Navtej Chahal

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.

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.

Radiation-induced carotid artery atherosclerosis

PURPOSE Carotid arteries frequently receive significant doses of radiation as collateral structures in the treatment of malignant diseases. Vascular injury following treatment may result in carotid artery stenosis (CAS) and increased risk of stroke and transient ischaemic attack (TIA). This systematic review examines the effect of radiotherapy (RT) on the carotid arteries, looking at the incidence of stroke in patients receiving neck radiotherapy. In addition, we consider possible surrogate endpoints such as CAS and carotid intima-medial thickness (CIMT) and summarise the evidence for radiation-induced carotid atherosclerosis. MATERIALS AND METHODS From 853 references, 34 articles met the criteria for inclusion in this systematic review. These papers described 9 studies investigating the incidence of stroke/TIA in irradiated patients, 11 looking at CAS, and 14 examining CIMT. RESULTS The majority of studies utilised suboptimally-matched controls for each endpoint. The relative risk of stroke in irradiated patients ranged from 1.12 in patients with breast cancer to 5.6 in patients treated for head and neck cancer. The prevalence of CAS was increased by 16-55%, with the more modest increase seen in a study using matched controls. CIMT was increased in irradiated carotid arteries by 18-40%. Only two matched-control studies demonstrated a significant increase in CIMT of 36% and 22% (p=0.003 and <0.001, respectively). Early prospective data demonstrated a significant increase in CIMT in irradiated arteries at 1 and 2 years after RT (p<0.001 and <0.01, respectively). CONCLUSIONS The incidence of stroke was significantly increased in patients receiving RT to the neck. There was a consistent difference in CAS and CIMT between irradiated and unirradiated carotid arteries. Future studies should optimise control groups.

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.

Clinical features of radiation-induced carotid atherosclerosis.

Carotid arteries frequently receive significant incidental doses of radiation during the treatment of malignant diseases, including head and neck cancer, breast cancer and lymphoma. Vascular injury after treatment may result in carotid artery stenosis and increased risk of neurological sequelae, such as stroke and transient ischaemic attack. The long latent interval from treatment to the development of clinical complications makes investigation of this process difficult, particularly in regard to the design of interventional clinical studies. Nevertheless, there is compelling clinical evidence that radiation contributes to carotid atherosclerosis. This overview examines the effect of radiotherapy on the carotid arteries, the underlying pathological processes and their clinical manifestations. The use of serum biomarkers in risk-prediction models and the potential value of new imaging techniques as tools for defining earlier surrogate end points will also be discussed.

Clinical Applications of Left Ventricular Opacification

The significant advances made in ultrasound microbubble technology now permits reliable, reproducible left ventricular opacification, and this review reiterates the evidence that has shown contrast echocardiography to be clinically effective, to reduce downstream costs and to spare patients further, potentially hazardous investigations. Despite the evidence and the advances, there remains ambivalence towards the administration of contrast agents in echocardiography laboratories throughout the world, particularly in the performance of rest studies. Therefore, this review also addresses some of the reasons for the suboptimal uptake of contrast agents and encourages physicians, sonographers, and accreditatory bodies to adopt a different approach towards the difficult-to-image patient.

Safety of contrast in stress echocardiography in stable patients and in patients with suspected acute coronary syndrome but negative 12-hour troponin.

Limited studies are available demonstrating the safety of contrast agents in patients undergoing stress echocardiography and none in patients with suspected acute coronary syndrome (ACS). Therefore, we sought to assess the safety profile of contrast agents in patients with stable chest pain and in those with suspected ACS (nondiagnostic electrocardiogram and negative initial 12-hour cardiac troponin test results). During a 4-year period, 3,704 patients underwent stress echocardiography (exercise or dobutamine), of whom, 929 (25%) had suspected ACS. Contrast agents (SonoVue 46%, Luminity 54%) were used in 1,150 patients (31%). No patients died with or without contrast administration. No nonfatal acute myocardial infarction occurred in patients administered contrast agents compared with 3 cases of acute myocardial infarction in the noncontrast group (p = 0.24). Two cases of sustained ventricular tachycardia developed, one in each group (p = 0.98). Compared with those who did not receive contrast, patients in both the stable chest pain and the suspected ACS groups had a greater burden of cardiovascular risk factors. The left ventricular function at rest was significantly worse in the patients who received contrast than in those who did not in the suspected ACS group. Also, a greater ischemic burden was present in those receiving contrast than in those not receiving it in both the stable chest pain and the suspected ACS groups. In conclusion, despite the presence of greater risk features compared with patients undergoing unenhanced stress echocardiography, the administration of ultrasound contrast agents (SonoVue and Luminity) in those with stable chest pain and those with suspected ACS was not associated with excess adverse events.

Coronary flow reserve assessed by myocardial contrast echocardiography predicts mortality in patients with heart failure.

AIMS the aim of the study was to assess whether myocardial contrast echocardiography (MCE) can predict mortality in patients with heart failure. Myocardial viability, ischaemia, and coronary flow reserve (CFR) are predictors of mortality in patients with heart failure. MCE can assess myocardial viability, ischaemia, and CFR at the bedside. However, its prognostic value is unknown in patients with heart failure. METHODS AND RESULTS eighty-seven patients (age: 68 ± 10 years, 62% male) with heart failure [left ventricular ejection fraction (LVEF): 35% ± 13] underwent low-power intermittent MCE at rest and 2 min after dipyridamole infusion. Resting and stress perfusion score index were derived qualitatively. CFR (MBF at stress/MBF at rest) was calculated by a quantitative method. All patients underwent coronary arteriography. Patients were followed up for mortality. Of the 87 patients, 43 (49%) patients had coronary artery disease. There were 28 (32%) deaths during a mean follow-up of 4.1 ± 1.7 years. Type 2 diabetes [P = 0.02, hazard ratios (HR) 2.43, confidence interval (CI) 1.13-5.22] and CFR (P = 0.001, HR 0.15, CI 0.05-0.45) were independent predictors of mortality. A CFR ≤ 1.5 had a significantly (P < 0.0001) higher mortality of 49 vs. 10% in patients with CFR > 1.5 over the 4 year follow-up period. CONCLUSION CFR determined by MCE is a powerful predictor of mortality in patients with heart failure.

The Feasibility and Clinical Utility of Myocardial Contrast Echocardiography in Clinical Practice: Results from the Incorporation of Myocardial Perfusion Assessment into Clinical Testing with Stress Echocardiography Study

BACKGROUND This prospective study investigated whether the incorporation of myocardial contrast echocardiography (MCE) into a clinical stress echocardiography service reproduces the benefits of assessing myocardial perfusion proved previously in research studies. METHODS MCE was performed during physiologic and pharmacologic clinical stress echocardiographic studies, and the value of myocardial perfusion to the reporting echocardiologists was categorized as of benefit (subclassified as incremental benefit over wall motion [WM] or greater confidence with WM) or of no added benefit. The presence and extent of inducible ischemia by WM and myocardial perfusion were documented and correlated with angiographic results in patients who underwent cardiac catheterization. RESULTS In total, 220 patients underwent simultaneous MCE during stress echocardiography by eight different operators. Overall, MCE was of benefit in 193 patients (88%), providing incremental benefit over WM in 25% and greater confidence with WM evaluation in 62%. MCE provided no added benefit in 27 patients (12%). MCE detected significantly more cases of ischemia than WM in the left anterior descending coronary artery territory (65% vs 53%, P = .02) and detected a greater ischemic burden than WM on a per patient basis (median, 5 [interquartile range, 3-8] vs 4 [interquartile range, 2-7] segments; P < .001) and across all coronary territories. MCE correctly identified a greater proportion of patients with multivessel disease than WM (76% vs 56%, P = .02) and a greater ischemic burden in patients with multivessel disease (median, 7 [interquartile range, 4-9] vs 5 [interquartile range, 1-8] segments; P < .001). CONCLUSIONS This prospective study is the first to demonstrate that the excellent feasibility and diagnostic utility of MCE, which have been documented in the research arena, are reproducible in the clinical arena.