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(Circulation. 2006;113:296-304.)
© 2006 American Heart Association, Inc.

Contemporary Reviews in Cardiovascular Medicine

Contractile Behavior of the Left Ventricle in Diastolic Heart Failure

With Emphasis on Regional Systolic Function

Gerard P. Aurigemma, MD; Michael R. Zile, MD; William H. Gaasch, MD

From the Division of Cardiology, Department of Medicine, University of Massachusetts Medical School, Worcester (G.P.A.); Division of Cardiology, Department of Medicine, Medical University of South Carolina and RHJ Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); and Department of Cardiovascular Medicine, Lahey Clinic, Burlington, Mass (W.H.G.).

Correspondence to Gerard P. Aurigemma, MD, Division of Cardiology, Department of Medicine, University of Massachusetts Medical School, Room S3-860, 55 Lake Ave N, Worcester, MA 01655. E-mail aurigemg{at}ummhc.org

Received March 31, 2005; revision received July 15, 2005; accepted July 21, 2005.

Key Words: diastole • echocardiography • ventricles

	Introduction

Top Introduction Structural Remodeling Diastolic Dysfunction and Heart... Contractile Behavior:... Contractile Behavior in... Conclusions References

 
In diastolic heart failure, the left ventricular (LV) ejection fraction (EF) is normal and there is increased passive stiffness with impaired relaxation of the ventricle, resulting in disturbances in the pattern of filling and elevated diastolic pressure.^1–3 The mechanism underlying such failure has been thought to be principally diastolic because LV diastolic function is universally abnormal and systolic performance, function, and contractility are normal.⁴ However, several reports suggest that abnormalities in regional shortening are present in diastolic heart failure.^5–9 The significance of these findings, especially their relation to the syndrome of heart failure, remains uncertain. Accordingly, we will review some of the structural and functional differences between systolic and diastolic heart failure, and, emphasizing the systolic or contractile behavior of the left ventricle, we will attempt to reconcile what appear to be disparate conclusions about LV systolic function in patients with diastolic heart failure.

	Structural Remodeling

Top Introduction Structural Remodeling Diastolic Dysfunction and Heart... Contractile Behavior:... Contractile Behavior in... Conclusions References

 
The hearts of patients with systolic heart failure differ dramatically from those of patients with diastolic heart failure in regard to both gross and microscopic anatomic features. As will be seen, these anatomic differences tend to parallel physiological and functional differences in systolic and diastolic heart failure^10,11 (Table 1).

View this table: [in this window] [in a new window]   TABLE 1. LV Structure and Function in Chronic Heart Failure

LV Chamber Remodeling
Patients with diastolic heart failure generally exhibit a concentric pattern of LV remodeling and a hypertrophic process that is characterized by a normal or near-normal end-diastolic volume, increased wall thickness, and a high ratio of mass to volume with a high ratio of wall thickness to chamber radius.¹² By contrast, patients with systolic heart failure exhibit a pattern of eccentric remodeling with an increase in end-diastolic volume, little increase in wall thickness, and a substantial decrease in the ratio of mass to volume and thickness to radius.¹² These differences are highlighted in Figure 1.

View larger version (58K): [in this window] [in a new window]   Figure 1. Autopsy (left) and echocardiographic (right) examples of the left ventricle imaged at the midventricular cross section in systolic heart failure (top), a normal heart (middle), and diastolic heart failure (bottom). Diastolic heart failure is characterized by a pattern of concentric LV remodeling with a normal or near-normal end-diastolic volume, increased wall thickness and mass, and a high ratio of mass to volume. By contrast, patients with systolic heart failure exhibit eccentric remodeling with an increased end-diastolic volume, little change in wall thickness, and a low ratio of mass to volume. (Cardiac specimen photographs courtesy of Dr Marvin Konstam. Reprinted from Journal of Cardiac Failure, volume 9, Konstam MA, "‘Systolic and diastolic dysfunction’ in heart failure? Time for a new paradigm," pp 1–3, Copyright 2003, with permission from Elsevier.)

The Cardiomyocyte and Extracellular Matrix
The aforementioned dramatic differences in organ morphology and geometry are paralleled by anatomic differences at the microscopic level. As shown in Figure 2, in diastolic heart failure the cardiomyocyte exhibits an increased diameter, and there is an increase in the amount of collagen with a corresponding increment in the width and continuity of the fibrillar components of the extracellular matrix.^13–16 By contrast, in systolic heart failure, the cardiomyocytes are elongated, and there is degradation and disruption of the fibrillar collagen.^13,14,17

View larger version (104K): [in this window] [in a new window]   Figure 2. Isolated cardiac muscle cells (left) and scanning electron micrographs (right) taken from an animal model of dilated cardiomyopathy (DCM) that produces systolic heart failure (top), a normal heart (middle), and an animal model of pressure-overload hypertrophy (POH) that produces diastolic heart failure (bottom). In diastolic heart failure, the cardiomyocyte diameter is increased, and there is an increase in the amount of collagen with a corresponding increment in the width and continuity of the fibrillar components of the extracellular matrix. By contrast, in systolic heart failure, the cardiomyocyte length is increased, and there is degradation and disruption of the fibrillar collagen.

	Diastolic Dysfunction and Heart Failure

Top Introduction Structural Remodeling Diastolic Dysfunction and Heart... Contractile Behavior:... Contractile Behavior in... Conclusions References

 
The term diastolic dysfunction indicates an abnormality of diastolic distensibility, filling, or relaxation of the left ventricle, regardless of whether the EF is normal or abnormal and whether the patient is symptomatic or asymptomatic. Thus, diastolic dysfunction refers to abnormal mechanical (diastolic) properties of the ventricle and is present in virtually all patients with heart failure. The term diastolic heart failure is used to describe patients with the signs and symptoms of heart failure, a normal EF, and LV diastolic dysfunction.

The structural remodeling of the heart that is seen in patients with heart failure is associated with substantial alterations in the systolic and diastolic function of the left ventricle. In systolic heart failure, the dominant abnormality is a contractile dysfunction with LV enlargement, afterload excess, and reduced EF. In diastolic heart failure, the dominant abnormality is diastolic dysfunction with normal or near-normal LV volume, increased relative wall thickness, normal EF, and elevated filling pressures. It should be recognized that not all patients with heart failure exhibit the gross structural changes shown in Figure 1. Indeed, some patients meet the criteria for diastolic heart failure with little or no evidence of LV hypertrophy or concentric remodeling. A minority exhibit relatively balanced systolic and diastolic dysfunction with a normal end-diastolic volume and a high LV mass to volume ratio but low EF.

Diastolic function is determined by the passive elastic properties of the left ventricle interacting with the active process of relaxation. Abnormalities of the passive elastic properties are largely caused by alterations in the extramyocardial collagen network, but changes within the cardiomyocyte as well as geometric remodeling of the whole ventricle also contribute to an increase in passive stiffness. Impaired relaxation caused by hypertrophy or ischemia can effect further stiffening of the ventricle. As a result, the LV diastolic pressure-volume relationship is shifted up and to the left, chamber compliance is reduced (stiffness is increased), the time course of filling is altered, and the diastolic pressure is elevated.^{3,10–12,18,19}

LV diastolic pressure-volume data from a group of patients with diastolic heart failure and a group with systolic heart failure are shown in Figure 3. In diastolic heart failure, the diastolic pressure-volume curve indicates an increase in LV passive stiffness. Thus, compared with a normal ventricle, the diastolic pressure is increased at any common volume. Under these circumstances, an increase in venous and/or arterial tone in association with a relatively small increase in central blood volume can produce a substantial increase in LV diastolic and pulmonary venous pressure, which may result in acute pulmonary edema.²⁰ By contrast, patients with systolic heart failure exhibit a diastolic pressure-volume relationship that is displaced to the right (decreased chamber stiffness) (Figure 4).

View larger version (17K): [in this window] [in a new window]   Figure 3. LV diastolic pressure-volume data from normal controls (solid line), patients with diastolic heart failure (DHF) (dotted line), and patients with systolic heart failure (SHF) (dashed line). In patients with diastolic heart failure, the diastolic pressure-volume curve is shifted up and left and the exponential stiffness constant (ß) is increased, indicating an increase in passive stiffness of the ventricle. In contrast, in patients with SHF, the diastolic pressure-volume curve is shifted down to the right and ß is decreased, indicating a decrease in passive stiffness.

View larger version (20K): [in this window] [in a new window]   Figure 4. Schematic LV pressure-volume relationship through 1 cardiac cycle in systolic heart failure (left), a normal control (center), and diastolic heart failure (right). The dominant functional abnormality in systolic heart failure is a decrease in LV contractility, as evidenced by a decrease in the slope of the end-systolic pressure-volume relationship (systolic elastance). By contrast, the predominant functional abnormality in diastolic heart failure is an increase in diastolic stiffness, as evidenced by an upward and leftward shift of the diastolic pressure-volume relationship.

The structural remodeling and functional disturbances described above are essential to the development of diastolic heart failure, but acute or subacute decompensation with congestive failure generally requires a precipitant or trigger. Thus, the underlying substrate for diastolic heart failure is often a hypertrophic or concentric remodeling of the ventricle with LV diastolic dysfunction. If the substrate is present, triggers acting alone or in combination can lead to decompensation and heart failure. In the absence of substrate, the triggers are generally well tolerated. The triggers (including dietary indiscretion with excessive sodium intake, medication noncompliance, hypertension, renal insufficiency, atrial fibrillation) are similar to those that precipitate decompensation in systolic heart failure.²¹

The prevalence of diastolic heart failure and the prognosis of patients with the syndrome are well described,^10,22 diagnostic criteria have been developed,^23,24 and a variety of therapeutic trials are under way.² However, questions and controversy about the contractile behavior of the left ventricle persist in part because of basic and important issues concerning terminology and definitions.

	Contractile Behavior: Definitions

Top Introduction Structural Remodeling Diastolic Dysfunction and Heart... Contractile Behavior:... Contractile Behavior in... Conclusions References

 
The most commonly used index of LV contractile function is the EF, which represents volume strain (change in volume divided by initial volume). It is, by definition, normalized and does not require consideration of body size. A large published body of literature supports the clinical utility of this parameter.^25,26,27 However, the EF is influenced by acute or short-term as well as chronic alterations in preload, afterload, and contractility. A full assessment of the contractile behavior of the ventricle requires the combined use of indices that reflect LV systolic performance, function, and contractility, as well as a consideration of global and regional function.²⁶ The definitions of these indices of contractile behavior are provided below.

Ventricular performance is a term that is used to describe the pumping ability of the left ventricle. The performance of the ventricle as a pump may be assessed by measuring the pressure developed by the ventricle, the stroke volume ejected by the ventricle, or preferably the stroke work generated by the ventricle. Stroke work can be determined invasively in the catheterization laboratory or estimated noninvasively with the use of echocardiographically measured stroke volume multiplied by the mean arterial pressure. A limitation of the noninvasive method is that total pressure (ie, peak systolic pressure) rather than developed pressure (ie, LV systolic pressure minus end-diastolic pressure) is used; this results in an overestimation of the work performed by the ventricle. Thus, stroke work calculated as the product of developed pressure and stroke volume credits the ventricle for pressure and shortening work in a single integrated index.

A classic ventricular function curve is constructed by plotting coordinates of performance (eg, stroke work) against an index of preload (eg, end-diastolic pressure or volume). When contractility is increased, the stroke work versus preload relationship is shifted upward, and when contractility is decreased, the relationship is shifted downward. A family of such ventricular function curves credits the ventricle for pressure development and ejection, and, importantly, it incorporates load and contractility. Thus, plots of stroke work against preload allow construction of a Frank-Starling ventricular function curve or a preload recruitable stroke work relationship.²⁸

In Figure 5, systolic performance is plotted against end-diastolic pressure (top left), and a normal relation is illustrated (solid line). If this heart were subjected to a volume load, the coordinates of systolic performance and end-diastolic pressure would move up the curve (from point N₁ to N₂). If a similar volume load were applied to a noncompliant heart from a patient with diastolic heart failure, the coordinates would move up along a "depressed" curve, from point D₁ to D₂. In this case, the downward position of the Frank-Starling curve suggests "depressed ventricular function." Recognizing the difference in the diastolic pressure-volume curve relations in the 2 hearts (Figure 5, bottom) and plotting performance against end-diastolic volume lead to a distinctly different conclusion, namely, that the relation between systolic performance and end-diastolic volume is normal (Figure 5, top right). Thus, during acute interventions, end-diastolic volume provides a more direct reflection of end-diastolic fiber stretch than does end-diastolic pressure; when Frank-Starling ventricular curves are constructed, the use of end-diastolic pressure can be misleading. The appropriate analysis relates systolic performance to end-diastolic volume (eg, preload recruitable stroke work).

View larger version (15K): [in this window] [in a new window]   Figure 5. The effect of diastolic dysfunction on the relation between LV systolic performance and preload. Classic ventricular function curves relating stroke work to end-diastolic pressure are shown in the top left panel; stroke work is related to end-diastolic volume in the top right panel; diastolic pressure-volume curves are shown below. When the LV end-diastolic pressure is used as an index of preload, ventricular systolic function in diastolic heart failure (D1, D2) appears to be less than normal (N1, N2). See text for details.

The term ventricular function has been generalized to include a variety of shortening parameters including EF and fractional shortening of the minor axis dimension. Midwall shortening has been used particularly in the study of hypertensive heart disease and concentric hypertrophic remodeling.^29,30 Regional shortening has also been studied noninvasively by the technique of MRI tagging.³¹ Echocardiographic parameters that describe apex to base shortening include fractional shortening of the long axis³² and mitral annular systolic velocity, which is an approximation of the long-axis shortening velocity; these parameters as well as mitral annular displacement (measured in centimeters) are not normalized and therefore must be considered limited indices of function. Developments in Doppler technology allow measurement of regional LV systolic strain and strain rate, both of which are normalized/dimensionless and do not require correction for LV size (or body size), as will be discussed below.

The term ventricular contractility refers to the contractile or inotropic state of the whole ventricle. Indices of ventricular contractility have conventionally been divided into isovolumic phase indices (eg, peak positive dP/dt), ejection phase indices (eg, systolic wall stress versus endocardial shortening), and indices determined at the end of ejection (eg, end-systolic elastance). The concept of ventricular contractility is similar to that of myocardial contractility, but all indices of ventricular contractility are inextricably linked to and influenced by loading conditions and ventricular remodeling. Only if loading conditions and ventricular remodeling are considered or incorporated in the analysis can these parameters of "function" reflect changes in ventricular "contractility." For example, peak positive dP/dt can be altered by an acute change in preload, but the influence of chronic geometric changes and remodeling on dP/dt is not well defined. By contrast, systolic elastance is not affected by acute changes in preload (it is determined by altering load); however, systolic elastance is affected by chronic changes in LV volume and mass.^25,33,34

Myocardial contractility refers to the basic property of heart muscle that reflects the intensity of cross bridge activity and is manifested as the extent and velocity of force development and fiber shortening. The contractile or inotropic state of the myocardium is therefore independent of loading and remodeling. Whereas myocardial contractility can be assessed in isolated cardiac muscle cells, muscle strips, or Langendorff-perfused hearts, its assessment in humans in vivo presents a continuing challenge.

	Contractile Behavior in Diastolic Heart Failure

Top Introduction Structural Remodeling Diastolic Dysfunction and Heart... Contractile Behavior:... Contractile Behavior in... Conclusions References

 
A description of LV contractile behavior requires measurement of the ability of the ventricle to develop force (pressure) and to shorten (stroke volume). A complete description requires measurement of both force and shortening and calculation of several indices of contractile behavior. There is, however, relatively little published information on LV contractile behavior in diastolic heart failure. The available data are reviewed below.

Standard Techniques
Using data derived from echocardiographic and catheterization studies, Baicu et al⁴ found that LV systolic performance, function, and contractility were normal in patients meeting published criteria for "definite" diastolic heart failure (Figure 6). In that study, stroke work and preload recruitable stroke work were normal and consonant with data published by others.^12,33 Baicu et al also found values for LV maximum systolic elastance that were higher than normal. Others have made similar observations, but it is doubtful that this reflects a true increase in contractility because some chronic structural changes (eg, hypertrophy) can increase systolic elastance.^33,34 If elastance is normalized for the LV mass/volume ratio, thereby adjusting for chronic remodeling, the result indicates normal contractility, a result that is more consistent with the data indicating normal performance and function.

View larger version (23K): [in this window] [in a new window]   Figure 6. Indices of LV systolic performance, function, and contractility in normal controls (open bars) and patients with diastolic heart failure (solid bars). The pumping function and contractility of the whole ventricle is normal in diastolic heart failure.4

Baicu et al⁴ found normal stress-shortening relations at the endocardial surface in patients with diastolic heart failure, but one third of the patients had depressed midwall stress-shortening relations (Figure 7). This has previously been described in hypertrophic hearts with normal shortening at the endocardium and no evidence of heart failure. For example, midwall indices of function are depressed in approximately one third of patients with hypertensive remodeling (either concentric LV hypertrophy or concentric LV remodeling),^30,35 in a substantial number of patients with aortic stenosis,³⁶ and even in some elderly individuals with concentric remodeling, in the absence of hypertension.³⁷ The work of Baicu et al indicates, however, that despite a reduction in midwall shortening, the pumping function of the whole ventricle appears to be normal in diastolic heart failure.

View larger version (20K): [in this window] [in a new window]   Figure 7. Stress-shortening relationships in patients with diastolic heart failure. Data from diastolic heart failure patients are plotted with reference to the mean ±95% prediction interval for normal controls. Endocardial fractional shortening is plotted against mean systolic stress (an index of LV contractility) in the left panel. All of the diastolic heart failure coordinates fell within the normal range. Midwall fractional shortening is plotted against mean systolic stress (an index of myocardial contractility) in the right panel. Two thirds of the diastolic heart failure coordinates fell within the normal range.

Tissue Doppler Techniques
Methods used to evaluate regional systolic myocardial function have evolved from invasive and experimental tools (such as radiopaque markers and sonomicrometry crystals) to widely available noninvasive clinical methods, such as MRI, echocardiography, and tissue Doppler imaging (TDI). Fundamentally, each technique is based on measurements of regional length and velocity, which, when normalized to initial length, can be used to derive strain and strain rate. The advances in TDI technology have made it relatively easy to measure regional strain and strain rate. However, interpretation of these quantitative indices remains dependent on knowledge of both the engineering principles used to develop them and the basic mechanical laws governing LV and myocardial function.

Methodology
Given the wealth of recent studies utilizing TDI in various cardiac diseases and its recent application to the study of systolic function in diastolic heart failure, this technique will be reviewed in some detail. The general principle involved in TDI is the same that is involved in the measurement of blood flow velocity by conventional Doppler. Modifications in the image acquisition process permit direct measurement of tissue velocities. Ultrasound reflections from the fast-moving blood pool are high frequency and low amplitude, whereas those from slower-moving tissue are low frequency and high amplitude. The TDI technique requires filtering of the high-frequency, low-amplitude echoes originating from the blood pool, enabling measurement of the velocity of myocardial tissue. The velocity profile thus recorded is displayed either as a color or spectral display (Figure 8). Details concerning the mathematical derivation of strain and strain rate methods can be found in the online-only Data Supplement.

View larger version (25K): [in this window] [in a new window]   Figure 8. Examples of TDI-derived velocity (top), strain (middle), and strain rate (bottom) in a normal control (left) and a patient with diastolic heart failure (right). In diastolic heart failure, systolic velocity is slightly lower than that seen in normal, systolic strain is 20% lower than normal, and strain rate is similar to normal. In diastolic heart failure, early filling velocity and diastolic strain rate are lower than normal.

Standard TDI allows a Doppler sample volume (region of interest) to be placed in any myocardial structure (eg, interventricular septum; anterior, posterior, inferior, lateral wall of the left ventricle; or mitral anulus) from LV apex to base. Therefore, regional shortening and lengthening can be measured in the longitudinal direction. To date, most of the studies have measured velocity in the long-axis direction from the echocardiographic apical 4-chamber view. Standard TDI examination of a single region of interest will yield values of myocardial velocity in centimeters per second. If this velocity signal is integrated with respect to time, displacement (in centimeters) is derived.

Myocardial strain rate imaging, utilizing a newer generation of TDI technology, examines the velocity gradient between 2 points along the ultrasound beam separated by a selected distance, generally 5 to 10 mm. This velocity gradient is used to calculate myocardial strain rate in units of inverse seconds. If strain rate is integrated, myocardial strain, expressed as a percentage, can be derived. Systolic strain represents the normalized extent of deformation of a region of the LV in systole; strain rate represents the rate of this systolic deformation.

Advantages/Disadvantages of Myocardial TDI
Velocity and/or displacement measurements obtained by standard TDI have difficulty discriminating between actively contracting and "tethered" myocardium, wherein an akinetic segment may demonstrate motion if it is pulled by an adjacent segment that is functioning normally. In addition, the velocity and displacement parameters are not normalized for length or size. As a result, systolic displacement and velocity of a given region would likely be greater in the heart of a larger subject than a smaller subject. Some of these limitations are avoided by using TDI measurements of myocardial systolic strain and strain rate. Because strain rate imaging measures a vector component of regional contraction, and the 2 points are equally affected by tethering and translation, the result is independent of the effect of tethering and translation.³⁸ Strain and strain rate measurements are also appropriately normalized for length and are therefore more appropriate than standard TDI velocity measurements in assessing regional myocardial function. Strain and strain rate derived from myocardial TDI velocity gradient imaging have been validated in gel phantoms and in an animal model in which sonomicrometric crystals were used,³⁹ and results agree closely with those obtained by MRI tissue tagging.⁴⁰

Indices of systolic function such as the extent and velocity of long-axis shortening, mitral annular systolic velocity, systolic atrioventricular plane displacement, and myocardial systolic strain and strain rate are not inherently less "load sensitive" than EF and fractional shortening. In fact, since all shortening or displacement indices are affected by loading conditions, it is not possible to conceive of a load-independent index of LV systolic function. For example, some investigators have confirmed a decline in myocardial strain and strain rate as afterload is increased in the normal heart.³⁹ When the myocardium was injured by hypoxia, the slope of the inverse relationship between strain or strain rate and afterload decreased, so that a relatively large change in load caused a small change in strain or strain rate. These data imply that TDI indices are not independent of or insensitive to load, but they can be interpreted to mean that shortening may be less load dependent in depressed than in normal myocardium. Therefore, to determine whether a change in any measurement represents a specific change in LV function or contractility, factors such as preload, afterload, and remodeling must be either held constant or considered in the analysis.

Clinical Data
The emerging interest in these new technologies has led to an expansion of our understanding of regional ventricular function in a wide variety of clinical conditions, primarily systolic heart failure and LV hypertrophy. There are, however, relatively few such studies in patients with diastolic heart failure^5–9; the principal findings of these 5 studies are summarized in Table 2. These studies indicate that systolic displacement or motion of the atrioventricular plane or mitral annulus (as well as some myocardial velocities) can be abnormal in some patients with diastolic heart failure. These results have been taken as evidence that heart failure is caused by "subtle" systolic dysfunction,^5,7 that diastolic heart failure exhibits a "coexistence" of or a "continuum" with systolic dysfunction,^5,6 and that "long-axis function" can be impaired in diastolic heart failure.^5,8 The implication is that the heart failure syndrome is related to, if not caused by, these regional disturbances in long-axis function. In our judgment, there are several reasons why this notion is problematic.

View this table: [in this window] [in a new window]   TABLE 2. Mitral Annular Motion and Velocities in Diastolic Heart Failure

First, more than half of the patients in these 5 studies did not exhibit abnormalities in the functional parameters that were utilized. The mechanism underlying heart failure in these patients is unlikely to be a disturbance of long-axis function when only a minority of the patients exhibit this abnormality. By contrast, the diastolic properties of the ventricle are virtually always abnormal in these patients.^3,41 Thus, it is more likely that the underlying mechanism(s) of the heart failure resides in diastole, especially when one considers the fact that patients with diastolic heart failure virtually always exhibit normal indices of LV systolic performance, function, and contractility.⁴

Second, abnormalities in shortening of the long axis have long been known to occur in patients with LV hypertrophy, in the absence of heart failure.^30–32 Because many, if not most, patients with diastolic heart failure exhibit some degree of hypertrophy and/or concentric remodeling, the confirmation of abnormal long-axis shortening is not unexpected. These abnormalities likely represent markers of a hypertrophic heart that may have prognostic value or other significance, but it would seem unlikely that they are the dominant cause of failure in patients with diastolic heart failure.

Third, variations in long-axis shortening have relatively little impact on the EF or stroke volume; most of the stroke volume is produced by shortening of the minor axis dimension.⁴² For example, a ventricle with an ellipsoidal geometry and a normal EF (eg, 65%) and a normal circumferential fractional shortening (eg, 33%) will exhibit a relatively small decline in EF (&6 to 7 percentage units) when long-axis shortening falls by one third. If long-axis shortening approaches zero, the EF can fall by as much as 10 percentage units, but the EF still remains >50%. This is seen, for example, after mitral valve replacement when the mitral chordae are transected.⁴³ Therefore, isolated abnormalities in long-axis function such as those presented in Table 2 are unlikely to be responsible for a clinically significant decrement in LV systolic performance or function and therefore are unlikely to be responsible for heart failure.

Fourth, appropriate normalization methods were not used in any of the studies that are summarized in Table 2. The principles of normalization, first published a century ago, have been applied in a variety of clinical and experimental studies^44,45; normalized indices of function (ie, those expressed in dimensionless terms) provide more consistent and reliable functional information than nonnormalized data (ie, those expressed in centimeters or centimeters per second). For example, some investigators have concluded that myocardial velocities at the base of the heart are substantially greater than those at the midventricular level.⁶ If, however, these velocities had been normalized for the initial diastolic length, the 2 velocities would have been found to be similar.

Future Use
Ultrasound technology has expanded to the remarkable point where it is now possible to measure regional myocardial strain and strain rate in humans with and without heart disease. In the future, such measurements will provide a more complete description of LV regional and global function. Regional myocardial strain and strain rate should be particularly useful in the assessment and evaluation of spatial and temporal nonuniformity, not only in patients with coronary heart disease but also in those with cardiomyopathy or valvular heart disease.⁴⁶ Strain and strain rate imaging is also likely to be applied in the assessment of myocardial viability.⁴⁷

Novel strain techniques have been described that do not depend on Doppler myocardial velocities and may eliminate the angle dependence of this technique. It appears that such nonvelocity strain techniques may therefore permit rapid measurement of not only longitudinal but also circumferential and radial strain.⁴⁸

	Conclusions

Top Introduction Structural Remodeling Diastolic Dysfunction and Heart... Contractile Behavior:... Contractile Behavior in... Conclusions References

 
Many echocardiographic and other indices of diastolic function are abnormal in patients with systolic heart failure, but the rightward displacement of the diastolic pressure-volume curve indicates increased volume compliance (ie, reduced chamber stiffness). Thus, ventricles with a low EF may relax slowly, and the pattern of filling may be abnormal, but in contrast to diastolic heart failure, an eccentric remodeling and dilatation is seen and the passive diastolic pressure-volume curve does not indicate increased chamber stiffness. Since all patients with systolic heart failure have depressed systolic function (by definition) as well as depressed contractility, and the diastolic pressure-volume curve does not indicate increased stiffness, we conclude that the dominant abnormality resides in systole and that the appropriate term for this form of heart failure is systolic heart failure.

In patients with diastolic heart failure, an abnormal and concentrically remodeled LV geometry is generally seen and the contractile behavior of the whole ventricle is normal, despite the presence of abnormal regional function in some patients. Parameters that reflect the diastolic properties of the ventricle are virtually always abnormal.^3,41 For these reasons we have concluded that (1) the dominant functional abnormality resides in diastole and (2) "subtle" abnormalities in regional systolic function are unlikely to be responsible for heart failure in patients with diastolic heart failure.

	Acknowledgments

 
The authors are indebted to Catalin Baicu, PhD, for contributions to the mathematical derivation as well as help with the illustrations, to Jacqueline Jolie for assistance with the preparation of the manuscript, and to Jeffrey Hill, RDCS, for assistance with the strain imaging data.

Disclosures

None.

	Footnotes

 
The online-only Data Supplement can be found with this article at http://circ.ahajournals.org/cgi/content/full/113/2/296/DC1.

	References

Top Introduction Structural Remodeling Diastolic Dysfunction and Heart... Contractile Behavior:... Contractile Behavior in... Conclusions References

 
1. Aurigemma GP, Gaasch WH. Diastolic heart failure. N Engl J Med. 2004; 351: 1097–1105.[Free Full Text]

2. Gaasch WH, Zile MR. Diastolic dysfunction and diastolic heart failure. Annu Rev Med. 2004; 55: 373–394.[CrossRef][Medline] [Order article via Infotrieve]

3. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure: abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004; 350: 1953–1959.[Abstract/Free Full Text]

4. Baicu CF, Zile MR, Aurigemma GP, Gaasch WH. Left ventricular systolic performance, function, and contractility in patients with diastolic heart failure. Circulation. 2005; 111: 2306–2312.[Abstract/Free Full Text]

5. Yip G, Wang, Zhang Y, Fung JWH, Ho PY, Sanderson JE. Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition. Heart. 2002; 87: 121–125.[Abstract/Free Full Text]

6. Yu C, Lin H, Yang H, Kong S, Zhang Q, Lee SW. Progression of systolic abnormalities in patients with "isolated" diastolic heart failure and diastolic dysfunction. Circulation. 2002; 105: 1195–1201.[Abstract/Free Full Text]

7. Petrie MC, Caruana L, Berry C, McMurray JJV. "Diastolic heart failure" or heart failure caused by subtle left ventricular systolic dysfunction? Heart. 2002; 87: 29–31.[Abstract/Free Full Text]

8. Nikitin NP, Witte KK, Clark AL, Cleland JGF. Color tissue Doppler-derived long-axis left ventricular function in heart failure with preserved global systolic function. Am J Cardiol. 2002; 90: 1174–1177.[CrossRef][Medline] [Order article via Infotrieve]

9. Bruch C, Herrmann B, Schmermund A, Bartel T, Mann K, Erbel R. Impact of disease activity on left ventricular performance in patients with acromegaly. Am Heart J. 2002; 144: 538–543.[CrossRef][Medline] [Order article via Infotrieve]

10. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure, part I: diagnosis, prognosis, measurements of diastolic function. Circulation. 2002; 105: 1387–1393.[Free Full Text]

11. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure, part II: causal mechanisms and treatment. Circulation. 2002; 105: 1503–1508.[Free Full Text]

12. Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM, Stewart KP. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 2002; 288: 2144–2150.[Abstract/Free Full Text]

13. Spinale FG, Tomita M, Zellner JL, Cook JC, Crawford FA, Zile MR. Collagen remodeling and changes in left ventricular function during development and recovery from supraventricular tachycardia. Am J Physiol. 1991; 261 (pt 2): H308–H318.[Medline] [Order article via Infotrieve]

14. Spinale FG, Zellner JL, Tomita M, Crawford FA, Zile MR. Relation between ventricular and myocyte remodeling with the development and regression of supraventricular tachycardia-induced cardiomyopathy. Circ Res. 1991; 69: 1058–1067.[Abstract/Free Full Text]

15. Hein S, Arnon E, Kostin S, Schónburg M, Elsässer A, Polyakova V, Bauer EP, Klóvekorn WP, Schaper J. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart. Circulation. 2003; 107: 984–991.[Abstract/Free Full Text]

16. Borbély A, van der Velden J, Papp Z, Bronzwaer JGF, Edes I, Stienen GJM, Paulus WJ. Cardiomyocyte stiffness in diastolic heart failure. Circulation. 2005; 111: 774–781.[Abstract/Free Full Text]

17. Janicki JS, Brower GL. The role of myocardial fibrillar collagen in ventricular remodeling and function. J Card Failure. 2002; 8 (suppl): S319–S325.[CrossRef][Medline] [Order article via Infotrieve]

18. Angeja BG, Grossman W. Evaluation and management of diastolic heart failure. Circulation. 2003; 107: 659–663.[Free Full Text]

19. Glantz SA, Parmley WW. Factors which affect the diastolic pressure-volume curve. Circ Res. 1978; 42: 171–180.[Free Full Text]

20. Gandhi SK, Powers JC, Nomeir AM, Fowle K, Kitzman DW, Rankin KM, Little WC. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med. 2001; 344: 17–22.[Abstract/Free Full Text]

21. Tsuyuki RT, McKelvie RS, Arnold JM, Avezum A Jr, Barretto AC, Carvalho AC, Isaac DL, Kitching AD, Piegas LS, Teo KK, Yusuf S. Acute precipitants of congestive heart failure exacerbations. Arch Intern Med. 2001; 161: 2337–2342.[Abstract/Free Full Text]

22. Senni M, Redfield MM. Heart failure with preserved systolic function: a different natural history? J Am Coll Cardiol. 2001;38:1277–82; JAMA. 2003; 289: 194–202.[Abstract/Free Full Text]

23. Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation. 2000; 101: 2118–2121.[Free Full Text]

24. Yturralde FR, Gaasch WH. Diagnostic criteria for diastolic heart failure. Prog Cardiovasc Dis. 2005; 47: 314–319.[CrossRef][Medline] [Order article via Infotrieve]

25. Aurigemma GP, Gaasch WH, Villegas B, Meyer TE. Noninvasive assessment of left ventricular mass, chamber volume, and contractile function. Curr Probl Cardiol. 1994; 20: 361–440.

26. Braunwald E. Heart Disease: A Textbook of Cardiovascular Disease. 3rd ed. Philadelphia, Pa: WB Saunders; 1988: 449–470.

27. Carabello BA. Evolution of the study of left ventricular function: everything old is new again. Circulation. 2002; 105: 2701–2703.[Free Full Text]

28. Karunanithi MK, Feneley MP. Single-beat determination of preload recruitable stroke work relationship: derivation and evaluation in conscious dogs. J Am Coll Cardiol. 2000; 35: 502–513.[Abstract/Free Full Text]

29. Shimizu G, Zile MR, Blaustein AS, Gaasch WH. Left ventricular chamber filling and midwall fiber lengthening in patients with left ventricular hypertrophy: overestimation of fiber velocities by conventional midwall measurements. Circulation. 1985; 71: 266–272.[Abstract/Free Full Text]

30. Aurigemma GP, Silver KH, Priest MA, Gaasch WH. Geometric changes allow for normal ejection fraction despite depressed myocardial shortening in hypertensive left ventricular hypertrophy. J Coll Cardiol. 1995; 26: 195–202.[CrossRef]

31. Palmon LC, Reichek N, Yeon SB, Clark NR, Brownson D, Hoffman E, Axel L. Intramural myocardial shortening in hypertensive left ventricular hypertrophy with normal pump function. Circulation. 1994; 89: 122–131.[Abstract/Free Full Text]

32. Heinein MY, Gibson DG. Long axis function in disease. Heart. 1999; 81: 229–231.[Free Full Text]

33. Kawaguchi M. Hay I, Fetics B, Kass DA. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation. 2003; 107: 656–658.[Free Full Text]

34. Pak PH, Maughan WL, Baughman KL, Kieval RS, Kass DA. Mechanism of acute mechanical benefit from VDD pacing in hypertrophied heart: similarity of responses in hypertrophic cardiomyopathy and hypertensive heart disease. Circulation. 1998; 98: 242–248.[Abstract/Free Full Text]

35. Sadler D, Aurigemma GP, Williams DW, Reda DJ, Materson BJ, Gottdiener JS. Systolic function in hypertensive men with concentric remodeling. Hypertension. 1997; 30: 777–781.[Abstract/Free Full Text]

36. Aurigemma GP, Silver KH, McLaughlin M, Mauser J, Gaasch WH. Impact of chamber geometry and gender on left ventricular systolic function in patients >60 years of age with aortic stenosis. Am J Cardiol. 1994; 74: 794–798.[CrossRef][Medline] [Order article via Infotrieve]

37. Aurigemma GP, Gaasch WH, McLaughlin M, McGinn R, Sweeney A, Meyer TE. Reduced left ventricular systolic pump performance and depressed myocardial contractile function in patients >65 years of age with normal ejection fraction and a high relative wall thickness. Am J Cardiol. 1995; 76: 702–705.[CrossRef][Medline] [Order article via Infotrieve]

38. Abraham TP, Nishimura RA. Myocardial strain: can we finally measure contractility? J Am Coll Cardiol. 2001; 37: 731–734.[Free Full Text]

39. Abraham TP, Laskowski C, Zhan WZ, Belohlavek M, Martin EA, Greenleaf JF, Sieck GC. Myocardial contractility by strain echocardiography: comparison with physiological measurements in an in vitro model. Am J Physiol. 2003; 285: H2599–H604.

40. Edvardsen T, Gerber BL, Garot J, Bluemke DA, Lima JA, Smiseth OA. Quantitative assessment of intrinsic regional myocardial deformation by Doppler strain rate echocardiography in humans: validation against three-dimensional tagged magnetic resonance imaging. Circulation. 2002; 106: 50–56.[Abstract/Free Full Text]

41. Zile MR, Gaasch WH, Carroll JD, Feldman MD, Aurigemma GP, Schaer GL, Ghali JK, Liebson PR. Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure? Circulation. 2001; 104: 779–782.[Abstract/Free Full Text]

42. Lewis RP, Sandler H. Relationship between changes in left ventricular dimensions and the ejection fraction in man. Circulation. 1971; 44: 548–557.[Abstract/Free Full Text]

43. Rozich JD, Carabello BA, Usher BW, Kratz JM, Bell AE, Zile MR. Mitral valve replacement with and without chordal preservation in patients with chronic mitral regurgitation: mechanisms for differences in postoperative ejection performance. Circulation. 1992; 86: 1718–1726.[Abstract/Free Full Text]

44. Mirsky I, Pasternac A, Ellison RC. General index for the assessment of cardiac function. Am J Cardiol. 1972; 30: 483–487.[CrossRef][Medline] [Order article via Infotrieve]

45. Quinones MA, Gaasch WH, Alexander JK. Echocardiographic assessment of left ventricular function: with special reference to normalized velocities. Circulation. 1974; 50: 42–51.[Abstract/Free Full Text]

46. Bax JJ, Ansalone G, Breithardt OA, Derumeaux G, Leclercq C, Schalij M, Sogaard P, St. John Sutton M, Nihoyannopoulos P. Echocardiographic evaluation of cardiac resynchronization therapy: ready for routine clinical use? J Am Coll Cardiol. 2004; 44: 1–9.[Abstract/Free Full Text]

47. Yip G, Abraham T, Belohlavek M, Khandheria BK. Clinical applications of strain rate imaging. J Am Soc Echocardiogr. 2003; 16: 1334–1342.[CrossRef][Medline] [Order article via Infotrieve]

48. Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, Kaluski E, Krakover R, Vered Z. Two-dimensional strain: a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr. 2004; 17: 1021–1029.[CrossRef][Medline] [Order article via Infotrieve]

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