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Beyond the Mitral Inflow: More Advanced Techniques to assess Diastolic Function and Left Ventricular Filling Pressures Georges Desjardins, M.D. FRCPC FASE Professor of Anesthesiology and Internal Medicine (Cardiology) Director, Division of Cardiothoracic Anesthesia Director, Division of Perioperative Echocardiography Co director Echocardiography Laboratory, VAMC University of Utah, Salt Lake City, USA Heart failure is a major public health problem in the Western world. We now know that cardiovascular disease can result in systolic and/or diastolic dysfunction of the heart. To date, echocardiography remains by far the most robust and widely used technique in the evaluation of diastolic function. The Problem: Intraoperative Assessment of diastolic function: In 2009, the American Society of Echocardiography published recommendations for the evaluation of left ventricular diastolic function by echocardiography (1). Its direct application in the perioperative period is questionable for several reasons. Most validation studies were performed on awake ambulatory patients breathing spontaneously using transthoracic echocardiography. It is questionable that all this data can be used and is applicable to the anesthetized patient undergoing surgery with possible fluid shifts and measurements performed with a TEE. For many perioperative physicians, Doppler assessment of the diastolic function is not part of the standard comprehensive intraoperative echocardiographic examination. Understanding diastole is an essential part of the assessment. Diastole is divided in four phases. Clinically, it is the time period that extends from the closure of the aortic valve to the termination of the mitral inflow (closure of the mitral valve). It includes isovolumic relaxation, early rapid filling, diastasis and atrial systole (contraction). Of note, physiologically, diastole actually starts with the initiation of isovolumetric relaxation time in the latter part of clinical systole (the aortic valve is not closed yet, and mitral valve is still closed) and extends to the early part of clinical diastole. Ventricular relaxation is an energy-­‐dependent process that physiologically commences during systole, continuing after mitral valve opening (clinical diastole) during rapid LV filling and lasts for the first third of this early filling phase. This normally accounts for 70% of total LV filling. Two important factors are involved during this phase: LA-­‐LV pressure gradient and LV suction. Active ventricular suction occurs as a result of the recoil of the compressed elastic myocardial fibers during contraction. Atrial contraction also called atrial filling phase contributes about 30% of the LV filling in normal conditions. From (3) The major determinants of diastolic function are active myocardial relaxation, LV compliance, LA function, heart rate and the pericardium. More recently, some authors have proposed ways to assess diastolic function perioperatively using a combination of preoperative transthoracic echocardiography to assess left atrial volume and intraoperative TEE using transmitral flow, pulmonary venous inflow, Tissue Doppler imaging (DTI) and transmitral flow propagation velocity to assess diastolic function (2-­‐3). Doppler Modalities for assessment of perioperative myocardial diastolic function From (2) Practical Approach to Assess diastolic Dysfunction From (2) Integrated preop TTE and intraop TEE approach From (3) These authors went in detail to try to adapt the most recent ASE recommendations to the perioperative period. Unfortunately, few of these modalities have been validated in the very dynamic perioperative period, in a patient intubated, receiving positive pressure ventilation, variable preload and afterload conditions. Thus, at the very least, all Doppler measurements should be done in the apneic patient in an attempt to limit some variables such as changes in intrathoracic pressures. It is also our experience that positioning the TEE probe to get optimal Doppler alignment during interrogation can be very difficult in many patients, especially for the measurements of septal and/or lateral E’ values. Most often, the angle of acquisition is more than 15 to 20 degrees, which results in underestimation of peak velocities and gradients. This in turn would result in overestimation of the E/E’ ratio. Beyond the mitral inflow: Several other modalities to assess LV systolic and diastolic functions have been proposed in recent years. The number of publications is extensive. Unfortunately, few of these modalities have made it to primetime where they can be used routinely by clinicians, with a few exceptions. We will review some of these recent modalities and emphasized the ones that are relatively easy to use and to apply today in clinical practice. Again, most of the validation studies for these modalities have been performed with transthoracic echocardiography in awake patient breathing spontaneously. LA volume index LA volume index > 34 ml/m2 is an independent predictor of death, heart failure, atrial fibrillation and ischemic stroke. One must remember that a dilated left atrium may be seen in patients with bradycardia and four chamber dilation, athlete’s heart, anemia and other high output states, atrial flutter or fibrillation and significant valvular disease, in the absence of diastolic dysfunction. One may have an enlarged left atrium without diastolic dysfunction but all patients with significant diastolic dysfunction will have an enlarged left atrium (1). The measurement of LA volume is highly feasible and reliable in most transthoracic echocardiographic studies, with the most accurate measurements obtained using the apical 4-­‐chamber and 2-­‐chamber views. LA size cannot be measured reliably with TEE in part because of the close proximity between the esophagus and the left atrium. The left atrium size increases when the LVEDP is increased persistently. LA size can be used as an indicator of chronic LVEDP. Doppler indices change dynamically but increased LA volume is a marker of persistent elevation of the LVEDP. Below can be found reference limits for LA volume as published in the ASE guidelines. From (4) End systolic LA volume measurement From (4) Deformation Measurements Echocardiographic strain imaging, also known as deformation imaging, has been developed as a means to objectively quantify regional myocardial function. First introduced as post-­‐processing of tissue Doppler imaging velocity converted to strain and strain rate, strain imaging has more recently also been derived from digital speckle tracking analysis. Strain imaging has been used to gain greater understanding into the pathophysiology of cardiac ischemia and infarction, primary diseases of the myocardium, the effects of valvular disease on myocardial function, quantify abnormalities in the timing of mechanical activation for heart failure patients undergoing cardiac resynchronization pacing therapy, and to advance our understanding of diastolic function. In most echocardiography laboratory and certainly in the operating room, strain imaging has been more often regarded as a research tool. Adoption of strain imaging in clinical practice is still limited today. Myocardial regional mechanics assessed by echo have been described by 4 principal types of strain or deformation: longitudinal, radial, circumferential, and rotational. Types of Strain Echocardiographic application of strain imaging has assessed longitudinal strain from apical windows and radial, circumferential, and rotational strain from parasternal windows. Equivalent views with TEE would be mid esophageal views and transgastric views. The term strain applied to echo in a simplistic sense to describe lengthening, shortening, or thickening, also known as regional deformation. A few definitions are essential to understand the different aspects of myocardial mechanics. Displacement is a parameter that defines the distance that a certain feature, such as a speckle or cardiac structure, has moved between two consecutives frames. Displacement is measured in cm. Velocity reflects displacement per unit of time, that is, how fast the location of a feature changes, and is measured in centimeter per second. Strain describes myocardial deformation, the fractional change in the length or thickening of a myocardial segment. Strain is unitless and is usually expressed as a percentage. Strain can have positive or negative values, which reflect lengthening or shortening respectively. In its simplest one-­‐
dimensional manifestation, a 10-­‐cm string stretched to 12 cm would have 20% positive strain. Strain rate is the rate of change in strain and is usually expressed as 1/sec. Global strain refers to average longitudinal (global longitudinal strain) or circumferential (global circumferential) component of strain in the entire myocardium. Strain values can be expressed for each segments (segmental strain), as an average value for all segments (global strain) or for each of the theoretical vascular distribution areas (territorial strain). The term left ventricular (LV) rotation refers to myocardial rotation around the long axis of the LV. It is rotational displacement and is expressed in degrees. Normally the base and the apex of the LV rotate in opposite directions. The absolute apex-­‐to-­‐
base difference in LV rotation is referred to as the net LV twist angle, also expressed in degrees. The term torsion refers to the base-­‐to-­‐apex gradient in the rotation angle along the long axis of the LV, expressed in degrees per centimeter. Using instantaneous tissue Doppler velocities, one can calculate an estimation of the strain rate using DTI spectral Doppler and DTI color Doppler. Signals derived by color DTI are processed off line and can be displayed either as color 2D images or reconstructed time versus distance or deformation (i.e. strain) curves. Curves from different segments can be analyzed for timing of events and/or amplitude. The DTI strain rate data could be integrated over time to determine strain. DTI strain is acquired from DTI (tissue) velocities, all this information is affected by the angle of incidence thus proper positioning is essential. The major strength of DTI is that it is readily available and allows objective quantitative evaluation of local myocardial dynamics. A more recent echo approach to strain analysis is speckle tracking. Speckle tracking is a post-­‐processing algorithm that uses the routine grayscale digital images. Routine grayscale digital images of the myocardium contain unique speckle patterns. The image-­‐processing algorithm automatically subdivides regions into blocks of pixels tracking stable patterns of speckles. Subsequent frames are then analyzed by searching for the new location of the speckle patterns within each of the blocks using the sum of absolute differences. Longitudinal Strain by Speckle Tracking Imaging in normal (A) and Heart failure (B) Because strain information obtained in this way is not dependent on Doppler angle of incidence like DTI strain, several more strain analysis are possible, including longitudinal, circumferential, radial and rotational. The big advantage of the use of deformation strain indices is that they offer high real time temporal resolution of deformation (sampling rates greater than 200 frames/sec). This permits detailed analysis of events in systole and diastole. As it applies to diastole, regional differences in the timing of transition from myocardial contraction to relaxation with strain rate imaging can identify ischemic segments and abnormal infiltrative cardiomyopathies. Also some studies combined global myocardial strain rate during isovolumetric relaxation period and transmitral flow velocities and showed that the mitral E velocity/global myocardial strain rate ratio predicted LV filling pressure in patients in whom E/e’ ratio was inconclusive and was more accurate than E/e’ in patients with normal LVEFs and those with regional dysfunction. Again, the advantage of deformation imaging is assessment of regional diastolic function. Studies have shown a decrease and delay in myocardial velocities in the setting of acute coronary occlusion and persistent compression (delay in expansion) can be used to diagnose CAD with good accuracy. Diastolic deformation measurements have also been applied to identify viable myocardium. Delayed relaxation is associated ischemia. In short, abnormal diastolic deformation measurements occur earlier and last longer than SWMA in the context of acute ischemia and resolution of the ischemic event. As published in the ASE guidelines on cardiac mechanics, measurement of diastolic strain and strain rate may be useful for research applications but is presently not recommended for routine clinical use (6). Left ventricular twisting and untwisting The LV twisting motion (torsion) is due to contraction of obliquely oriented fibers in the subepicardium, which course toward the apex in a counterclockwise spiral. The forces of the subepicardial fibers dominate over the subendocardial fibers, which form a spiral in opposite direction. Therefore, when viewed from the apex toward the base, the LV apex shows systolic counterclockwise rotation and the LV base shows a net clockwise rotation. Untwisting starts in late systole but mostly occurs during the isovolumetric relaxation period and is largely finished at the time of mitral valve opening. Diastolic untwist represents elastic recoil due to the release of restoring forces that have been generated during the preceding systole. The rate of untwisting is often referred to as the recoil rate. LV twist appears to play an important role for normal systolic function, and diastolic untwisting contributes to LV filling through suction generation. With the recent introduction of speckle tracking echocardiography, it is now possible to quantify LV rotation, twist and untwist clinically. LV torsion is the summation of the apical and the basal twisting. Under normal circumstances, apical rotation exceeds basal rotation and accounts for most of the observed twisting. It has been shown that torsion and circumferential strain are normal in patients with diastolic heart failure whereas longitudinal and radial deformation are reduced. Torsion has been shown to increase during the initial stage of diastolic dysfunction so that it may be helpful in identifying patients with mild diastolic dysfunction. Because subendocardial function is impaired in patients with diastolic heart failure, the subepicardial torque plays an unopposed dominant role in determining LV twist and explains the presence of normal torsion in this disease. This is in contrast to myocardial dysfunction involving the midwall and subepicardial layers in patients with systolic heart failure and leads to a reduction in circumferential strain and torsion. It is likely that the normal circumferential strain and torsion are responsible for the preservation of a normal ejection fraction in patients with diastolic heart failure, compensating for the abnormally depressed longitudinal function. Twisting leads to storage of potential energy that is released in early diastole during untwisting. It has been assumed that the reduction in LV untwisting with attenuation or loss of diastolic suction contributes to diastolic dysfunction in diseased hearts. These findings have been challenged recently. As stated the latest ASE guidelines, measurements of LV twist and untwisting rate is not recommended currently for routine clinical use. Diastolic Function in atrial fibrillation Atrial fibrillation is a challenging clinical situation for non invasive as well as for invasive hemodynamic assessment. However, it has been shown that a short deceleration time of the E wave (<130 ms) is associated with a poor prognosis, probably because of increased filling pressure and advanced heart failure. Some studies have shown the reliability of E/e’ as an estimate of LV filling pressures even in atrial fibrillation. Another echocardiographic measurement that can be used is the deceleration time of the pulmonary venous diastolic velocity. A value less than 175 ms is associated with elevated LV filling pressures. References: 1-­‐ Nagueh et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography. J Am Soc Echocardiogr 2009;22:107-­‐133 2-­‐ Matyal R et al. Perioperative Assessment of Diastolic Dysfunction. Anesth Analg 2011;113:449-­‐472. 3-­‐ Mahmood F et al. A Practical Approach to Echocardiographic Assessment of Perioperative Diastolic Dysfunction. J Cardiothorac Vasc Anesth 2012;26: 1115-­‐1123. 4-­‐ Lang RM et al. Recommendation for Chamber Quantification: A Report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, Developed in Conjunction with the European Association of Echocardiography, a Branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440-­‐
1463. 5-­‐ Gorcsan J et al. Echocardiographic Assessment of Myocardial Strain. JACC 2011;58:1401-­‐1413. 6-­‐ Mor-­‐Avi V et al. Current and Evolving Echocardiographic Techniques for the Quantitative Evaluation of Cardiac Mechanics: ASE/EAE Consensus Statement on Methodology and Indications. J Am Soc Echocardiogr 2011;24:277-­‐313.