A multifaceted intervention to improve treatment with oral anticoagulants in atrial fibrillation (IMPACT-AF): an international, cluster-randomised trial.

BACKGROUND: Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. METHODS: This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group). Randomisation was carried out centrally, using the eClinicalOS electronic data capture system. The intervention involved education of providers and patients, with regular monitoring and feedback. The primary outcome was the change in the proportion of patients treated with oral anticoagulants from baseline assessment to evaluation at 1 year. The trial is registered at ClinicalTrials.gov, number NCT02082548. FINDINGS: 2281 patients from five countries (Argentina, n=343; Brazil, n=360; China, n=586; India, n=493; and Romania, n=499) were enrolled from 48 clusters between June 11, 2014, and Nov 13, 2016. Follow-up was at a median of 12·0 months (IQR 11·8-12·2). Oral anticoagulant use increased in the intervention group from 68% (804 of 1184 patients) at baseline to 80% (943 of 1184 patients) at 1 year (difference 12%), whereas in the control group it increased from 64% (703 of 1092 patients) at baseline to 67% (732 of 1092 patients) at 1 year (difference 3%). Absolute difference in the change between groups was 9·1% (95% CI 3·8-14·4); odds ratio of change in the use of oral anticoagulation between groups was 3·28 (95% CI 1·67-6·44; adjusted p value=0·0002). Kaplan-Meier estimates showed a reduction in the secondary outcome of stroke in the intervention versus control groups (HR 0·48, 95% CI 0·23-0·99; log-rank p value=0·0434). INTERPRETATION: A multifaceted and multilevel educational intervention, aimed to improve use of oral anticoagulation in patients with atrial fibrillation and at risk for stroke, resulted in a significant increase in the proportion of patients treated with oral anticoagulants. Such an intervention has the potential to improve stroke prevention around the world for patients with atrial fibrillation. FUNDING: Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer.

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.

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.

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.

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.

Comparative reproducibility of the noninvasive ultrasound methods for the assessment of vascular function.

The aim of this work was to assess the reproducibility of ultrasound parameters of vascular function, since these measurements are currently recommended by the guidelines for the evaluation of the cardiovascular risk. Twenty subjects (51 ± 17 years, 11 men) had vascular ultrasound (Aloka Prosound α10) performed by two observers, at the level of the right common carotid artery for assessment of intima-media thickness (IMT), "wall tracking", and "wave-intensity analysis", and at the level of the right brachial artery for the assessment of flow-mediated dilation (FMD). Wave intensity is a hemodynamic index, evaluating ventriculo-arterial interaction and can be measured in real time by a double-beam ultrasound technique through simultaneous recording of carotid arterial blood flow velocity and diameter. Carotido-femoral pulse wave velocity (PWV) was determined using the Complior method. Intra- and inter-observer reproducibility was assessed during a first session, when three consecutive acquisitions were made (first observer → second observer → first observer); repeatability was evaluated 1 week later (second observer). The most reproducible and repeatable parameters were PWV (intraobserver ±3.3%, interobserver ±2.6%, repeatability ±5.6%) and IMT (±3.7, ±4.3, ±4.9%, respectively). Intraobserver reproducibility for arterial stiffness and ventriculo-arterial coupling parameters was the highest for the beta index (±3.8%), and the lowest for the second systolic peak (±22.4%). Interobserver reproducibility and repeatability varied between very good for the wave speed (±5.5 and ±4.3%), and unsatisfactory for the negative area (±31.8 and ±38.6%). FMD had good reproducibility (intraobserver ±11.6%, interobserver ±8%, repeatability ±7%), whereas augmentation index had only satisfactory results (±17.8, ±8.4, ±23.8%, respectively). Only some parameters of vascular function have good reproducibility and repeatability, better or similar to other ultrasound methods and, therefore, these are ready to be used in routine clinical practice.

Atrial fibrillation is associated with large beat-to-beat variability in mitral and tricuspid annulus dimensions.

AIMS: Beat-to-beat variability in cycle length is well-known in atrial fibrillation (Afib); whether this also translates to variability in annulus size remains unknown. Defining annulus maximal size in Afib is critical for accurate selection of percutaneous devices given the frequent association with mitral and tricuspid valve diseases. METHODS AND RESULTS: Images were obtained from 170 patients undergoing 3D echocardiography [100 (50 sinus rhythm (SR) and 50 Afib) for mitral annulus (MA) and 70 (35 SR and 35 Afib) for tricuspid annulus (TA)]. Images were analysed for differences in annular dynamics with a commercially available software. Number of cardiac cycles analysed was 567 in mitral valve and 346 in tricuspid valve. Median absolute difference in maximal MA area over four to six cycles was 1.8 cm2 (range 0.5-5.2 cm2) in Afib vs. 0.8 cm2 (range 0.1-2.9 cm2) in SR, P < 0.001. Maximal MA area was observed within 30-70% of the R-R interval in 81% of cardiac cycles in SR and in 73% of cycles in Afib. Median absolute difference in maximal TA area over four to six cycles was 1.4 cm2 (range 0.5-3.6 cm2) in Afib vs. 0.7 cm2 (range 0.3-1.7 cm2) in SR, P < 0.001. Maximal TA area was observed within 60-100% of the R-R interval in 81% of cardiac cycles in SR, but only in 49% of cycles in Afib. CONCLUSION: MA and TA reach maximal size within a broad time interval centred around end-systole and end-diastole, respectively, with significant beat-to-beat variability. Afib leads to a larger beat-to-beat variability in both timing of occurrence and values of annulus size than in SR.

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 ß stiffness index (ß), Young elastic modulus (Ep), arterial compliance (AC), one-point pulse wave velocity (PWVß) and the wave reflection augmentation index (AI). RESULTS: Univariate analysis showed that the following variables are significant in determining CH: ß > 8.4, Ep > 136 kPa, PWVß > 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), PWVß > 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.

The Assessment of Subclinical Cardiovascular Dysfunction in Treated Rheumatoid Arthritis.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) causes frequently cardiovascular complications, probably determined by early atherosclerosis in connection to chronic systemic inflammation. Purpose of our study was to assess subclinical cardiac and vascular dysfunction, and to evaluate the mechanisms of ventriculo-arterial interaction, in patients with correctly treated RA vs. normal subjects. METHODS: We evaluated 46 subjects (55±10 years, 2 men): 29 patients with seropositive treated RA (mean duration of 11±9 years), without documented cardiovascular or pulmonary disease, and 17 control subjects, matched for age, sex, and distribution of conventional major risk factors. All RA patients were under long-term treatment (more than 6 months) with Methotrexat + Sulfasalasine (22 patients) or Methotrexat + Sulfasalasine + Infliximab (7 patients). We determined biomarkers of inflammation (P-selectin, interleukines 1, 6, 10, 18, seric amiloid A, á-TNF, ã-interferon, C-reactive protein, anti-oxidated LDL antibodies), myocardial fibrosis (â-crosslaps) and ventricular overload (BNP). We assessed the parameters of cardiac function by standard and tissue Doppler echocardiography, intima-media thickness and arterial stiffness by "e-tracking" and "wave intensity analysis" (at the level of the right carotid artery), endothelial function by flow mediated dilation (FMD), and carotid-femoral pulse wave velocity by the Complior method. RESULTS: Biological parameters of inflammation, markers of myocardial fibrosis and of ventricular overload were not different between the 2 study groups. Also, parameters of subclinical cardiac and vascular function were similar between the two groups. RA patients had subclinical RV dysfunction, correlated to the duration of the disease. They also tended to have higher values of systolic pulmonary artery pressure than normals. CONCLUSION: Correctly treated patients with RA, with controlled systemic inflammation, have normal LV, endothelial and arterial function. However, in the absence of documented pulmonary disease, they do have subclinical RV dysfunction, correlated with the duration of disease. This suggests an intrinsic RV myocardial involvement but, since pulmonary artery pressure was also higher, a secondary mechanism might be also involved.

The impact of blood pressure variability on subclinical ventricular, renal and vascular dysfunction, in patients with hypertension and diabetes.

BACKGROUND: Blood pressure variability (BPV) was proved as a cardiovascular risk factor. One of its mechanisms is related to arterial stiffness and ventriculo-arterial coupling; however its impact on subclinical cardiovascular dysfunction has not been evaluated yet. OBJECTIVES: To assess the relationship between BPV on 24 hours, and subclinical left ventricle (LV), renal, and vascular dysfunction in diabetic and hypertensive patients. MATERIAL AND METHODS: We studied 56 patients (57±9 years, 29 men) with mild-to-moderate hypertension and type 2 diabetes, no cardiovascular disease, normal ejection fraction and normal renal function. 24 hours ambulatory blood pressure monitoring (ABPM) was used to assess BPV, daytime (d) and night time (n), by: 1. mean (M); 2. standard deviation of mean (SD); 3. variance (Vr); 4. coefficient of variation (CV); 5. day/night variation: reverse dippers, non-dippers, dippers and extreme dippers; conventional and 2D speckle tracking echo to assess LV function; myocardial deformation was measured as global longitudinal strain (GLS). Endothelial (flow mediated dilation, FMD) and arterial function (intima media-thickness, IMT; pulse wave velocity, PWV), microalbuminuria were tested. OUTCOMES: Daytime BPV correlates inversely with subclinical myocardial function evaluated through GLS. Daytime systolic BPV correlates positively with IMT (all rho > 0.30, all p < 0.05). Also, there is a significantly inverse correlation between mean BP and GLS. We found a direct correlation between mean BP, but not BPV, and microalbuminuria (all rho > - 0.30 and all p < 0.05). We found no correlation between BPV and FMD, PWV. There were no differences for GLS, microalbuminuria and FMD between dipper groups. CONCLUSIONS: In diabetic patients with mild-to-moderate hypertension, increased daytime blood pressure variability correlates with subclinical left ventricular dysfunction and arterial function (IMT), while microalbuminuria correlates with elevated blood pressure, but not with blood pressure variability.

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.