Myocardial function has been extensively studied in the context of congenital heart disease. The focus to date has been on systolic function due to its importance and ease of measurement. However, the heart also needs to be adequately filled in order to function optimally, and this aspect of cardiac function is relatively under-investigated. The difficulties (as with systolic function) come when attempting to measure the relaxation of the myocardium while negating any effect of pre- or afterload. This is a difficult task and has led to the development of several tools which track myocardial movement independently of the usual flow-based parameters; the latter are heavily influenced by loading conditions. This article will summarize the current assessment of diastolic function using echocardiography and cardiac magnetic resonance (CMR) imaging in the normal heart and in patients with congenital heart disease.

Diastole denotes the filling phase of the cardiac cycle. Filling is determined by myocardial relaxation as well as atrial contraction and atrial and ventricular compliance. Myocardial relaxation begins when the myofibrils return to an unstressed state and this precedes mitral valve (MV) opening (isovolumic relaxation). ATP is used to actively uncouple calcium from the contractile apparatus and return it to the sarcoplasmic reticulum. Active relaxation is only responsible for early diastolic filling, whereas compliance is important throughout filling and especially during atrial contraction.

The early part of diastole is active relaxation, which is an energy-consuming process. The latter part is due to compliance or stiffness of the ventricle. Isovolumic relaxation time (IVRT) can be measured by invasive catheterization measurements. The index used in its measurement is the time constant of isovolumic pressure decline (τ). In non-invasive measurement, IVRT is the closest measurement to assess this value. However, as with all indices of diastolic function, the loading conditions must be taken into account.

The stiffness of the myocardium also plays an important role in diastolic function. The mass of the left ventricular (LV) affects the stiffness as do the viscoelastic properties of the myocardium (cellular and extracellular components). Attempts are made to measure this increase in myocardial stiffness. However, the difficulty arises in the mechanism of measurement as well as the timing and nature of diastole. Flow-based measurements rely on a change in volume to occur, and so they are unable to quantify isovolumic relaxation as they assess only the last stage of diastole. There is also no universal measurement of diastole [equivalent to ejection fraction (EF) in systole] and torsion and dyssynchrony are difficult to quantify.

There are different grades of DD. Early (grade I/impaired relaxation) dysfunction is caused by a decrease in LV compliance, thereby leading to increased LV filling pressure. This delays atrial emptying and prolongs the E wave deceleration time (DT > 240 ms). Atrial contraction becomes more vigorous, reducing the E/A ratio to <0.9. Worsening LV DD leads to increased atrial pressure and a decrease in the pressure gradient between the LA and LV, thereby leading to a shortened DT. The E/A ratio increases (0.9–1.5), but the E/A profile may appear normal (grade II or pseudonormalization). However, the e′ velocity on tissue Doppler imaging (TDI) (see below) remains low, giving a clue to the underlying abnormality (18). In grade III dysfunction (restrictive), the E/A ratio is >2, DT <160 ms, and the inflow profile can be altered by the Valsalva maneuver. This works because LA pressure is reduced during the strain phase of the Valsalva maneuver, and this unmasks the underlying DD. In grade IV dysfunction, the abnormalities are fixed in the face of the Valsalva maneuver, as LA pressure is too elevated to respond to decreased preload (see Figure 2). The timing of onset of E and e′ waves is important. Normally, the e′ occurs at the onset of or before the E wave. If the LA pressure is elevated, the E wave may precede e′ (19, 20).

Magnetic resonance imaging can be used to assess diastolic function by the inflow of blood or the movement of myocardium in much the same way as echocardiography. A number of techniques exist which can help to evaluate diastolic function: gradient echo assesses functional dimensions; phase-contrast measures flow, and myocardial tagging measures regional dynamics (46). Flow measurements are more complete as they include the entire annulus, rather than a point as in echocardiography. Tissue phase mapping (TPM) can be used to measure myocardial velocities and obtain similar information to TDI. This process allows calculation of E/Ea ratio (E = MV inflow E wave and Ea = early myocardial relaxation on TPM).

It is also possible to evaluate tissue characteristics (47), including interstitial and replacement fibrosis using CMR. In a study of 50 patients, with reduced EF, late gadolinium enhancement (a technique which identifies replacement fibrosis) was correlated with a lower septal E/e′ ratio than patients without a scar (P = 0.05).

Measurement of dimensions and flow are evaluated similarly to echocardiographic measures, although volumes are more accurate. In tagging, the myocardium is labeled using selective saturation prepulses in specific myocardial regions perpendicular to the imaging plane. This allows strain and 3-D motion analysis (48).

Increased ventricular stiffness and a change in the microscopic structure of the myocardium are inevitable parts of aging. This, coupled with changes in vascular stiffness, may lead to increased vulnerability in certain groups to developing symptomatic HF (1). Traditional assessment of systolic heart function will not identify these patients. The increased stiffness of the myocardium is thought to be due to changes in the collagen content of the extracellular matrix and increased fibrosis (49). There are other changes including reduced phosphorylation of sarcomeric proteins (50) and changes in Titin (51), which may be of importance at a cellular level.

As with the left ventricle, the right ventricle can become stiff and restrictive due to hypertrophy. In Tetralogy of Fallot, the RV becomes a stiff conduit due to RV outflow tract obstruction, with poor diastolic function. This is evidenced by anterograde pulmonary flow with atrial contraction (end-diastolic forward flow in the PA). The presence of DD is a marker of poor short-term surgical outcome. In a study of 50 children with TOF (mean age 5.0 years), 24 had restrictive RV physiology as described. This correlated with lower E/A ratio and IVRT duration. DD also correlated with prolonged intensive care unit stay, longer duration of ionotropic support, and higher doses of diuretics. It was more commonly seen in patients after transannular patch repair (53). In a study of 112 patients, 50 were found to have a restrictive RV. This was associated with larger RV dimensions and RA dimensions, and increased LA length and LA indexed volume on echocardiography (54). There appeared to be a bigger effect on late filling than early filling of the LV and RV restriction appeared to affect LV filling and diastole (decreasing filling and increasing diastolic pressures). This may be due to mechanical effects of the RV on LV filling or increased fibrosis of the LV. Interestingly, children with restrictive RV have an increased RV volume, whereas adults have a reduced volume (55–57). After the initial period, restrictive RV physiology appears to be protective, with decreased duration of pulmonary regurgitation and better maximum oxygen uptake seen in patients with restriction (58).

The Fontan procedure suddenly offloads a previously volume-overloaded ventricle. There is evidence that even in patients with normal systolic function, diastolic function is impaired (59). This is correlated with the length of time since the Fontan operation and decreases over time. Both left and right systemic single ventricles appear to experience systolic and DD, although systemic right ventricular function is more depressed (60). This may be due to adverse remodeling of the right ventricle, which is being exposed to an abnormally high afterload. A study of 28 patients showed a significant correlation between LV filling pressures (measured by E/e′ ratio) and ventilatory efficiency (VE/VO₂ slope) (r = 0.93; P < 0.01) (61). This is interesting as parameters of CPET are correlated with hospitalization in Fontan patients (62).

In the presence of an ASD with normal pulmonary pressures, the left–right shunt results in reduced LV filling and SV, reduced tissue perfusion, fluid accumulation, increased RV volume, greater RV SV, and finally normalization of LV filling and SV (63). In a small study of patients (n = 18) undergoing percutaneous device closure of their ASD, there were no significant changes in TDI and Doppler M-mode indices of diastolic function after closure. However, E wave velocity and E/e′ ratio at the MV annulus did increase significantly, thereby suggesting they are more load-dependent parameters (64). In children with ASD, TDI velocities do not change immediately after device closure. There is also no indication of elevation of left heart filling pressures after device closure in children, suggesting that children are able to accept increased preload and preserve diastolic function (65). This has implications on timing of closure, suggesting that earlier closure is beneficial.

In a study of patients with aortic valve disease (8–39 years), those with aortic stenosis or mixed disease were found to have DD, which was related to the degree of left ventricular hypertrophy (LVH). E/e′ correlated with LV end-diastolic pressure on catheterization. DD was found in 37% of all patients in the study, consisting of 37% of those with AS and 47% of those with mixed valve disease (66). Increased chamber stiffness is related to an increased LV mass/EDV ratio. Patients with aortic stenosis have increased interstitial fibrosis, which is related to a worse prognosis (67) and is known to be related to increased chamber stiffness. Secondary pulmonary hypertension may occur due to DD (68).

Cardiac magnetic resonance has a role in functional assessment of the LV in patients with AS. It is also used in tissue characterization and can quantify the degree of interstitial fibrosis and replacement fibrosis (69). There is some evidence that the degree of fibrosis can predict surgical outcome (67).

An incompetent aortic valve increases the end-diastolic volume of the left ventricle. The LV remodels to cope with this extra volume and becomes more compliant, so that diastolic pressures remain normal. Over time, decompensation may occur, in which case diastolic pressures increase as the LV loses the ability to compensate further (70). This is due to increased myocyte cellular diameter and fibrous content of the myocardium (71).

In aortic regurgitation with normal diastolic function, MV inflow consists of predominant E wave filling and annular e′ is increased or normal due to increased LV SV. However, E/e′ is not increased and PA pressures are normal. With the onset of DD (DD), LV filling pressures are elevated on exercise initially and then at rest.

Mitral stenosis results in increased LV filling pressure and reduced LV filling due to the restriction of blood flow through the MV. Most patients have normal intrinsic systolic and diastolic myocardial function. Some studies have found DD using conductance catheters, which are independent of loading conditions and acutely reversed after balloon valvuloplasty (72). The mechanism for this is not clear and may be due to restriction of LV relaxation by an immobile and thickened MV.

In isolated MR, LV compliance usually decreases as it dilates to accommodate an increased volume (73). In acute MR, increased LV diastolic pressure is due to increased LV dilatation and a shift upward on the pressure–volume relationship. Chronic MR often leads to remodeling and LV dilatation, thereby retaining LV SV (74).

MR, in the absence of LV DD, will cause an increase in E/A ratio (>1) and increase in transmitral E velocity (75). The e′ velocity is also increased, and E/e′ is not indicative of filling pressures (76). However, A reversal wave velocity does relate to LV diastolic pressures independently of MR (77). The ratio of IVRT to T_E–e′ can also be used to assess diastolic function irrespective of MR (77).

Diastolic dysfunction is a characteristic of many types of congenital heart disease as well as of infancy and the aging heart. Thorough and thoughtful evaluation of diastolic function can help to explain symptoms and affect the treatment of patients with seemingly normal ventricular function. Ventricular function should be thought of as a combination of ventricular filling as well as systolic ejection so that the contribution of ventricular compliance to overall heart function is taken into account. Finally, loading conditions and effects of exertion should be taken into account during evaluation.

Literature search and writing initial draft: DP. Critical revision and editing: MB. Final draft: DP.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.