Guidelines for the Evaluation of Prosthetic Valve Function With Cardiovascular Imaging: A Report From the American Society of Echocardiography Developed in Collaboration With the Society for Cardiovascular Magnetic Resonance and the Society of Cardiovascular Computed Tomography.

In patients with significant cardiac valvular disease, intervention with either valve repair or valve replacement may be inevitable. Although valve repair is frequently performed, especially for mitral and tricuspid regurgitation, valve replacement remains common, particularly in adults. Diagnostic methods are often needed to assess the function of the prosthesis. Echocardiography is the first-line method for noninvasive evaluation of prosthetic valve function. The transthoracic approach is complemented with two-dimensional and three-dimensional transesophageal echocardiography for further refinement of valve morphology and function when needed. More recently, advances in computed tomography and cardiac magnetic resonance have enhanced their roles in evaluating valvular heart disease. This document offers a review of the echocardiographic techniques used and provides recommendations and general guidelines for evaluation of prosthetic valve function on the basis of the scientific literature and consensus of a panel of experts. This guideline discusses the role of advanced imaging with transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance in evaluating prosthetic valve structure, function, and regurgitation. It replaces the 2009 American Society of Echocardiography guideline on prosthetic valves and complements the 2019 guideline on the evaluation of valvular regurgitation after percutaneous valve repair or replacement.

Semi-automated analysis of dynamic changes in myocardial contrast from real-time three-dimensional echocardiographic images as a basis for volumetric quantification of myocardial perfusion.

AIMS: Despite the potential of real-time three-dimensional (3D) echocardiography (RT3DE) to assess myocardial perfusion, there is no quantification method available for perfusion analysis from RT3DE images. Such method would require 3D regions of interest (ROI) to be defined and adjusted frame-by-frame to compensate for cardiac translation and deformation. Our aims were to develop and test a technique for automated identification of 3D myocardial ROI suitable for translation-free quantification of myocardial videointensity over time, MVI(t), from contrast-enhanced RT3DE images. METHODS AND RESULTS: Twelve transthoracic RT3DE (Philips) data sets obtained in pigs during transition from no contrast to steady-state enhancement (Definity) were analysed using custom software. Analysis included: (i) semi-automated detection of left ventricular endo- and epicardial surfaces using level-set techniques in one frame to define a 3D myocardial ROI, (ii) rigid 3D registration to reduce translation and rotation, (iii) elastic 3D registration to compensate for deformation, and (iv) quantification of MVI(t) in the 3D ROI from the registered and non-registered data sets to assess the effectiveness of registration. For each MVI(t) curve we computed % variability during steady-state enhancement (100 x SD/mean) and goodness of fit (r2) to the indicator dilution equation MVI(t) = A[1-exp(-betat)]. Analysis of myocardial contrast throughout contrast inflow was feasible in all data sets. Three-dimensional registration improved MVI(t) curves in terms of both % variability (2.8 +/- 1.8 to 1.5 +/- 0.9%; P < 0.05) and goodness of fit (r2 from 0.79 +/- 0.2 to 0.90 +/- 0.1; P < 0.05). CONCLUSION: This is the first study to describe a new technique for semi-automated volumetric quantification of myocardial contrast from RT3DE images that includes registration and thus provides the basis for 3D measurement of myocardial perfusion.

Imaging and quantification of myocardial perfusion using real-time three-dimensional echocardiography.

OBJECTIVES: We tested the feasibility of real-time three-dimensional echocardiographic (RT3DE) perfusion imaging and developed and validated an algorithm for volumetric analysis of myocardial contrast inflow. The study included three protocols wherein perfusion was measured: 1) in an ex-vivo model of controlled global coronary flow, 2) in an in-vivo model during regional perfusion variations, and 3) in humans during pharmacologically induced hyperemia. BACKGROUND: The RT3DE technology offers an opportunity for myocardial perfusion imaging without multi-slice reconstruction and repeated contrast maneuvers. METHODS: Electrocardiographically triggered harmonic RT3DE datasets were acquired (Philips 7500) while infusion of Definity was initiated and reached a steady state. Protocol 1 was performed in nine isolated rabbit hearts and included three coronary flow levels. In protocol 2, changes in regional perfusion caused by partial left anterior descending artery occlusion were measured in five pigs. In protocol 3, adenosine-induced changes in perfusion were measured in eight normal volunteers. Myocardial video-intensity (MVI) was measured over time in three-dimensional (3D) slices to calculate peak contrast inflow rate (PCIR). In pigs, PCIR was measured on a regional basis and validated against microspheres. RESULTS: The RT3DE imaging allowed selection of slices for perfusion analysis in rabbit hearts, pigs, and humans. Administration of contrast resulted in clearly visible and quantifiable changes in MVI. In rabbits, The PCIR progressively decreased with coronary flow (p < 0.0001). In pigs, coronary occlusion caused a 59 +/- 26% decrease in PCIR exclusively in the left anterior descending artery territory (p < 0.05) in agreement with microspheres. In humans, adenosine increased PCIR to 198 +/- 57% of baseline (p < 0.05). CONCLUSIONS: Contrast-enhanced RT3DE imaging provides the basis for volumetric imaging and quantification of myocardial perfusion.

Quantitative echocardiographic evaluation of myocardial perfusion using interrupted contrast infusion technique: in vivo validation studies and feasibility in human beings.

BACKGROUND: We recently developed a new approach for contrast echocardiographic quantification of myocardial perfusion, based on brief interruptions of contrast infusion, which was designed to overcome the limitations of existing techniques. In this study, our technique was initially validated in a series of animal experiments designed to detect regional perfusion variations in vivo. Subsequently, clinical feasibility of perfusion measurements was tested. METHODS: Regional perfusion was measured transthoracically in 6 anesthetized pigs during baseline, partial left anterior descending coronary artery occlusion, and reperfusion, and validated with fluorescent microspheres. Adenosine-induced changes in perfusion were measured in 8 healthy volunteers. In both protocols, imaging was optimized during contrast infusion (Definity). Infusion was interrupted to allow contrast clearance and images were acquired during subsequent contrast inflow. Myocardial videointensity was measured over time and peak contrast inflow rate was calculated. RESULTS: In pigs, partial coronary occlusion resulted in a 47 +/- 23% decrease in peak contrast inflow rate in the left anterior descending coronary artery perfusion territory (P < .05), which was reversed during reperfusion, without concomitant decrease in other perfusion territories. These changes were in agreement with microspheres. In human beings, adenosine increased peak contrast inflow rate to 278 +/- 123% of baseline (P < .05). CONCLUSION: The interruption of contrast infusion technique is a sensitive tool for accurate quantification of myocardial perfusion, which may constitute an alternative to currently used techniques.

Interrupted infusion of echocardiographic contrast as a basis for accurate measurement of myocardial perfusion: ex vivo validation and analysis procedures.

BACKGROUND: Echocardiographic quantification of myocardial perfusion is based on analysis of contrast replenishment after destructive high-energy ultrasound impulses (flash-echo). This technique is limited by nonuniform microbubble destruction and the dependency on exponential fitting of a small number of noisy time points. We hypothesized that brief interruptions of contrast infusion (ICI) would result in uniform contrast clearance followed by slow replenishment and, thus, would allow analysis from multiple data points without exponential fitting. METHODS: Electrocardiographic-triggered images were acquired in 14 isolated rabbit hearts (Langendorff) at 3 levels of coronary flow (baseline, 50%, and 15%) during contrast infusion (Definity) with flash-echo and with a 20-second infusion interruption. Myocardial videointensity was measured over time from flash-echo sequences, from which characteristic constant beta was calculated using an exponential fit. Peak contrast inflow rate was calculated from ICI data using analysis of local time derivatives. Computer simulations were used to investigate the effects of noise on the accuracy of peak contrast inflow rate and beta calculations. RESULTS: ICI resulted in uniform contrast clearance and baseline replenishment times of 15 to 25 cardiac cycles. Calculated peak contrast inflow rate followed the changes in coronary flow in all hearts at both levels of reduced flow (P < .05) and had a low intermeasurement variability of 7 +/- 6%. With flash-echo, contrast clearance was less uniform and baseline replenishment times were only 4 to 6 cardiac cycles. beta Decreased significantly only at 15% flow, and had intermeasurement variability of 42 +/- 33%. Computer simulations showed that measurement errors in both perfusion indices increased with noise, but beta had larger errors at higher rates of contrast inflow. CONCLUSION: ICI provides the basis for accurate and reproducible quantification of myocardial perfusion using fast and robust numeric analysis, and may constitute an alternative to the currently used techniques.

The role of still-frame parametric imaging in magnetic resonance assessment of left ventricular wall motion by non-cardiologists.

BACKGROUND: Cardiac magnetic resonance (MR) images are often reviewed by non-cardiologists who are not trained in the interpretation of regional left ventricular (LV) function. We hypothesized that the use of still-frame parametric MR images of wall motion could aid in the assessment of regional LV function. METHODS: Dynamic, electrocardiogram-gated, steady-state free precession (FIESTA) short-axis images were obtained in 6 to 10 slices in 18 consecutive patients. Each loop was used to automatically generate a still-frame image, in which each pixel is assigned a value equal to the amplitude of cyclic variation in local intensity, resulting in higher intensity in pixels that change between blood and tissue during the cardiac cycle. The dynamic images were reviewed by an expert cardiologist who provided gold standard grades for regional wall motion and by four radiologists. Then the radiologists reviewed and graded the same MR images in combination with parametric images. Grades assigned to each segment in the two sessions were compared with the gold standard. RESULTS: According to expert interpretation, 6 patients had normal wall motion, and 12 had wall motion abnormalities. Parametric images showed a bright band in the area spanned by endocardial motion, with reduced brightness and thickness in areas of hypokinesis. The agreement between the radiologists' grades and the gold standard significantly improved by adding parametric images (from 77% to 81%), which also resulted in reduced interobserver variability (from 52% to 33%). CONCLUSIONS: Still-frame parametric images aid in the assessment of regional wall motion by non-cardiologists who are required to interpret cardiac images.

Automated quantitative assessment of wall motion in patients with poor acoustic windows.

BACKGROUND: No technique exists for objective evaluation of left ventricular wall motion in contrast-enhanced images. We tested a new technique for quantification of regional fractional area change using contrast-enhanced power modulation imaging with color kinesis. METHODS: The feasibility of this technique for detecting acute ischemia was first tested in 11 pigs. Next, the accuracy for detecting resting wall-motion abnormalities was determined in 52 patients requiring contrast and compared with conventional interpretation of 2-dimensional images by inexperienced readers. Expert interpretation of 2-dimensional images served as the gold standard. RESULTS: In pigs, coronary occlusion resulted in reversible hypokinesis and reduced regional fractional area change. In patients with poor acoustic windows, this technique's accuracy for quantitative detection of resting wall-motion abnormalities was 86% compared with 81% for conventional interpretation by inexperienced readers (P <.01). CONCLUSIONS: Regional wall motion can be accurately assessed using color-encoded power modulation imaging for patients requiring contrast. This technique may prove a useful diagnostic aid to echocardiographers of varying levels of experience.

Secondary coronary artery vasospasm promotes cardiomyopathy progression.

Genetic defects in the plasma membrane-associated sarcoglycan complex produce cardiomyopathy characterized by focal degeneration. The infarct-like pattern of cardiac degeneration has led to the hypothesis that coronary artery vasospasm underlies cardiomyopathy in this disorder. We evaluated the coronary vasculature of gamma-sarcoglycan mutant mice and found microvascular filling defects consistent with arterial vasospasm. However, the vascular smooth muscle sarcoglycan complex was intact in the coronary arteries of gamma-sarcoglycan hearts with perturbation of the sarcoglycan complex only within the adjacent myocytes. Thus, in this model, coronary artery vasospasm derives from a vascular smooth muscle-cell extrinsic process. To reduce this secondary vasospasm, we treated gamma-sarcoglycan-deficient mice with the calcium channel antagonist verapamil. Verapamil treatment eliminated evidence of vasospasm and ameliorated histological and functional evidence of cardiomyopathic progression. Echocardiography of verapamil-treated, gamma-sarcoglycan-null mice showed an improvement in left ventricular fractional shortening (44.3 +/- 13.3% treated versus 37.4 +/- 15.3% untreated), maximal velocity at the aortic outflow tract (114.9 +/- 27.9 cm/second versus 92.8 +/- 22.7 cm/second), and cardiac index (1.06 +/- 0.30 ml/minute/g versus 0.67 +/- 0.16 ml/minute/g, P < 0.05). These data indicate that secondary vasospasm contributes to the development of cardiomyopathy and is an important therapeutic target to limit cardiomyopathy progression.

Harmonic imaging for endocardial visualization and myocardial contrast echocardiography during transesophageal echocardiography.

BACKGROUND: Although harmonic imaging (HI) improves endocardial visualization and is necessary for myocardial perfusion imaging, it has yet to be implemented in transesophageal echocardiography. Our goal was to determine whether HI implemented in a prototype transesophageal echocardiography probe improved endocardial visualization and allowed perfusion imaging. METHODS: In 23 patients, fundamental and harmonic images were obtained in the transgastric short-axis (TSAX) and midesophageal 4-chamber views, and reviewed for endocardial visualization by 3 readers blinded to imaging mode. In 14 additional patients, perfusion imaging was performed in the TSAX view during contrast infusion. RESULTS: HI improved overall endocardial visualization, most noticeably in the anterior and lateral segments (P <.004) in the TSAX view, and in the lateral segments (P <.01) in the midesophageal 4-chamber view. The salvage rate was 8.3% in the TSAX view and 12.6% in the midesophageal 4-chamber view. Myocardial perfusion was consistently confirmed in the inferior (86%), posterior (100%), and lateral (79%) segments, but rarely in the septal (21%), anteroseptal (0%), and anterior (14%) segments. CONCLUSION: Use of HI with transesophageal echocardiography improves endorcardial visualization and allows partial assessment of myocardial perfusion.

Simultaneous real-time echocardiographic imaging of myocardial perfusion and regional function using color-encoded, contrast-enhanced power modulation.

We hypothesized that color-encoded, contrast-enhanced, power modulation imaging could allow simultaneous quantification of myocardial perfusion and regional left ventricular function. We studied 12 anesthetized, closed-chest pigs at baseline, during acute ischemia, and during reperfusion, and 8 patients after acute myocardial infarction. Color kinesis was used to color encode endocardial motion during real-time contrast perfusion imaging with high-energy ultrasound pulses. Wall motion was assessed by calculating regional fractional area changes. Translation-free perfusion analysis was performed in automatically identified myocardial regions of interest. Steady-state intensity and postimpulse rate of contrast replenishment were calculated. In all animals, ischemia caused reversible changes in the images and the perfusion- and function-calculated indices. A significant decrease in pixel intensity (14%) and contrast replenishment rate (66%) in left anterior descending coronary artery segments, in agreement with fluorescent microspheres measurements, coincided with a decrease in fractional area change (34%). For patients, respective perfusion and function indices were 61%, 51%, and 58% lower in segments where perfusion defects, regional wall-motion abnormalities, or both were noted in gray scale images. Color-encoded, contrast-enhanced power modulation allows simultaneous real-time imaging and quantitative analysis of myocardial perfusion and regional left ventricular function.

Use of echocardiography for the phenotypic assessment of genetically altered mice.

Transgenic mice displaying abnormalities in cardiac development and function represent a powerful new tool for understanding molecular mechanisms underlying normal cardiovascular function and the pathophysiological bases of human cardiovascular disease. Complete cardiac evaluation of phenotypic changes in mice requires the ability to noninvasively assess cardiovascular structure and function in a serial manner. However, the small mouse heart beating at rates in excess of 500 beats/min presents unique methodological challenges. Two-dimensional and Doppler echocardiography have been recently used as effective, noninvasive tools for murine imaging, because quality images of cardiac structures and valvular flows can be obtained with newer high-frequency transthoracic transducers. We will discuss the use of echocardiography for the assessment of 1) left ventricular (LV) chamber dimensions and wall thicknesses, 2) LV mass, 3) improved endocardial border delineation using contrast echocardiography, 4) LV contractility using ejection phase indices and load-independent indices, 5) vascular properties, and 6) LV diastolic performance. Evaluation of cardiovascular performance in closed chest mice is feasible in a variety of murine models using Doppler echocardiographic imaging.

Quantification of regional myocardial perfusion using semiautomated translation-free analysis of contrast-enhanced power modulation images.

Quantitative analysis of myocardial perfusion is currently based on manual tracing and frame-by-frame realignment of regions of interest. We developed a technique for semiautomated identification of myocardial regions from power modulation images as a potential tool for quantification of myocardial contrast enhancement. This approach was tested in 13 anesthetized pigs during continuous intravenous infusion of contrast at baseline, left anterior descending coronary artery occlusion, and reperfusion. Regional pixel intensity was calculated for each consecutive end-systolic frame after a high-energy ultrasound impulse, and fitted with an exponential function. Perfusion defects caused by occlusion of left anterior descending coronary artery were confirmed by a significant decrease in both postimpulse steady-state intensity and the initial rate of contrast replenishment (P <.05), which were reversed with reperfusion. Automated measurements of myocardial intensity correlated highly with conventional manual tracing (r = 0.90 to 0.97), and resulted in improved signal-to-noise ratios. This technique allows translation-free quantification of regional myocardial perfusion, without the need for manual tracing.

Improvement in echocardiographic evaluation of left ventricular wall motion using still-frame parametric imaging.

BACKGROUND: Conventional echocardiographic assessment of left ventricular wall motion is based on visual interpretation of dynamic images, which depends on readers' experience. We tested the feasibility of evaluating endocardial motion using still-frame parametric images. METHODS AND RESULTS: In protocol 1, integrated backscatter images were obtained in 8 anesthetized pigs at baseline, 5, and 60 seconds after left anterior descending coronary occlusion and during reperfusion. Images from 1 cardiac cycle were analyzed offline to create a parametric image of local video intensity oscillations. Ischemia-induced changes were quantified by segmenting the parametric images and calculating regional pixel-intensity profiles. In protocol 2, parametric images were obtained from contrast-enhanced echocardiograms in 30 patients (18 with wall-motion abnormalities; 12 control subjects). "Gold standard" for wall motion was determined from independent interpretations of dynamic images made by 3 experienced reviewers. Dynamic images were independently classified by 3 inexperienced and 3 intermediate-level readers. Interpretation was then repeated in combination with parametric images. Parametric images showed a bright band in the area spanned by endocardial motion, which gradually decreased in brightness and thickness in the left anterior descending territory during coronary occlusion in all animals. In patients, the agreement with the gold standard correlated with the readers' experience (68% inexperienced, 87% intermediate) and significantly improved by adding parametric images (83% and 91%, respectively). CONCLUSION: Parametric imaging provides a still-frame display of regional endocardial motion, sensitive to track ischemia-induced abnormalities. When combined with dynamic images, this technique improves the accuracy of the interpretation of wall motion, especially by less experienced echocardiographers.

Objective assessment of left ventricular wall motion from contrast-enhanced power modulation images.

There is no method to objectively evaluate left ventricular (LV) function from contrast-enhanced images. We tested the feasibility of evaluating regional LV function by using power modulation imaging. In protocol 1, 9 anesthetized closed-chest pigs were studied. Images were obtained during contrast infusion at baseline, during LAD occlusion and reperfusion. In protocol 2, images were obtained in 20 patients (14 wall-motion abnormalities; 6 controls) during contrast enhancement. Off-line, frame-by-frame, semiautomated endocardial border detection was followed by color encoding of endocardial motion, followed by segmentation and calculation of regional fractional area changes. In all animals, coronary occlusions resulted in hypokinesis and decreased fractional area changes in LAD-related segments only, which were reversed during reperfusion. In patients, wall-motion analysis was in agreement with an expert reader of dynamic images in 92.5% segments, with interobserver variability of 12.5%. Color encoding of endocardial motion from contrast-enhanced power modulation images allows accurate quantitative assessment of regional LV function.