Over the past twenty years, under the impetus of technological innovations and the drive for cost-effectiveness, stress echocardiography has developed into a well-established technique that is versatile, patient friendly, and relatively inexpensive. This growth has been reflected in the increasing size of past editions of Stress Echocardiography, all of which have been praised for their clarity and scope. This fifth edition of the book has been extensively revised and updated to reflect the further progress achieved over the past few years. The early chapters place the technique within a historical context and describe its pathophysiological basis. Thereafter, all aspects of stress echocardiography are discussed, clearly and in detail, by the distinguished pioneer, Eugenio Picano, and other contributors carefully selected for their expertise in the topic under consideration. Both mainstream and emerging applications are explained, and systematic comparisons with competing and complementary cardiac imaging techniques are provided from a clinically oriented perspective.
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Stress echocardiography SE has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease CAD. We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities.
The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease such as hypertrophic cardiomyopathy.
This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities.
The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls.
For a long time, the scope of stress echo SE remained focused on coronary artery disease CAD [ 1 , 2 ]. In the last ten years, SE has exploded in its breadth and variety of applications [ 3 , 4 ].
From a one-fits-all approach wall motion by 2D-echo in the patient with known or suspected CAD , the field has progressed to an omnivorous, next-generation laboratory employing a variety of technologies from M-Mode to 2D, from pulsed, continuous, color and tissue Doppler to lung ultrasound on patients covering the entire spectrum of severity from elite athletes to patients with end-stage heart failure and ages from children with congenital heart disease to the elderly with aortic stenosis [ 4 ] Fig.
As a consequence of this rapid growth, the clinical use of SE often lacks the necessary supportive evidence and is slowed by unavoidable confusion on methodological issues in a rapidly evolving field. This situation represents a challenge and an opportunity for the SE community.
It is also an opportunity, because today SE has the unprecedented advantages of economic sustainability, lack of radiation, portability and versatility making it especially attractive in the current era of increasing societal concerns about cardiac imaging costs and long-term risks due to ionizing radiation [ 11 ]. In the box, the contemporary spectrum of patients for whom SE can offer potentially unique diagnostic information: coronary artery disease; heart failure with either reduced or preserved left ventricular function ; hypertrophic cardiomyopathy; valvular heart disease; extreme physiology; adult repaired congenital heart disease; early, at risk, or borderline pulmonary arterial hypertension.
For each clinical condition, a different key SE parameter can be used, evaluated at rest left column and during stress right column , maximizing the versatility of the technique. From top to bottom rows, regional wall motion for ischemia and viability , coronary flow velocity reserve CFVR , mitral insufficiency, end-systolic volume of the left ventricle necessary to assess left ventricular elastance , and B-lines a marker of extravascular lung water.
Modified and adapted from ref 4 Picano and Pellikka [ 4 ]. The study theater is the international network of cardiology SE laboratories, and the study is endorsed and promoted by the Italian Society of Cardiovascular Echography.
The main documents from protocols to case report form to software and website platform will be in English, so that selected highly motivated and experienced centers may join specific subprojects, setting the stage for an international upscaling of the project in the coming years. Laboratories from Brazil, Serbia, and Hungary have already joined the project. The recruitment plan forecasts patients by the end of , with doubling of the rate of enrollment in subsequent years, in parallel with the increasing number of recruiting labs fulfilling quality control criteria, reaching the target number of at the end of the 5-year schedule.
As recommended by guidelines, we will adopt a segment model of the left ventricle, with 1-to-4 segmental scoring system [ 5 , 6 ]. All laboratories will share a standardized case report form coded in a database format to facilitate retrieval and communication. For applications outside CAD and for CAD testing with vasodilator stress, no atropine is given on top of pharmacological stress.
Although data collection with a dedicated project-specific case report form is allowed, we encourage implementing a dedicated, free ad-hoc system for data storage and reporting developed at the National Research Council, Institute of Clinical Physiology. The software provides a suitable informatics infrastructure for the SE Italian multicenter study, with an intuitive graphic interface, eye-catching graphic format and convenient reporting option.
It could represent the trade-off between the comprehensive information required by scientific standards and the smooth workflow priority of busy, high-volume, clinically-driven activities [ 14 ]. As an illustrative example, the report page for regional wall motion abnormalities and Wall Motion Score Index is shown in Fig. The software was developed and tested in Italian and the translation of the last release in other languages English, Portuguese and Serbian is currently in progress.
The computerized case report form for the regional wall motion abnormalities of the SE study. The grading of the response is reported in tabular right side , lower panel and graphic right side , upper panel format, with normal values of Wall Motion Score Index in green , mild impairment in yellow , moderate in orange , and severe impairment in red.
In patients with coronary angiographic information, diagnostic sensitivity, specificity, positive and negative predictive value will be assessed for any combination of the wall motion score index, coronary flow velocity reserve, left ventricular contractile reserve and B-lines. One-sample comparisons will be performed using Wilcoxon test, and the chi-squared test without Fisher's correction for categorical data.
Event rates will be estimated with Kaplan—Meier curves and compared by the log-rank test. Univariable analyses by Cox proportional hazards models will be performed to assess the association between each candidate variable and outcome. Goodness of fit of the models will be based on C-statistics and its variants, adjusting for optimism using bootstrap replications at least A receiver operating characteristic analysis will be used to obtain the best prognostic predictor for the individual SE variables.
We will also analyze the data according to a clinically guided stepwise procedure, where the variables will be included in the model in the same order in which they are actually considered by the cardiologist. It is well-known that the diagnostic performance of SE is closely related to the level of expertise of the cardiologist-echocardiographer performing the test, since the evaluation of regional wall motion is subjective and qualitative, with considerable variability even among experienced centers of undisputed reputation [ 15 ].
The reproducibility and accuracy of wall motion reading can be substantially increased with limited training [ 16 ] and through development of conservative, pre-specified reading criteria [ 17 ].
Therefore, quality control of the diagnostic performance in the various laboratories is a must in order to enter meaningful information in the data bank. The burden of quality control is on the hub center of the principal investigator of each subproject, where various spoke centers may converge. For the general project, the hub center for regional wall motion analysis is Pisa-CNR, in coordination with the principal investigator.
There are five different levels of quality control, with increasing levels of complexity:. Level 1, pre-requisite: a volume activity of the lab of at least SE tests per year, which is the requirement for credentialing of SE activity by scientific societies [ 18 ]. Level 2, spoke centers read hub SE images, consisting in 20 selected studies for regional wall motion analysis.
For each test, a multiple choice 6-answer test is given. Level 3, hub centers read spoke centers studies, consisting in 20 any-quality consecutive studies recorded by the spoke center. Level 4, core lab reading. All centers should grant full access to images of SE studies entered in the data bank for audit or reading by core lab laboratory, which is the standard for specific subprojects such as number 10 for genetic SE, when every effort needs to be made to minimize variability and a single reader will analyze all studies acquired by different centers, as required by recommendations for small-to-medium sample studies, when resources allow [ 20 ].
Level 5, specific protocols quality control. Although the SE quality control has proved to work well for regional wall motion analysis, novel SE applications involve different parameters, methodology of acquisition and reading criteria. Therefore, for each subproject, a web-based training session and quality control is organized by the specific hub center and principal investigator to assure consistency of data [ 21 ].
The principal investigator of each subproject will prepare a set of 20 studies with rest-stress images. For each test, a multiple choice 6-answers test is given only 1 correct. This study is also intended as a special level of voluntary accreditation and expertise in the specific field of interest, well above the volume activity criteria requested by guidelines.
The accreditation process is run and certified by the Italian scientific society of echocardiography strictly following criteria and procedures of the European association of cardiovascular imaging to ensure standardization and independence of the process. When not otherwise specified, resting and SE measurements are performed according to the latest joint recommendations of European and North-American societies [ 22 ].
A simplified view of each lab's road to SE is shown in Fig. After adoption of dedicated SE computerized software by the lab allowing direct entry of the information in a format compatible with the data bank and voluntary certification for project-specific SE reading, the center can start recruiting. The road to SE for the individual stress echo laboratories. The overall recruitment plan for SE targets 10, patients by the end of We will collect the experience of Italian, Brazilian, Hungarian and Serbian SE labs over the 5-year period from to Different study projects will cover the entire spectrum of disease, age and clinical status of current patients.
Some degree of overlap is unavoidably present for some projects, for instance with subjects eligible for project 2 who are also recruitable for project 1 if they undergo cardiac resynchronization therapy or for project 5 if they have heart failure with preserved ejection fraction. Over time, patients may move from one project to another: for instance, first-degree relatives of hypertrophic cardiomyopathy patients with negative phenotype enrolled in project 10 may subsequently develop overt forms of disease and be enrolled in project 3.
All these potential gray-zone situations will be readily identified in individual SE reports. The investigator is allowed to enter the patient in only one subproject at a given time. Although the setting will be mainly the Italian cardiological community, all essential documents will be written in English and we plan to extend the project to other communities with long-standing history of cooperation and experience in multicenter trials.
Brazilian, Hungarian and Serbian centers are already recruiting and additional laboratories from other countries are now entering the process of accreditation. The project is curiosity-driven, independent from sponsors, and clinically oriented. However, after the planning and start-up phase, support from public or private funding agencies or industries is possible — provided that it is unrestricted and does not interfere in any way with data collection and analysis.
There is no bonus payment for subject recruitment and subject referral. Enrolled patients are referred to the SE lab for clinically-driven indications. Each patient signs an informed consent form allowing scientific utilization of data, respectful of privacy rights, at the time of testing. Ethics committee approval will be sought by each participating center, as needed. A brief synopsis of each project is presented for each sub-study, which places emphasis on different parameters tailored on the specific diagnostic question Fig.
The key echocardiographic parameter for each project, around the logo of SE QRS width remains the single established criterion to assess intraventricular dyssynchrony according to guidelines; however, there is no accepted consensus on which imaging parameter is best to predict cardiac resynchronization therapy response. Inconsistent results have been obtained with several echocardiographic indices of left ventricular dyssynchrony [ 23 ].
The presence of myocardial contractile reserve assessed during SE predicted the response to cardiac resynchronization therapy: the use of SE had obvious potential for a better selection of cardiac resynchronization therapy candidates, in whom a preserved contractility is related to a higher percentage of clinical and echocardiographic responders to cardiac resynchronization therapy [ 24 — 27 ].
The primary aim is to evaluate the feasibility of several indices of SE including the well- established, such as wall motion score index, and more innovative ones such as left ventricular elastance in the evaluation of patient candidates for cardiac resynchronization therapy.
The tertiary aim is to assess the prognostic value of SE indices for prognostic stratification in the medium-long term. Any patient excluded from cardiac resynchronization therapy and kept on optimal medical therapy will be included in the follow-up, since the presence of contractile reserve may predict the functional improvement in these patients as well [ 13 ]. About the same number is required to predict the response to medical therapy in patients eventually not undergoing cardiac resynchronization therapy.
The presence of contractile reserve is associated with a better prognosis and greater chance of functional recovery with cardiac resynchronization therapy. Evaluation of B-lines in HEart Failure patients with depressed ejection fraction. B- lines are a semiquantitative sign of extravascular lung water present in 1 out of 3 heart failure patients at rest and in 1 out of 2 during stress, and potentially useful for refining prognostic stratification and titrating diuretic therapy in these patients.
The primary aim is to assess the feasibility of several indices of SE including the well- established such as left ventricular ejection fraction and more innovative ones such as B-lines or left anterior descending coronary flow reserve in evaluating patients with known or suspected heart failure with reduced ejection fraction.
The secondary aim is to assess the value of each of these parameters in predicting the functional impairment, indicated by New York Heart Association class, cardiac natriuretic peptides concentration, peak VO2 and other indices.
The tertiary aim is to assess the prognostic value of SE indices for prognostic stratification in the medium-long -term. B-lines will be scored with the regions antero-lateral chest assessment as previously described at baseline and immediately after stopping exercise [ 31 ].
A simplified 8-region or 4-region scan is also allowed in order to save time without loss of critical information. The integrated assessment of 5 major echocardiographic variables during stress adds power to the prognostic stratification operated by isolated echocardiographic predictors in heart failure patients.
The prognostically meaningful signs explore 5 key links in the patho-physiologic chain behind cardiovascular response in heart failure: left ventricular systolic function — left ventricular diastolic function - mitral valve regurgitation - lung water accumulation - right ventricular function.
The impact of SE in hypertrophic cardiomyopathy is limited by lack of standardization and outcome data. Current guidelines recommend SE solely for evaluation of left ventricular outflow tract obstruction [ 33 ]. However, large-scale registry data show that SE positivity for ischemic criteria such as new wall motion abnormalities and coronary flow velocity reserve rather than inducible gradients predict adverse outcome in hypertrophic cardiomyopathy [ 34 ].
Thus, important prognostic as well as functional information may be derived from SE, although their clinical impact remains limited due lack of standardized data collection and uniform protocols.
Currently there are virtually no two centers performing SE in the same way in hypertrophic cardiomyopathy patients, and the test remains grossly underutilized due to unjustified concerns with safety.
Stress echo 2020: the international stress echo study in ischemic and non-ischemic heart disease
It seems that you're in Germany. We have a dedicated site for Germany. In a societal and economic climate of increasing pressure for appropriate, justified and optimized imaging, stress echocardiography offers the great advantages of being radiation-free, relatively low cost, and with a staggering versatility: we can get more information with less cost and risk. For a long time, the scope and application of stress echo remained focused on coronary artery disease. In the last ten years, it has exploded in its breadth and variety of applications. From a black-and-white, one-fits-all approach wall motion by 2D-echo in the patient with known or suspected coronary artery disease now we have moved on to a omnivorous, next-generation laboratory employing a variety of technologies from M-Mode to 2D and pulsed, continuous, color and tissue Doppler, to lung ultrasound and real time 3D echo, 2D speckle tracking and myocardial contrast echo on patients covering the entire spectrum of severity from elite athletes to patients with end-stage heart failure and ages from children with congenital heart disease to the elderly with low-flow, low-gradient aortic stenosis.
The life and career of Professor Eugenio Picano, Edler Lecture invitee
Stress echocardiography SE has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease CAD. We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease such as hypertrophic cardiomyopathy. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios.
This sixth edition is enriched by over figures, tables and a video-companion collecting more than cases also presented in the format of short movies and teaching cartoons. This extensively revised and enlarged edition of this long-seller documents the very significant advances made since the fifth edition and is entirely written by Eugenio Picano, a pioneer in the field sharing his lifetime experience with the help of an international panel of 50 contributors from 22 countries representing some of the best available knowledge and expertise in their respective field. In a societal and economic climate of increasing pressure for appropriate, justified and optimized imaging, stress echocardiography offers the great advantages of being radiation-free, relatively low cost, and with a staggering versatility: we can get more information with less cost and risk. For a long time, the scope and application of stress echo remained focused on coronary artery disease. In the last ten years, it has exploded in its breadth and variety of applications. From a black-and-white, one-fits-all approach wall motion by 2D-echo in the patient with known or suspected coronary artery disease now we have moved on to a omnivorous, next-generation laboratory employing a variety of technologies from M-Mode to 2D and pulsed, continuous, color and tissue Doppler, to lung ultrasound and real time 3D echo, 2D speckle tracking and myocardial contrast echo on patients covering the entire spectrum of severity from elite athletes to patients with end-stage heart failure and ages from children with congenital heart disease to the elderly with low-flow, low-gradient aortic stenosis. Stress Echocardiography.
The new clinical standard of integrated quadruple stress echocardiography with ABCD protocol
The detection of regional wall motion abnormalities is the cornerstone of stress echocardiography. Today, stress echo shows increasing trends of utilization due to growing concerns for radiation risk, higher cost and stronger environmental impact of competing techniques. However, it has also limitations: underused ability to identify factors of clinical vulnerability outside coronary artery stenosis; operator-dependence; low positivity rate in contemporary populations; intermediate risk associated with a negative test; limited value of wall motion beyond coronary artery disease. Nevertheless, stress echo has potential to adapt to a changing environment and overcome its current limitations. Four parameters now converge conceptually, logistically, and methodologically in the Integrated Quadruple IQ -stress echo. IQ-Stress echo allows a synoptic functional assessment of epicardial coronary artery stenosis wall motion , lung water B-lines , myocardial function left ventricular contractile reserve and coronary small vessels coronary flow velocity reserve in mid or distal left anterior descending artery.