Simona Buralli

Speckle-Tracking Echocardiography A New Technique for Assessing Myocardial Function

Speckle‐tracking echocardiography has recently emerged as a quantitative ultrasound technique for accurately evaluating myocardial function by analyzing the motion of speckles identified on routine 2‐dimensional sonograms. It provides non‐Doppler, angle‐independent, and objective quantification of myocardial deformation and left ventricular systolic and diastolic dynamics. By tracking the displacement of the speckles during the cardiac cycle, strain and the strain rate can be rapidly measured offline after adequate image acquisition. Data regarding the feasibility, accuracy, and clinical applications of speckle‐tracking echocardiography are rapidly accumulating. This review describes the fundamental concepts of speckle‐tracking echocardiography, illustrates how to obtain strain measurements using this technique, and discusses their recognized and developing clinical applications.

Vasodilation to Bradykinin Is Mediated by an Ouabain-Sensitive Pathway as a Compensatory Mechanism for Impaired Nitric Oxide Availability in Essential Hypertensive Patients

BACKGROUND In essential hypertension, endothelium-dependent vasodilation is impaired because of reduced nitric oxide (NO) availability, which is mainly caused by oxidative stress. The present study was designed to identify the mechanism(s) responsible for NO-independent vasodilation to bradykinin in patients with essential hypertension. METHODS AND RESULTS In 16 healthy subjects (49.5+/-5.8 years; 118.6+/-3.5/78.9+/-2.9 mm Hg) and 16 patients with essential hypertension (47.9+/-4.8 years; 154.6+/-4.5/102.9+/-3.2 mm Hg), we measured modifications in forearm blood flow (strain-gauge plethysmography) during intrabrachial infusion of bradykinin (5, 15, or 50 ng/100 mL of forearm tissue per minute) in the presence of saline, N(omega)-monomethyl-L-arginine (L-NMMA; used to inhibit NO synthase; 100 microg/100 mL of forearm tissue per minute), and ouabain (to block Na(+)K(+)/ATPase and prevent hyperpolarization; 0.7 microg/100 mL of forearm tissue per minute). In healthy subjects, vasodilatation to bradykinin was significantly blunted by L-NMMA and unaffected by ouabain. In hypertensive patients, vasodilatation to bradykinin was not modified by L-NMMA, but it was significantly reduced by ouabain. In an adjunctive group of 8 hypertensive patients (49.9+/-3.8 years; 155.9+/-5.5/103.7+/-3.9 mm Hg), the response to bradykinin was repeated during the administration of intrabrachial vitamin C (a scavenger for oxygen free radicals; 8 mg/100 mL of forearm tissue per minute). In these patients, L-NMMA-induced inhibition of vasodilation to bradykinin was restored, and ouabain was no longer effective. In a final group of 6 normotensive controls (45.9+/-4.1 years; 115.1+/-2.9/79.3+/-2.1 mm Hg), vasodilation to bradykinin residual to L-NMMA blockade was further inhibited by simultaneous ouabain infusion. CONCLUSIONS Vasodilation to bradykinin is impaired in essential hypertensive patients because of an NO-system alteration caused by oxidative stress, and it is mediated by an alternative pathway, possibly involving endothelium-dependent hyperpolarization.

Echocardiography in patients with hypertrophic cardiomyopathy: usefulness of old and new techniques in the diagnosis and pathophysiological assessment

Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiomyopathy. The identification of patients with HCM is sometimes still a challenge. Moreover, the pathophysiology of the disease is complex because of left ventricular hyper-contractile state, diastolic dysfunction, ischemia and obstruction which can be coexistent in the same patient. In this review, we discuss the current and emerging echocardiographic methodology that can help physicians in the correct diagnostic and pathophysiological assessment of patients with HCM.

Plasma matrix metalloproteinase-9 better predicts outcome than N-terminal protype-B natriuretic peptide in patients with systolic heart failure and a high prevalence of coronary artery disease.

Metalloproteinases have been proposed as biochemical markers of left ventricular (LV) remodeling in systolic heart failure (HF). However, their role in the prognostic stratification of these patients remains controversial. In the present study, we aimed at investigating the value of plasma metalloproteinases-3 and -9 in comparison with N-terminal protype-B natriuretic peptide in patients with systolic HF. One hundred and 27 consecutive patients hospitalized for systolic HF (LV ejection fraction < 45%) were enrolled. Coronary artery disease (CAD) was the aetiology in 67% of the study patients. Plasma metalloproteinases-3 and -9 and N-terminal protype-B natriuretic peptide levels were assessed. A complete echocardiographic and Doppler examination was also performed. Follow-up period was 24-15 months. On univariate analysis, a number of measurements predicted cardiac events in the following order of power: NYHA class >2, LV ejection fraction < 25%, metalloproteinases-9 > 238 ng/ml, mitral E wave deceleration time < 150 ms, N-terminal protype-B natriuretic peptide > 1586 pg/ml and metalloproteinases-3 > 15 ng/ml. However, on multivariate analysis the only independent variables of cardiac events were NYHA class (OR=2.26, p=0.059) and plasma metalloproteinases-9 (OR=2.00, p=0.029). On Kaplan-Meier survival analysis, patients with elevated levels of metalloproteinases-9 exhibited a significantly worse event free-survival at 45 months than those without (21% vs. 54%, log-rank: 13.93, p=0.0002). A worse survival was also observed in patients with elevated N-terminal protype-B natriuretic peptide levels with respect to those without (18% vs. 46%, log-rank: 9.11, p=0.025). Our results demonstrated the value of plasma metalloproteinases-9 levels for prognostication of patients with systolic HF and a high prevalence of CAD.

Plasma metalloproteinase-9 and restrictive filling pattern as major predictors of outcome in patients with ischemic cardiomyopathy

OBJECTIVE Assessment of plasma matrix metalloproteinase-9 (MMP-9) and Doppler markers of increased left ventricular (LV) filling pressure may be added to risk stratify patients with ischemic cardiomyopathy (IC). Therefore, we aimed at investigating the value of plasma MMP-9 and restrictive filling pattern (RFP) in IC patients. METHODS Eighty-eight consecutive patients hospitalized for heart failure (LV ejection fraction ≤ 40%) due to IC were enrolled. A complete M-mode and two-dimensional echo-Doppler examination were performed. Patients were defined as having RFP if they had a mitral E wave deceleration time<150 ms. Plasma MMP-9 and N-terminal protype-B natriuretic peptide levels were assessed at the time of the index echocardiogram. The end point was all-cause mortality or hospitalization for worsening HF. Follow-up period was 25 ± 17 months. RESULTS Median value of MMP-9 was 714 ng/ml. On univariate analysis, a number of measurements predicted the composite end point: NYHA class>2, RFP, MMP-9>60.5 ng/ml, LV ejection fraction<27%, anemia, pulmonary pressure ≥ 35 mm Hg, N-terminal protype-B natriuretic peptide>1742 pg/ml, and glomerular filtration rate<60 ml/min/1.73 m(2). Independent variables of outcome were anemia (HR=1.9, p=0.031), and the combination of plasma MMP-9 and RFP (HR=3.2, p=0.004). On Kaplan-Meier survival curves, patients with elevated MMP-9 levels and RFP had the lowest event-free survival rate (log-rank: 29.0, p<0.0001). The net reclassification improvement showed a significant increase in the prediction model when elevated MMP-9 and RFP were added to the base model that included clinical, biochemical and echocardiographic parameters (p<0.0001). CONCLUSION MMP-9 levels and RFP have an incremental predictive value to risk classify IC patients.

Surrogate end points of antihypertensive treatment: Left ventricular hypertrophy and structural alteration of carotid arteries

The present paper provides a critical overview of left ventricular hypertrophy (LVH) and structural changes of carotid arteries as surrogate end points for antihypertensive treatments. LVH is known to be associated with a number of pathophysiologic alterations underlying cardiovascular risk. The quantification of left ventricular mass is feasible and well standardized by echocardiography, even if the reproducibility of measurements is still limited. LVH has been clearly demonstrated to be an independent predictor for cardiovascular morbidity and mortality, and recent data suggest that left ventricular geometric pattern and depressed myocardial function may represent additional risk factors. Although clinical trials have shown that an adequate blood pressure control can be associated with a significant reduction in left ventricular mass, the prognostic impact of LVH regression is still debated. Serial measurements of the carotid artery intima-media complex by B-mode ultrasound have been proposed as an accurate noninvasive approach for the evaluation of progression and regression of the atherosclerotic process over time. The methodology of measurement is not as well standardized as that of LVH, and the reproducibility of measurements is too close to the magnitude of structural changes over time. In addition, sounder data are required concerning the pathophysiologic relationship between carotid lesions and clinical events.

[PP.19.24] DETERMINANTS OF INAPPROPRIATELY HIGH PULSE WAVE VELOCITY IN HYPERTENSIVE PATIENTS: A RETROSPECTIVE CROSS-SECTIONAL COHORT STUDY

Objective: Age and blood pressure (BP) are known to be the main determinants of large artery stiffness. However other factors may lead to an inappropriately high pulse wave velocity (PWV) on top of these two factors. We investigated the determinants of inappropriately high PWV in hypertensive patients, and their possible role in causing organ damage accrual. Design and method: Hypertensive patients were selected among those attending a visit in our Hypertension Outpatient Clinic and undergoing carotid-femoral PWV by applanation tonometry, and cardiac and carotid ultrasound during a 5-year period (2006–2011). Inappropriately high pulse wave velocity (PWV) was calculated as the ratio between the observed value and the values predicted according to the formula derived from international reference values stratified by age and mean BP (oPWV/pPWV). Results: 731 hypertensive patients were selected (age 30–88 years, 42% women, 57% taking BP-lowering drugs). Median oPWV/pPWV was 102% (range 61–196%). In a multiple linear regression model, independent determinants of oPWV/pPWV were: daylight hours (beta -1.72, p < 0.001), age (beta -0.73, p < 0.001), BMI (beta 0.49, p = 0.01), blood glucose (beta 0.18, p < 0.001), mean BP (beta = -0.25, p = 0.002) and heart rate (beta = 0.22, p = 0.003). Though oPWV/pPWV was significantly higher in men and current smokers, the association disappeared in the multiple regression model. There was no association between oPWV/pPWV and any BP-lowering drug class. oPWV/pPWV was not associated with left ventricular mass. Conversely, oPWV/pPWV was an independent determinant of the presence of carotid plaques (beta 7.35, 5–95%CL 2.36–12.34). Conclusions: In hypertensive patients, inappropriately elevated PWV is associated more tightly than observed PWV to younger age and high blood glucose, thus it might help to better depict vascular aging in younger hypertensives and in those with metabolic alterations. A more advanced atherosclerotic process might also contribute to excess aortic stiffness. Whether an inappropriately high PWV translates into an increased cardiovascular risk should be determined in longitudinal studies.