Systolic and Diastolic Left Ventricular Dysfunction: From Risk Factors to Overt Heart Failure

Tatiana Kuznetsova; Lieven Herbots; Yu Jin; Katarzyna Stolarz-Skrzypek; Jan A Staessen


Expert Rev Cardiovasc Ther. 2010;8(2):251-258. 

In This Article

LV Diastolic Dysfunction

Measurements of Diastolic Function

Diastolic dysfunction refers to a condition in which abnormalities in LV function are present during diastole. The gold standard for assessing diastolic function remains the LV pressure–volume relationship, but this requires an invasive approach. Conventional echocardiography together with Doppler measurements of transmitral and pulmonary veins flows, and the TDI mitral annular velocities created the possibility of noninvasively evaluating diastolic function and filling properties.[6] However, these techniques are complex and no single measurement on its own reflects diastolic function. Thus, a comprehensive assessment of a number of variables is required to evaluate diastolic function as correctly as possible.[7]

Slowing and prolongation of LV relaxation becomes apparent at an early stage of LV diastolic dysfunction, because this part of the cardiac cycle is metabolically demanding. Impaired myocardial relaxation is characterized by decreased early, but enhanced atrial LV filling as well as less vigorous mitral annulus motion during early diastole compared to late diastolic motion. Thus, lower transmitral ratio of peak early filling (E) to peak atrial filling (A) and lower mitral annular early:late diastolic (E':A') velocity ratios along with the prolongation of isovolumetric relaxation time might reflect impaired myocardial relaxation. Studies in the general population demonstrated that LV relaxation, as reflected by these indices, substantially decreased with age, not only in the whole study sample, but also in a selected healthy reference population (Figure 1).[8,9] Current guidelines propose criteria to diagnose diastolic dysfunction that are not standardized for age.[1,6] It is likely that by ignoring age and by applying the same threshold values for the Doppler indexes throughout the age range, one may underestimate the prevalence of subclinical diastolic dysfunction (impaired relaxation), especially in young subjects with risk factors such as hypertension, obesity and diabetes (Figure 2A & B).

Figure 1.

Age-specific percentiles of the (A) E:A and (B) E:E' for the healthy reference sample (n = 239).
A: Atrial mitral inflow; E: Early mitral inflow; E': Early diastolic annular velocity.
Data from [9].

Figure 2.

Examples of different patterns of diastolic function as assessed by transmitral Doppler and mitral annular tissue Doppler imaging velocities. (A) 61-year-old women with a normal age-specific transmitral E:A ratio (from 2.5th to 97.5th percentiles of the reference subgroup, Figure 1) and without evidence of increased LV filling pressures (E:E' = 7.4). (B) 60-year-old man with an abnormally low age-specific transmitral E:A ratio (0.62) indicative of impaired relaxation (<2.5th percentile of the reference subgroup), but without evidence of increased LV filling pressures (E:E' = 7.5). (C) 68-year-old women who had moderately elevated end-diastolic filling pressure (E:E' = 16.7), but E:A ratio within the normal age-specific range (from 2.5th to 97.5th percentiles of the reference subgroup). (D) 54-year-old women with an elevated E:E' ratio (15.2) and an abnormally low age-specific E:A (0.70).
A: Atrial mitral inflow; A': Late diastolic annular velocity; E: Early mitral inflow; E': Early diastolic annular velocity; LV: Left ventricular; TDI: Tissue Doppler imaging.
Data from [9].

The Doppler blood flow measurements and the TDI mitral annulus velocities can reflect abnormal LV relaxation as well as elevated LV filling pressure, another feature of LV diastolic dysfunction. Combining transmitral flow velocity with annular velocity (E:E' ratio) might be a tool for estimating LV filling pressure (Figure 2C).[10,11] In our population study, the 97.5th percentile of E:E' ratio in the healthy reference subgroup was 8.4.[9] In previous invasive studies, an E:E' under 8 and E:E' over 15 accurately indicated normal and elevated LV end-diastolic filling pressure, respectively.[10] However, the majority of patients with elevated LV end-diastolic filling pressure in the presence of normal EF (>50%), as invasively determined in several previous studies from pressure-volume loops, had an E:E' ratio between 8 and 15.[10,12] Ommen et al. suggested that an accurate prediction of LV filling pressures for an individual patient requires further characterization of the intermediate E:E' group, for instance by measurement of blood flow in the pulmonary vein and left atrial (LA) volume.[10]

Left atrial enlargement reflects chronic exposure to increased LV filling pressure, and it may serve as an integrative, easily obtainable measure of diastolic dysfunction.[13] Molecular mechanisms responsible for LA wall remodeling in patients with/or at risk of HF have not yet been examined. The loss of LA mechanical function, as for instance occurs with the onset of atrial fibrillation, frequently triggers cardiac decompensation. Studies examining atrial function in patients with symptomatic diastolic HF recently confirmed the presence of reduced LA systolic function, particularly under stress conditions.[14]

Prevalence & Determinants of Diastolic Dysfunction in a General Population

Presently, only a few population studies have described the prevalence of preclinical LV diastolic dysfunction using the new TDI indices along with classical pulsed-wave Doppler velocities.[9,15,16] These studies applied a comprehensive Doppler analysis to grade LV diastolic dysfunction in older adults (aged 60–86 years),[15] in subjects aged 45 years or older,[16] or in the general population (aged 17–89 years).[9] The reported prevalence of diastolic dysfunction in these studies varied from 27.3 to 34.7%, and was influenced by a number of factors, including the characteristics of the population studied, and the criteria applied to diagnose LV diastolic dysfunction.[9,15,16] The prevalence of diastolic dysfunction increased with age (Figure 3) & (Table 1), but depended on applied arbitrary cut-off levels. Moreover, the risk of diastolic dysfunction increased significantly and independently with higher BMI, heart rate, systolic blood pressure, serum insulin and creatinine (Figure 3).[9] Women were more at risk than men (Figure 3). In a cross-sectional study of participants of the Flemish Study on Environment Genes and Health Outcomes (FLEMENGHO), approximately 50% of hypertensive subjects had impairment of LV diastolic function, whereas only 12% of normotensive subjects could be classified as having abnormalities of LV diastolic function.[9]

Figure 3.

Association between diastolic dysfunction, and clinical and biochemical characteristics. Squares and horizontal lines represent the odds ratios and 95% confidence intervals for the mutually adjusted covariates, identified by stepwise regression.
NT-ProBNP: N-terminal pro-brain natriuretic peptide; OR: Odds ratio; SBP: Systolic blood pressure.
Data from [9].

Prognostic Significance of LV Diastolic Dysfunction

Recent clinical and community-based studies explored the prognostic role of classical Doppler and the new TDI-derived indices. Transmitral E:A ratio and mitral annular E' velocity as well as E:E' ratio had an independent prognostic value in patients with overt HF,[17,18] hypertension[19] or myocardial infarction.[20] Population-based studies are essential to investigate the natural history of subclinical diastolic LV dysfunction and to determine its prognostic significance.

The Olmsted study described the predictive significance of preclinical LV diastolic dysfunction, using the comprehensive approach of combining new TDI indexes along with classical transmitral Doppler velocities.[16] In multivariable-adjusted analyses while controlling for age, sex and EF, mild diastolic dysfunction (hazard ratio: 8.31; p < 0.001) and moderate or severe diastolic dysfunction (hazard ratio: 10.17; p < 0.001) predicted all-cause mortality. However, in this study, the authors did not adjust the models for other important cardiovascular risk factors, such as systolic blood pressure, BMI, serum creatinine and total cholesterol. The Copenhagen City Heart Study explored the isolated prognostic impact of the new TDI indices such as E' and A' velocities, and the E':A' and E:E' ratios.[21] In 1036 participants enrolled in the study, low systolic (S') and A' velocities derived from color Doppler imaging and averaged from 16 myocardial segments independently predicted total mortality.[22] The authors did not report transmitral velocities and did not explore whether the new TDI indexes captured prognostic information over and beyond classical Doppler measurements of diastolic function.