Andrea O. Ciobanu

Reversal of subclinical left ventricular dysfunction by antihypertensive treatment: a prospective trial of nebivolol against metoprolol.

Objectives To assess the effects of antihypertensive treatment on subclinical left ventricular dysfunction and to compare the effects of nebivolol with metoprolol. Methods This is a prospective, randomized, parallel, active-controlled, PROBE design study (ClinicalTrials.org: NCT00942487) in 60 patients (53 ± 9 years, 67% men) with arterial hypertension, left ventricular hypertrophy, normal ejection fraction, and no coronary heart disease, randomized to either a nebivolol-based or a metoprolol-based treatment, who had conventional and tissue Doppler echocardiography, at rest and during dobutamine stress, at baseline and after 6 months. Results SBP and DBP, and resting heart rate decreased by 13, 13, and 12%, respectively, on nebivolol, and by 11, 13, and 7%, respectively, on metoprolol (all, P < 0.01). Mean longitudinal early diastolic velocity increased by 16% (P < 0.05) on nebivolol compared with 9% (P = not significant) on metoprolol (P = not significant for intergroup differences), whereas flow propagation velocity increased by 34% on nebivolol (P < 0.05) and did not change on metoprolol (P < 0.01 for intergroup differences). Mean longitudinal displacement increased by 10% on nebivolol (P < 0.05) and did not change on metoprolol (P < 0.05 for intergroup differences), whereas ejection time increased by 5% on nebivolol (P < 0.05) and did not change on metoprolol. All the other parameters of left ventricular function were not different between the two treatment arms. Conclusion Patients with mild-to-moderate hypertension have a beneficial effect from 6-month antihypertensive treatment on diastolic longitudinal left ventricular function; effects are significant with nebivolol, but not with metoprolol.

Cumulative impact of cardiovascular risk factors on regional left ventricular function and reserve: progressive long-axis dysfunction with compensatory radial changes.

Background: The risk factors that contribute to atherosclerosis also predict clinical heart failure, but it is unclear how they affect myocardial function. Aims were to assess if major cardiovascular risk factors cause subclinical myocardial dysfunction in asymptomatic subjects. Methods: We measured regional left ventricular (LV) function at rest and during dobutamine stress echocardiography in 246 subjects (54 ± 12 years, 54% men) analyzed in five groups according to the presence of six risk factors (diabetes, hypertension, obesity, dyslipidemia, smoking, and family history; age was similar in the five groups). LV longitudinal function was assessed from the mean velocities of four basal segments, and radial function from the velocities of the basal posterior wall. Results: Risk factors did not affect LV ejection fraction, but longitudinal systolic velocity decreased progressively with the number of risk factors, at rest (6.8 ± 1.3 vs. 6.2 ± 1.6 vs. 5.8 ± 1.5 vs. 5.4 ± 1.3 vs. 5.3 ± 1.3 cm/sec, for the five groups, respectively) and at peak stress (14.3 ± 3.3 vs. 12.9 ± 3.2 vs. 11.8 ± 3.4 vs. 11.3 ± 2.6 vs. 11.1 ± 2.3 cm/sec) (both P < 0.0001). Radial systolic velocity increased according to the number of risk factors (P < 0.01). By multivariate regression, determinants of reduced longitudinal systolic velocity at rest were body mass index, diastolic blood pressure, age, and fasting plasma glucose (r = 0.57, r2= 0.32, P < 0.0001). Conclusion: Asymptomatic subjects have impaired LV long‐axis function at rest and during stress, according to their number of major cardiovascular risk factors. Global LV systolic function is maintained by compensatory increases in radial function. These changes provide new targets for preclinical diagnosis and for monitoring responses to preventive strategies. (Echocardiography 2011;28:813‐820)

The effect of indapamide versus hydrochlorothiazide on ventricular and arterial function in patients with hypertension and diabetes: results of a randomized trial.

OBJECTIVE The objective of this study is to compare the effects of 2 types of diuretics, indapamide and hydrochlorothiazide, added to an angiotensin-converting enzyme inhibitor, on ventricular and arterial functions in patients with hypertension and diabetes. METHODS This is a prospective, randomized, active-controlled, PROBE design study in 56 patients (57 ± 9 years, 52% men) with mild-to-moderate hypertension and type 2 diabetes, with normal ejection fraction, randomized to either indapamide (1.5 mg Slow Release (SR)/day) or hydrochlorothiazide (25 mg/d), added to quinapril (10-40 mg/d). All patients had conventional, tissue Doppler and speckle tracking echocardiography and assessment of endothelial and arterial functions and biomarkers, at baseline and after 6 months. RESULTS Baseline characteristics were similar between groups; systolic and diastolic blood pressures decreased similarly, by 15% and 9% on indapamide and by 17% and 10% on hydrochlorothiazide (P < .05). Mean longitudinal systolic velocity and longitudinal strain increased by 7% and 14% on indapamide (from 5.6 ± 1.8 to 6.0 ± 1.1 cm/s and from 16.2% ± 1.8% to 18.5% ± 1.1%, both P < .05), but did not change on hydrochlorothiazide (P < .05 for intergroup differences), whereas ejection fraction and radial systolic function did not change. Similarly, mean longitudinal early diastolic velocity increased by 31% on indapamide (P < .05), but did not change on hydrochlorothiazide (P < .05 for intergroup differences). These changes were associated with improved endothelial and arterial functions on indapamide, but not on hydrochlorothiazide. CONCLUSION Indapamide was found to improve measures of endothelial and arterial functions and to increase longitudinal left ventricular function compared with hydrochlorothiazide in patients with hypertension and diabetes, after 6 months of treatment. This study suggests that indapamide, a thiazide-like diuretic, has important vascular effects that can improve ventriculoarterial coupling.

A clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AF): design and rationale

Atrial fibrillation (AF) is common, increasing as the population ages, and a major cause of embolic stroke. While oral anticoagulation (OAC) is highly effective at preventing stroke in patients with AF, it continues to be underused in eligible patients worldwide. The objective of this prospective, cluster randomized controlled trial (IMPACT-AF; ClinicalTrials.gov #NCT02082548) is to determine whether a comprehensive customized intervention will increase the rate and persistence of use of OAC in patients with AF. IMPACT-AF will be conducted in approximately 50 centers in 5 low- to middle-income countries. Before randomization, sites within countries will be paired to match in size, practice type and baseline rate of OAC use. Site pairs will be randomized to intervention versus control. In total, 40 to 70 patients with AF and at least 2 CHA2DS2-VASc risk factors will be enrolled at each site using a consecutive enrollment strategy, with the goal of capturing actual practice patterns. We aim for patients with a new diagnosis of AF to comprise at least 30% of the study cohort. Assuming an average baseline OAC use of 60% and a post-intervention use of 70% with a post-control rate of 60%, there will be roughly 94-98% power with 25 clusters per group (intracluster correlation coefficient of 0.02). While this trial focuses on improving treatment use and reducing preventable strokes, we also aim to better understand the reasons for OAC underuse. This will improve the intervention with the goal of creating educational recommendations to improve care for patients with AF.

Catastrophic mitral prosthesis dehiscence diagnosed by three-dimensional transesophageal echocardiography

In emergency situations, real‐time three‐dimensional transesophageal echocardiography (RT 3‐dimensional TEE) may provide unique anatomic insights on prosthetic valves when two‐dimensional imaging is inconclusive. We report the case of a 76‐year‐old woman, in cardiogenic shock, who had undergone mitral valve replacement 3 months ago. RT 3‐dimensional TEE revealed almost total, catastrophic prosthesis dehiscence following infective endocarditis, the prosthesis being perpendicular to the normal mitral plane. Corrective surgery was not feasible, and the patient died shortly after admission. Although the outcome was unfortunate, RT 3‐dimensional TEE helped rapidly reach a definitive diagnosis, essential for decision‐making. Three‐dimensional TEE should be used as a complementary technique in difficult cases.

Regional differences in presentation and antithrombotic treatment of patients with atrial fibrillation: Baseline characteristics from a clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with atrial fibrillation (IMPACT-AF)

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there are few contemporary comparative data on AF from middle-income countries. METHODS Baseline characteristics of the IMPACT-AF trial were analyzed to assess regional differences in presentation and antithrombotic treatment of AF from 5 middle-income countries (Argentina, Brazil, China, India, and Romania) and factors associated with antithrombotic treatment prescription. RESULTS IMPACT-AF enrolled 2281 patients (69 ± 11 years, 47% women) at 48 sites. Overall, 66% of patients were on anticoagulation at baseline, ranging from 38% in China to 91% in Brazil. The top 3 reasons for not prescribing an anticoagulant were patient preference/refusal (26%); concomitant antiplatelet therapy (15%); and risks outweighing the benefits, as assessed by the physician (13%). In a multivariable model, the most significant factors associated with prescription of oral anticoagulants were no prior major bleeding (odds ratio [OR] = 4.34; 95% CI = 2.22-8.33), no alcohol abuse (OR = 2.27; 95% CI = 1.12-4.55), and history of rheumatic valvular heart disease (OR = 2.10; 95% CI = 1.36-3.26), with a strong predictive accuracy (c statistic = 0.85), whereas the most significant factors associated with prescription of a combination of oral anticoagulants and antiplatelet drugs were prior coronary revascularization (OR = 5.10; 95% CI = 2.88-9.05), prior myocardial infarction (OR = 2.24; 95% CI = 1.38-3.63), and no alcohol abuse (OR = 2.22; 95% CI = 1.11-4.55), with a good predictive accuracy (c statistic = 0.76). CONCLUSIONS IMPACT-AF provides contemporary data from 5 middle-income countries regarding antithrombotic treatment of AF. Lack of prior major bleeding and coronary revascularization were the most important factors associated with prescription of oral anticoagulants and their combination with antiplatelet drugs, respectively.

The expression of MMP-1 and MMP-9 is up-regulated by smooth muscle cells after their cross-talk with macrophages in high glucose conditions

Patients with diabetes mellitus have an increased risk of myocardial infarction and coronary artery disease‐related death, exhibiting highly vulnerable plaques. Many studies have highlighted the major role of macrophages (MAC) and smooth muscle cells (SMC) and the essential part of metalloproteases (MMPs) in atherosclerotic plaque vulnerability. We hypothesize that in diabetes, the interplay between MAC and SMC in high glucose conditions may modify the expression of MMPs involved in plaque vulnerability. The SMC‐MAC cross‐talk was achieved using trans‐well chambers, where human SMC were grown at the bottom and human MAC in the upper chamber in normal (NG) or high (HG) glucose concentration. After cross‐talk, the conditioned media and cells were isolated and investigated for the expression of MMPs, MCP‐1 and signalling molecules. We found that upon cross‐talk with MAC in HG, SMC exhibit: (i) augmented expression of MMP‐1 and MMP‐9; (ii) significant increase in the enzymatic activity of MMP‐9; (iii) higher levels of soluble MCP‐1 chemokine which is functionally active and involved in MMPs up‐regulation; (iv) activated PKCα signalling pathway which, together with NF‐kB are responsible for MMP‐1 and MMP‐9 up‐regulation, and (v) impaired function of collagen assembly. Taken together, our data indicate that MCP‐1 released by cell cross‐talk in diabetic conditions binds to CCR2 and triggers MMP‐1 and MMP‐9 over‐expression and activity, features that could explain the high vulnerability of atherosclerotic plaque found at diabetic patients.

The Relationship of Carotid Arterial Stiffness and Left Ventricular Concentric Hypertrophy in Hypertension.

BACKGROUND Left ventricular hypertrophy (LVH) and geometry patterns vary in different hemodynamic profiles The concentric hypertrophy (CH) pattern has been proved to have the worst prognosis. OBJECTIVES The aim of the study was to test the hypothesis that carotid artery stiffness, as a marker of vascular damage, is associated with CH, independently of other potential determinants such as demographic factors (age, sex, BMI), clinical parameters (smoking, diabetes, creatinine level) and hemodynamic variables (blood pressure, pulse pressure [PP]). MATERIAL AND METHODS The study involved 262 subjects (89 men): 202 patients with hypertension (153 untreated, 49 on medication), aged 55.7 ± 10 years, and 60 age-matched normal controls. The subjects were examined by echocardiography and carotid ultrasound with a high-resolution echo-tracking system. Based on the left ventricular mass index (LVMI) and relative wall thickness (RWT), the patients with hypertension were divided into four patterns of LVH and geometry: normal geometry (N, n = 57), concentric remodeling (CR, n = 48), concentric hypertrophy CH (n = 62) and eccentric hypertrophy (EH, n = 35). Intima-media thickness (IMT) and the parameters of arterial stiffness were also assessed using the β stiffness index (β), Young elastic modulus (Ep), arterial compliance (AC), one-point pulse wave velocity (PWVβ) and the wave reflection augmentation index (AI). RESULTS Univariate analysis showed that the following variables are significant in determining CH: β > 8.4, Ep > 136 kPa, PWVβ > 7.1 m/s, AI > 21.9%, systolic BP > 151 mm Hg, PP > 54, IMT > 0.56 and the presence of diabetes. However, by multivariate analysis only AI (OR 3.65, p = 0.003), PWVβ > 7.1 m/s (OR 2.86, p = 0.014), systolic BP (OR 3.12, p = 0037) and the presence of diabetes (OR 3.75, p = 0.007) were associated independently with the occurrence of CH. CONCLUSIONS Concentric hypertrophy in hypertension is strongly associated with carotid arterial stiffness and wave reflection parameters, independently of the influence of systolic blood pressure and diabetes.

SUCCESSFUL THROMBOLISYS FOR MOBILE MASSIVE RIGHT HEART THROMBOSIS

Right heart thrombi, particularly when mobile, are associated with significantly high risk of early mortality in patients with acute pulmonary embolism, up to 80-100% when left untreated. Urgent therapy is mandatory. However, guidelines recommendations for the treatment of choice, thrombolysis or

Isolated Double Orifice Mitral Valve - a Rare Finding in an Elderly Man.

We present herein several transesophageal echocardiogram (TEE) images of a 60-year-old man referred to the cardiac surgeon for a triple coronary artery bypass graft procedure, in which a normally-functioning double orifice mitral valve (DOMV) was an incidental finding during routine intraoperative TEE. This is a very rare congenital malformation, even rarer as an isolated anomaly in an elderly patient. Three-dimensional TEE (3D-TEE) confirmed the diagnosis and provided complete and fast assessment of the mitral valve and the surrounding structures and all the information needed to reassess the surgical strategy in the very short pre‑bypass period.