Diagnosis of Diastolic Heart Failure

Diagnosis of Diastolic Heart Failure Hidekatsu Fukuta, MD, and William C. Little, MD Corresponding author William C. Little, MD Cardiology Section, W...
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Diagnosis of Diastolic Heart Failure Hidekatsu Fukuta, MD, and William C. Little, MD

Corresponding author William C. Little, MD Cardiology Section, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045, USA. E-mail: [email protected] Current Cardiology Reports 2007, 9:224–228 Current Medicine Group LLC ISSN 1523-3782 Copyright © 2007 by Current Medicine Group LLC

Nearly half of patients with heart failure (HF) have a normal ejection fraction (EF) and have been labeled as having diastolic HF. Diastolic HF is characterized by a normal EF, a variable amount of concentric left ventricular hypertrophy, and abnormal diastolic function. Differentiating diastolic HF from HF with a reduced EF (systolic HF) is important because these two forms of HF have different pathophysiology and thus might require different therapeutic approaches. Nevertheless, patients with diastolic HF and those with systolic HF have similar clinical symptoms and signs. Thus, clinical history and physical examination do not differentiate between diastolic and systolic HF. There is accumulating evidence that diastolic dysfunction is related to the severity of HF and prognosis regardless of EF. Thus, it is important to evaluate both systolic and diastolic function not only to differentiate between diastolic and systolic HF but also to identify high-risk patients.

tricle to empty can be quantified as LV emptying fraction or an ejection fraction (EF—a ratio of stroke volume to end-diastolic volume). Thus, LV systolic dysfunction is defined as a decreased EF. The EF can be obtained by determining the LV volume by use of two-dimensional echocardiography, contrast ventriculography, or radionuclide ventriculography. EF has been used as an index of myocardial contractile performance. The EF, however, is not only influenced by myocardial contractility but also by LV afterload [1]. Furthermore, in the presence of a left-sided valvular regurgitation (mitral or aortic regurgitation) or a leftto-right shunt (ventricular septal defect or patent ductus arteriosus), the LV stroke volume may be high while the forward stroke volume (stroke volume minus regurgitant volume or shunt volume) is lower. Thus, the effective EF is defined as the forward stroke volume divided by enddiastolic volume [2]. The effective EF is a useful means to quantify systolic function for two reasons. First, the effective EF represents the functional emptying of the left ventricle, which contributes to cardiac output. Second, the effective EF is relatively independent of LV end-diastolic volume over the clinically relevant range. An operational definition of systolic dysfunction is an effective EF of less than 0.50 [2]. When defined in this manner, systolic dysfunction results from impaired myocardial function, increased LV afterload, and/or structural abnormalities of the left ventricle [2].

Introduction

Diastolic performance

Heart failure (HF) is defined as the pathologic state in which the heart is unable to pump blood at a rate required by the metabolizing tissues or can do so only with an elevated filling pressure. Inability of the heart to pump blood sufficiently to meet the needs of the body’s tissues may be due to the inability of the left ventricle to fill (diastolic performance) and/or eject (systolic performance) blood. Thus, consideration of the systolic and diastolic performance of the left ventricle provides a conceptual basis to classify and understand the pathophysiology of HF.

For the left ventricle to function effectively as a pump, it must not only be able to eject but also fill blood (diastolic function). Diastolic function has conventionally been assessed on the basis of the LV end-diastolic pressure–volume relationship. A shift of the curve upward and to the left has been considered to be the hallmark of diastolic dysfunction (Fig. 1, curve A) [3]. In this situation, each LV end-diastolic volume is associated with a high end-diastolic pressure, and thus, the left ventricle is less distensible. Decreased LV distensibility is caused by aging, systemic hypertension, and hypertrophic or restrictive cardiomyopathy [2]. Furthermore, impaired relaxation may result in persistent pressure generation at end-diastole and may thus contribute to the altered diastolic distensibility. Impaired relaxation is observed in patients with hypertrophic cardiomyopathy and during ischemia [2]. The invasive nature of the procedures for obtaining the LV end-diastolic

Left Ventricular Systolic and Diastolic Performance Systolic performance

Left ventricular (LV) systolic performance is the ability of the left ventricle to empty. The ability of the left ven-

LV end-diastolic pressure

Diagnosis of Diastolic Heart Failure  Fukuta and Little  225

A Normal

B

∆P ∆V

LV end-diastolic volume Figure 1. A shift of the curve to A indicates that a higher left ventricular Current Cardiology Reports CR09-3-2-01 fig. 1 (LV) pressure will be required to distend the left ventricle to a similar 240 pts. W/ 144 pts. D (20 x 12) volume, indicating the ventricle is less distensible. Author:that Little Editor: Michele Artist: The Danslope of the LV end-diastolic pressure–volume relationship indicates the passive chamber stiffness. Because the relationship is exponential in shape, the slope (∆P/∆V) increases as the end-diastolic pressure increases. (From Little [3]; with permission.)

Figure 2. Transmitral inflow velocity, pulmonary vein flow velocity, mitral annular velocity, and color M-mode imaging in stages of diastolic dysfunction. A—late diastolic mitral inflow velocity; AM —late diastolic mitral annular velocity; D—diastolic pulmonary vein velocity; E—early diastolic mitral inflow velocity; EM —early diastolic mitral annular velocity; S—systolic pulmonary vein velocity; SM —systolic mitral annular velocity; VP—velocity of propagation of mitral inflow to the apex.

pressure–volume relationship, however, limits its clinical use for assessment of diastolic dysfunction. Diastolic function has also been assessed based on LV filling patterns by use of Doppler echocardiography [4]. In the absence of mitral stenosis, three patterns of LV filling indicate progressive impairment of diastolic function: 1) reduced early diastolic filling with a compensatory increase in importance of atrial filling (impaired relaxation); 2) most filling early in diastole but with rapid

deceleration of mitral flow (pseudonormalization); and 3) almost all filling of the left ventricle occurring very early in diastole in association with very rapid deceleration of mitral flow (restrictive filling) (Fig. 2). These Doppler LV filling patterns, however, are influenced not only by LV diastolic properties alone but also by left atrial pressure. In contrast, tissue Doppler measurement of mitral annular velocity and color M-mode measurement of the velocity of propagation of mitral inflow to the apex are much less load-sensitive. The peak early diastolic mitral annular velocity (E M) provides a relatively load-insensitive measure of LV relaxation [5]. E M progressively decreases with increasing severity of diastolic dysfunction [6,7]. The velocity of propagation of mitral inflow to the apex (V P) is also reduced in conditions with impaired LV relaxation [7]. Thus, reduced EM and VP can be used to differentiate pseudonormalized from normal filling pattern. Furthermore, analysis of pulmonary venous flow pattern provides useful information on LV compliance and left atrial pressure [8]. With increase in LV end-diastolic pressure, the pulmonary venous atrial flow reversal velocity increases and duration also increases longer than duration of mitral late-diastolic velocity. With decrease in LV compliance and increase in mean left atrial pressure, the systolic component of pulmonary venous flow decreases and the diastolic component of pulmonary venous flow increases. Figure 2 shows stages of diastolic dysfunction incorporating pulmonary venous flow and tissue Doppler and color M-mode imaging. Finally, Doppler echocardiography provides a noninvasive accurate estimate of LV filling pressure. Because early diastolic mitral inflow velocity (E) becomes higher and relaxation-related parameters (E M and V P) remain reduced as filling pressure increases, the E/E M and E/V P can estimate LV filling pressure with a reasonable accuracy over a wide range of an EF [9,10]. Thus, if these Doppler parameters are interpreted with other twodimensional echocardiographic parameters, including LV size and motion, the position of the LV end-diastolic pressure–volume relation (left upward or right downward shift) can be estimated noninvasively [11].

Definitions of Systolic and Diastolic HF When HF occurs in the presence of a reduced EF, the pathologic state may be called systolic HF. In contrast, when HF is associated with diastolic dysfunction in the absence of a reduced EF, the pathologic state may be called diastolic HF. It is important to recognize that HF, whether it occurs in the presence or absence of a reduced EF, is a clinical syndrome and that both systolic and diastolic HF are heterogeneous disorders. Systolic HF is accompanied by diastolic dysfunction [2,3,12]. Diastolic abnormalities play an important role in the mechanisms of exercise intolerance in systolic HF [13]. Although patients with

226  Management of Heart Failure

diastolic HF have diastolic dysfunction, they frequently also have systolic contractile abnormalities (despite normal EF) [12,14,15,16••]. In addition, comorbidities such as hypertension, anemia, and renal dysfunction are commonly seen in patients with diastolic HF and may contribute to the development of HF.

Diastolic dysfunction and diastolic HF The term diastolic dysfunction is used to describe abnormal mechanical (diastolic) properties of the ventricle and includes decreased LV distensibility, delayed relaxation, and abnormal filling, regardless of whether the EF is normal or reduced and whether the patient is symptomatic or asymptomatic. In contrast, the term diastolic HF is used to describe patients with the symptoms and signs of HF, a normal EF, and diastolic dysfunction.

Diastolic HF and HF with normal EF There are many clinical conditions that cause HF with a normal EF. These include diastolic dysfunction, valvular diseases, pericardial diseases, and intracardiac mass; among them, diastolic dysfunction is the most common cause of HF with a normal EF.

Pathophysiology of systolic and diastolic HF Systolic HF and diastolic HF have several similarities in LV structural and functional characteristics, including increased LV mass and elevated LV end-diastolic pressure [17]. The clearest difference between the two forms of HF is the difference in LV geometry and LV function; systolic HF is characterized by eccentric LV hypertrophy and a reduced EF, whereas diastolic HF is characterized by a variable amount of concentric LV hypertrophy, a normal EF, and abnormal diastolic function. Furthermore, cardiomyocyte diameter is higher in patients with diastolic HF than in those with systolic HF, but collagen levels may be equally elevated [18,19]. Thus, the pathophysiology of systolic HF is primarily dependent on progressive LV dilatation and abnormal systolic function. On the other hand, the pathophysiology of diastolic HF is predominantly dependent on concentric LV hypertrophy and abnormal diastolic function.

Diagnosis of Diastolic HF Nearly half of patients with HF have diastolic HF [20•,21,22]. Differentiating diastolic HF from systolic HF is important because these two forms of HF have different pathophysiology and thus might potentially require different therapeutic approaches [11,23,24]. Nevertheless, clinical symptoms and signs are similar in systolic and diastolic HF [23,25]. This may be because systolic HF is accompanied by diastolic dysfunction and therefore symptoms and signs related to pulmonary congestion are commonly observed in systolic HF [2]. Thus, clinical history and physical examination do not discriminate between systolic and diastolic HF.

Several criteria have been proposed for the diagnosis of diastolic HF [26,27]. In summary, for the definite diagnosis of diastolic HF to be made, the following evidence is required: 1) clinical evidence of HF; 2) normal systolic function (LVEF > 0.50); and 3) objective evidence of impaired LV relaxation, filling, and/or passive stiffness. If strictly applied, the definition of diastolic HF would include the patients with acute mitral or aortic regurgitation or mechanical causes of diastolic dysfunction (mitral stenosis or constrictive pericarditis); these could be avoided by additional screening.

Timing of EF measurement The Vasan and Levy [27] criteria require a normal EF within 72 hours of an episode of pulmonary congestion to make a definite diagnosis of diastolic HF. It is possible, however, that the acute pulmonary congestion may be due to transient systolic dysfunction or acute mitral regurgitation produced by hypertension and/or myocardial ischemia that had resolved by the time the LVEF was measured. To address this issue, Gandhi et al. [28] used Doppler echocardiography to evaluate LVEF, regional wall motion, and mitral regurgitation in 38 patients, both during an acute episode of hypertensive pulmonary edema and 24 to 72 hours later, after treatment and resolution of the hypertension and pulmonary congestion. They found that LVEF and regional wall motion were similar, both during the acute episode of hypertensive pulmonary edema and after resolution of the congestion and control of blood pressure. No patient had severe mitral regurgitation during the acute episode. They also found that one half of the patients had an EF greater than or equal to 0.50 during their presentation with acute pulmonary edema, and that 88% of the patients with an EF greater than or equal to 0.50 after treatment had an EF greater than or equal to 0.50 during the acute episode, and all of these patients had an EF of at least 0.43. Thus, they concluded that the EF obtained 1 to 3 days after the acute presentation of patients with hypertensive pulmonary edema accurately identified patients with a preserved EF during acute presentation. Similar observations are reported by Bogaty et al. [29]. These studies suggest that measuring the EF within 72 hours of an acute episode of pulmonary congestion is sufficient to meet the diagnostic criteria proposed by Vasan and Levy [27].

Is measurement of diastolic function necessary? Recognizing the difficulties inherent in the clinical assessment of the LV diastolic performance, Zile et al. [30,31] tested the hypothesis that measurements of the LV relaxation and passive stiffness were not necessary to make the diagnosis of diastolic HF. They studied 47 patients with a history of HF, a normal LVEF (> 0.50) and an at least mild LV hypertrophy (LV mass ≥ 125 g/m 2) or concentric LV remodeling (LV chamber dimension < 55 mm combined with LV wall thickness ≥ 11 mm and relative

Diagnosis of Diastolic Heart Failure  Fukuta and Little  227 wall thickness ≥ 0.45 mm). They then assessed LV diastolic function during cardiac catheterization. They found that all the patients had evidence of abnormalities of LV relaxation and passive stiffness and that the diastolic pressure–volume relation was shifted up and to the left in the patients compared with normal controls [30,31]. Thus, they concluded that objective evidence of abnormalities of LV relaxation or distensibility was not necessary to make the diagnosis of diastolic HF if there was evidence of LV hypertrophy or concentric remodeling. Assessment of diastolic function by Doppler echocardiography, however, provides useful information on the severity of HF and prognosis regardless of EF [12,32–36]. Specifically, Brucks et al. [12] examined the association of systolic and diastolic function with plasma B-type natriuretic peptide (BNP) levels and 2-year survival in 104 HF patients with an EF less than 0.50 and 102 HF patients with an EF greater than or equal to 0.50. They found that increasing grade of diastolic dysfunction, but not reduced EF, was associated with increased plasma BNP levels. They also found that greater diastolic dysfunction, but not reduced EF, predicted worse survival. When analysis was restricted to HF patients with an EF of less than 0.50, both reduced EF and the greater diastolic dysfunction predicted worse survival. Similarly, Dokainish et al. [35] reported that an increased (> 15) E/E M was a powerful predictor for cardiac events during a mean follow-up of 1.5 years in 116 consecutive patients hospitalized with HF. Thus, although measurement of diastolic function may not be necessary for the diagnosis of diastolic HF, its measurement with Doppler echocardiography is critical for identifying high-risk patients.

Conclusions If patients have clinical evidence of HF, the EF should be measured within 72 hours of an acute episode of pulmonary congestion. If the EF is less than 0.50, the diagnosis of systolic HF can be made. If the EF is greater than 0.50 and there is evidence of LV hypertrophy or concentric remodeling, the diagnosis of diastolic HF can be made. In the absence of LV hypertrophy or concentric remodeling, the diagnosis of diastolic HF may be supported by the presence of left atrial enlargement [37,38]. When the diagnosis of diastolic HF remains uncertain, Doppler echocardiography or cardiac catheterization provides a definitive diagnosis. Importantly, the severity and prognosis of HF are more closely related to the degree of diastolic filling abnormalities than EF. Thus, evaluation of both systolic and diastolic function is critical not only for making a diagnosis of diastolic HF but also for identifying high-risk patients.

References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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