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Biomedical subjects

James D Thomas

Publications and source records attributed to James D Thomas.

At least 19 recordsLinked to original sources

Contrast-enhanced tissue Doppler imaging of the left atrial appendage is a new quantitative measure of spontaneous echocardiographic contrast in atrial fibrillation.

AIMS: Although left atrial appendage spontaneous echo contrast (LAASEC) is a marker of increased thromboembolic risk in atrial fibrillation, it has previously only been evaluated qualitatively. We sought to determine if an intravenous contrast echocardiographic agent combined with tissue Doppler imaging (TDI) of the LAA could accurately quantify LAA-SEC in patients with atrial fibrillation. METHODS AND RESULTS: We prospectively identified 55 patients with persistent atrial arrhythmias (mean age 63+/-13 years) undergoing a transesophageal echocardiography (TEE), with LAA-SEC prior to direct current cardioversion. In addition to off-line calculation of backscatter index and shear rate, quantification of the velocity in a color TDI region of interest was performed in the LAA cavity following a 0.5-mL intravenous bolus of Optison. LAA-SEC was qualitatively graded by a blindedreader as mild (n = 29) or severe (n = 26), and was compared off-line to TEE-derived quantitative variables. Compared to patients with mild LAA-SEC, those with severe LAA-SEC had significantly decreased LAA emptying velocity, LAA TDI mean velocities and shear rate. Over the whole group, the mean maximal velocity of the LAA using TDI correlated with LAA emptying velocity (r = 0.59; P < 0.0001), shear rate (r = 0.55; P < 0.0001) and LAA area (r = 0.34; P = 0.014). Severe LAA-SEC was found with 72% sensitivity and 82% specificity if TDI mean velocity was <6.13 cm/s. On logistic regression analysis, LAA-TDI was the only predictor of qualitative LAA-SEC grade. CONCLUSION: Contrast-enhanced TDI is an original new tool that provides a quantification of the mean velocity of LAA-SEC that might improve our decision making in patients with atrial fibrillation.

Albumins↗

Incorporation of myofilament activation mechanics into a lumped model of the human heart.

The success and usefulness of lumped cardiovascular models are directly dependent on the physiological fidelity of their formulation. In most existing lumped formulations for the heart, the compliance of the chamber is modeled based on its electrical analog, the capacitor. This has traditionally resulted in the use of a pre-described time-varying stiffness modulus for simulating the cardiac contractions. Unfortunately, such a time-varying stiffness does not include any physiological contractile machinery and thus no dependency on fiber sarcomere length and intracellular calcium concentrations, key mechanisms responsible for proper cardiac function. In this paper a lumped cardiovascular model is presented that is based on the incorporation of detailed myofilament activation for simulating the ventricular calcium binding and cross-bridging mechanism. Upon validation against experimental data, it is shown that the new myofilament activation-based model considerably increases the physiological validity and internal consistency of the cardiovascular simulations in comparison to the traditional variable compliance-based models. It is also shown, through specific case studies, that the present model can serve as a quick response tool for testing various hypotheses concerning the impact of the calcium binding and crossbridge kinetics on the overall performance of the cardiovascular system.

Actin Cytoskeleton↗

Impact of left atrial appendage exclusion on left atrial function.

OBJECTIVES: We sought to investigate the short-term and midterm effects of left atrial appendage exclusion on left atrial function. Left atrial appendage exclusion is considered a possible therapeutic option for stroke prevention in patients with atrial fibrillation. Favorable outcomes have encouraged widespread use of left atrial appendage exclusion for cardiac surgical patients-even for patients in sinus rhythm who have stroke risk factors; however, the chronic effects on left atrial function of left atrial appendage exclusion are unclear. METHODS: Nineteen mongrel dogs (29.7 +/- 5.2 kg) in sinus rhythm were studied. The Doppler signals from the pulmonary venous flow, transmitral flow, and tissue Doppler imaging of mitral annular motion were obtained before and after left atrial appendage exclusion. Dogs were evaluated in the same manner at 7 days (n = 2), 30 days (n = 7), or 90 days (n = 10) after left atrial appendage exclusion. RESULTS: Except for a significant increase in early diastolic transmitral flow velocity after left atrial appendage exclusion (P = .01), no significant differences were found in any parameters related to the transmitral flow and tissue Doppler imaging measurements throughout follow-up. The systolic components of pulmonary venous flow at follow-up revealed a significant reduction relative to baseline (peak systolic velocity P < .0001, systolic velocity-time integral P < .0001), despite the lack of significant changes in left atrial pressure, left ventricular volume, and stroke volume. CONCLUSION: Left atrial appendage exclusion may affect left atrial reservoir function in the short-term and midterm periods. Further long-term studies with more clinically relevant models are needed.

Animals↗

Genetic connectivity in the Florida reef system: comparative phylogeography of commensal invertebrates with contrasting reproductive strategies.

Effective spatial management of coral reefs including design of marine protected areas requires an understanding of interpopulation genetic connectivity. We assessed gene flow along 355 km of the Florida reef system and between Florida and Belize in three commensal invertebrates occupying the same host sponge (Callyspongia vaginalis) but displaying contrasting reproductive dispersal strategies: the broadcast-spawning brittle star Ophiothrix lineata and two brooding amphipods Leucothoe kensleyi and Leucothoe ashleyae. Multiple analytical approaches to sequence variation in the mitochondrial COI gene demonstrated a high degree of overall connectivity for all three species along the Florida reef system. Ophiothrix lineata showed significant genetic structuring between Florida and Belize, and a pattern of isolation by distance but no significant genetic structuring along the Florida coastline. Bayesian estimates of migration detected a strong southerly dispersal bias for O. lineata along the Florida reef system, contrary to the general assumption of northerly gene flow in this region based on the direction of the Florida Current. Both amphipods, despite direct development, also showed high gene flow along the Florida reef system. Multiple inferences of long-distance dispersal from a nested clade analysis support the hypothesis that amphipod transport, possibly in detached sponge fragments, could generate the high levels of overall gene flow observed. However, this transport mechanism appears much less effective across deep water as connectivity between Florida and Belize (1072 km) is highly restricted.

Amphipoda↗

Assessment of left ventricular function by cardiac ultrasound.

Our understanding of the physical underpinnings of the assessment of cardiac function is becoming increasingly sophisticated. Recent developments in cardiac ultrasound permit exploitation of many of these newer physical concepts with current echocardiographic machines. This review will first focus on the current approach to the assessment of cardiovascular hemodynamics by cardiac ultrasound. The next focus will be the assessment of global cardiac mechanics in systole and diastole. Finally, relationships between the cardiac structure and regional myocardial function, and the way regional function can be quantified by ultrasound, will be presented. This review also discusses the clinical impact of echocardiography and its future directions and developments.

Coronary Circulation↗

3D geometry of a normal tricuspid annulus during systole: a comparison study with the mitral annulus using real-time 3D echocardiography.

AIM: This study was done to explore the 3D geometry of the normal tricuspid annulus and compare it with the mitral annulus (MA), using real-time 3D echocardiography (RT3DE) and newly developed 3D computer software. METHODS: Thirteen left ventricular (LV) and 13 right ventricular (RV) volumetric images were obtained using RT3DE from normal subjects. LV and RV volumetric data were segmented into 16 rotational apical planes (angle increment=11.25 degrees ) around the rotational axis from the apex through the center of two annuli, using newly developed 3D software (TomTec, Co., Munich, Germany). Two hinge points of the MA and the TA were traced in each plane during early and late systole. The MA and the TA were then automatically reconstructed with those 32 traced points. 3D surface (3DMAA, 3DTAA) and 2D projected areas (2DMAA, 2DTAA) of the annuli were calculated automatically as well, from those fitted data. For a comparison between the two annuli, the 3D and 2D area measurements of both annuli were corrected (c) according to the height of each patient (c2DMAA, c2DTAA, c3DMAA, and c3DTAA). Non-planarity of the annuli was estimated by their non-planar angles (MA: the angle between the anterior and posterior parts of the annulus; TA: the angle between the septal and free wall parts of the annulus). RESULTS: The TA revealed a less non-planar saddle shape than did the MA, which had a significantly wider non-planar angle (167.7+/-3.2 vs 145.5+/-6.1 degrees , p<0.01) and a round or oval appearance on the projected view. The c2DTAA was significantly larger than the c2DMAA during early systole (p<0.01). However, there was no significant difference between the c3DTAA and c3DMAA during early and late systole (p>0.01). CONCLUSION: We assessed the 3D geometry of the MA and the TA by 3D reconstruction using RT3DE and newly developed computer software. The TA had a less non-planar shape compared with the MA, with either a round or oval appearance on the projected view.

Adult↗

Value of mitral valve tenting volume determined by real-time three-dimensional echocardiography in patients with functional mitral regurgitation.

This study sought to evaluate mitral valve tenting volume (TnV) as a clinical parameter using real-time 3-dimensional echocardiography in patients with functional mitral regurgitation (MR). In 27 patients with functional MR and 4 controls without mitral disease, real-time 3-dimensional echocardiographic images were obtained to measure TnV frame by frame from presystole to end-systole. The maximal and minimal TnVs during systole were identified in each patient, and mitral annular areas and tenting heights were also measured. Using 2-dimensional echocardiography, tenting area (TnA) was measured from the apical long-axis, apical 4-chamber, and apical 2-chamber views. The regurgitant orifice area was measured by the proximal isovelocity surface area method. Maximal and minimal TnVs occurred at the time of 2 +/- 6% and 78 +/- 6% of whole systolic duration, respectively, and the systolic percentage change of TnV was related to that of tenting height but not to that of mitral annular area. TnA on the long-axis images was significantly larger than that on the 4- and 2-chamber images (2.5 +/- 1.4 vs 1.7 +/- 1.3 and 1.9 +/- 1.4 cm(2), respectively, p <0.001). Regurgitant orifice area was significantly correlated with maximal TnV (r = 0.90), minimal TnV (r = 0.86), and TnA on the long-axis (r = 0.79), 4-chamber (r = 0.75), and 2-chamber (r = 0.73) images. Among minimal TnV and 3 TnAs, minimal TnV was the only independent determinant of regurgitant orifice area (p <0.001). Minimal TnV >or=3.90 ml identified significant functional MR with a sensitivity of 86% and a specificity of 100%. In conclusion, TnV derived from real-time 3-dimensional echocardiography is a preferable novel single index for assessing mitral valve tethering in functional MR to TnA that is dependent on the location of 2-dimensional planes.

Blood Flow Velocity↗

Three-dimensional geometry of the tricuspid annulus in healthy subjects and in patients with functional tricuspid regurgitation: a real-time, 3-dimensional echocardiographic study.

BACKGROUND: Most rings currently used for tricuspid valve annuloplasty are formed in a single plane, whereas the actual tricuspid annulus (TA) may have a nonplanar or 3-dimensional (3D) structure. The purpose of this study was therefore to investigate the 3D geometry of the TA in healthy subjects and in patients with functional tricuspid regurgitation (TR). METHODS AND RESULTS: This study consisted of 15 healthy subjects and 16 patients with functional TR who had real-time 3D echocardiography. With our customized software, 8 points along the TA were determined with the rotated plane around the axis at 45 degrees intervals. The TA was traced during a cardiac cycle. The distance between diagonals connecting 2 points was measured. The height was defined as the distance from the plane determined by least-squares regression analysis at all 8 points. Both the maximum (7.5+/-2.1 versus 5.6+/-1.0 cm2/m2) and minimum (5.7+/-1.3 versus 3.9+/-0.8 cm2/m2) TA areas in patients with TR were larger than those in healthy subjects (both P<0.01). Healthy subjects had a nonplanar-shaped TA with homogeneous contraction. The posteroseptal portion was the lowest toward the apex from the right atrium, and the anteroseptal portion was the highest. In patients with functional TR, the TA was dilated in the septal to lateral direction, resulting in a more circular shape than in healthy subjects. A similar 3D pattern was observed in patients with TR, but it was more planar than that in healthy subjects. CONCLUSIONS: Real-time 3D echocardiography showed a complicated 3D structure of the TA, which appeared to be different from the "saddle-shaped" mitral annulus, suggesting an annuloplasty for TR different from that for mitral regurgitation.

Adult↗

Determinants of recurrent or residual functional tricuspid regurgitation after tricuspid annuloplasty.

BACKGROUND: The durability of tricuspid valve (TV) repair by annuloplasty is limited. Identification of mechanisms of recurrent or residual tricuspid regurgitation (TR) after annuloplasty is necessary to improve results of TV repair. The purpose of this study was to investigate echocardiographic determinants of mid-term outcome after TV annuloplasty. METHODS AND RESULTS: This study consisted of 39 patients with functional TR who had echocardiography preoperatively, early postoperatively (5+/-2 days), and >1 year (20+/-6 months) after TV annuloplasty. Detailed echocardiographic measurements were performed, including TR severity, TV annular dimension, TV leaflet displacement, left ventricular (LV) function, and right ventricular (RV) function and pressures. Preoperative leaflet tethering height and area predicted early and mid-term outcome of annuloplasty. Early postoperative LV ejection fraction and TR severity influenced degree of TR >1 year after surgery. In addition, increased RV pressure was related to worse TR during late follow-up. CONCLUSIONS: Although TV tethering is an important determinant of recurrent or residual TR, LV and RV function and pressures impact repair durability. These factors identify patients at risk for repair failure; such individuals require development of additional surgical strategies to improve results of tricuspid valve repair and close surveillance after surgery.

Aged↗

Echocardiographic predictors of successful versus unsuccessful mitral valve repair in ischemic mitral regurgitation.

Mitral valve (MV) annuloplasty is the standard surgical technique for the management of ischemic mitral regurgitation (MR). However, < or = 1/3 of patients develop recurrent MR after annuloplasty. Therefore, we sought to identify the preoperative echocardiographic parameters that predict annuloplasty failure in patients with ischemic MR. Intraoperative transesophageal echocardiograms from 365 patients who underwent MV repair for ischemic MR were reviewed. Of the 365 patients, 297 (81%) had satisfactory outcomes with < 2+ MR, and 68 (19%) had recurrent MR (> or = 2+) during a mean follow-up of 269 days. The mitral annular parameters, including mitral annular diameter, tethering height, and tethering area of the mitral leaflets, were determined in 3 different echocardiographic views. On multiple logistic stepwise regression analysis, a higher mitral annular diameter, higher tethering area, and higher MR severity were identified as independent predictors for failure of MV repair (p < 0.0001). In conclusion, these results demonstrated that preoperative echocardiographic findings can be used to identify patients with ischemic MR at increased risk of repair failure. These echocardiographic measurements should be used to guide the cardiologist and cardiac surgeon in the choice of MV repair versus replacement in patients with ischemic MR.

Adult↗

Maturational and adaptive modulation of left ventricular torsional biomechanics: Doppler tissue imaging observation from infancy to adulthood.

BACKGROUND: Left ventricular (LV) torsional deformation, based in part on the helical myocardial fiber architecture, is an important component of LV systolic and diastolic performance. However, there is no comprehensive study describing its normal development during childhood and adult life. METHODS AND RESULTS: Forty-five normal subjects (25 children and 20 adults; aged 9 days to 49 years; divided into 5 groups: infants, children, adolescents, and young and middle-age adults) underwent assessment of LV torsion and untwisting rate by Doppler tissue imaging. LV torsion increased with age, primarily owing to augmentation in basal clockwise rotation during childhood and apical counterclockwise rotation during adulthood. Although LV torsion and untwisting overall showed age-related increases, when normalized by LV length, they showed higher values in infancy and middle age. The proportion of untwisting during isovolumic relaxation was lowest in infancy, increased during childhood, and leveled off thereafter, whereas peak untwisting performance (peak untwisting velocity normalized by peak LV torsion) showed a decrease during adulthood. CONCLUSIONS: We have shown the maturational process of LV torsion in normal subjects. Net LV torsion increases gradually from infancy to adulthood, but the determinants of this were different in the 2 age groups. The smaller LV isovolumic untwisting recoil during infancy and its decline in adulthood may suggest mechanisms for alterations in diastolic function.

Adaptation, Physiological↗

Enhanced ventricular untwisting during exercise: a mechanistic manifestation of elastic recoil described by Doppler tissue imaging.

BACKGROUND: The cascade of events by which early diastolic left ventricular (LV) filling increases with exercise is not fully elucidated. Doppler tissue imaging (DTI) can detect myocardial motion, including torsion, whereas color M-mode Doppler (CMM) can quantify LV intraventricular pressure gradients (IVPGs). METHODS AND RESULTS: Twenty healthy volunteers underwent echocardiographic examination with DTI at rest and during submaximal supine bicycle exercise. We assessed LV long-/short-axis function, torsion, volume, inflow dynamics, and early diastolic IVPG derived from CMM data. LV torsion and untwisting velocity increased with exercise (torsion, 11+/-4 degrees to 24+/-8 degrees ; untwisting velocity, -2.0+/-0.7 to -5.6+/-2.3 rad/s) that was associated with an increase in IVPG (1.4+/-0.5 to 3.7+/-1.2 mm Hg). Untwisting in normal subjects occurred during isovolumic relaxation and early filling, significantly before long-axis lengthening or radial expansion. The clinical feasibility of this method was tested in 7 patients with hypertrophic cardiomyopathy (HCM); torsion was higher at rest but did not increase with exercise (16+/-4 degrees to 14+/-6 degrees), whereas untwisting was delayed and unenhanced (-1.6+/-0.8 to -2.3+/-1.2 rad/s). In concert, IVPG was similar at rest (1.2+/-0.3 mm Hg), but the exercise response was blunted (1.6+/-0.8 mm Hg). In normal subjects and HCM patients, there was a similar linear relation between IVPG and untwisting rate, with an overall correlation coefficient of r=0.75 (P<0.0001). CONCLUSIONS: LV untwisting appears to be linked temporally with early diastolic base-to-apex pressure gradients, enhanced by exercise, which may assist efficient LV filling, an effect that appears blunted in HCM. Thus, LV torsion and subsequent rapid untwisting appear to be manifestations of elastic recoil, critically linking systolic contraction to diastolic filling.

Adult↗

Scaling of diastolic intraventricular pressure gradients is related to filling time duration.

In early diastole, pressure is lower in the apex than in the base of the left ventricle (LV). This early intraventricular pressure difference (IVPD) facilitates LV filling. We assessed how LV diastolic IVPD and intraventricular pressure gradient (IVPG), defined as IVPD divided by length, scale to the heart size and other physiological variables. We studied 10 mice, 10 rats, 5 rabbits, 12 dogs, and 21 humans by echocardiography. Color Doppler M-mode data were postprocessed to reconstruct IVPD and IVPG. Normalized LV filling time was calculated by dividing filling time by RR interval. The relationship between IVPD, IVPG, normalized LV filling time, and LV end-diastolic volume (or mass) as fit to the general scaling equation Y = kM beta, where M is LV heart size parameter, Y is a dependent variable, k is a constant, and beta is the power of the scaling exponent. LV mass varied from 0.049 to 194 g, whereas end-diastolic volume varied from 0.011 to 149 ml. The beta values relating normalized LV filling time with LV mass and end-diastolic volume were 0.091 (SD 0.011) and 0.083 (SD 0.009), respectively (P < 0.0001 vs. 0 for both). The beta values relating IVPD with LV mass and end-diastolic volume were similarly significant at 0.271 (SD 0.039) and 0.243 (SD 0.0361), respectively (P < 0.0001 vs. 0 for both). Finally, beta values relating IVPG with LV mass and end-diastolic volume were -0.118 (SD 0.013) and -0.104 (SD 0.011), respectively (P < 0.0001 vs. 0 for both). As a result, there was an inverse relationship between IVPG and normalized LV filling time (r = -0.65, P < 0.001). We conclude that IVPD decrease, while IVPG increase with decreasing animal size. High IVPG in small mammals may be an adaptive mechanism to short filling times.

Adult↗

Geometric predictor of significant mitral regurgitation in patients with severe ischemic cardiomyopathy, undergoing Dor procedure: a real-time 3D echocardiographic study.

BACKGROUND AND PURPOSE: Significant mitral regurgitation (MR) is frequently associated with coronary artery disease. The precise geometric predictors of significant MR in ischemic cardiomyopathy are not clearly defined. We performed real-time 3D echocardiography (RT3DE) in 48 patients scheduled for infarct exclusion surgery or Dor procedure, 22 of whom had moderate or severe MR (DorMR) and 26 with no or trivial MR (DorNoMR). METHODS: Two orthogonal apical volumetric planes of LV, commissure-commissure (CC) and antero-posterior (AP) planes, were generated during mid-systole. Mitral valve tenting height (MVTht) and area (MVTa) were measured. The degree of leaflet tethering was estimated by the angles between the annular plane and each leaflet (anterior leaflet: Aalpha, posterior leaflet: Palpha). RESULTS: MVTht (1.11+/-0.14 vs 0.78+/-0.20 cm, P<0.01) and MVTa (1.30+/-0.34 vs 0.87+/-0.27 cm(2), P<0.01) were significantly larger in DorMR compared with DorNoMR. In DorMR, both Aalpha (38+/-6 vs 31+/-7 degrees , P<0.01) and Palpha (60+/-7 vs 41+/-8 degrees , P<0.01) significantly increased more than those in DorNoMR. Multiple logistic regression analysis found Palpha to be the most important geometric predictor of significant MR. MV tenting area was found to be the strongest determinant of MR severity in ischemic cardiomyopathy patients with significant MR by multivariate linear regression analysis. CONCLUSIONS: Detecting significant posterior leaflet tethering, the most important predictor of significant MR, and measuring MV tenting area, the strongest determinant of MR severity, using RT3DE may be helpful in decision making of additive surgical intervention for MR in patients with severe ischemic cardiomyopathy.

Cardiomyopathies↗

Clinical features of mixed physiology of constriction and restriction: echocardiographic characteristics and clinical outcome.

AIMS: An entity of patients with mixed physiology of constriction and restriction has been reported, however, the characteristics of these patients have not been well documented. We evaluated the clinical features and the outcome of these patients. METHODS AND RESULTS: Study subjects consisted of 38 patients (57+/-14 years, 8 females, 30 males) who were diagnosed as having mixed physiology based on transthoracic and/or transesophageal echocardiography, MRI (or CT), cardiac catheterization, endomyocardial biopsy and/or surgical findings. Prior radiation therapy was the most frequent (50%) cause of mixed physiology followed by coronary artery bypass graft without prior radiation (24%) and heart transplantation (8%). The respiratory variation of peak early diastolic transmitral flow velocity by pulsed Doppler transesophageal echocardiography was 10.7% in patients with sinus rhythm and 18.1% in patients with atrial arrhythmia. Pericardial thickening was noted adjacent to the right-sided chambers in 19 patients, left-sided chambers in 10 patients, or both in 9 patients. All-cause 5-year mortality was 40% and unrelated to age, etiology, left ventricular systolic function and therapeutic course. There was a statistically significant difference (p<0.01) between the survival rates in patients with mixed physiology and in patients with pure constriction (n=125). CONCLUSIONS: Due to the high mortality in this disease, discrimination of the entity from the patients with pure constriction is mandatory. Transthoracic and transesophageal echocardiography are helpful noninvasive techniques in the diagnosis and the understanding of the physiology of patients with mixed constriction and restriction.

Adult↗

Tissue synchronization imaging and optimal left ventricular pacing site in cardiac resynchronization therapy.

The optimal pacing site in cardiac resynchronization therapy (CRT) remains controversial. Tissue synchronization imaging is a novel echocardiographic technique that color-codes for areas of maximal delay in myocardial velocities. This study aimed to identify whether the left ventricular (LV) pacing lead position in CRT should be guided by a patient's area of maximal mechanical delay. Fifty-four patients with advanced heart failure were assessed echocardiographically before and 6 months after CRT. Response was analyzed according to the relation between the LV lead position and the area of maximal delay to peak velocity by tissue synchronization imaging in the first half of the ejection phase: group 1 (n = 22) had lead placement corresponding to the segment of maximal delay; group 2 (n = 13) had lead placement 1 segment adjacent; and group 3 (n = 19) had lead placement remote from this site. Evidence of LV reverse remodeling and improved systolic function was documented in group 1 (mean percentage decrease in end-systolic volume 23%) more than in group 2 (mean decrease 15%), and more than in group 3 (mean increase 8.9%, p <0.0001 compared with groups 1 and 2). In group 1, 16 of 22 patients had reverse remodeling (>15% decrease in end-systolic volume); reverse remodeling was seen in 7 of 13 patients in group 2 and 1 of 19 in group 3. The placing of the lead position proximal to the site of maximal delay by tissue synchronization imaging was correlated with reverse remodeling (r = 0.449, p = 001). Of 7 patients with delay confined to the septum and anterior wall only, none had evidence of reverse remodeling after CRT. In conclusion, pacing at the site of maximal mechanical delay was associated with reverse remodeling. Individually tailored LV lead positioning should be considered before CRT.

Adult↗

Rationale and design: the VALsartan In Diastolic Dysfunction (VALIDD) Trial: evolving the management of diastolic dysfunction in hypertension.

BACKGROUND: Although 50% of hypertensive patients in the community are estimated to have diastolic dysfunction, there is no specific guideline for diastolic dysfunction therapy at present despite the condition's clear association with increased cardiovascular risk. Although the efficacy of angiotensin II receptor blockers (ARBs) in hypertension and left ventricular hypertrophy regression has been established, the effect of angiotensin II receptor blockade on intrinsic parameters of diastolic function has not been evaluated in large-scale studies. METHODS: The VALIDD Trial is an investigator-initiated randomized, controlled, double-blind clinical trial on approximately 350 patients designed to explore whether antihypertensive therapy with the ARB valsartan, in addition to standard therapy, would improve intrinsic diastolic properties of the myocardium in patients with hypertension and evidence of diastolic dysfunction. The result of such therapy will be compared with placebo after 38 weeks of treatment. The primary efficacy variable is change in early diastolic lateral mitral annular relaxation velocity measured by tissue Doppler imaging on week 38. CONCLUSIONS: We expect the VALIDD Trial to provide novel insights into the specific effects of ARBs on diastolic dysfunction, as assessed by tissue Doppler imaging, in hypertensive patients. The trial may provide clinically useful data on whether such therapy can directly improve diastolic function in patients with hypertension.

Angiotensin II Type 1 Receptor Blockers↗