Tasneem Z. Naqvi

MANNHEIM CAROTID INTIMA-MEDIA THICKNESS AND PLAQUE CONSENSUS (2004–2006–2011)

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial

BACKGROUND Diastolic dysfunction might represent an important pathophysiological intermediate between hypertension and heart failure. Our aim was to determine whether inhibitors of the renin-angiotensin-aldosterone system, which can reduce ventricular hypertrophy and myocardial fibrosis, can improve diastolic function to a greater extent than can other antihypertensive agents. METHODS Patients with hypertension and evidence of diastolic dysfunction were randomly assigned to receive either the angiotensin receptor blocker valsartan (titrated to 320 mg once daily) or matched placebo. Patients in both groups also received concomitant antihypertensive agents that did not inhibit the renin-angiotensin system to reach targets of under 135 mm Hg systolic blood pressure and under 80 mm Hg diastolic blood pressure. The primary endpoint was change in diastolic relaxation velocity between baseline and 38 weeks as determined by tissue doppler imaging. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170924. FINDINGS 186 patients were randomly assigned to receive valsartan; 198 were randomly assigned to receive placebo. 43 patients were lost to follow-up or discontinued the assigned intervention. Over 38 weeks, there was a 12.8 (SD 17.2)/7.1 (9.9) mm Hg reduction in blood pressure in the valsartan group and a 9.7 (17.0)/5.5 (10.2) mm Hg reduction in the placebo group. The difference in blood pressure reduction between the two groups was not significant. Diastolic relaxation velocity increased by 0.60 (SD 1.4) cm/s from baseline in the valsartan group (p<0.0001) and 0.44 (1.4) cm/s from baseline in the placebo group (p<0.0001) by week 38. However, there was no significant difference in the change in diastolic relaxation velocity between the groups (p=0.29). INTERPRETATION Lowering blood pressure improves diastolic function irrespective of the type of antihypertensive agent used.

Carotid Intima-Media Thickness and Plaque in Cardiovascular Risk Assessment

Carotid intima-media thickness (CIMT) has been shown to predict cardiovascular (CV) risk in multiple large studies. Careful evaluation of CIMT studies reveals discrepancies in the comprehensiveness with which CIMT is assessed-the number of carotid segments evaluated (common carotid artery [CCA], internal carotid artery [ICA], or the carotid bulb), the type of measurements made (mean or maximum of single measurements, mean of the mean, or mean of the maximum for multiple measurements), the number of imaging angles used, whether plaques were included in the intima-media thickness (IMT) measurement, the report of adjusted or unadjusted models, risk association versus risk prediction, and the arbitrary cutoff points for CIMT and for plaque to predict risk. Measuring the far wall of the CCA was shown to be the least variable method for assessing IMT. However, meta-analyses suggest that CCA-IMT alone only minimally improves predictive power beyond traditional risk factors, whereas inclusion of the carotid bulb and ICA-IMT improves prediction of both cardiac risk and stroke risk. Carotid plaque appears to be a more powerful predictor of CV risk compared with CIMT alone. Quantitative measures of plaques such as plaque number, plaque thickness, plaque area, and 3-dimensional assessment of plaque volume appear to be progressively more sensitive in predicting CV risk than mere assessment of plaque presence. Limited data show that plaque characteristics including plaque vascularity may improve CV disease risk stratification further. IMT measurement at the CCA, carotid bulb, and ICA that allows inclusion of plaque in the IMT measurement or CCA-IMT measurement along with plaque assessment in all carotid segments is emerging as the focus of carotid artery ultrasound imaging for CV risk prediction.

Evidence that high-density lipoprotein cholesterol is an independent predictor of acute platelet-dependent thrombus formation

Plasma total and low-density lipoprotein (LDL) cholesterol are established risk factors for atherosclerotic vascular disease and may also contribute to a prothrombotic risk via enhanced platelet reactivity. This study examines whether high-density lipoprotein (HDL) cholesterol, which is inversely correlated with coronary artery disease, is associated with a reduced thrombogenic potential. Platelet thrombus formation was evaluated by exposing porcine aortic media placed in Badimon perfusion chambers to flowing nonanticoagulated venous blood for 5 minutes at a shear rate of 1,000 s(-1). Forty-five subjects, 23 normal (LDL 104 +/- 31, HDL 50 +/- 15 mg/dl) and 22 hypercholesterolemic (LDL 181 +/- 45, HDL 41 +/- 10 mg/dl) patients without coronary artery disease were studied. Platelet aggregation and CD62 antigen expression, and assay for circulating prothrombotic factors were also performed. In univariate analysis platelet thrombus formation correlated with weight (r = 0.33, p = 0.03), diastolic blood pressure (r = 0.39, p = 0.01), HDL cholesterol (r = -0.45, p = 0.003), total/HDL cholesterol (r = 0.43, p = 0.004) and LDL/HDL (r = 0.38, p = 0.01) ratios, and platelet CD62 expression (r = 0.41, p = 0.02). In multiple regression analysis only HDL cholesterol showed significant correlation with platelet thrombus formation (p = 0.03). Platelet aggregation and circulating prothrombotic factors did not correlate with platelet thrombus formation. A comparison between normal and hypercholesterolemic subjects revealed enhanced thrombus area (0.026 +/- 0.20 vs 0.045 +/- 0.039 mm2/mm; p = 0.04), resting CD62 expression (6 +/- 7% vs 15 +/- 10% positive platelets, p = 0.02), and platelet aggregation (16.7 +/- 5.2 vs 21.7 +/- 6.7 ohms, p = 0.04) in hypercholesterolemic subjects. Our results demonstrate that HDL cholesterol is a significant independent predictor of ex vivo platelet thrombus formation.

Myocardial contractile reserve on dobutamine echocardiography predicts late spontaneous improvement in cardiac function in patients with recent onset idiopathic dilated cardiomyopathy.

OBJECTIVES The purpose of this study was to determine whether identification of contractile reserve with dobutamine would predict recovery of myocardial function during follow-up in patients with recent onset idiopathic dilated cardiomyopathy (IDC). BACKGROUND The prognosis of patients presenting with new onset IDC is variable and difficult to predict. METHODS Twenty-two patients (17 men, 5 women, 46 +/- 14 years) with recently diagnosed IDC (4 +/- 3 months) underwent dobutamine echocardiography. Left ventricular ejection fraction (LVEF) and LV sphericity before and at peak dobutamine infusion (30 +/- 11 microg/kg/min) were determined. A follow-up echocardiographic assessment was done at 6 +/- 4 months. RESULTS The LVEF on dobutamine was directly related to baseline LV mass expressed as g/ml (Pearson r = 0.65, p = 0.0003). Baseline variables that were significantly predictive of follow-up LVEF were deceleration time (r = 0.69, p = 0.0006), wall motion score index (WMSI) (r = -0.63, p = 0.002), LV mass (r = 0.56, p = 0.008) and LVEF on dobutamine (r = 0.84, p = 0.0001). When either deceleration time or WMSI or LV mass was entered into a regression equation to predict follow-up LVEF, the LVEF on dobutamine added significantly to predictive power. However, if LVEF on dobutamine was entered first, none of the other three variables added significantly to prediction. Baseline LV sphericity at end diastole (ED) (r = 0.13, p = 0.6) did not correlate with follow-up LV sphericity in ED, whereas LV sphericity in ED on dobutamine (ED [r = 0.70, p = 0.0004]) correlated with LV sphericity in ED on follow up. CONCLUSIONS This study demonstrates that dobutamine-induced improvement in baseline LVEF and LV sphericity identifies patients with IDC who exhibit substantial improvement in LV function and geometry over time.

Guidelines for noninvasive vascular laboratory testing: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology

Accompanying the rapid growth of interest in percutaneous vascular interventions, there has been increasing interest among cardiologists in performing noninvasive vascular testing using ultrasound. In an attempt to provide recommendations on the best practices in vascular laboratory testing, this report has been prepared by a writing group from the American Society of Echocardiography (ASE) and the Society for Vascular Medicine and Biology. The document summarizes principles integral to vascular duplex ultrasound--including color Doppler, spectral Doppler waveform analysis, power Doppler, and the use of contrast. Appropriate indications and interpretation of carotid artery, renal artery, abdominal aorta, and peripheral artery ultrasound imaging are described. A dedicated section summarizes noninvasive techniques for physiologic vascular testing of the lower extremity arteries--including measurement of segmental pressures and pulse volume plethysmography. The use of exercise testing in the evaluation of peripheral artery disease, ultrasound evaluation of the lower extremities after percutaneous revascularization, and the diagnosis and management of iatrogenic pseudoaneurysm (PSA) is also discussed. A section on the important topic of vascular laboratory accreditation is included. Finally, additional details regarding proper technique for performance of the various vascular tests and procedures are included in the Appendix.

Comparison of usefulness of dipyridamole stress myocardial contrast echocardiography to technetium-99m sestamibi single-photon emission computed tomography for detection of coronary artery disease (PB127 multicenter phase 2 trial results)

We hypothesized that assessment of hyperemic myocardial blood flow (MBF) velocity using myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD). We also postulated that only a single MCE study during stress is required for the detection of CAD in patients with normal function at rest. Patients with known or suspected CAD referred for dipyridamole stress technetium-99m sestamibi single-photon emission computed tomographic (SPECT) studies were enrolled. MCE was performed concurrently with SPECT using continuous infusions of PB127 during intermittent harmonic power Doppler imaging at multiple pulsing intervals. MCE and SPECT were compared in 43 of 54 patients who had adequate studies using both techniques. In 15 of the 43 patients, coronary angiography was performed within 30 days of the MCE/SPECT tests. Overall concordance for classification of patients as normal versus abnormal was 84% (kappa = 0.63) between the 2 tests. When false-negative SPECT scans were corrected for results of angiography, concordance increased to 93% (kappa = 0.82). For territorial analysis, concordance between MCE and SPECT for location of perfusion defects was 65% (kappa = 0.41) and 74% (kappa = 0.61) after SPECT was corrected by angiography. In patients with normal function at rest, a single stress MCE perfusion study allowed identification of CAD with the same concordance as rest/stress perfusion studies. In conclusion, visual assessment of regional differences in MBF velocity using PB127 allows detection of CAD with good concordance compared with technetium-99m sestamibi SPECT. In patients with normal left ventricular function at rest, a single stress PB127 MCE perfusion study is adequate for the detection of CAD.

Assessment of aortic stenosis by three-dimensional echocardiography: an accurate and novel approach

Background: Accurate assessment of aortic valve area (AVA) is important for clinical decision-making in patients with aortic valve stenosis (AS). The role of three-dimensional echocardiography (3D) in the quantitative assessment of AS has not been evaluated so far. Objectives: To evaluate the reproducibility and accuracy of real-time three-dimensional echocardiography (RT3D) and 3D-guided two-dimensional planimetry (3D/2D) for assessment of AS, and compare these results with those of standard echocardiography and cardiac catheterisation (Cath). Methods: AVA was estimated by transthoracic echo-Doppler (TTE) and by direct planimetry using transoesophageal echocardiography (TEE) as well as RT3D and 3D/2D. 15 patients underwent assessment of AS by Cath. Results: 33 patients with AS were studied (20 men, mean (SD) age 70 (14) years). Bland–Altman analysis showed good agreement and small absolute differences in AVA between all planimetric methods (RT3D vs 3D/2D: −0.01 (0.15) cm2; 3D/2D vs TEE: 0.05 (0.22) cm2; RT3D vs TEE: 0.06 (0.26) cm2). The agreement between AVA assessment by 2D–TTE and planimetry was −0.01 (0.20) cm2 for 3D/2D; 0.00 (0.15) cm2 for RT3D; and −0.05 (0.30) cm2 for TEE. Correlation coefficient r for AVA assessment between each of 3D/2D, RT3D, TEE planimetry and Cath was 0.81, 0.86 and 0.71, respectively. The intraobserver variability was similar for all methods, but interobserver variability was better for 3D techniques than for TEE (p<0.05). Conclusions: The 3D echo methods for planimetry of the AVA showed good agreement with the standard TEE technique and flow-derived methods. Compared with AV planimetry by TEE, both 3D methods were at least as good as TEE and had better reproducibility. 3D aortic valve planimetry is a novel non-invasive technique, which provides an accurate and reliable quantitative assessment of AS.

American society of echocardiography report. Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology.

Noninvasive measures of atherosclerosis have emerged as adjuncts to standard cardiovascular disease (CVD) risk factors in an attempt to refine risk stratification and the need for more aggressive preventive strategies. Two such approaches, carotid artery imaging and brachial artery reactivity testing (BART), are ultrasound based. Numerous carotid artery imaging protocols have been used, and methodologic aspects are described in detail in this review. The panel recommends that protocols: (1) use end-diastolic (minimum dimension) images for intimal-medial thickness (IMT) measurements; (2) provide separate categorization of plaque presence and IMT; (3) avoid use of a single upper limit of normal for IMT because the measure varies with age, sex, and race; and (4) incorporate lumen measurement, particularly when serial measurements are performed to account for changes in distending pressure. Protocols may vary in the number of segments wherein IMT is measured, whether near wall is measured in addition to far wall, and whether IMT measurements are derived from B-mode or M-mode images, depending on the application. BART is a technique that requires meticulous attention to patient preparation and methodologic detail. Its application is substantially more challenging than is carotid imaging and remains largely a research technique that is not readily translated into routine clinical practice.

Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age ≤65 years old

OBJECTIVES We examined the hypothesis that mitral annulus calcification (MAC), aortic valve sclerosis (AVS) and aortic root calcification (ARC) are associated with coronary artery disease (CAD) in subjects age < or =65 years. BACKGROUND Mitral annulus calcification, AVS and ARC frequently coexist and are associated with coronary risk factors and CAD in the elderly. METHODS We studied 338 subjects age < or =65 years who underwent evaluation of chest pain with myocardial perfusion single photon emission computed tomography (SPECT) and a two-dimensional transthoracic echocardiogram for other indications. The association of MAC, AVS and ARC with abnormal SPECT was evaluated by using chi-square analyses and logistic regression analyses. RESULTS Compared with no or one calcium deposit and no or one coronary risk factor other than diabetes, multiple (> or =2) calcium (or sclerosis) deposits with diabetes or multiple (> or =2) coronary risk factors were significantly associated with abnormal SPECT in women age < or =55 years old (odds ratio [OR], 20.00), in women age >55 years old (OR, 10.00) and in men age < or =55 years old (OR, 5.55). Multivariate analyses identified multiple calcium deposits as a significant predictor for an abnormal SPECT in women (p < 0.001), younger subjects age < or =55 years (p < 0.05) and the total group of subjects (p < 0.01). CONCLUSIONS When coronary risk factors are also taken into consideration, the presence of multiple calcium deposits in the mitral annulus, aortic valve or aortic root appears to be a marker of CAD in men < or =55 years old and women.