Echocardiography predicts adverse cardiac remodelling in heart failure

Abstract

Congestive heart failure remains a primary cause of cardiovascular-related events. Heart failure patients face two health care challenges. First, they are uncertain about their prognosis and second, they have an unpredictable clinical course with recurrent exacerbations of heart failure. The echocardiogram is an easily accessible bedside test without any associated procedural complications. Additionally, it provides a wealth of information about chamber size and function, valve integrity and the pericardial sac. In the present review, the most common echocardiographic predictors of impending cardiac events in congestive heart failure are described.

In spite of significant therapeutic advances, congestive heart failure (CHF) continues to be a major public health problem. In the United States alone, there are approximately five million heart failure patients, and an additional 550,000 new patients are diagnosed with heart failure each year (1). Heart failure is the first most common cause of hospitalization in the United States, with approximately one million people hospitalized each year. The newer treatment strategies for the management of heart failure are expensive and impose a considerable economic burden on the world population. Therefore, it is important to direct the costly treatment strategies to patients at high risk for cardiac events. There is no single test that accurately predicts the prognosis of heart failure; however, echocardiography has served as a major tool for this purpose in the past few decades.

Although oxygen consumption (VO₂) during exercise and levels of brain naturetic peptide are used as markers of CHF, echocardiography has been used to identify the etiology of heart failure. It provides important information about the pathophysiological basis of heart failure noninvasively. Echocardiography estimates the severity of systolic and diastolic dysfunction of the ventricular chambers (2–4), and associated abnormalities, such as pulmonary hypertension, thrombus, valvular dysfunction and pericardial diseases can be identified. Evaluation of ischemia and viability in heart failure patients is another important application of echocardiography (5–7).

ECHOCARDIOGRAPHIC MARKERS OF PROGNOSIS IN HEART FAILURE

The prognostic value of echocardiography was evaluated in a number of studies. Several markers which point to an adverse outcome in heart failure are outlined briefly as follows.

Chamber dimensions

Cardiac enlargement is associated with increased morbidity and mortality, even among healthy, middle-aged and elderly people (8–10). Increased cardiac size is also an important determinant of clinical outcome in patients with mild or severe heart failure (11–13).

Dilated left ventricle predicts adverse outcomes in heart failure patients:

Marked increases in end-diastolic and end-systolic dimensions are important prognostic markers in all forms of heart failure (14,15), especially in the presence of mitral and aortic valve regurgitation (16–18). Systolic indices correlate best with postoperative improvement in ventricular function in valvular regurgitation. End-diastolic dimension is one of the important predictors of outcome in chronic heart failure and is also important in assessing the efficacy of different therapeutic strategies in heart failure (19,20). Different types of volume reduction surgery have been shown to improve clinical outcomes (21).

Ballester-Rodes and Westaby (22) calculated the approximate risk and probability of death due to heart failure or heart transplantation in patients with idiopathic dilated cardiomyopathy (DCM) within a two-year period after presentation. The most important parameters included were left ventricular (LV) end-diastolic dimension, New York Heart Association (NYHA) functional class, LV ejection fraction (LVEF), heart to lung ratio of antimyosin uptake and whether the presentation was acute or chronic. Patients with LV end-diastolic dimension of greater than 7.5 cm had a similar prognostic implication as that of patients with a low LVEF (less than 30%). The risk of death or requirement of transplantation within two years in patients with advanced chronic CHF (NYHA class 3 or class 4) due to idiopathic DCM ranged from 55% to 65% (if the end-diastolic LV dimension was less than 7.5 cm and LVEF was greater than 30%) to 70% to 80% (if LV diastolic dimension was 7.5 cm and LVEF was less than 30%) (Figure 1).

Figure 1).

Apical four-chamber view of a transthoracic echocardiogram of a healthy heart (left panel) and a patient with idiopathic dilated cardiomyopathy showing four-chamber enlargement (right panel)

Dilated right ventricle predicts adverse prognosis especially in patients with LV dysfunction due to myocardial infarction:

The presence of a dilated right ventricle (RV) has also been observed as an independent marker for poor functional capacity in patients with CHF. RV systolic performance is important for the maintenance of LV cardiac output, especially during exercise. The presence of markedly impaired RV systolic performance can result in more symptoms and may lead to recurrent hospitalizations due to worsening heart failure. RV function is an independent predictor of death and the development of heart failure in patients with LV dysfunction after myocardial infarction (MI) (23). In patients with advanced heart failure, preserved RV function, as indicated by an echocardiographically derived RV shortening greater than 1.25 cm, is a strong predictor of survival (24). RV shortening was measured as the difference of the end-diastolic distance minus the end-systolic distance between the tricuspid annulus and the RV apex. At a cutoff point of RV shortening of 1.25 cm, this value had a sensitivity of 90%, specificity of 80% and overall predictive accuracy of 83% to distinguish survivors from nonsurvivors in a mean follow-up at 14 months in patients with advanced heart failure (24).

Left atrial dilation may increase the incidence of atrial arrhythmias, which can cause worsening of heart failure:

In elderly patients (older than 70 years of age) with systolic LV dysfunction, indexed left atrial (LA) size (greater than 26 mm/m²) was the single best predictor of death (25). When demographics, such as clinical, echocardiographic and Doppler measurements, were analyzed in a hierarchical order, indexed LA size yielded the most valuable contribution to predicting the combined end point of death and decompensated heart failure. This suggests that LA enlargement has an independent and additional prognostic value in elderly patients with LV dysfunction (Figure 2).

Figure 2).

Parasternal long axis (left panel) and apical (right panel) views of four chambers in a transthoracic echocardiogram of a patient presenting with congestive heart failure long after a myocardial infarction who was found to have a four-chamber apical aneurysm. This patient later underwent an implantable defibrillator placement for sustained ventricular tachycardia. Arrow shows left ventricular aneurysm

Echoparameters of LV systolic performance

Various LV systolic function measures have been described as prognostic indicators of heart failure. However, the easiest and more practicable method is to measure LVEF (26). LVEF expresses the relationship between the maximal diastolic and minimal systolic ventricular volumes. This measurement has been shown to be capable of risk stratifying patients for cardiovascular events including death, transplantation and worsening of heart failure requiring recurrent hospitalization. A long-term follow-up showed that patients with systolic heart failure had lower admission-free survival rates. In a small study by Niebauer et al (27), three-year survival was low when ejection fraction was very low (less than 20%). However, there was no difference in the survival of patients with an LVEF of 11% and 20%.

Echocardiographic parameters of LV diastolic function

Parameters of LV diastolic function are powerful predictors of major cardiac adverse events in patients with DCM. They may also be used to predict clinical success of medical treatment. Invasive and noninvasive parameters of diastolic function reveal comparable information for the estimation of prognosis in patients with DCM (28). LV diastolic function is estimated by Doppler echocardiography and its use for determining prognosis relies on the principle of change in flow characteristics with alteration in the pressure between chambers. The different factors that interplay with compliance of the chambers result in a change of flow characteristics.

Various Doppler measurements have been described for the assessment of LV diastolic function. A few have been correlated to diagnosis and have shown prognostic significance in patients with cardiomyopathy. These measurements include mitral valve inflow Doppler pattern, tissue Doppler velocity, pulmonary vein Doppler velocity and mitral regurgitation. Doppler flow velocities are mainly used to assess the relaxation characteristics of the left ventricle. Four grades of diastolic dysfunction have been described, namely, impaired relaxation pattern (grade 1), pseudonormalization pattern (grade 2), restrictive filling pattern reversible by preload reduction (grade 3) and restrictive filling pattern which is irreversible (grade 4) (Table 1).

TABLE 1.

Grades of diastolic dysfunction (DD) and their Doppler criteria

Grade of DD	E/A ratio	DT (ms)	IVRT (ms)	Pulmonary vein flow Doppler velocities
Grade 1	>1 and <2	>240	>90	PVs2>>PVd
Grade 2	<1	160–200	<90	PVs2<PVd
Grade 3	>2	<160	<70	PVs2<<PVd
Grade 4	>2	<160	<70	PVs2<<PVd

DT Mitral E wave deceleration time; E/A ratio Ratio of mitral inflow E to A wave Doppler velocities; IVRT Isovolumetric relaxation time; PVd Diastolic velocity; PVs2 Systolic velocity

In patients with systolic dysfunction, the presence of relaxation abnormality of the LV has an ominous prognosis and becomes more significant with restrictive filling of the LV. Various studies have evaluated the clinical importance of diastolic dysfunction in heart failure. In patients with LV systolic dysfunction and advanced functional class, mitral E wave deceleration time (DT) is a powerful independent predictor of functional capacity and prognosis (29). A shortened DT (less than 130 ms) identified a subgroup of patients with a worse outcome, especially when combined with a reduced peak VO₂ (less than 14 mL/kg/min). Patients with a DT of less than 130 ms had a significantly lower event-free survival than patients with a DT of greater than 130 ms. Patients with both a DT of less than 130 ms and a peak VO₂ less than 14 mL/kg/min had the highest rate of events at one year, with a relative risk of 3.75 (29). In another study (30) involving patients with advanced heart failure, DT was found to be predictive of survival and was an independent prognostic factor associated with a worse prognosis. Other factors that had a prognostic implication in these patients were ischemic origin of heart failure, 6 min walk distance and brain naturetic peptide levels. The presence of more than one of these factors was associated with bad prognosis (30).

A restrictive LV filling pattern (RFP) was found to be the strongest predictor of an adverse outcome independent of ejection fraction during follow-up after a first acute MI. An ejection fraction of 40% or less was an independent predictor of cardiac death and readmission to hospital with CHF (31). Patients with RFP had a lower admission-free survival rate than those without RFP; this was found irrespective of the presence or absence of severe systolic dysfunction. Hence, RFP has an independent prognostic value in patients with heart failure (32). Diastolic filling patterns, peak VO₂ and LV end-diastolic diameters were independent predictors of cardiac mortality. In patients with a peak VO₂ of 14 mL/min/kg or less, the outcome was markedly poorer in the presence of RFP compared with their absence (two-year survival rate 52% versus 80%, respectively). Similarly, despite peak VO₂ levels greater than 14 mL/min/kg, the outcome was less favourable in the presence of RFP (two-year survival rate 80% versus 94%) (33). A short DT, an RFP and fusion of mitral E and A waves were associated with a poor clinical outcome. The prognostic value of these Doppler variables was greater than that of ejection fraction (34).

The index of myocardial performance relates to the global ventricular performance by incorporating systolic and diastolic time intervals (35). This index, defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time, was significantly higher in patients with DCM than normal subjects (36). It was also significantly higher in patients who developed CHF or died than in survivors who were free of CHF after an acute MI. The Doppler index reflects the severity of LV function and has an incremental prognostic value in patients with acute MI. An index of 0.60 or less and deceleration time of 140 ms or less were independent predictors of outcome (37). The Doppler index can also be used to assess the RV performance (38).

Pulmonary vein Doppler flow velocity patterns also predict outcome in patients with CHF (Table 1). A significant relationship has been reported between profiles of pulmonary venous flow and LA pressure. The pattern of systolic and diastolic pulmonary venous flow velocities depends on the compliance of both the LV and LA. It has been shown that the pattern of systolic and diastolic pulmonary vein Doppler flow velocities accurately reflect LV compliance. There are two systolic velocities (PVs1 and PVs2), diastolic velocity and an atrial flow reversal. PVs1 occurs due to atrial relaxation decreasing the LA pressure and occurs in early systole. PVs2 is due to an increase in pulmonary venous pressure causing the second systolic flow into the LA in mid- to late systole. Atrial flow reversal occurs due to atrial contraction, allowing blood to flow back into pulmonary veins. Transthoracic echocardiograms often provide a good profile of the LA filling pattern. However, if more than one pulmonary vein had to be studied to increase the accuracy, these flow indexes could be better assessed by transesophageal echocardiography (39).

There is evidence suggesting a significant role of LV diastolic function in ventricular remodelling. For example, the preload and afterload contribute to systolic and diastolic failure. Heart rate and hemodynamic steady-state situation may also play significant roles in the development of CHF.

The contribution of stress echocardiogram, tissue Doppler imaging (TDI), and biventricular pacing under echocardiogram/TDI can contribute to inter- and intraventricular resynchronization followed by subsequent clinical improvement in adults versus children. TDI plays important role in the analysis of regional myocardial function including segmental contractility, segmental synchrony and time delay measurements. It is apparent that TDI represents a new milestone in noninvasive assessment of myocardial function in CHF.

Pulmonary artery pressure

A noninvasive assessment of pulmonary hypertension using a continuous-wave Doppler of tricuspid regurgitation (TR) predicts morbidity and mortality in patients with ischemic or idiopathic DCM. Overall mortality due to myocardial failure and hospitalization for CHF were higher in patients with a high velocity of TR (greater than 2.5 m/s) compared with those with low velocity (40). The peak velocity of TR was the strongest prognostic variable in this group of patients for mortality and hospitalization with heart failure (40). Pulmonary artery pressure (PAP) and thermodilution-derived RV ejection fraction were inversely related and both of these parameters were independent prognostic predictors for survival (41). It was found that RV ejection fraction was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure (41).

Valvular dysfunction

CHF is a chronic, progressive disease and its central element is remodelling of the cardiac chamber associated with ventricular dilation. Secondary mitral regurgitation (MR) is a complication of end-stage cardiomyopathy and is associated with poor prognosis. As discussed earlier, RFP is a powerful independent predictor of mortality in patients with nonischemic cardiomyopathy. However, the risk associated with RFP is greatest among patients who have MR (42). Mitral valve surgery for severe MR in patients with end-stage heart failure improves both their symptoms and prognosis. Also, current methods of percutaneous mitral valve repair are promising in patients with DCM and severe MR. Heart failure secondary to acute MR in MI often needs urgent surgical intervention and carries a poor prognosis.

The severity of TR is seldom described as an important predictor of mortality in patients with DCM. In a small study (43), there was suggestion that presence of TR along with LV end-diastolic dimension, NYHA functional class and systolic blood pressure predicted mortality due to sudden death and refractory heart failure. As discussed above, the presence of significant pulmonary hypertension, as assessed by the TR velocity jet, is an important prognostic predictor.

LV aneurysm

Presence of LV aneurysm in symptomatic patients with heart failure leads to more complications and poorer prognosis if untreated. Factors influencing prognosis in these patients are the extent of the aneurysm, the association of asynergic segments, the ejection fraction of the residual ventricle, the LV end-diastolic pressure and the presence of ventricular extrasystoles at the time of diagnosis. The mere presence of aneurysm is not, in itself, an indication for operation. Incapacitating angina and refractory CHF are the most valuable indications for surgical resection. Arrhythmias and CHF dominate the causes of death. The survival rate is only 46.3% in those who were symptomatic at the time of the initial diagnosis (44) (Table 2).

TABLE 2.

Echocardiogram parameters that have prognostic implication and also predict cardiac events in heart failure patients

Two-dimensional echocardiography	Doppler echocardiography	Colour Doppler
LV dimension >7.5 cm	Mitral E wave DT <130 ms	Severe MR
LVEF <30%	Mitral E/A ratio >2	Severe TR
RV dilation	IVRT <70
LA dilation	PVs2<<PVd
Four-chamber dilation	Mitral A duration <PVa duration
LV aneurysm	Elevated PA pressure

DT Deceleration time; E/A ratio Ratio of mitral inflow E to A wave Doppler velocities; IVRT Isovolumetric relaxation time; LA Left atrial; LV Left ventricular; LVEF Left ventricular ejection fraction; MR Mitral regurgitation; PA Pulmonary artery; PVa Atrial flow reversal; PVd Diastolic velocity; PVs2 Systolic velocity; RV Right ventricular; TR Tricuspid regurgitation

SUMMARY

Echocardiography can be used to assess the determinants of prognosis in patients with heart failure. It is an easily available tool to assess LVEF, size and shape, LA and PAP and size and function of right atrium and RV. The availability of continuous-wave Doppler has permitted the evaluation pulmonary artery systolic pressure from TR which provides additional information. In long-standing heart failure, pulmonary artery wedge pressure is a predictor of survival, and aggressive therapy to reduce wedge pressure improves survival. Noninvasive estimation of LA pressure and LV filling pressure has been attempted by continuous-wave Doppler echocardiography in patients with heart failure and MR and by tissue Doppler imaging at the mitral annulus level. Two-dimensional echocardiographic evaluation of ventricular size and function and pulsed- and continuous-wave Doppler recordings from the pulmonary artery, pulmonary vein and mitral inflow are combined to provide these data. These are both qualitative and quantitative, and permit the estimation of ventricular ejection fraction, LA pressure and cardiac output. It would be important to risk-stratify patients with CHF based on their noninvasive testing results so that appropriate therapies could be targeted to high risk patients.