Echocardiography in heart failure: Beyond diagnosis

It is a great honor for me to deliver this year's Euro Echo Lecture in this beautiful city of Florence and I appreciate the European Association of Echocardiography for the invitation and this opportunity to discuss the role of echocardiography in systolic and diastolic heart failure as the single most useful test, not only in diagnosis, but also as a tool to provide insights into the pathophysiological mechanism of various etiologies of heart failure, as a tool to monitor patient's response to various treatment options, and as a tool to help us develop innovative new therapies for heart failure. According to the ESC guidelines published in 2005, heart failure is defined as “a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of ventricles to fill with or eject blood” which includes diastolic as well as systolic heart failure. 1 ACC/AHA guidelines as well as ESC guidelines state that echocardiography is the single most useful test in the diagnosis of heart failure since structural abnormality, systolic dysfunction, diastolic dysfunction, or a combination of these abnormalities needs to be documented in patients who present with resting or/and exertional symptoms of heart failure to establish a definitive diagnosis of heart failure. 1,2 It is important to demonstrate an objective evidence of structural or functional abnormalities to explain patient's symptoms of heart failure since symptoms of heart failure are not specific and more than a third of patients with a clinical diagnosis of heart failure may not actually have heart failure. It is also interesting to note from the SHAPE study that only 3% of more than 7000 subjects surveyed from nine European countries recognized breathlessness, fatigue, and edema as symptoms of heart failure. 3 Moreover, even when someone presents with typical symptoms of heart failure, a diagnostic test, most frequently an echocardiography examination, is required to establish the underlying etiology for an optimal management strategy. In this lecture, I like to review with you how echocardiography is used for detection of structural abnormality, diagnosis and management of systolic heart failure, and evaluation of diastolic function in patients with symptoms of heart failure. When a cardiac structural abnormality is responsible for patient's heart failure, it is usually obvious on 2-dimensional echocardiogram. Fig. 1 illustrates an echocardiographic image of a middle age woman with increasing dyspnea. Parasternal long axis view demonstrated an enlarged right ventricle consistent with right ventricular volume or pressure overload which provides a list of differential diagnoses such as severe tricuspid regurgitation, pulmonary hypertension, or intracardiac shunt to be investigated. A subcostal view subsequently showed a large secundum atrial septal defect. Echocardiographic detection of most structural abnormalities responsible for heart failure is straight forward, but some structural abnormalities demands a more detective work and echocardiographer's knowledge as illustrated in a 55-year-old woman with increasing shortness of breath and history of radiation to the chest. Because of her radiation history, restrictive myopathy, pericardial disease, coronary disease, and valvular heart disease are considered and evaluated. 4 However, echocardiography showed an unusual flow directed to the right atrium and the tricuspid valve which was initially thought of as an atrial septal defect, but there was no evidence of right ventricular enlargement or volume overload. Further investigation with color-flow imaging and Doppler echocardiography demonstrates that the flow was originated from the coronary sinus with a peak velocity of greater than 2m/sec. Because of a concern for coronary sinus stenosis, transesophageal echocardiography was performed and it confirmed the presence of high velocity jet originating from the stenotic coronary sinus ostium. That was followed by the cardiac catheterization, and coronary sinus venography demonstrated a tight ostium which was stented successfully. Her LV end-diastolic pressure was increased (29mmHg) due to the coronary sinus stenosis. Three months after the stent, the patient's symptoms markedly improved. This is a good example of identifying an uncommon but clinically important structural abnormality responsible for patient's heart failure. I believe it would have been difficult for other diagnostic imaging tests to be able to identify such an uncommon abnormality so readily. Parasternal long axis view from 54-year-old woman with increasing shortness of breath. The right ventricle (RV) is enlarged. In real time 2-D echocardiographic image, the left ventricle (LV) was of normal size and function. Subsequent views from subcostal window showed a large secundum atrial septal defect with left-to-right shunt resulting in right ventricular volume overload. Ao=Aorta, LA=left atrium. Heart failure due to systolic dysfunction is relatively easy to diagnose by echocardiography which demonstrates a dilated left ventricle with a reduced ejection fraction. In systolic heart failure, however, echocardiography has many other roles beyond the recognition of systolic heart failure since dilatation of the LV results in alteration of intracardiac geometry and hemodynamics leading to increased morbidity and mortality. New medication strategies, devices, and surgical therapies are being developed to manage systolic heart failure. Echocardiography has been essential in identifying structural and hemodynamic abnormalities associated with systolic heart failure and to monitor patient's response to new and novel therapies. It has been well documented for the last 20years that the left ventricular volume is one of the most important prognostic indicators for the patients with ischemic or dilated cardiomyopathy. 4,5 White and his associates demonstrated that worsening of patient's survival was associated with increased end systolic volume after an acute myocardial infarction. With LV remodeling and a progressive dilatation of the heart, although initially an adaptive process to the myocardial damage, the left ventricle becomes more spherical, and the mitral annulus is dilated with apical displacement of the mitral leaflets causing functional mitral valve regurgitation. 6–8 A combination of LV dilatation and mitral valve regurgitation results in increased filling pressure, symptoms of heart failure, and death. Grayburn and his collaborators in the BEST trial demonstrated that among various echocardiography parameters, LV end-diastolic volume, deceleration time of early diastolic mitral inflow velocity which is a surrogate for pulmonary capillary wedge pressure, and severity of mitral valve regurgitation were the strongest predictors of survival in patients with ejection fraction of 35% or less 5 ( Fig. 2 ). Since a smaller LV with less amount of mitral regurgitation is associated with a better functional capacity and survival, there are many management attempts to reduce the left ventricular volume and MR with the use of surgical, pacing, and other percutaneous devices, as well as medications and surgical revascularization. In this context, echocardiography is a valuable tool since it can measure or assess LV dimensions, volumes, sphericity index, severity of mitral regurgitation, diastolic filling parameters, and pulmonary artery systolic pressure. Survival curve of patients with reduced left ventricular ejection fraction in the Best Trial. LVEDVI=left ventricular end diastolic volume index, DT=deceleration time, and VCW=vena contracta width (Reproduced with permission from Ref. 5). SAVE trial was one of the first studies where echocardiography was used in a systolic heart failure trial to show that adverse cardiac events were associated with increased left ventricular size after acute myocardial infarction. 8 Biventricular pacing has been found to improve functional status and survival of patients with reduced LVEF and ventricular conduction delay. 9–11 Echocardiography has been used to assess the success of the device therapy by documenting smaller LV volume, increased LVEF, increased dP/dT, and less amount of mitral regurgitation which are all signs of reverse remodeling. Another potentially critical role of echocardiography in biventricular pacing is to identify the patients who respond positively to the therapy since 30–50% of patients who receive biventricular pacing may not improve. Currently, mechanical dyssnchrony measures obtained by tissue Doppler imaging velocities are considered to be best in that role. Time intervals from the onset of QRS to the time of peak systolic velocity of 2 to 12 segments of LV are used to determine the maximum or standard deviation interval. 12,13 The maximum interval of 100msec or standard deviation interval of 34msec were found to have the highest predictive power for identifying positive responder. However, we have found that such intervals by TDI are present in normal subjects and patients without reduced ejection fraction or conduction delay. 14 Instead, time intervals from the QRS to the peak negative strain from 12 segments correlated best with LV remodeling parameters and hemodynamic improvement after cardiac resynchronization therapy. 15 It is, however, time consuming and challenging to obtain tissue Doppler or strain imaging from 12 segments. Further clinical experience and simplification of current strain imaging procedure are required to use echocardiography in identification of positive responders to CRT routinely in clinical practice. Another innovative device for reducing LV volume or achieving reverse LV remodeling is a passive constraint device called ACORN. 16 Mayo Clinic Echocardiography Core Lab has been working for the US clinical trial of this device which was recently completed. I would like also to acknowledge that many European centers were the initial clinical sites for development and testing the safety of this device. There was a progressive and significant reduction in left ventricular volume measured by echocardiography in patients treated with this device compared to a control group. The left ventricular volume reduction was associated with significant reduction in major cardiac procedures including cardiac transplantation. Surgical Ventricular Restoration or Reconstruction (SVR) procedure which was pioneered by Dr. Dor in 1984 is a surgical attempt to restore LV size and shape by excluding the scarred and akinetic apical segments. 17 The results from SVR procedure in more than 1000 patients were reported with an overall 30day mortality of 5.3%. 18 LVEF improved from 29% to 39% and LV end-systolic volume index decreased from 80mL/m 2 to 56mL/m 2 . Patients with a larger ventricle and worse functional class preoperatively had worse outcome after SVR. However, this report did not come from a randomized trial, and there is no way to compare this result with the intensive medical therapy, other device therapy, or revascularization therapy alone in patients with reduced ejection fraction and akinetic apex. If SVR procedure has an incremental beneficial effect, echocardiography should be helpful in identifying ideal patients with the large left ventricle, akinetic reduced LVEF as well as and hemodynamic response to the SVR can be by echocardiogram. However, the structural and functional result of SVR procedure is not and clinical trial is required to demonstrate beneficial of SVR compared to other device and therapy. the long axis becomes by but the axis and mitral annulus may to in some patients which may to more severe mitral valve regurgitation and diastolic filling pressure. echocardiography should be able to provide an and of the structural and hemodynamic outcome of the SVR. In patients with severe coronary artery disease, reduced LVEF, and heart failure, there has not been a clinical trial to surgical revascularization better than medical the has akinetic SVR procedure improve functional class and survival of the patients with ischemic important clinical are being by In patients with artery disease and Heart trial in which patients with ischemic and coronary disease are randomized to intensive medical therapy, coronary artery and SVR. The first of trial of surgical was in the early with 1000 patients The of medical therapy surgical therapy be in early trial is an trial with many European clinical centers In in has the of patients in the study and should be on This study provide a imaging since all patients in the trial have and and patients have cardiac imaging and Mayo Clinic Echo Core Lab is all echocardiography for the to the determine the use of echocardiography to assess LV systolic and diastolic dysfunction, cardiac and valvular regurgitation in the can identify a that a or a significant from surgical as by mortality. assess the of the randomized treatment on parameters of cardiac systolic and diastolic dysfunction, and the severity of valvular regurgitation and as compared to as to in functional class and the clinical of and Echocardiography from patients from all the with ischemic be and correlated with clinical and other are to many interesting results from this echocardiographic I like to to of diastolic function in patients who present with symptoms of heart failure. It has been well that of patients with new onset of heart failure have a normal ejection fraction. have that this be called heart failure with ejection fraction since diastolic dysfunction may not be a underlying mechanism for heart failure. However, the is also since there are many other than a myocardial disease which can heart failure with ejection fraction such as severe valvular heart disease, heart disease, and intracardiac Since the most etiology for heart failure with ejection fraction and no other structural abnormalities is due to diastolic dysfunction, diastolic heart failure to be a better to this disease This is difficult to be by 2-D echocardiography alone although there are diagnostic in echocardiography to a normal heart, the heart with diastolic dysfunction has less mitral annulus and early to the of myocardial the left ventricular to be than and the left atrial size is abnormalities that the patient's diastolic dysfunction is and a more Doppler is Doppler evaluation of diastolic function the and diastolic velocities of the mitral time of mitral early diastolic mitral annulus velocity pulmonary and mitral inflow velocity obtained by ( Fig. 3 ). It usually with of mitral inflow velocities which the and LV This the of mitral inflow with myocardial and increased filling pressure. inflow velocity of normal subjects is by early diastolic filling with of myocardial which is usually an initial diastolic abnormality A and the other increased filling pressure has an on these Doppler an early of diastolic dysfunction with myocardial and normal filling pressure, mitral inflow velocity alone is usually for diastolic function filling pressure with worsening of diastolic mitral velocity with and A velocity with flow When diastolic dysfunction is filling pressure is markedly mitral inflow velocity is However, mitral inflow velocity may normal called mitral in patients with of filling pressure. in this a to time and atrial flow is helpful in from normal mitral inflow It is important to in that mitral inflow is a of myocardial and of filling pressure. In this context, Doppler to myocardial is critical in evaluation of diastolic function. Doppler of myocardial tissue velocities and it that early diastolic velocity of the mitral annulus well with or the status of LV myocardial is the septal annulus compared to the annulus and we use the septal annulus in all patients when there is abnormality in the and the of mitral inflow may be beneficial in to diastolic function and filling flow velocity progressive reduction of systolic flow velocity compared to the diastolic flow velocity with increased filling pressure ( Fig. 4 ). In all of diastolic dysfunction, early diastolic velocity of the mitral annulus is reduced and it not with high filling pressure. Since mitral velocity with a filling pressure and tissue Doppler the of the mitral velocity and the mitral annulus velocity of has a good with the pulmonary capillary wedge pressure or left ventricular filling pressure. usually pulmonary capillary wedge pressure of greater than when septal is and the the filling pressure is usually normal and for the 8 and we may diastolic parameters to diastolic filling or velocity of the mitral annulus can also be from long axis and apical views of 2-dimensional of filling pressure by 2-dimensional and Doppler echocardiography is useful in patients with systolic dysfunction as well as in patients with normal studies have demonstrated a good prognostic of Doppler echocardiographic of filling also have demonstrated that was one of the strongest predictors for survival after acute myocardial LVEF was normal or This work of review was by who was a from the and has a study to his of prognostic power of and echocardiographic parameters in patients with acute myocardial infarction. the last that LVEF, and septal were predictors of morbidity acute myocardial infarction. septal was found to be the single most of death. In volume was found to be also prognostic for after acute of filling pressure should also be an of echocardiographic evaluation in patients with reduced me with you how echocardiographic evaluation of diastolic function should be used in patients with symptoms of heart failure and normal I with an example of a who with onset of to the pulmonary but was normal and the echocardiography showed normal ejection fraction and in LV Because of the normal and ejection the patient's clinical and were thought to be of etiology However, when his was more it was obvious that LV myocardial was markedly annulus was and diastolic evaluation showed was than the 15 Subsequent evaluation showed a critical left coronary artery disease and LV end diastolic pressure of When and mitral were correlated with pulmonary capillary wedge pressure, was better for the mitral compared to the has been to be helpful in patients with in the but we should be that the and the of for increased filling pressure is less than and than echocardiographic of filling pressure. when high filling pressure is by in patients with heart failure, echocardiography be to establish an etiology and to provide an optimal In patients with heart failure and normal LVEF, optimal therapy has not been although there are studies some in this of I large clinical to identify the most management in diastolic heart failure and echocardiography be an of for identification of ideal patients and the response of various therapies. of Doppler of mitral mitral inflow and tissue Doppler of the septal mitral annulus in normal diastolic function and various of diastolic (Reproduced with permission from Parasternal long axis view from a with heart failure. It normal left ventricular with increased and enlarged left atrium. The left ventricular systolic function was well There was a amount of pericardial and large LA=left ventricle, A of mitral inflow pulmonary tissue Doppler velocity of the mitral annulus and of mitral inflow flow velocity inflow velocity of 2 and deceleration time of which is in the normal flow however, reduction in systolic flow velocity and decreased deceleration time of diastolic flow velocity consistent with increased filling pressure. annulus velocity reduction in early diastolic velocity to which of myocardial is reduced in of the highest velocity in the of mitral inflow is an which heart failure in patients with normal LVEF and is potentially hemodynamic are to of myocardial and it is challenging to from restrictive or other myocardial With we should be able to diagnose in all There are of which are not present in myocardial and intracardiac and in result in diastolic filling which can be by Doppler mitral inflow early diastolic velocity with and diastolic flow with However, the of mitral inflow velocities may not be present in some Doppler of mitral annulus velocity has an important diagnostic in since velocity which is reduced in all myocardial is increased in ( Fig. 5 ). such as ventricular septal with and septal in can be from evaluation of 2-D more to these echocardiographic of increased detection of this in patients with heart failure which has been responsible for of 15 in to more than in detection of has been a valuable of diastolic function by and myocardial tissue Three patients with a of shortness of breath. the mitral inflow tissue Doppler velocity from the mitral septal The of the mitral inflow The left is from a normal from a with a myocardial disease The right is from a with The mitral inflow velocity the in all with of However, early diastolic velocity of the mitral annulus is markedly reduced in the with myocardial disease the early diastolic velocity of the mitral annulus is normal in normal and in the with middle of mitral inflow demonstrates normal flow in the normal and the with pericardial However, it is usually reduced the left in patients with myocardial disease but may be normal when LV is relatively such as in for early of cardiac the right me I have so the role of echocardiography in patients with symptoms of heart failure. When heart failure is clinically echocardiography is the single most important diagnostic imaging In a of patients with a diagnosis of heart failure, transesophageal echocardiography demonstrates a major structural functional abnormality such as in systolic heart failure, severe valvular heart disease, heart disease, or It is more difficult to diagnose heart failure when there are no obvious structural and functional abnormalities in 2-dimensional In the other of patients with heart failure, most diastolic heart failure, there may be abnormalities in 2-dimensional but a diagnosis of diastolic heart failure Doppler and myocardial tissue If mitral inflow velocity demonstrates a restrictive filling high filling pressure resting the diagnosis of diastolic heart failure or is usually Doppler imaging of the septal mitral annulus is helpful in from normal mitral inflow and from myocardial It is more when diastolic function evaluation relatively normal filling pressure or myocardial In this right heart failure, pulmonary and process should be Another important we to is increased filling pressure responsible for patient's symptoms of shortness of breath with we to assess filling pressure with as well as resting The mitral annulus velocity which the status of mitral actually with or increased when myocardial is but velocity not as with pressure or with when is with increased we that in normal subjects mitral inflow velocity and mitral annulus velocity with a result that less than 15 resting and However, in patients with diastolic dysfunction and exertional velocity with but the velocity reduced or less with with compared with the resting in patients with diastolic used a or test for of filling pressure with and we diastolic parameters of mitral inflow and mitral annulus velocities which we performed diastolic test in This work was initially by Dr. from and by Dr. from working in It was found that in normal mitral velocity increased with from and deceleration time decreased an of to and velocity increased also the of and in with normal diastolic function. we performed test in patients with exertional and were able to identify of The first of patients was found to have filling and the with in The of patients had relatively normal filling pressure and myocardial on mitral inflow velocity which to a restrictive filling with with ( Fig. ). The third of patients had normal filling pressure and and with The patients with increased filling pressure with or not had normal filling pressure first and had compared to the patients third with normal filling pressure and with we have performed cardiac and Doppler echocardiography in patients who were testing in the cardiac for an evaluation of exertional dyspnea. In this correlated well with pulmonary capillary wedge pressure not only resting but also with we believe that we have a diagnostic to diastolic filling resting and with and his have also demonstrated a good and and also have use of the the onset of mitral velocity and the onset of mitral annulus This or time interval has been well correlated with the filling pressure and also the status of myocardial I had an opportunity to an to the current status of diastolic parameters to diastolic filling and I in from in this that echocardiography is able to left ventricular filling pressure various clinical When I this the that the echocardiography is be to is able which I did not was a I to the but when the was I was to of is able to left ventricular filling it is not able to left ventricular filling which the of but I that some of you who the were able to the obvious mitral inflow and tissue Doppler demonstrate 1 diastolic dysfunction velocity of and deceleration time of with myocardial but normal filling pressure with of and tricuspid regurgitation velocity was also normal normal pulmonary artery systolic pressure. With of velocity increased to and deceleration time from to however, increased from to increased from to velocity increased from to (Reproduced with permission from Ref. and I to for you in the current clinical use of echocardiography in patients with heart failure, not only systolic but also diastolic heart failure. There are many new and of echocardiography such as strain and myocardial I that these new and improve the role of echocardiography in but more so in patients with symptoms of heart failure. echocardiography is the single most useful test in patients with symptoms of heart failure. It is essential in the diagnosis and identification of underlying etiology of heart failure. However, we should beyond the of echocardiography as only a diagnostic tool in patients with heart failure, use this and to insights of various of heart failure, to help identify or establish an optimal therapy for the patients with heart failure, to monitor treatment to and to be an important tool in clinical heart failure for the invitation to Euro Echo Lecture and you all for