INTRODUCTION
Heart failure (HF) is defined as the pathological 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) or eject blood (systolic performance) or both. Thus, consideration of the systolic and diastolic performance of the left ventricle provides a conceptual basis to classify and understand the pathophysiology of HF.
PATHOPHYSIOLOGY
Systolic Performance
Left ventricular (LV) systolic performance is the ability of the left ventricle to empty, which can be quantified as an 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 with or without contrast, radionuclide ventriculography, or magnetic resonance imaging.
The EF has been used as an index of myocardial contractile performance. However, it is influenced not only by myocardial contractility but also by LV afterload. Furthermore, in the presence of a left-sided valvular regurgitation (mitral or aortic regurgitation) or a left-to-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 end diastolic volume. 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 that 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. When defined in this manner, systolic dysfunction results from impaired myocardial function, increased LV afterload, structural abnormalities of the left ventricle, or a combination thereof.
Diastolic Performance
For the left ventricle to function effectively as a pump, it must be able not only to eject but also to fill, which is its diastolic function. Diastolic function conventionally has been assessed on the basis of the LV end diastolic pressure-volume (P-V) relation (see Chapter 7 ). A shift of the curve upward and to the left has been considered to be the hallmark of diastolic dysfunction ( Fig. 6-1 , curve A). 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.
Diastolic function also has been assessed based on LV filling patterns by use of Doppler echocardiography. 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. 6-2 ).
These Doppler LV filling patterns, however, are influenced not only by LV diastolic properties but also by left atrial (LA) 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 appear to be less load sensitive. The peak early diastolic mitral annular velocity (E M ) provides a relatively load insensitive measure of LV relaxation. E M is decreased with increasing severity of diastolic dysfunction. The color M-mode imaging performed from the apex provides a temporal and spatial map of the velocities of blood flow in early diastole along the long axis of the left ventricle. The velocity of propagation of mitral inflow to the apex (V P ) is reduced in conditions with impaired LV relaxation.
A pseudonormalized LV filling pattern can be distinguished from a normal filling pattern by demonstrating reduced E M and V P . Furthermore, since 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. Last, color M-mode imaging provides a noninvasive measurement of the diastolic intraventricular pressure gradient between the apex and the base during early diastole.
Finally, analysis of pulmonary venous flow patterns provides useful information on LV compliance and LA pressure. With increase in LV end diastolic pressure, the reversal velocity of pulmonary venous atrial flow increases, and duration increases longer than that of mitral late diastolic velocity. With decrease in LV compliance and increase in mean LA pressure, the systolic component of pulmonary venous flow decreases and the diastolic component of pulmonary venous flow increases. Table 6-1 and Figure 6-2 show stages of diastolic dysfunction incorporatingpulmonary venous flow, tissue Doppler, and color M-mode indices.
| PARAMETER | NORMAL (YOUNG) | NORMAL (ADULT) | DELAYED RELAXATION | PSEUDONORMAL FILLING | RESTRICTIVE FILLING |
|---|---|---|---|---|---|
| E/A | >1 | >1 | <1 | 1-2 | >2 |
| DT (msec) | <220 | <220 | >220 | 150–200 | <150 |
| IVRT (msec) | <100 | <100 | >100 | 60-100 | <60 |
| S/D | <1 | ≥1 | ≥1 | <1 | <1 |
| AR (cm/sec) | <35 | <35 | <35 | ≥35 | ≥25 * |
| Vp (cm/sec) | >55 | >45 | <45 | <45 | <45 |
| Em (cm/sec) | >10 | >8 | <8 | <8 | <8 |
Definition of Systolic and Diastolic Heart Failure
When the HF is associated with a reduced EF, the pathological state may be called systolic HF. In contrast, when the HF is associated with diastolic dysfunction in the absence of a reduced EF, the pathological state may be called diastolic HF. It is important to recognize that the HF, whether it results from systolic or diastolic dysfunction, is a clinical syndrome and that both systolic HF and diastolic HF are heterogeneous disorders. Patients with systolic HF have abnormalities of diastolic function, and those with diastolic HF may have abnormalities of systolic contractile function that are not detected by measurement of an EF.
Terminology
Diastolic Dysfunction and Diastolic Heart Failure
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 and a normal EF and diastolic dysfunction.
Diastolic Heart Failure and Heart Failure with Normal Ejection Fraction
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. Diastolic HF is associated with LV diastolic abnormalities. It is important to recognize that although patients with diastolic HF have diastolic dysfunction, frequently they also have systolic contractile abnormalities (despite the normal EF). 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.
Comparison of Pathophysiology in Systolic and Diastolic Heart Failure
Table 6-2 shows the comparison of LV structural and functional characteristics in systolic and diastolic HF (see Chapter 2 ). Systolic HF and diastolic HF have several similarities in LV structural and functional characteristics, including increased LV mass and increased LV end diastolic pressure. The most significant difference between the two forms of HF is in LV geometry and LV function: Systolic HF is characterized by LV dilatation, eccentric LV hypertrophy, and abnormal systolic and diastolic function, whereas diastolic HF is characterized by concentric LV hypertrophy, a normal EF, and abnormal diastolic function. Thus, the pathophysiology of systolic HF is dependent predominantly on progressive LV dilatation and abnormal systolic function. On the other hand, the pathophysiology of diastolic HF is dependent predominantly on concentric LV hypertrophy and abnormal diastolic function.
| CHARACTERISTICS | SYSTOLIC HF | DIASTOLIC HF |
|---|---|---|
| Remodeling | ||
| LV end diastolic volume | ↑ | N |
| LV end systolic volume | ↑ | N |
| LV mass | ↑ eccentric | ↑ concentric |
| Relative wall thickness | ↓ | ↑ |
| Cardiomyocyte | ↑ length | ↑ diameter |
| Extra cellular matrix collagen | ↓ | ↑ |
| Diastolic properties | ||
| LV end diastolic pressure | ↑↑ | ↑↑ |
| Relaxation time constant | ↑ | ↑↑ |
| Filling rate | ↓ | ↓↓ |
| Chamber stiffness | N–↓ | ↓ |
| Myocardial stiffness | N–↑ | ↓ |
| Systolic properties | ||
| Performance | ||
| Stroke volume | ↓ | N–↓ |
| Stroke work | ↓ | N |
| Function | ||
| Ejection fraction | ↓ | N |
| Ejection rate | ↓ | N |
| PRSW | ↓ | N |
| Contractility | ||
| Positive dp/dt | ↓ | N |
| Ees | ↓ | N–↑ |
| FS vs. stress | ↓ | N |
| Preload reserve | Exhausted | Limited |
| Ea | ↓ | ↑ |
| Arterial-ventricular coupling (Ea/Ees) | ↓ | N |
CLINICAL APPLICATIONS
Diagnosis of Diastolic Heart Failure
A distinction between systolic and diastolic HF is important because these two forms have different pathophysiologies and thus might potentially require different therapeutic approaches. Nevertheless, clinical symptoms and signs are similar in systolic and diastolic HF ( Table 6-3 ). This may be because systolic HF is often accompanied by diastolic dysfunction, by which symptoms and signs related to pulmonary congestion are commonly observed. Thus, clinical history and physical examination do not provide useful information in discriminating between systolic and diastolic HF.
