Gianpaolo Bezante

Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension

Increased urine albumin excretion is associated with an unfavourable cardiovascular risk profile and prognosis in primary hypertension, even though its pathogenesis is currently unknown. Microalbuminuria (Mi) has been proposed as an integrated marker to identify patients with subclinical organ damage, but its routine use is still too often neglected in clinical practice. The aim of our study was to evaluate the relationship between urinary albumin excretion and early signs of subclinical target organ damage (TOD), namely left ventricular hypertrophy and carotid atherosclerosis in a large group of non diabetic hypertensive patients. A group of 346 never treated patients with primary hypertension (212 men, 134 women, mean age 47 ± 9 years) referred to our clinic were included in the study. They underwent the following procedures: (1) family and personal medical history and physical examination; (2) clinical blood pressure measurement; (3) routine blood chemistry and urine analysis including determination of urinary albumin excretion (ACR); (4) electrocardiogram; (5) ultrasound evaluation of left ventricular mass (LVMI) and carotid artery thickness (IMT). The overall prevalence of Mi, left ventricular hypertrophy, and carotid plaque was 13, 51, and 24% respectively. Mi was significantly correlated with LVMI (P < 0.0001), IMT (P < 0.0001) and several metabolic and non-metabolic risk factors (blood pressure, body mass index, serum lipids). Cluster analysis identified three subgroups of patients who differ significantly with regards to TOD and albuminuria (P ⩽ 0.001 for each of the examined variables). Patients with higher IMT and LVMI values also showed increased ACR levels. Furthermore, patients with microalbuminuria were more likely to have both LVH and IMT values above the median for the study population (OR 21, C.I. 4.6–99.97, P < 0.0001). Mi is an integrated marker of subclinical organ damage in patients with primary hypertension. Evaluation of urinary albumin excretion is a specific, cost-effective way to identify patients at higher risk for whom additional preventive and therapeutic measures are advisable.

Enhanced left ventricular endocardial border delineation with an intravenous injection of SonoVue, a new echocardiographic contrast agent : A European multicenter study.

The safety and efficacy of SonoVue (also referred to as BR1), a new contrast agent for delineating endocardial border of the left ventricle after intravenous administration, was assessed. Two hundred and eighteen patients with suspected coronary artery disease undergoing fundamental echocardiography for the assessment of left ventricle were enrolled in a prospective multicenter, single blind, cross‐over study with random sequence allocation of four different doses of SonoVue. Endocardial border definition in the apical and parasternal views was scored as O = not visible, 1 = barely visible, and 2 = well visualized before and after contrast enhancement. Analysis was performed by two pairs of off‐site observers. Safety of SonoVue was also assessed. Results of our study indicated that the mean improvements in the endocardial border visualization score were as follows: 3.1 ± 7.8 (95% CI, 2.5 and 3.7) for 0.5 ml, 3.4 ± 8.0 (95% CI, 2.8 and 4.0) for 1 ml, 3.4 ± 7.9 (95% CI, 2.8 and 4.0) for 2 ml, and 3.7 ± 8.0 (95% CI, 3.1 and 4.3) for 4 ml (P < 0.05 for all doses from baseline). Changes from baseline in endocardial visualization scores were also seen in the apical views (P < 0.05) and they were dose‐dependent (P < 0.001). Similar enhancements of endocardial visualization scores were observed in the apical views in patients with suboptimal baseline echocardiographic images. Diagnostic confidence for assigning a score and image quality also were significantly better following contrast enhancement. No significant changes in the laboratory parameters and vital signs were noted following contrast enhancement, and the side effects were minimal. It was concluded that SonoVue is safe and effective in delineating endocardial border, including in patients with suboptimal baseline images.

Comparison of sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography with gated single-photon emission computed tomography for detection of significant coronary artery disease: a large European multicenter study

OBJECTIVES The purpose of this study was to compare sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography (MCE) with single-photon emission computed tomography (SPECT) relative to coronary angiography (CA) for assessment of coronary artery disease (CAD). BACKGROUND Small-scale studies have shown that myocardial perfusion assessed by SonoVue-enhanced MCE is a viable alternative to SPECT for CAD assessment. However, large multicenter studies are lacking. METHODS Patients referred for myocardial ischemia testing at 34 centers underwent rest/vasodilator SonoVue-enhanced flash-replenishment MCE, standard (99m)Tc-labeled electrocardiography-gated SPECT, and quantitative CA within 1 month. Myocardial ischemia assessments by 3 independent, blinded readers for MCE and 3 readers for SPECT were collapsed into 1 diagnosis per patient per technique and were compared to CA (reference standard) read by 1 independent blinded reader. RESULTS Of 628 enrolled patients who received SonoVue (71% males; mean age: 64 years; >1 cardiovascular [CV] risk factor in 99% of patients) 516 patients underwent all 3 examinations, of whom 161 (31.2%) had ≥70% stenosis (131 had single-vessel disease [SVD]; 30 had multivessel disease), and 310 (60.1%) had ≥50% stenosis. Higher sensitivity was obtained with MCE than with SPECT (75.2% vs. 49.1%, respectively; p < 0.0001), although specificity was lower (52.4% vs. 80.6%, respectively; p < 0.0001) for ≥70% stenosis. Similar findings were obtained for patients with ≥50% stenosis. Sensitivity levels for detection of SVD and proximal disease for ≥70% stenosis were higher for MCE (72.5% vs. 42.7%, respectively; p < 0.0001; 80% vs. 58%, respectively; p = 0.005, respectively). CONCLUSIONS SonoVue-enhanced MCE demonstrated superior sensitivity but lower specificity for detection of CAD compared to SPECT in a population with a high incidence of CV risk factors and intermediate-high prevalence of CAD. (A phase III study to compare SonoVue® enhanced myocardial echocardiography [MCE] to single photon emission computerized tomography [ECG-GATED SPECT], at rest and at peak of low-dose Dipyridamole stress test, in the assessment of significant coronary artery disease [CAD] in patients with suspect or known CAD using Coronary Angiography as Gold Standard-SonoVue MCE vs SPECT; EUCTR2007-003492-39-GR).

Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes

PurposeThe aim of this study was to validate a new method to measure regional myocardial perfusion reserve (MPR) with technetium-labelled tracers in patients with type 2 diabetes mellitus (DM2).MethodsA total of 40 consecutive DM2 patients without history of coronary artery disease (CAD) and 7 control subjects were recruited. Dipyridamole myocardial blood flow index (MBF) was assessed by measuring first transit counts in the pulmonary artery and myocardial count rate from gated SPECT images using 99mTc-labelled tracers. The corresponding MBF index was estimated 2 h later according to the same procedure. Regional myocardial perfusion reserve (MPR) was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular (LV) model. Coronary flow reserve (CFR) was estimated by transthoracic contrast echo Doppler monitoring of flow velocity in the left anterior descending coronary artery (LAD) during the same session.ResultsEstimated MPR was higher in control subjects than in patients (3.36 ± 0.66 vs 1.91 ± 0.61, respectively, p < 0.01). In patients, LAD CFR and LAD MPR were 2.01 ± 0.78 vs 1.93 ± 0.63, respectively (p = ns). The agreement between the two techniques was documented by their close correlation (r = 0.92, p < 0.001) and confirmed by the Bland-Altman analysis. Reversible perfusion defects occurred in 13 patients (32%) who showed similar MPR values as the remaining 27 (2.10 ± 0.71 vs 1.83 ± 0.71, respectively, p = ns). Finally, MPR was closely correlated with age (r = −0.50, p < 0.01) and time elapsed from the diagnosis of DM2 (r = −0.51, p < 0.01).ConclusionLV regional MPR can be accurately estimated with the broadly available single photon technology. Application of this method to DM2 patients documents the presence of a microvascular dysfunction homogeneously distributed throughout the LV walls and most frequently not associated with reversible perfusion defects.

Early Noninvasive Evaluation of Coronary Flow Reserve after Angioplasty in the Left Anterior Descending Coronary Artery Identifies Patients at High Risk of Restenosis at Follow-Up

BACKGROUND Coronary restenosis is the most important clinical limitation after percutaneous coronary intervention (PCI), and coronary flow reserve (CFR) is reduced in the presence of significant coronary stenosis. This study evaluated whether detection of early reduction of Doppler echocardiographically derived CFR in the left anterior descending coronary artery can identify patients at high risk for developing restenosis after successful PCI. METHODS Doppler echocardiographically derived CFR was studied in 124 consecutive patients at 1-month and 6-month follow-up after PCI in the left anterior descending coronary artery, together with coronary angiography. RESULTS Restenosis was detected in 39 angiographic examinations (group A) and no coronary restenosis in the remaining 85 (group B) at 6 months. At 1 month, CFR was reduced in group A compared with group B (P < .0001), and a significant reduction of CFR in group A (P < .0001) but not in group B (P = .89) was detected at 6 months. CFR ≤ 2.5 at 1 month was 67% sensitive and 87% specific for predicting significant restenosis, with positive and negative predictive values of 67% and 87%, respectively. CONCLUSIONS CFR ≤ 2.5 detected 1 month after PCI in the left anterior descending coronary artery has the potential to identify patients at higher risk for developing coronary restenosis and indicates the need for close clinical follow-up.

Metabolic syndrome is associated with left ventricular dilatation in primary hypertension

Metabolic syndrome (MS) has been shown to predict cardiovascular events in hypertension. Recently, a new four-group left ventricular (LV) hypertrophy classification based on both LV dilatation and concentricity was proposed. This classification has been shown to provide a more accurate prediction of cardiovascular events, suggesting that the presence of LV dilatation may add prognostic information. We investigated the relationship between MS and the new classification of LV geometry in patients with primary hypertension. A total of 372 untreated hypertensive patients were studied. Four different patterns of LV hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The overall prevalence of MS and LV hypertrophy (LVH) was 29% and 61%, respectively. Patients with MS showed a higher prevalence of LVH (P=0.0281) and dilated LV geometries, namely eccentric dilated and concentric dilated hypertrophy (P=0.0075). Moreover, patients with MS showed higher LV end-diastolic volume (P=0.0005) and prevalence of increased LV end-diastolic volume (P=0.0068). The prevalence of LV chamber dilatation increased progressively with the number of components of MS (P=0.0191). Logistic regression analysis showed that the presence of MS entails a three times higher risk of having LV chamber dilatation even after adjusting for several potential confounding factors. MS is associated with LV dilatation in hypertension. These findings may, in part, explain the unfavourable prognosis observed in patients with MS.

Diagnostic value of ischemia severity at myocardial perfusion imaging in elderly persons with suspected coronary disease.

Aims Myocardial perfusion and ischemia scores obtained from myocardial perfusion scintigraphy (MPS) have strong independent prognostic value in elderly individuals without known coronary artery disease (CAD). Herein we aimed to assess their independent diagnostic value and accuracy for CAD while considering different thresholds of myocardial ischemia. Methods We estimated the summed rest score (SRS), summed stress score (SSS) and summed difference score (SDS) in 322 elderly individuals (mean age 72 ± 7 years, 68% men) who underwent coronary angiography following an MPS. Abnormal perfusion at stress was defined as an SSS greater than 3, and ischemia as an SDS of at least 2, and further categorized as mild (2–4), moderate (5–7) or severe (>7). Multivariate logistic regressions were used to establish the independent diagnostic value and accuracy of MPS parameters. Results CAD was diagnosed in 182 individuals (56%). In multivariate analysis accounting for clinical variables associated with CAD including the Framingham risk score, both SRS [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.01–1.18, P = 0.03] and SSS (OR 1.10, 95% CI 1.04–1.16, P = 0.0006) and SDS (OR 1.12, 95% CI 1.04–1.21, P = 0.003) were independently associated with CAD. An SSS greater than 3 was also independently associated with CAD (OR 2.51, 95% CI 1.43–4.39, P = 0.0013), whereas an SDS of 2 or greater was not (OR 1.62, 95% CI 0.89–2.93, P = 0.12), but only when at least 5 (OR 2.31, 95% CI 1.32–4.03, P = 0.003). The probability of CAD was proportional to the amount of myocardial ischemia in those with an SSS greater than 3, and lower and comparable in those with an SSS of at least 3 or an SSS greater than 3 with SDS of 1 or less (P = 0.19). Increasing the threshold of myocardial ischemia determined a decrease in sensitivity and increase in specificity of MPS for both diagnosis and severity of CAD. Conclusion We established the diagnostic value and accuracy of continuous scores and thresholds of abnormal myocardial perfusion and ischemia previously validated in prognostic studies. Their more widespread use could potentially improve the diagnostic yield of coronary angiography in elderly individuals with suspected CAD.

K036 Left ventricular geometry and function in patients with essential hypertension and microalbuminuria

BACKGROUND Microalbuminuria has recently emerged as a strong, independent predictor of cardiovascular mortality in patients with essential hypertension, yet the pathophysiological mechanisms underlying this association remain to be elucidated. OBJECTIVE To study the relationship between microalbuminuria and left ventricular geometry and function and extra-cardiac vascular changes in a group of 211 untreated hypertensive patients. METHODS Albuminuria was evaluated as albumin-to-creatinine ratio in three non-consecutive first morning urine samples. Left ventricular mass index and function were assessed by M-B mode echocardiography and carotid wall thickness by high-resolution ultrasound scan. RESULTS The prevalences of microalbuminuria and left ventricular hypertrophy were 14 and 47% respectively. Patients in the top quartile of albuminuria showed a higher left ventricular mass index (57 +/- 1.8, 55 +/- 2, 47 +/- 1.4 and 48 +/- 1.6 g/m2.7, respectively; P< 0.0001) as well as a higher prevalence of left ventricular hypertrophy (72, 65, 26 and 25%, respectively; P< 0.001) and especially concentric hypertrophy (56, 47, 17 and 21%, respectively; P< 0.0001) in the four quartiles of albuminuria. Microalbuminuric patients showed depressed left ventricular performance as indicated by a reduced midwall fractional shortening (15.7 +/- 0.3, 15.9 +/- 0.3, 16.7 +/- 0.4 and 16.8 +/- 0.3%, respectively; P< 0.02). Furthermore patients in the top quartile of albuminuria showed increased carotid wall thickness as compared to normoalbuminuric patients (0.78 +/- 0.03, 0.7 +/- 0.04, 0.65 +/- 0.03 and 0.6 +/- 0.03 mm, respectively; P < 0.001). CONCLUSIONS Hypertensive patients with microalbuminuria show a higher prevalence of unfavourable left ventricular geometric patterns, depressed left ventricular function and early signs of extra-cardiac vascular damage. These findings strengthen the role of microalbuminuria as an indicator of subclinical cardiovascular disease and may account for the worse outcome that is usually associated with increased urinary albumin excretion in essential hypertension.