Tiong Keng Lim

Increased left atrial volume index is an independent predictor of raised serum natriuretic peptide in patients with suspected heart failure but normal left ventricular ejection fraction : Implication for diagnosis of diastolic heart failure

Left atrial volume index (LAVI) is increasingly recognised as a relatively load‐independent marker of left ventricular (LV) filling pressures. We assessed the capacity of LAVI to predict LV diastolic dysfunction in comparison with N‐terminal pro B‐type natriuretic peptide (NTproBNP) in patients with suspected heart failure and a normal ejection fraction (EF).

Normative reference values for the tissue Doppler imaging parameters of left ventricular function: a population-based study

OBJECTIVE Tissue Doppler imaging (TDI) is used routinely to quantify left ventricular function and filling pressure. However, there remains a lack of percentile-based normative reference values for these clinically important parameters. METHODS Four hundred and fifty-three healthy subjects aged 35-75 years were included for analysis from the London Life Sciences Prospective Population (LOLIPOP) study. Subjects were free of manifest cardiovascular disease, cardiovascular risk factors, and significant coronary artery disease as determined by electron-beam computed tomography. They underwent 2D and Doppler echocardiography for assessment of left heart structure and function. TDI was performed at the septal and lateral mitral annular sites enabling on-line derivation of myocardial systolic velocity (Sa), diastolic velocity (Ea), and the ratio of Ea to transmitral E-wave (E/Ea). RESULTS Reference ranges (5th and 95th percentile values) for septal, lateral, and average mitral annular Sa velocity, Ea velocity, and E/Ea ratio were derived for the whole cohort and for each of the four age groups (35-44, 45-54, 55-64, 65-75). Increasing age was associated with a significant attenuation in myocardial velocity when averaged from both the septal and lateral mitral annulus, exerting a greater influence upon average Ea velocity (P < 0.001) compared with average Sa velocity (P = 0.04). Average E/Ea ratio increased significantly with advancing age (P < 0.001). CONCLUSION The reference ranges presented for the TDI parameters of Sa velocity, Ea velocity, and E/Ea ratio will help to standardize the assessment of LV function by tissue Doppler echocardiography.

Ethnicity-related differences in left ventricular function, structure and geometry: a population study of UK Indian Asian and European white subjects

Objectives The authors studied healthy UK Indian Asian and European white subjects to assess whether functional, structural and geometrical properties of the left heart are intrinsically related to ethnicity. Background Quantitative assessment of cardiac function and structure is necessary to diagnose heart failure syndromes and is validated to refine risk prediction. A better understanding of the demographic factors that influence these variables is required. Methods 458 healthy subjects were recruited from the London Life Sciences Prospective Population (LOLIPOP) study. They underwent 2-D and tissue Doppler echocardiography for quantification of left ventricular (LV) function, LV volumes, left atrial volume index (LAVI), left ventricular mass index (LVMI) and relative wall thickness (RWT). Results Indian Asians had attenuated mitral annular systolic velocity (8.9 cm/s vs 9.5 cm/s, p<0.001), lower mitral annular early diastolic velocity (10.3 cm/s vs 11.0 cm/s, p<0.001) and higher E/Ea ratio (7.9 vs 7.0, p<0.001) compared to European white subjects. Although Indian Asians had significantly smaller left heart volumes and LVMI, they had a significantly higher RWT (0.37 vs 0.35, p<0.001). After adjustment for covariates, these ethnicity-related differences remained highly significant (p<0.001). Conclusion Compared to European white people, Indian Asians had attenuated longitudinal LV function, higher LV filling pressure and demonstrated a greater degree of concentric remodelling independent of other demographic and clinical parameters.

Effects of Left Bundle-Branch Block on Cardiac Structure, Function, Perfusion, and Perfusion Reserve Implications for Myocardial Contrast Echocardiography Versus Radionuclide Perfusion Imaging for the Detection of Coronary Artery Disease

Background— We aimed to investigate the cardiac effects of left bundle-branch block (LBBB) using myocardial contrast echocardiography (MCE) to ascertain the value of MCE for detecting coronary artery disease (CAD) and to uncover the mechanism that affects the accuracy of single-photon emission computed tomography (SPECT) in these patients. Methods and Results— Sixty-three symptomatic LBBB patients (group A), 10 left ventricular ejection fraction–matched control subjects without LBBB and no CAD (group B), and 10 normal control subjects (group C) underwent resting echocardiography. Rest and vasodilator MCE and SPECT were undertaken in LBBB patients. Septal (SW) and posterior wall (PW) thickness, thickening, quantitative myocardial blood flow (MBF), and MBF reserve were measured. SW/PW thickness and percentage thickening ratios were lower (P<0.01 and P<0.05, respectively) in group A compared with both groups B and C, but resting SW/PW MBF and MBF reserve ratios were similar in all 3 groups. MBF reserve but not MBF was reduced in groups A and B (2.2±0.7 versus 2.2±0.2; P=0.98) compared with group C (3.1±0.5; P<0.01). SW thickness was an independent predictor (P=0.006) of SPECT perfusion defects in LBBB patients without CAD. MCE (92%) had a sensitivity similar to SPECT (92%); however, the specificity of MCE (95%) was superior (P<0.0001) to SPECT (47%) for the detection of CAD. Conclusions— Despite asymmetrical reduction in SW thickness and function, MBF is preserved and MBF reserve is homogeneously reduced in LBBB patients with left ventricular systolic dysfunction. Because of partial volume effects, the accuracy of SPECT for detecting CAD was significantly compromised compared with MCE in this patient cohort.

Population-based reference values for 3D echocardiographic LV volumes and ejection fraction.

OBJECTIVES The purpose of this study was to define age-, sex-, and ethnicity-specific reference values for 3-dimensional echocardiographic (3DE) left ventricular (LV) volumes and LV ejection fraction (LVEF) in a large cohort of European white and Indian Asian subjects. BACKGROUND Transthoracic 3DE imaging is recommended for the routine evaluation of LV volumes and function. However, there remains a lack of population-based reference values for 3DE LV volumes and LVEF, hindering adoption of this technique into routine clinical practice. METHODS We identified subjects from the LOLIPOP (London Life Sciences Prospective Population) study who were free of clinical cardiovascular disease, hypertension, and type 2 diabetes. All subjects underwent transthoracic 2-dimensional and 3D echocardiography for quantification of LV end-systolic volume index, LV end-diastolic volume index, and LVEF. RESULTS 3DE image quality was satisfactory in 978 subjects (89%) for the purposes of LV volumetric analysis. Indexed 3DE LV volumes were significantly smaller in female compared with male subjects and in Indian Asians compared with European whites. Upper limit of normal (mean ± 2 SD) reference values for the LV end-systolic volume index and LV end-diastolic volume index for the 4 ethnicity-sex subgroups were, respectively, as follows: European white men, 29 ml/m(2) and 67 ml/m(2); Indian Asian men, 26 ml/m(2) and 59 ml/m(2); European white women, 24 ml/m(2) and 58 ml/m(2); Indian Asian women, 23 ml/m(2) and 55 ml/m(2), respectively. Compared with 3DE studies, 2-dimensional echocardiography underestimated the LV end-systolic volume index and LV end-diastolic volume index by an average of 2.0 ml/m(2) and 4.7 ml/m(2), respectively. LVEF was similar between in all 4 groups and between 2- and 3-dimensional techniques, with a lower cutoff of 52% for the whole cohort. CONCLUSIONS These reference values are based on the largest 3DE study performed to date that should facilitate the standardization of the technique and encourage its adoption for the routine assessment of LV volumes and LVEF in the clinical echocardiography laboratory. This study supports the application of ethnicity-specific reference values for indexed LV volumes.

Independent value of left atrial volume index for the prediction of mortality in patients with suspected heart failure referred from the community

Background: The left atrial volume index (LAVI) reflects left ventricular (LV) filling pressure and has been shown to predict outcome in various cardiovascular diseases. However, its value for the prediction of mortality in patients referred for suspected heart failure (HF) is unknown. Objective: To assess the value of LAVI for the prediction of mortality independently of clinical, electrocardiographic (ECG) and echocardiographic prognostic parameters in patients with suspected HF referred from the community. Methods: 356 (mean (SD) age 72 (13) years) patients with suspected HF referred from the community were followed up for mortality after undergoing clinical assessment, ECG and echocardiography, including Doppler, to assess LV filling. Results: Data were obtained for 335/356 (94%) patients (162 male, 173 female) over a mean (SD) follow-up period of 30 (10) months, during which 38 (11.3%) died. The univariate predictors for all-cause mortality were age, symptom of leg swelling, clinical signs of HF, abnormal ECG, LV ejection fraction, LAVI, LV end-systolic (LVESD) and diastolic dimension, septal wall thickness and the presence of other significant cardiac abnormalities. The only independent predictors of mortality were age (hazard ratio (HR) = 2.15, 95% CI 1.42 to 3.25, p<0.001), symptom of leg swelling (HR = 2.83, 95% CI 1.43 to 5.59, p = 0.005), LAVI (HR = 1.25, 95% CI 1.01 to 1.54, p = 0.04) and LVESD (HR = 1.32, 95% CI 1.02 to 1.70, p = 0.04). Conclusion: LAVI provided independent information over clinical and other echocardiographic variables for predicting mortality in patients with suspected HF referred from the community.

New insights into the relationship of left ventricular geometry and left ventricular mass with cardiac function: A population study of hypertensive subjects.

AIMS Remodelling of the left ventricle (LV) is associated with adverse cardiovascular events, but the mechanisms of these effects remain undefined. We investigated the relationship of LV mass and geometry to LV function in a large cohort of hypertensive subjects. METHODS AND RESULTS We studied 1074 hypertensive individuals without cardiovascular disease recruited from the London Life Sciences Prospective Population (LOLIPOP) study. All subjects underwent echocardiography for derivation of LV mass index (LVMI), measurement of transmitral filling pattern, and LV ejection fraction (EF). The tissue Doppler parameters of peak myocardial systolic velocity (Sa), diastolic velocity (Ea), and of LV filling pressure (E/Ea) were measured. Left ventricular function was correlated with degree of concentric remodelling, determined by relative wall thickness, and with LV geometric pattern. The presence of LV hypertrophy was independently associated with significantly worse systolic function, diastolic function, and higher LV filling pressure when compared with subjects with normal LV geometry or non-hypertrophic concentric remodelling. After adjustment for covariates including LVMI, peak Sa velocity and EF increased (P < 0.001), whereas peak Ea velocity decreased significantly (P < 0.001) with increasing degrees of concentric remodelling. CONCLUSION In hypertensives, hypertrophic remodelling is independently associated with impaired LV function and increased LV filling pressure. Increasing degrees of non-hypertrophic concentric remodelling are associated with attenuated diastolic function, but augmented systolic function, possibly representing an adaptive response to pressure overload physiology.

Cost Effectiveness of the B Type Natriuretic Peptide, Electrocardiography, and Portable Echocardiography for the Assessment of Patients from the Community with Suspected Heart Failure

To analyze the cost efficiency of guidelines proposed by the European Society of Cardiology for investigation of patients in the community with suspected heart failure (HF). The guidelines recommend electrocardiography (ECG) and/or measurement of N‐terminal pro B type natriuretic peptide (NTproBNP) prior to referral for echocardiography. Portable echocardiography is a new but validated technique for the evaluation of HF. Accordingly, 137 suspected HF patients (mean age 71±13 years) from the community underwent ECG and NTproBNP estimation prior to portable echocardiography. Cost effective analysis for ECG, NTproBNP, portable echocardiography and a combination of these; to define valvular heart disease, right ventricular dysfunction and left ventricular systolic and diastolic dysfunction were compared. The cost of abnormal NTproBNP followed by portable echocardiography, abnormal ECG followed by portable echocardiography and portable echocardiography alone for the detection per case of left ventricular systolic dysfunction were  €313,  €310, and  €296 respectively and that for detection per case of any of the aforementioned cardiac abnormalities were  €198,  €223, and  €170 respectively. Portable echocardiography alone for the assessment of suspected HF patients resulted in a cost reduction of up to  €1083 for the detection per case of cardiac abnormality. While a strategy where initial NTproBNP estimation is cost effective in detecting any causes of heart failure, portable echocardiography remains the most costeffective strategy to assess patients from the community with suspected heart failure.

Clinical benefits of contrast-enhanced echocardiography during rest and stress examinations

Despite the recent introduction of tissue harmonic imaging in echocardiography, 10-15% of patients have poor endocardial border definition. This may lead to erroneous assessment of regional and global left ventricular (LV) function or to further diagnostic imaging with another modality thus increasing the costs for the healthcare system. The recent development of second generation contrast echocardiography agents such as SonoVue has resulted in several studies showing the value of these agents to outline endocardium clearly, thereby improving assessment of LV function. The use of these contrast agents has also opened the possibility of automated and quantitative LV function assessment, making it more accurate and reproducible. Other major clinical uses of these contrast agents are evaluation of LV masses such as thrombus and tumors, and better definition of LV structure such as delineating LV aneurysm, pseudoaneurysm; and non-compaction of LV and apical cardiomyopathy. Furthermore, the use of these contrast agents during stress not only improved the assessment of wall motion but also made possible the evaluation of myocardial perfusion, thereby increasing diagnostic accuracy for the detection of coronary artery disease.

The Distinct Relationships of Carotid Plaque Disease and Carotid Intima-Media Thickness with Left Ventricular Function

BACKGROUND Subclinical carotid atherosclerosis has been associated with impaired left ventricular (LV) function and the development of heart failure. Whether impaired LV function is related primarily to increased intima-media thickness (IMT) or burden of plaque disease or both remains to be determined. METHODS A total of 2,279 subjects without clinical cardiovascular disease recruited from the London Life Sciences Prospective Population cohort study were studied. Carotid ultrasonography and transthoracic echocardiography were performed on all subjects. Carotid IMT and plaque scores were measured, and their relationships with LV volumes, LV ejection fraction, myocardial LV longitudinal function (Sa and Ea velocities), and LV filling pressure (E/Ea ratio) were assessed before and after adjustment for covariates. RESULTS Compared with those without carotid artery disease, subjects with either increased IMT and/or presence of plaque disease had identical Sa velocities (both 9.0 cm/sec), lower Ea velocities (8.7 vs 9.9 cm/sec, P < .001) and higher E/Ea ratios (8.4 vs 7.6, P < .001). After multiple linear regression analysis, increasing IMT remained independently related to reduced Ea velocity (P < .001) but not LV ejection fraction, Sa velocity, or E/Ea ratio. In a separate adjusted analysis, subjects with severe burdens of carotid plaque disease (more than five plaques) had reduced LV ejection fractions (β = -2.9; 95% confidence interval [CI], 1.0 to 4.8, P = .003), attenuated Sa velocities (β = -0.79; 95% CI, -1.2 to -0.3, P = .003), attenuated Ea velocities 2 (β = -0.79; 95% CI, -1.3 to -0.2, P = .007), and increased E/Ea ratios (β = 0.84; 95% CI, 0.2 to 1.5, P = .009) compared to individuals without carotid plaques. CONCLUSION These findings demonstrate that subclinical carotid plaque disease rather than IMT is more closely related to LV systolic function and LV filling pressure. These data support the application of carotid ultrasonography beyond cardiovascular disease risk prediction, while providing insight into potential mechanisms underlying the development of subclinical LV dysfunction.