prevalence. While traditional Doppler echocardiographic parameters enable only semiquantitative assessment of diastolic function and cannot reliably distinguish perturbations in loading conditions from altered diastolic functions, new technologies enable detailed quantification of global and regional diastolic function. The most readily available technique for the quantification of subclinical diastolic dysfunction is tissue Doppler imaging, which has been integrated into routine contemporary clinical practice, whereas cine magnetic resonance imaging (CMR) remains a promising complementary research tool for investigating the molecular mechanisms of the disease. Diastolic function is reported to vary linearly with age in normal persons, decreasing by 0.16 cm/s each year. Diastolic function in diabetes and the metabolic syndrome is determined by cardiovascular risk factors that alter myocardial stiffness and myocardial energy availability/bioenergetics. The latter is corroborated by the improvement in diastolic function with improvement in metabolic control of diabetes by specific medical therapy or lifestyle modification. Accordingly, diastolic dysfunction reflects the structural and metabolic milieu in the myocardium, and may allow targeted therapeutic interventions to modulate cardiac metabolism to prevent heart failure in insulin resistance and diabetes.

[Augmentation of myocardial function by improved glycemic control in patients with type 2 diabetes mellitus]. / Verbesserung der Myokardfunktion durch verbesserte Stoffwechselkontrolle bei Typ-2-Diabetes.

BACKGROUND: In patients with type 2 diabetes mellitus diastolic dysfunction is a frequent manifestation of myocardial disease with poor prognosis. The hypothesis that better glycemic control results in improved myocardial function was tested using tissue Doppler. METHODS: During a short-term (3 weeks) and a long-term (52 weeks) study, metabolic control and myocardial function were evaluated in 33 and 50 patients, respectively, with type 2 diabetes. Systolic (Vs) and diastolic (Ve) myocardial velocity were assessed by tissue Doppler. In the short-term study, antidiabetic therapy was intensified in 25 patients (Int3) and compared to those eight individuals with unchanged therapy (Con3), similarly to the long-term study with Int52 (n = 39) and Con52 (n = 11). RESULTS: In Int3, fasting serum glucose was reduced by 69+/-47 mg/dl (p < 0.01) compared to baseline and was associated with an increase of Ve from 8.0 +/- 1.6 to 8.8 +/- 1.6 cm/s (p < 0.01) and Vs from 6.2 +/- 1.1 to 6.6 +/- 1.3 cm/s, p < 0.04. In Con3, serum glucose and myocardial velocities were unchanged. In Int52, fasting serum glucose was reduced by 20 +/- 43 mg/dl (p < 0.017) compared to baseline and was associated with an increase of Ve from 7.6 +/- 1.3 to 8.3 +/- 1.7 cm/s (p < 0.002) and a similar trend in Vs (p < 0.07). In Con52, serum glucose and myocardial velocities remained unchanged. Evaluating pooled data, the changes of diastolic myocardial velocity correlated significantly with the changes of serum glucose (r = 0.49, p < 0.004 short- and r = 0.45; p < 0.002 long-term study, respectively). CONCLUSION: In patients with type 2 diabetes subclinical diastolic myocardial dysfunction, measured as diastolic myocardial velocity by tissue Doppler, improves with better glycemic control.

Global myocardial perfusion and diastolic function are impaired to a similar extent in patients with type 2 diabetes mellitus and in patients with coronary artery disease--evaluation by contrast echocardiography and pulsed tissue Doppler.

AIMS/HYPOTHESIS: Using modern echocardiography, we quantified the extent of global myocardial function and perfusion abnormalities in patients with type 2 diabetes and compared this with the hypothetically similar extent of impairments in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: This case-control study (66 patients) compared four age-matched groups: control, type 2 diabetic, CAD, and diabetic subjects with CAD (DCAD) and left ventricular ejection fraction >50%. CAD patients had 1-2 vessel disease. Diastolic and systolic myocardial velocities were assessed with pulsed tissue Doppler. Global myocardial perfusion was assessed with contrast echocardiography as indices of capillary blood volume and myocardial blood flow at maximal vasodilatation. In CAD and DCAD patients, functional and perfusion parameters were additionally assessed in the territory with a normal coronary angiogram reading, providing a model for comparison with the global data from control and diabetic patients. RESULTS: Comparing diabetic with control subjects, myocardial velocity at early diastole was impaired (8.8+/-1.8 vs 10.1+/-1.7 cm/s; p=0.02) and correlated inversely with age, HbA(1c) and pulse pressure (R (2)=0.761). Capillary blood volume (16.6+/-5.0 vs 24.4+/-4.9%) and blood flow (56+/-35 vs 114+/-40) were decreased (p=0.001). In CAD patients, myocardial velocity at early diastole was similarly decreased (p=0.02). CAD and DCAD patients were receiving more cardiovascular preventive therapy for the same extent of impaired global perfusion as in the less extensively treated diabetes group without CAD (p<0.002), but had superior perfusion of the 'normal' coronary territory than that group (p<0.05). CONCLUSIONS/INTERPRETATION: In patients with diabetes, global diastolic function and myocardial capillary blood volume and blood flow are impaired to the same extent as in patients with CAD. These impairments could form the basis of new therapeutic concepts.

Myocardial contrast echocardiography yields best accuracy using quantitative analysis of digital data from pulse inversion technique: comparison with second harmonic imaging and harmonic power Doppler during simultaneous dipyridamole stress SPECT studies.

AIMS: This prospective study assesses the (1) feasibility of quantifying ultrasound myocardial perfusion studies based on the densitometric analysis of digital data and the (2) comparison of pulse inversion, second harmonic and harmonic power Doppler modalities with SPECT. METHODS AND RESULTS: Twenty-three patients with suspected ischaemic heart disease had i.v. injections of Tc-Sestamibi and Optison during a dipyridamole stress test for echocardiography in pulse inversion, second harmonic and harmonic power Doppler mode. Analysis was (a) visual by scoring and (b) quantitative by densitometry of digital data for background subtracted myocardial opacification (a.u.) and normalized contrast effect (%). In the nine control patients, myocardial opacification at stress was greater (P< or =0.002) than in the pathologic group (5. +/- 3.3 vs 2.6 +/- 2.5 a.u. in pulse inversion, 5.4 +/- 2.1 vs 2.4 +/- 1.8 in second harmonic and 7.1 +/- 3.7 vs 4.9 +/- 3.7 a.u. in harmonic power Doppler). In the pathologic group, normalized contrast effect decreased significantly during stress (23.7 +/- 18.8 to 11.3 +/- 10.8%, P<0.003) only in pulse inversion. Kappa values for patient based diagnostic agreement with SPECT were 0.75 by pulse inversion, 0.62 by second harmonic and 0.52 by harmonic power Doppler for quantitative analysis, and 0.51, 0.37 and 0.35 respectively, for visual assessment. CONCLUSION: Myocardial contrast echocardiography should be analysed using densitometry of digital data. The new technique pulse inversion demonstrates best agreement with SPECT data.

Shu 508 A (Levovist)-enhanced Doppler echocardiography improves the assessment of valvular heart disease.

OBJECTIVE: To investigate whether intravenous injection of SHU 508 A improves the diagnostic accuracy of Doppler echocardiography in the assessment of valvular pathologies. METHODS AND RESULTS: One hundred and twenty-five consecutive patients with valvular pathology (aortic stenosis, n = 48; aortic regurgitation, n = 20; mitral stenosis, n = 21; and mitral regurgitation, n = 36) and diagnostically insufficient Doppler signal were enrolled in this multicenter study. The severity of valvular pathology was graded on a four-point scale using unenhanced and contrast-enhanced Doppler echocardiography as well as cardiac catheterization. Agreement with cardiac catheterization findings increased from 63% using the unenhanced examination to 73% using the contrast-enhanced Doppler examination. Grading was possible in all patients using SHU 508 A, whereas the unenhanced Doppler examination remained inconclusive in six patients. The weighted kappa coefficient between contrast-enhanced Doppler and cardiac catheterization for all diagnoses was 0.76 as compared to 0.68 between unenhanced Doppler and cardiac catheterization. Agreement was especially improved in aortic stenosis (kappa 0.69 unenhanced vs 0.81 contrast-enhanced) and in aortic regurgitation (kappa 0.45 unenhanced vs 0.75 contrast-enhanced). Patients with mitral stenosis and mitral regurgitation experienced less improvement. CONCLUSIONS: In case of an inconclusive unenhanced Doppler echo study, the administration of a left heart contrast agent should be considered. SHU 508 A is especially useful in improving the severity grading of aortic stenosis and aortic regurgitation, while grading of mitral stenosis and mitral regurgitation is less improved.

[Determining myocardial perfusion--contribution of contrast echocardiography]. / Bestimmung der myokardialen Perfusion--Beitrag der Kontrast-Echokardiographie.

There is great demand for a non-radioactive bed-side method for the assessment of myocardial perfusion by contrast echocardiography, which may gain clinical relevance for diagnostic strategies only with i.v. application of the contrast agent as opposed to the intracoronary application used until recently. This has finally become true after many years of developing left heart contrast agents and more adequate ultrasound acquisition methods. This leads to the question: Where are we now? Myocardial contrast echocardiography yields unique information on the pathophysiology of microcirculation in vivo due to the fact that microbubbles remain strictly intravascular. Experimental and clinical studies using intracoronary contrast application have shown that infarct size and area at risk are depicted with high accuracy and furthermore that reflow vs no reflow phenomena are demonstrated after the revascularization procedure. In addition, presence and prognostic implications of collateralization may be assessed. Microvascular integrity plays an important role for functional recovery after revascularization. The breakthrough to a potentially clinical role of contrast echocardiography is mainly due to the development of new acquisition methods, such as pulse inversion technique, which allow differentiation of the microbubble signature from the surrounding myocardium. Initial publications show good diagnostic accuracy for the assessment of infarct size and area at risk as well as for the reflow vs no reflow phenomena and microvascular integrity, in particular also as follow up after protective interventions to improve microcirculation. Now, it is conceivable to assess relative or absolute changes of myocardial perfusion. This may be achieved by using non-video signals for analysis and by understanding attenuation effects and other artifacts. Further intensive and critical evaluation and standardization of imaging and analysis techniques is required before general clinical acceptance. New insight into the dynamic nature of perfusion, however, may already allow progress in some urgent questions of microvascular protection.

Regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing: a comparison with stress echocardiography and perfusion scintigraphy.

OBJECTIVES: We evaluated regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing. BACKGROUND: Evaluation and quantification of diastolic myocardial function remain a challenge for imaging techniques in stress tests. METHODS: A prospective study compared the detection of coronary artery stenosis: 1) by pulsed Doppler myocardial mapping, 2) by two-dimensional echocardiographic dobutamine stress test, and 3) by perfusion scintigraphy in 64 patients using coronary angiography for reference. An age matched subgroup of 10 patients with normal angiograms and two-dimensional echocardiographic stress test served as control group. Peak myocardial contraction velocity (Vc) and lengthening rate during early diastolic left ventricular (LV) filling (VE) were measured in 12 LV segments from three apical views. RESULTS: In controls, myocardial velocities increased during stress by > or =3.6 cm/s (p < 0.001). In LV segments depending on a stenosed artery (n = 70), VE decreased by > or =1 cm/s and, thus, was different from control segments (n = 112, p < 0.001) and from scar segments (n = 13, p < 0.01), whereas the change of Vc was similar to that in scar segments. A stress induced 2 cm/s reduction of VE discerned the best diagnostic accuracy (sensitivity 84%, specificity 93%) in comparison with two-dimensional echocardiography (78% and 71%) and perfusion scintigraphy (61% and 86%). Using receiver operating curves at incremental levels of luminal narrowing, these relations persisted. CONCLUSIONS: Quantification of diastolic myocardial function by pulsed Doppler myocardial mapping during dobutamine stress test was shown to be a feasible, accurate, reproducible, noninvasive technique that should be considered to be a sensitive alternative to the present echocardiographic and scintigraphic imaging techniques for stress tests.

[Contrast echocardiography]. / Kontrastechokardiographie.

The intravenous application of an ultrasound contrast agent induces enhanced display of blood in all its pathways. Within cardiology, this principle is mainly utilized for signal enhancement of color Doppler and spectral Doppler in order to improve quantification of congenital and acquired valvular lesions and also for improved endocardial delineation during stress tests and in the evaluation of LV function. The new domaine of myocardial perfusion imaging by contrast echocardiography, however, needed profound technical developments before realization of the clinical potential could even be conceived. These are based on the complex reactions of microbubbbles in the acoustic field in order to allow the sensitive and bubble specific display of intramyocardial contrast effects. The presently available acquisition techniques, second harmonic imaging and harmonic power Doppler, demonstrate significant improvements if compared to traditional fundamental 2-d echocardiography; however, they are still subjected to important limitations. There are many anatomical, physiological, and technical reasons for insufficient display of intramyocardial microbubbles, the most important one being attenuation. It is hoped that the most recently developed imaging modality, pulse inversion technique, allows the necessary diagnostic accuracy and reproducibility in myocardial perfusion imaging.

[New techniques for the quantification of myocardial function: acoustic quantification, color kinesis, tissue Doppler and "strain rate imaging"]. / Neue Techniken zur Quantifizierung der Myokardfunktion: Akustische Quantifizierung, Color Kinesis, Gewebedoppler und "Strain Rate Imaging".

In this article, the authors discuss different semi-quantitative methods for the analysis of global and regional myocardial function. Analysis of endocardial motion and direct measurements of myocardial velocities are the basic principles. The former is a two-dimensional technique which, however, requires good image quality and which is influenced by motion artefacts. The latter technique has a better signal to noise ratio and offers the opportunity to sufficiently quantify diastole. Strain rate imaging is a new and interesting way to display and evaluate regional myocardial deformation.

[A standardized documentation structure for data documentation in echocardiography. Work Team on Standards and LV Function of the Work Group on Cardiovascular Ultrasound of the German Society of Cardiology, Heart and Circulation Research]. / Eine standardisierte Dokumentations-struktur zur Befunddokumentation in der Echokardiographie. Für den Arbeitskreis Standardisierung und LV-Funktion der Arbeitsgruppe Kardiovaskulärer Ultraschall der Deutschen Gesellschaft für Kardiologie--Herz- und Kreislaufforschung.

Presently, there are no well-defined standards for documentation of echocardiographic studies. Nevertheless, standards are essential to provide comparability of data and to realize electronic communication, both essential for quality management in echocardiography. Therefore, the working group "Standards and LV function" of the German Society of Cardiology developed a consensus for documentation of echocardiographic studies. In the present paper this consensus is presented and illustrated by typical clinical examples. Additionally, a prototype of a user-oriented software based on this data set is presented. The complete data set for transesophageal and transthoracic echocardiography and the software prototype can be downloaded at http:@echo.ma.uni-heidelberg.de.

Noninvasive localization of accessory pathways in patients with Wolff-Parkinson-White syndrome with the use of myocardial Doppler imaging.

This study sought to examine the diagnostic accuracy of noninvasive prediction of accessory pathway localization in patients with manifest Wolff-Parkinson-White syndrome with the use of myocardial Doppler imaging as a new noninvasive mapping procedure. Myocardial Doppler imaging measures myocardial velocities and therefore can determine the site of earliest ventricular activation in patients with accessory bypass tracts. Twenty-five patients with manifest preexcitation were studied with the use of pulsed wave and M-mode myocardial Doppler imaging for the evaluation of the shortest electromechanical time interval in 9 basal myocardial segments. The new diagnostic test was compared with 3 electrocardiographic algorithms. An invasive mapping procedure served as reference standard. Abnormally short electromechanical time intervals were found in preexcited segments (27 +/- 12 ms vs 64 +/- 27 ms). Myocardial Doppler imaging correctly localized 84% of the accessory pathways and electrocardiographic algorithms only 48% to 60% of cases. Noninvasive prediction of accessory pathway localization by myocardial Doppler imaging is accurate and proved to be superior to prediction based on electrocardiographic algorithms.

Combined use of contrast-enhanced 2-dimensional and color Doppler echocardiography for improved left ventricular endocardial border delineation using Levovist, a new venous echocardiographic contrast agent.

Transthoracic echocardiography often provides inadequate endocardial border visualization, particularly of the left ventricular apex. The aim of this study was to determine whether the transpulmonary echocardiographic contrast agent, Levovist, could improve endocardial visualization. Accordingly, 43 patients underwent 2-dimensional echocardiography before and after intravenous administration of Levovist. Definition of the left ventricular septal, apical and lateral borders was graded: 0 = no definition, 1 = partial definition, 2 = complete definition. Color Doppler was performed before and after contrast in 32/43 patients and similarly scored to determine any further benefit in apical border detection. There was significant (p < 0.001) improvement of the average end-diastolic scores of the septal, apical and lateral regions (1.4 +/- 0.5, 0.6 +/- 0.7 and 0.9 +/- 0.5 before and 1.8 +/- 0.4, 1.4 +/- 0.6 and 1.7 +/- 0.5 after Levovist). The average end-systolic score was significantly different (p < 0.001) from end-diastolic values in the apex only (0.3 +/- 0.6 before and 0.8 +/- 0.7 after Levovist). Average apical scores using color Doppler improved from 0.3 +/- 0.6 and 0.1 +/- 0.2 during end-diastole and end-systole to 1.7 +/- 0.5 and 1.2 +/- 0.6, respectively, after Levovist (p < 0.001); the average end-diastolic contrast-enhanced color Doppler score was significantly higher than the corresponding grey scale score (p < 0.001). We conclude that left ventricular endocardial border definition is significantly improved by Levovist. The use of contrast enhanced color Doppler can compensate for limited efficacy of this method in the apex.

[Enhancement of Doppler signals in aortic and mitral valve diseases]. / Verstärkung von Doppler-Signalen bei Aorten- und Mitralvitien.

Ultrasound contrast media increase backscatter from blood, thus improving the signal-to-noise ratio. Potential clinical applications of intravenous ultrasound contrast are reviewed. Contrast enhancement of continuous wave Doppler is indicated when the native recordings are noisy and no complete envelope of the Doppler spectrum is obtained. In aortic stenosis several investigations showed good agreement between the gradient calculated from Doppler measurements and the results of cardiac catheterization. In mitral insufficiency maximum area of the regurgitant jet is a widely used parameter for estimation of the severity of the regurgitation. However, assessment of the maximum jet area may not be possible because of poor acoustic windows. Contrast enhancement provides complete display of the regurgitant jet in most of the patients. The diagnostic confidence of the Doppler investigation is further improved by the recording of the pulmonary venous flow, which can be recorded in most of the patients following contrast injection. Therefore contrast enhanced transthoracic Doppler is an alternative to transesophageal Doppler investigation in patients with poor transthoracic windows.

Doppler energy: a new acquisition technique for the transthoracic detection of myocardial perfusion defects with the use of a venous contrast agent.

AIMS: This animal experiment was designed to study whether the new technique of Doppler energy imaging could display myocardial perfusion abnormalities with the use of a combination of transthoracic imaging and right atrial injection of a myocardial contrast agent. METHODS AND RESULTS: A series of 11 pigs were studied during (1) normal perfusion, (2) dipyridamole-induced coronary dilatation, and (3) during and after temporary occlusion of the left anterior descending or circumflex artery after a right atrial injection of 8 ml Levovist, 400 mg/ml. Short-axis views were obtained with the four following imaging modes: gray scale imaging (two-dimensional and M-mode), Doppler energy imaging (two-dimensional and M-mode). Visual inspection and off-line video densitometry (results expressed in arbitrary videointensity units 0 to 255) with digital background subtraction were performed. Doppler energy was significantly more sensitive in detecting the presence of contrast than gray scale imaging (background subtracted peak videointensity 32 +/- 17 versus 17 +/- 12, p < 0.001). Mean background-subtracted videointensity increased during dipyridamole-induced coronary hyperemia (40 +/- 14 versus 31 +/- 9, p < 0.003) using Doppler energy technique. Doppler energy imaging consistently detected absent perfusion (background subtracted videointensity -6 +/- 6) and immediate reperfusion (background subtracted peak videointensity 29 +/- 15, p < 0.001). CONCLUSIONS: With the use of a galactose-based contrast agent, Doppler energy data acquisition was superior to standard gray scale imaging in transthoracic evaluation of regional myocardial perfusion, absence of perfusion, and reperfusion.

Clinical evaluation of left heart Doppler contrast enhancement by a saccharide-based transpulmonary contrast agent. The Levovist Cardiac Working Group.

OBJECTIVES: A multicenter study was carried out to evaluate the efficacy with which SHU 508A enhances left heart Doppler signals and improves the clinical quantification of valve disease. BACKGROUND: Poor signal-to-noise ratio often limits the Doppler interrogation of left heart flows. This problem may be resolved by the enhancement of Doppler signals by an ultrasound contrast agent capable of pulmonary transmission, such as the recently developed SHU 508A. METHODS: Left heart contrast enhancement was tested for 1) continuous wave Doppler evaluation in 51 patients with aortic stenosis, 2) pulsed Doppler transthoracic evaluation of pulmonary venous flow in 85 patients, and 3) color Doppler evaluation of mitral regurgitation in 60 patients. Studies were performed immediately before and during the intravenous administration of SHU 508A (16 ml of 200 mg/ml) and compared with unenhanced transesophageal data in representative subsets of patients. RESULTS: SHU 508A had no serious adverse effects. A significant increase in left heart Doppler signal intensity lasted for 30 to 300 s. The continuous wave Doppler velocity envelope was enhanced for all jets, but Doppler peak velocity was not altered in high quality baseline studies. However, Doppler contrast enhancement resulted in higher measured peak gradients (p < 0.001) in 29 patients with aortic stenosis who had poor quality baseline studies. This improved the overall correlation with invasive pressure measurements (r = 0.73 vs. r = 0.89, p < 0.01). The enhanced pulsed Doppler traces of transthoracic pulmonary venous flow allowed quantitative analysis in 92% patients (vs. 27% at baseline) and correlated well with peak velocities and velocity profiles obtained by transesophageal echocardiography (r = 0.91, p < 0.001). The enhanced color Doppler display of regurgitant jets increased jet area with a high interindividual variability (mean 276%), resulting in almost identical jet areas as unenhanced transesophageal values (r = 0.97, p < 0.001). CONCLUSIONS: SHU 508A is a safe transpulmonary contrast agent that significantly enhances both spectral and color Doppler signals in the left heart. In specific patient subsets, the increase in signal-to-noise ratio improved the quantitative assessment of aortic stenosis, pulmonary venous flow and mitral regurgitation.

Enhancement of mitral regurgitation and normal left atrial color Doppler flow signals with peripheral venous injection of a saccharide-based contrast agent.

OBJECTIVES: The saccharide ultrasound contrast agent SHU 508 A was used to test the hypothesis that an intravenous, transpulmonary contrast method can enhance color Doppler flow signals in the left atrium in a clinically useful manner. BACKGROUND: Color Doppler display of mitral regurgitation may be unreliable because of variable signal to noise ratios that are at times poor. Traditional contrast agents enhance color Doppler flow signals in the right heart chambers. This study describes our observation of a recently developed contrast agent, SHU 508 A, capable of pulmonary transit after peripheral venous injection. METHODS: Control subjects (n = 10) and patients with suspected mitral regurgitation (n = 23) were studied by color Doppler flow imaging before and after 3-g intravenous doses of SHU 508 A. Reference grading of mitral regurgitation (0 to 3) was formulated from left ventricular angiography. In the four-chamber view of the left atrium, we selected for analysis the systolic frame with the maximal retrograde jet of mitral regurgitation (aliased/blue) and the diastolic frame with the maximal color coding from anterograde pulmonary venous flow (red) for planimetry and for grading the intensity of the color Doppler signal (0 to 5). RESULTS: The score of the color Doppler signal intensity increased by > or = 2.5 after 3 g of SHU 508 A (p < 0.001). Flow detection improved, as shown by the increased jet area of mitral regurgitation (> or = 170%), after 3 g of SHU 508 A (3 +/- 3 vs. 12 +/- 8 cm2, p < 0.001) and by a > or = 200% increase in normal anterograde flow area (p < 0.001) in both the mitral regurgitation group and the control group. After contrast enhancement, the correlation between angiographic grading and the relation of jet area to the left atrial area increased from r = 0.79 to r = 0.91. CONCLUSIONS: Contrast-mediated increased echogenicity of the left atrial blood pool improves the signal to noise ratio of Doppler images of mitral regurgitation and anterograde atrial flow. The technique is safe and simple and seems to minimize variability due to instrument design and anatomic signal attenuation.