REVIEW ARTICLE

https://doi.org/10.5005/jp-journals-10089-0098
Journal of Acute Care
Volume 2 | Issue 3 | Year 2023

Diastolic Function and Dysfunction: Echocardiography

Sucharitha Das¹, Ravi Naik²

^1,2Department of Critical Care Medicine, Narayana Hrudyalaya Institute of Medical Sciences, Bengaluru, Karnataka, India

Corresponding Author: Sucharita Das, Department of Critical Care Medicine, Narayana Hrudyalaya Institute of Medical Sciences, Bengaluru, Karnataka, India, Phone: +91 9972940386, e-mail: drsucharita.das@gmail.com

Received: 17 March 2023; Accepted: 04 December 2023; Published on: 19 February 2024

ABSTRACT

Cardiac failure is an increasingly prevalent community health issue that affects both developed and developing countries globally. The increasing incidence and prevalence of cardiac failure have been attributed to longer life expectancy and ongoing population aging. About 6.2 million adults in America aged 20 years and above were noted to have heart failure (HF) between 2013 and 2016, an increase from the 5.7 million cases between 2009 and 2012. The incidence of congestive cardiac failure (CCF) is estimated to be around 10 per 1,000 after 65 years of age, with 550,000 new cases reported annually. HF affects 14 million people in Europe and is thought to affect 20 million people on the Indian subcontinent.

Up to 40–50% of patients with CCF suffer from diastolic dysfunction; the systolic function is normal or almost normal. There is now a realization that cardiac performance depends not only on systolic factors of contractile force generation but also on how well the heart can relax and fill during diastole.

How to cite this article: Das S, Naik R. Diastolic Function and Dysfunction: Echocardiography. J Acute Care 2023;2(3):129–135.

Source of support: Nil

Conflict of interest: None

Keywords: Congestive heart failure, Diastole, Diastolic dysfunction, Heart failure

CARDIAC CYCLE AND PHYSIOLOGY OF DIASTOLE

The American Heart Association (AHA) and the National Institutes of Health (NIH) regularly release updated statistics related to heart disease, stroke, and cardiovascular risk factors. About 6.2 million adults in America aged 20 years and above were noted to have heart failure (HF) between 2013 and 2016, an increase from the 5.7 million cases between 2009 and 2012.¹The cardiac cycle comprises two distinct phases, namely systole and diastole. Systole is the capability of the ventricle to contract and eject, and diastole is the capability of the ventricle to relax and fill. During the cardiac cycle, diastole starts with the closure of the aortic valve and ends at the closure of the mitral valve. Diastole involves relaxation of the left ventricle (LV), which allows blood from the left atrium (LA) to enter the LV.

Traditionally, diastole is classified into four consecutive physiologic phases:

(1) Isovolumetric relaxation: from closing of the aortic valve to mitral valve opening; (2) early rapid filling: rapid filling of LV occurs; (3) diastasis: mid-diastolic period of low flow; and (4) late rapid filling: filling of LV is aided by atrial contraction (Fig. 1). The myocardium relaxes during diastole, but this action requires energy and results from the influx of calcium into the sarcoplasmic reticulum from the cytosol.

Fig. 1: The four physiologic phases of the cardiac cycle

During diastole, the LV fills with blood, leading to an increase in its preload without a noticeable increase in the chamber pressure. The LV’s capacity to withstand a broad range of blood volume without noticeably raising the filling pressure is a hallmark of LV during diastole.

The following are linked to myocardial relaxation during diastole: (1) calcium detachment from tropomyosin C; (2) release of cross-bridges and lysis of action-myosin tension bonds; (3) phosphorylation of phospholamban: sarcoplasmic reticulum adenosine triphosphatase (ATPase) pump activity is regulated by this myocyte protein, and phosphorylation of this protein accelerates calcium sequestration; (4) sodium/calcium exchange via secondary active transport; and (5) return of the sarcomere to its resting length. Sarcolemmal ATPases aid in the influx of calcium from the cytosol into the sarcoplasmic reticulum.

The diastolic function of the heart is critically important both for maintaining cardiac as well as pulmonary physiology. Diastole provides adequate LV filling (cardiac preload) in parallel with LV ejection (stroke volume) both at rest and during exertion.

Pulmonary function is also influenced by LV diastole. The LV, LA, pulmonary venous circulation, and pulmonary capillary circulation create nearly a “common chamber” during diastole. As a result of their continuity, these chambers impact one another. The pressure in the LV after the diastole [LV end-diastolic pressure (LVEDP)] is influenced by the end-diastolic LV volume and the diastolic distensibility of the LV. Therefore, it is easy to comprehend that, depending on the degree of rise in LVEDP, an increase in the LVEDP can also raise the pulmonary capillary pressure, which will result in dyspnea, pulmonary capillary edema, and limitations on exercise (Fig. 2).

Fig. 2: Schematic representation of LV in diastole; when the mitral valve opens, the LV and pulmonary circulation form a common chamber, continuous with the pulmonary capillary bed; the LVEDP determines the pulmonary capillary hydrostatic pressure and, hence, the quantum of pulmonary interstitial water; elevated LV end-diastolic pressure causes pulmonary congestion and explains the ease with which patients suffering from diastolic impairment develop dyspnea and pulmonary congestion

Chamber Stiffness

This is mathematically defined as the change in LV pressure for a given increment in LV volume at a particular instant or the first derivative of LV pressure by volume (dP/dV). Since there is a nonlinear, complex relation between LV pressure and volume, diastolic volume will affect stiffness. More recent research indicates that the LV P-V connection is sigmoid in shape, with a concave downward component on the left of the typical exponential rise, even though it was originally thought to be exponential in shape (concave upward).

Relaxation

At the end of systole, calcium reuptake causes myocardial relaxation, which lowers LV pressure (at a fixed volume). The calcium reuptake velocity and the LV volume determine the rate at which LV pressure decreases as the ventricle relaxes. The end-diastolic pressure curve sets a limit on the potential pressure drop, which decreases with decreasing volume. Since LV lengthening during relaxation further modifies the rate of calcium absorption, real relaxation can only be assessed during the isovolumic phase. Significantly, and especially during activity, LV relaxation is an ongoing process that has a major impact on the patient’s final diastolic pressure.

DOPPLER EVALUATION OF DIASTOLIC FUNCTION

A Practical Approach to Grade Diastolic Dysfunction

Based on the evaluation of four characteristics, patients with a normal LV ejection fraction (LVEF) may or may not have diastolic dysfunction (Fig. 3). These characteristics include (1) average E/e’ > 14; (2) LA volume index > 34 mL/m; (3) peak tricuspid regurgitation (TR) velocity of > 2.8 m/second; and (4) septal e’ < 7 or lateral e’ < 10 cm/second (Fig. 4). At least half of these variables should be normal (> 50% positive) for LV diastolic dysfunction (LVDD) to be ruled out; if half of the variables fall below the cutoff value, the study is considered indeterminate (50% positive). Figure 5 represents grading of diastolic dysfunction in subjects with reduced LVEF.

Figs 3A to D: Schematic representation of Doppler findings in diastolic dysfunction—panel A shows LV pressure and LAP during diastole; panel B shows transmitral Doppler LV inflow velocity; panel C shows pulmonary venous Doppler velocity profiles; panel D shows Doppler tissue velocity in different types of diastolic dysfunction; there are four different filling patterns; normal patterns of relaxation and filling (column 1 from left); impaired relaxation, or stage 1 mild diastolic dysfunction (column 2 from left); pseudonormal, or stage II moderate diastolic dysfunction (column 3 from left), and restrictive filling pattern, or stage III severe diastolic dysfunction (column 4 from left); patients with an impaired filling pattern have a reduced e1, a prolonged E deceleration or early diastolic filling, and an increased A; a pseudonormal filling pattern is denoted by an increased E wave in the face of a decreased e1 (this resembles normal diastolic function profile E/A if only mitral inflow pattern is taken into account, hence, called “pseudonormal”); a restrictive filling pattern is denoted by an even larger E-wave and even smaller e1, with a shortened IVRT and a decreased E DT; the presence of restrictive patterns predicts poor prognosis and an increased mortality rate; E, peak early diastolic flow velocity; A, peak late diastolic flow velocity caused by atrial contraction; IVRT, isovolumetric relaxation time; DT, E-wave diastolic declaration time; IVRT, isovolumic relaxation time; s’, myocardial velocity during systole; e’, myocardial velocity during early filling; and a’, myocardial velocity during filling produced by atrial contraction

Fig. 4: A practical approach to grading diastolic function/dysfunction in subjects with normal LVEF; LVEF, left ventricular ejection fraction; E/e’, ratio of early diastolic mitral inflow and early diastolic tissue Doppler velocity, TR, tricuspid regurgitation; LA, left atrium

Fig. 5: A practical approach to grading diastolic function/dysfunction in subjects with reduced LVEF; E/A, ratio of early and late mitral inflow velocity; LAP; left atrial pressure; CAD, coronary artery disease

Assessment of Diastolic Function: Transthoracic Echocardiography vs Transesophageal Echocardiography

Special Situations

The diastolic function assessment in hypertrophic obstructive cardiomyopathy is based on the following parameters (Table 1): (1) average E/e’ ratio (>14); (2) LA volume index (>34 mL/m); (3) pulmonary vein atrial reversal velocity (Ar-A duration of >30 milliseconds); and (4) peak velocity of TR jet by continuous wave Doppler (>2.8 m/second). These four variables can be used regardless of whether patients have mitral regurgitation (MR) or dynamic LV outflow obstruction; however, only the TR jet peak velocity and Ar-A duration will be considered valid in patients with severe MR.² Grade II diastolic dysfunction and high LAP are diagnosed if more than two parameters satisfy the cutoff values.

**Table 1:** Assessment of diastolic function by transthoracic echocardiography (TTE) vs transesophageal echocardiography (TEE)
Parameter	Abnormal value	TTE	TEE
Average E/e’ ratio	Average of >14 Septal of >15 Lateral of >13	Apical four-chamber: E-wave: (i) computational fluid dynamics (CFD) imaging for optimal alignment of PWD with blood flow; (ii) PWD sample volume (1–3 mm axial size) between mitral leaflet tips; (iii) use low wall filter setting (100–200 MHz) and low signal gain; optimal spectral waveforms should not display spikes or feathering	ME four-chamber: E-wave: pulsed-wave Doppler (PWD) sample volume (1–3 mm axial size) between mitral leaflet tips
		Apical four-chamber: e’: (i) PWD sample volume (usually 5–10 mm) at lateral or septal basal regions; use ultrasound system presets for wall filter and lowest signal gain; optimal spectral waveforms should be sharp (no signal spikes, feathering or ghosting)Analysis: E velocity divided by e’ velocity	ME four-chamber: e’: PWD sample volume (usually 5–10 mm) at lateral or septal basal regions
e’ velocity	Septal < 7 cm/second Lateral < 10 cm/second	Apical four-chamber view: PWD sample volume (usually 5–10 mm axial size) at lateral or septal basal regions; use ultrasound system presets for wall filter and lowest signal gain; optimal spectral waveforms should be sharp (no signal spikes, feathering or ghosting)	ME four-chamber view: PWD sample volume (usually 5–10 mm axial size) at lateral or septal basal regions; use ultrasound system presets for wall filter and lowest signal gain; optimal spectral waveforms should be sharp (no signal spikes, feathering or ghosting)
TR jet velocity	>2.8 m/second	Parasternal and apical four-chamber view with CFD to get the highest velocity aligned with CWD; adjust gain and contrast to display a complete spectral envelope (no signal spikes or feathering)	ME-RV inflow–outflow view or ME four-chamber view with CFD to get the highest velocity aligned with CWD; adjust gain and contrast to display a complete spectral envelope (no signal spikes or feathering)
LA volume	> 34 mL/m²	Apical four-chamber and two-chamber: acquire freeze frames (1–2 frames before MV opening). LA volume measured in dedicated views (length and transverse diameters maximized) Do not include LA appendage or pulmonary veins in tracings	Deep TG LAX or TG LAXD view
E/A	<0.8 or >2	Apical four-chamber view: PWD sample volume (usually 5–10 mm axial size) placed at the tips of mitral leaflets. Optimal spectral waveforms should be sharp (no signal spikes, feathering or ghosting)	ME four-chamber view: PWD sample volume (usually 5–10 mm axial size) at tips of mitral valve leaflets; optimal spectral waveforms should be sharp (no signal spikes, feathering or ghosting)
PVD		Apical four-chamber view: PWD sample volume (usually 5–10 mm axial size) placed within the pulmonary veins. Optimal spectral waveforms should be sharp (no signal spikes, feathering or ghosting)	ME two-chamber view: PWD sample volume (usually 5–10 mm axial size) placed within the pulmonary veins. Optimal spectral waveforms should be sharp (no signal spikes, feathering or ghosting)
Vp		Apical four-chamber view: obtain a color M-mode of the mitral inflow. Early diastolic propagation velocity is determined for the slope of the isovelocity contour	ME four-chamber view: obtain a color M-mode of the mitral inflow; early diastolic propagation velocity is determined for the slope of the isovelocity contour

Restrictive cardiomyopathy (RCM): When the disease is first diagnosed, patients typically exhibit grade I diastolic dysfunction, which worsens into grade II if the disease progresses. Grade III diastolic dysfunction may be seen in advanced RCM and is established by diminished septal and lateral e’ velocities (3–5 cm/second), E-wave deceleration time (DT) of <150 milliseconds, and isovolumic relaxation time (IVRT) of <50 milliseconds.

Patients with constrictive pericarditis exhibit’ annulus reversus’, which means that the septal e’ velocity will be higher than lateral e’ velocity. In constrictive pericarditis, the E/e’ ratio may give a wrong estimate of LV filling pressures.

Valve diseases:

Left ventricular (LV) diastolic function is difficult to evaluate in patients with mitral stenosis. IVRT, TE-e’, and peak velocity of mitral inflow at early and late diastole may be used in the estimation of approximate mean LV pressure. TE-e’, or the time interval from early mitral inflow velocity (E) and mitral annular early diastolic velocity (e’), can be used to assess filling pressures in mitral disease patients.³^,⁴
The Ar-A time interval and IVRT/TE-e’ ratio may help in the estimation and forecast of LV filling pressure and normal EF in mitral valve regurgitation. However, the E/e’ ratio should only be taken into consideration in those who have concurrent MR and low EF.
In cases of aortic stenosis, regardless of its severity, the same guidelines for patients with normal valvular function may be followed, except in those who have significant mitral annular calcification.
Premature mitral valve closure, diastolic MR, LA enlargement, average E/e’ ratio of >14, and TR peak velocity of >2.8 m/second are indicative of higher LV filling pressures in all individuals with severe aortic regurgitation.

Heart transplantation:

Following heart transplantation, patients with preserved EFs frequently exhibit a restrictive filling pattern. This is seen in normal LV diastolic function since heart transplants are typically sourced from young, healthy people.
It does not seem that any diastolic indicator may accurately forecast graft rejection. If pulmonary disease has been ruled out, pulmonary arterial systolic pressure estimated by using the TR jet may be used as an indirect measure of mean LA pressure (LAP).

Atrial fibrillation:

The peak velocity of the TR jet of >2.8 m/second suggests elevated LAP.
Mitral DT of <160 milliseconds is fairly accurate in predicting elevated LV diastolic pressure and may signify a poor prognosis in LV systolic dysfunction.
Additional Doppler measurements, such as IVRT < 65 msec, peak acceleration rate of mitral E velocity of >1900 cm/second, E/e’ ratio of >11.4, E/Vp ratio of >1.4, and DT of pulmonary venous diastolic velocity of <220 milliseconds can be used in patients with incomplete TR jet. Atrial fibrillation (AF) patients may benefit from knowing the fluctuation of mitral inflow velocities with the varying R-R intervals since patients with higher filling pressures exhibit less beat-by-beat variations.⁵^,⁶

Atrioventricular (AV) block:

Providing the mitral E and A velocities remain distinct from each other, the variables used to diagnose diastolic dysfunction and assess filling pressures in individuals with first-degree AV block probably hold true.
Mitral annular velocity and the E/e’ ratio are possibly unreliable in patients with left bundle branch block or who have had cardiac resynchronization therapy or RV pacing.
The only velocity that can be utilized to determine LV filling pressures, if mitral A velocity is the only parameter available, is the TR peak velocity (>2.8 m/second).

Novel Indices of Diastolic Dysfunction

The time constant of LV relaxation (t) significantly correlates with LV global longitudinal diastolic strain rate measurements made by speckle-tracking echocardiography early in diastole and during the isovolumic relaxation period. These variables, coupled with mitral E velocity, have been utilized to assess LV filling pressures and prognosticate multiple disease scenarios.
When assessing individuals with adequate LV volumes and EF but diastolic dysfunction, the peak untwisting rate timing can be useful. There is frequently a delayed peak in LV untwisting rate in the latter set of patients.
The mean wedge pressure and LA systolic strain have an inverse relationship. While promising, there are technological drawbacks, and prior experience is necessary.

Impact of Left Ventricular Diastolic Dysfunction in Critically Ill Patients

It is widely accepted that LVDD leads to poor prognosis in critically ill patients. Diastolic dysfunction was seen in 48% of patients with sepsis, severe sepsis, and septic shock, and it was found to be strongly linked with death in a meta-analysis of these patients.⁷ It is noteworthy that only 30% of cases had systolic dysfunction, and this condition was unrelated to death.

Another meta-analysis publication has suggested that LA volume index, mitral lateral e’, E/lateral e’, and Sequential Organ Failure Assessment score may reliably predict LVDD in septic shock patients and may lead to a higher rate of mortality in intensive care patients with sepsis and LVDD.⁸

Failure to Wean-off Mechanical Ventilation

Failure to liberate from mechanical ventilation (MV) may be linked to tachycardia, hypertension, and adrenergic stimulation, which in certain at-risk patients may result in diastolic dysfunction. The most potent independent predictor of spontaneous breathing trial failure in an observational study of patients weaning off of MV was found to be echocardiographic evidence of diastolic dysfunction.⁹ Later research confirmed this study’s findings, demonstrating that LV systolic dysfunction did not predict weaning failure, while LV diastolic failure did.¹⁰ Following liberation from MV, the patient will experience a shift from positive to negative pressure ventilation. This may lead to an increase in both LV preload and afterload and a risk of increased LV filling pressures, especially in those with LVDD.¹¹ Results of multiple studies confirm that abnormal TDI values (e’ velocity and E/e’ ratio) may predict failure of weaning from MV.¹²

The impact of LVDD on postoperative patients has also been explored, with most studies focusing on cardiac surgery, in whom LVDD shows poor outcomes.³^,¹³ Major vascular surgeries have also shown similar results.¹⁴^,¹⁵ In noncardiac, nonvascular surgery, a study has shown that elevated E/e’ ratio may lead to postoperative cardiovascular complications (pulmonary edema and arrhythmias) and also lengthier stay in ICU and hospital.¹⁶

The diagnosis of LVDD is complex and seldom assessed in noncardiac, nonvascular surgical patients, but implementing artificial intelligence technologies may improve the quality and the quantity of data available for accurate diagnosis.¹⁷

CONCLUSION

Diastolic dysfunction is a common anomaly that is prevalent in older people, hypertensive patients, and diabetics. Evaluation of diastolic function is essential for a comprehensive understanding of cardiovascular physiology in the critically ill.

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