Umberto Cucchini

Worldwide management of oral anticoagulant therapy: the ISAM study.

A multicenter, observational, retrospective, cross-sectional study of patients, receiving oral anticoagulation therapy (OAT) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF) was conducted in the US, Canada, France, Italy and Spain according to their predominant model of care [routine medical care (RMC) or Anticoagulation Clinic care (ACC)]. The study objectives were to assess anticoagulation control (time in target range), and to describe the features of the local model of care. Consecutive patients were recruited on the basis of a minimum of 60 days of oral anticoagulant treatment over a 12 month period, and clinic and physician details were captured by means of a structured face-to-face or telephone interview. Time in therapeutic range (TTR) was calculated by using linear interpolation between INR values. A total of 1511 patients were recruited, of whom 1445 were included in the analysis of TTR. TTR was higher in ACC (69.5% and 64.9% for Italy and Spain, respectively) with respect to RMC (58.1%, 62.8% and 59.3% for the US, Canada and France, respectively). Mean intervals between INR determinations were between 3 and 4 weeks. Dose changes in case of INR outside therapeutic range were more frequent in Spain and less frequent in France. Striking differences were observed in type of VKA used, specialists involved in patient management, and dosage instructions. Studying of anticoagulation management based on local models of care highlights important discrepancies among countries and suggests further standardization of the management of this important therapy is necessary.

Right atrial size and function assessed with three-dimensional and speckle-tracking echocardiography in 200 healthy volunteers

AIMS Right atrial (RA) size predicts the outcome in some pathological conditions but reference values for RA volumes and myocardial function remain to be defined. Thus, we used two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE) to define normative reference values of RA volumes and function. METHODS AND RESULTS Two hundreds healthy volunteers (43 ± 15 years, range 18-75; 44% men) underwent two-dimensional echocardiography (2DE) to obtain RA volumes and longitudinal strain (LS) of RA wall using 2D-STE, and 3DE to measure maximal (Vmax), minimal, and preA volumes to calculate total, passive, and active emptying volumes (TotEV, PassEV, and ActEV) and emptying fractions (TotEF, PassEF, and ActEF). Three-dimensional echocardiography volumes (Vmax, 52 ± 15 mL vs. 41 ± 14 mL), EVs (TotEV, 33 ± 10 mL vs. 24 ± 9 mL), and EFs (TotEF, 63 ± 9 vs. 58 ± 9%) were larger than 2DE ones (all P < 0.0001). Indexed 3D volumes were significantly larger in men than in women. RA TotEF correlated with total LS (r = 0.24, P = 0.025) and PassEF with positive LS (LSpos; r = 0.34, P < 0.0001). Ageing was associated with a decrease in passive (LSpos, r = -041; PassEV, r = -0.26; PassEF, r = -0.38; all P < 0.0001) and an increase in active RA function (negative LS, r = 0.34; ActEV, r = 0.25; all P < 0.0001; and ActEF, r = 0.15; P = 0.035) in order to maintain TotEV (r = -0.14, P = 0.05). CONCLUSION Our study provides normative values for RA volumes and function measured by 3DE and 2D-STE in a relatively large cohort of healthy subjects with a wide age range. These data will help clinicians to identify RA remodelling and dysfunction.

Normal Left Ventricular Mechanics by Two-dimensional Speckle-tracking Echocardiography. Reference Values in Healthy Adults

INTRODUCTION AND OBJECTIVES Two-dimensional speckle-tracking echocardiography is a novel tool to assess myocardial function. The purpose of this study was to evaluate left ventricular myocardial strain and rotation parameters by two-dimensional speckle-tracking echocardiography in a large group of healthy adults across a wide age range to establish their reference values and to assess the influence of age, sex, and hemodynamic factors. METHODS Transthoracic echocardiograms were acquired in 247 healthy volunteers (139 women, 44 years [standard deviation, 16 years old] (range, 18-80 years). We measured longitudinal, circumferential, and radial peak systolic strain values, and left ventricular rotation and twist. RESULTS Average values of global longitudinal, radial, and circumferential strain were -21.5% (standard deviation, 2.0%), 40.1% (standard deviation, 11.8%) and -22.2% (standard deviation, 3.4%), respectively. Longitudinal strain was significantly more negative in women, whereas radial and circumferential strain and rotational parameters were similar in both sexes. Accordingly, lower limits of normality for the strain components were -16.9% in men and -18.5% in women for longitudinal strain, and -15.4% for circumferential and 24.6% for radial strain, irrespective of sex. Longitudinal strain values were more negative at the base than at apical segments. Mean rotational values were -6.9° (standard deviation, 3.5°) for the base, 13.0° (standard deviation, 6.5°) for apical rotation, and 20.0° (standard deviation, 7.3°) for net twist. CONCLUSIONS We report the comprehensive assessment of normal myocardial deformation and rotational mechanics in a large cohort of healthy volunteers. We found that women have more negative longitudinal strain, accounting for their higher left ventricular ejection fraction. Availability of reference values for these parameters may foster their implementation in the clinical routine.

Left Ventricular Myocardial Strain by Three-Dimensional Speckle-Tracking Echocardiography in Healthy Subjects: Reference Values and Analysis of Their Physiologic and Technical Determinants

BACKGROUND Despite growing interest in applying three-dimensional (3D) speckle-tracking echocardiography (STE) to measure left ventricular (LV) myocardial deformation in various diseases, normative values for 3D speckle-tracking echocardiographic parameters and the effects of demographic, hemodynamic, and technical factors on these values are unknown. METHODS In 265 healthy volunteers (age range, 18-76; 57% women), longitudinal strain (3DLε), circumferential strain (3DCε), radial strain (3DRε), and area strain (3DAε) were measured by using vendor-specific (Vsp) 3D speckle-tracking echocardiographic equipment. LV strain was also measured by using Vsp two-dimensional (2D) and vendor-independent 3D speckle-tracking echocardiographic software packages, for comparison. RESULTS Reference values (lower limit of normality) for Vsp 3D STE were -17% to -21% (-15%) for 3DLε, -17% to -20% (-14%) for 3DCε, -31% to -36% (-26%) for 3DAε, and 47% to 59% (38%) for 3DRε. Three-dimensional longitudinal strain decreased, whereas 3DCε increased, with aging (P < .003), with different trends in men and women. Men had lower 3DLε, 3DRε, 3DAε, and 2D longitudinal strain than women (P < .02). LV 3D strain parameters were also influenced by LV volumes and mass, image quality, and temporal resolution (P < .02). Reference values obtained by Vsp 2D STE were -20% to -23% (-18%) for 2D longitudinal strain, -20% to -24% (-17%) for 2D circumferential strain, and 39% to 54% (28%) for 2D radial strain (P < .001 vs Vsp 3D STE). Significantly different 3DCε and 3DRε values were obtained with vendor-independent versus Vsp 3D STE (P < .001). CONCLUSIONS In healthy subjects, reference values of LV 3D strain parameters were significantly influenced by demographic, cardiac, and technical factors. Limits of normality of LV strain by Vsp 3D STE should not be used interchangeably with Vsp 2D STE or with Vin 3D STE software.

Sex- and method-specific reference values for right ventricular strain by 2-dimensional speckle-tracking echocardiography

Background—Despite the fact that assessment of right ventricular longitudinal strain (RVLS) carries important implications for patient diagnosis, prognosis, and treatment, its implementation in clinical settings has been hampered by the limited reference values and the lack of uniformity in software, method, and definition used for measuring RVLS. Accordingly, this study was designed to establish (1) the reference values for RVLS by 2-dimensional speckle-tracking echocardiography; and (2) their relationship with demographic, hemodynamic, and cardiac factors. Methods and Results—In 276 healthy volunteers (55% women; age, 18–76 years), free wall and septum RVLS (6 segments) and free wall RVLS (3 segments) using both 6- and 3-segment regions of interest were obtained. Feasibility of 6-segment RVLS was 92%. Free wall RVLS from 3- versus 6-segment regions of interest had similar values, yet 6-segment region of interest was more feasible (86% versus 73%; P<0.001) and reproducible. Reference values (lower limits of normality) were as follows: 6-segment RVLS, −24.7±2.6% (−20.0%) for men and −26.7±3.1% (−20.3%) for women; 3-segment RVLS, −29.3±3.4% (−22.5%) for men and −31.6±4.0% (−23.3%) for women (P<0.001). Free wall RVLS was 5±2 strain units (%) larger in magnitude than 6-segment RVLS, 10±4% larger than septal RVLS, and 2±4% larger in women than in men (P<0.001). At multivariable analysis, age, sex, pulmonary systolic pressure, right atrial minimal volume, as well as right atrial and left ventricular longitudinal strain resulted as correlates of RVLS values. Conclusions—This is the largest study providing sex- and method-specific reference values for RVLS. Our data may foster the implementation of 2-dimensional speckle-tracking echocardiography–derived RV analysis in clinical practice.

A comparison between six- and four-week intervals in surveillance of oral anticoagulant treatment

We determined whether international normalized ratio (INR) monitoring at 6 weeks rather than 4 weeks would benefit patients and reduce costs. Patients receiving stable oral anticoagulation treatment (target INR, 3.0) with a prosthetic mechanical heart valve for more than 6 months were randomized for a maximum interval between INR determinations of 6 weeks (group 1, n = 59) or 4 weeks (group 2 [control], n = 65). Patients were followed up for 2 years. The primary end point of the study was the biologic risk of overanticoagulation or underanticoagulation, estimated as the rate of values at risk (INR, < 1.5 and > 5). The rates of INR values at risk for hemorrhagic (INR, > 5) or thromboembolic (INR, < 1.5) complications were 3.27% in group 1 and 3.09% in group 2 (P = .81). The INRs of patients in group 1 trended toward higher values, but no difference between groups was observed in time spent at various INR ranges by using the method of linear change. The mean time between INR determinations was 24.9 +/- 18.1 days (1.20 per month) in group 1 and 22.5 +/- 9.5 days (1.33 per month) in group 2 (P < .0003). For patients in stable condition with a prosthetic heart valve who are monitored at an anticoagulation clinic, a 6-week interval between INR determinations does not increase the biologic risk of thromboembolic or hemorrhagic events.

Quantitative analysis of mitral annular geometry and function in healthy volunteers using transthoracic three-dimensional echocardiography.

BACKGROUND Quantitative assessment of the mitral annulus provides information regarding the pathophysiology of mitral regurgitation and aids in the planning of reparative surgery. Three-dimensional (3D) transthoracic echocardiographic data sets acquired with current scanners have enough spatial and temporal resolution to allow the quantitative analysis of the mitral annulus. Accordingly, the authors performed (1) a validation study to assess the agreement of quantitative analysis of the mitral annulus performed on 3D transthoracic echocardiography (TTE) and 3D transesophageal echocardiography (TEE) and (2) a normative study to obtain the reference values of 3D transthoracic echocardiographic parameters for mitral annular (MA) geometry and dynamics. METHODS Mitral valve data sets were obtained by 3D TEE and 3D TTE in 30 consecutive patients with clinically indicated TEE (validation study) and 3D TTE in 224 healthy volunteers (aged 18-76 years) (normative study). RESULTS In the validation study, MA measurements obtained by 3D TTE were similar to those obtained by 3D TEE (P = NS). In the normative study, MA analysis by 3D TTE was feasible (94.5%) and reproducible (intraclass correlation coefficient = 0.78-0.97). MA diameters, area, and circumference were correlated with body surface area (r > 0.50 for all) but not with age. Men had larger MA areas than women (4.9 ± 1.0 vs 4.5 ± 0.7 cm(2)/m(2), P = .004). During systole, MA area decreased by 29 ± 5%. This decrease was related mainly to anteroposterior diameter shortening (20 ± 7%). CONCLUSIONS MA quantitative analysis by 3D TTE was accurate compared with 3D TEE in unselected patients with mitral valve disease. In healthy subjects, it was highly feasible and reproducible. The availability of reference values for MA geometry and dynamics may foster the implementation of MA quantitative analysis by 3D TTE in clinical settings.

Dynamic Changes in Tricuspid Annular Diameter Measurement in Relation to the Echocardiographic View and Timing during the Cardiac Cycle

BACKGROUND Tricuspid annular (TA) size and function play important roles in planning the need for associated TA annuloplasty in patients undergoing cardiac surgery for left-sided heart valve diseases. However, TA diameter normative values and the extent of TA dynamic changes during cardiac cycle remain to be established. METHODS This was a prospective, cross-sectional study of 219 healthy volunteers (mean age, 43 ± 15 years; 57% women), using conventional two-dimensional transthoracic echocardiographic (2DE) imaging to assess the variability of TA diameter measurement in relation to 2DE view and timing during cardiac cycle. TA diameter was obtained from apical right ventricular (RV)-focused four-chamber, parasternal long-axis RV inflow, and parasternal short-axis at aortic plane 2DE views at five time points during the cardiac cycle. Right atrial and RV volumes were measured using three-dimensional echocardiography. RESULTS TA diameters differed significantly among the three 2DE views and changed significantly during the cardiac cycle in all views. Moreover, mean fractional shortening of TA diameter was 24 ± 6% in the four-chamber view, 20 ± 7% in the parasternal long-axis RV inflow view, and 29 ± 11% in the parasternal short-axis at aortic plane view. One multivariate linear regression analysis, age, gender, and right atrial and RV volumes were independently correlated with TA diameters and accounted for 55% of the variance of midsystolic TA diameter in the four-chamber view. CONCLUSIONS This study provides references values for TA diameters and dynamics using 2DE imaging. Age, gender, and right chamber sizes, as well as the 2DE view and time during the cardiac cycle, significantly influenced TA diameters in healthy individuals. These data may help better identify TA dilatation using 2DE imaging for surgical planning.

Physiological Performance of a Detergent Decellularized Heart Valve Implanted for 15 Months in Vietnamese Pigs: Surgical Procedure, Follow‐up, and Explant Inspection

This study features the longest experimental follow-up for decellularized heart valves implanted in an animal model. Porcine aortic heart valves were decellularized according to a disclosed standardized method in which TRITON X-100 and sodium cholate (TRICOL) are used in succession, followed by a further treatment with the endonuclease Benzonase to completely remove the nucleic acid remnants. Experimental animals (n = 17), represented by Vietnamese pigs (VPs), received a decellularized aortic allograft as a substitute for the replacement of their right ventricular outflow tract. The surgical implantation of the TRICOL-treated aortic valve conduit was successful in 11 VPs, while perioperative or postoperative complications occurred in the remaining six animals. In the sham-operated group (n = 4), the native pulmonary root was excised and immediately reimplanted orthotopically in the same animal. Echocardiography demonstrated a satisfactory hemodynamic performance of the TRICOL-treated valves during follow-up as well as the absence of relevant leaflet alterations concerning thickness and motility or valve insufficiency. At explantation, macroscopic inspection of tissue-engineered heart valve conduits did not evidence calcifications and showed a decreased wall thickness, comparable to that of the reimplanted native pulmonary roots. Noteworthy, extended functional performance, recovery of DNA content, and active extracellular matrix precursor incorporation are apparently compatible with the properties of a living self-supporting substitute.

Low-intensity oral anticoagulant plus low-dose aspirin during the first six months versus standard-intensity oral anticoagulant therapy after mechanical heart valve replacement: a pilot study of low-intensity warfarin and aspirin in cardiac prostheses (LIWACAP).

The objective of this study was to evaluate the safety and efficacy of low-intensity warfarin treatment plus aspirin during the first 6 months after surgery in patients undergoing heart valve substitution with mechanical prostheses. Vitamin K antagonists (VKA) are able to reduce but not eliminate thrombosis and systemic embolism in patients with mechanical heart valves. The intensity of treatment and additional use of aspirin in these patients is still controversial. Consecutive patients undergoing aortic or mitral valve replacement (or a combination of the two) with mechanical prostheses were invited to participate in the study. After stratifying for site of prosthesis, patients were randomized to receive low intensity VKA treatment (target INR 2.5) plus aspirin (100 mg/day) for the first six months (Group A) or standard-intensity (INR target 3.7) VKA treatment (Group B). Mean follow-up was 1.5 years. Principal outcome events were systemic embolism, major bleeding, and vascular death. A total of 94 patients in Group A and 104 in Group B were randomized and followed up for 144 and 163 patient years, respectively. There were 5 (5%) events in Group A (4 major bleeding events and 1 vascular death) and 4 (4%) in group B (2 major bleeding events and 2 ischemic stroke). All the events except 1 occurred within the first 6 months after surgery. Cumulative incidence of primary outcome events was 5.8% (95% CI 0.9 to 10.7) in Group A and 4.3% (95% CI 0,2 to 8.4) in Group B (p=0.6). Low-intensity treatment plus aspirin during the first six months after surgery appears to be as effective and safe as moderate-high-intensity anticoagulation.