High-resolution, genome-wide mapping of positive supercoiling in chromosomes.

Supercoiling impacts DNA replication, transcription, protein binding to DNA, and the three-dimensional organization of chromosomes. However, there are currently no methods to directly interrogate or map positive supercoils, so their distribution in genomes remains unknown. Here, we describe a method, GapR-seq, based on the chromatin immunoprecipitation of GapR, a bacterial protein that preferentially recognizes overtwisted DNA, for generating high-resolution maps of positive supercoiling. Applying this method to Escherichia coli and Saccharomyces cerevisiae, we find that positive supercoiling is widespread, associated with transcription, and particularly enriched between convergently oriented genes, consistent with the 'twin-domain' model of supercoiling. In yeast, we also find positive supercoils associated with centromeres, cohesin-binding sites, autonomously replicating sites, and the borders of R-loops (DNA-RNA hybrids). Our results suggest that GapR-seq is a powerful approach, likely applicable in any organism, to investigate aspects of chromosome structure and organization not accessible by Hi-C or other existing methods.

The Smc5/6 Core Complex Is a Structure-Specific DNA Binding and Compacting Machine.

The structural organization of chromosomes is a crucial feature that defines the functional state of genes and genomes. The extent of structural changes experienced by genomes of eukaryotic cells can be dramatic and spans several orders of magnitude. At the core of these changes lies a unique group of ATPases-the SMC proteins-that act as major effectors of chromosome behavior in cells. The Smc5/6 proteins play essential roles in the maintenance of genome stability, yet their mode of action is not fully understood. Here we show that the human Smc5/6 complex recognizes unusual DNA configurations and uses the energy of ATP hydrolysis to promote their compaction. Structural analyses reveal subunit interfaces responsible for the functionality of the Smc5/6 complex and how mutations in these regions may lead to chromosome breakage syndromes in humans. Collectively, our results suggest that the Smc5/6 complex promotes genome stability as a DNA micro-compaction machine.

From bead to rod: Comparison of theories by measuring translational drag coefficients of micron-sized magnetic bead-chains in Stokes flow.

Frictional drag force on an object in Stokes flow follows a linear relationship with the velocity of translation and a translational drag coefficient. This drag coefficient is related to the size, shape, and orientation of the object. For rod-like objects, analytical solutions of the drag coefficients have been proposed based on three rough approximations of the rod geometry, namely the bead model, ellipsoid model, and cylinder model. These theories all agree that translational drag coefficients of rod-like objects are functions of the rod length and aspect ratio, but differ among one another on the correction factor terms in the equations. By tracking the displacement of the particles through stationary fluids of calibrated viscosity in magnetic tweezers setup, we experimentally measured the drag coefficients of micron-sized beads and their bead-chain formations with chain length of 2 to 27. We verified our methodology with analytical solutions of dimers of two touching beads, and compared our measured drag coefficient values of rod-like objects with theoretical calculations. Our comparison reveals several analytical solutions that used more appropriate approximation and derived formulae that agree with our measurement better.

mDia1 senses both force and torque during F-actin filament polymerization.

Formins, an important family of force-bearing actin-polymerizing factors, function as homodimers that bind with the barbed end of actin filaments through a ring-like structure assembled from dimerized FH2 domains. It has been hypothesized that force applied to formin may facilitate transition of the FH2 ring from an inhibitory closed conformation to a permissive open conformation, speeding up actin polymerization. We confirm this hypothesis for mDia1 dependent actin polymerization by stretching a single-actin filament in the absence of profilin using magnetic tweezers, and observe that increasing force from 0.5 to 10 pN can drastically speed up the actin polymerization rate. Further, we find that this force-promoted actin polymerization requires torsionally unconstrained actin filament, suggesting that mDia1 also senses torque. As actin filaments are subject to complex mechanical constraints in living cells, these results provide important insights into how formin senses these mechanical constraints and regulates actin organization accordingly.

Bacillus subtilis RecA with DprA-SsbA antagonizes RecX function during natural transformation.

Bacillus subtilis DprA and RecX proteins, which interact with RecA, are crucial for efficient chromosomal and plasmid transformation. We showed that RecA, in the rATP·Mg2+ bound form (RecA·ATP), could not compete with RecX, SsbA or SsbB for assembly onto single-stranded (ss)DNA, but RecA·dATP partially displaced these proteins from ssDNA. RecX promoted reversible depolymerization of preformed RecA·ATP filaments. The two-component DprA-SsbA mediator reversed the RecX negative effect on RecA filament extension, but not DprA or DprA and SsbB. In the presence of DprA-SsbA, RecX added prior to RecA·ATP inhibited DNA strand exchange, but this inhibition was reversed when RecX was added after RecA. We propose that RecA nucleation is more sensitive to RecX action than is RecA filament growth. DprA-SsbA facilitates formation of an active RecA filament that directly antagonizes the inhibitory effects of RecX. RecX and DprA enable chromosomal transformation by altering RecA filament dynamics. DprA-SsbA and RecX proteins constitute a new regulatory network of RecA function. DprA-SsbA contributes to the formation of an active RecA filament and directly antagonizes the inhibitory effects of RecX during natural transformation.

Dependence of the structure and mechanics of metaphase chromosomes on oxidized cysteines.

We have found that reagents that reduce oxidized cysteines lead to destabilization of metaphase chromosome folding, suggesting that chemically linked cysteine residues may play a structural role in mitotic chromosome organization, in accord with classical studies by Dounce et al. (J Theor Biol 42:275-285, 1973) and Sumner (J Cell Sci 70:177-188, 1984a). Human chromosomes isolated into buffer unfold when exposed to dithiothreitol (DTT) or tris(2-carboxyethyl)phosphine (TCEP). In micromanipulation experiments which allow us to examine the mechanics of individual metaphase chromosomes, we have found that the gel-like elastic stiffness of native metaphase chromosomes is dramatically suppressed by DTT and TCEP, even before the chromosomes become appreciably unfolded. We also report protein labeling experiments on human metaphase chromosomes which allow us to tag oxidized and reduction-sensitive cysteine residues. PAGE analysis using fluorescent labels shows a small number of labeled bands. Mass spectrometry analysis of similarly labeled proteins provides a list of candidates for proteins with oxidized cysteines involved in chromosome organization, notably including components of condensin I, cohesin, the nucleosome-interacting proteins RCC1 and RCC2, as well as the RNA/DNA-binding protein NONO/p54NRB.

Three-dimensional propagation imaging of left ventricular activation by speckle-tracking echocardiography to predict responses to cardiac resynchronization therapy.

BACKGROUND: On the basis of the electromechanical coupling theory, an activation imaging system has been developed with three-dimensional speckle-tracking echocardiography. The aim of this study was to determine the association between left ventricular (LV) propagation patterns by activation imaging and response to cardiac resynchronization therapy (CRT). METHODS: This was a retrospective, single-center study. Eighty-one patients undergoing CRT, of whom 50 (61.7%) had left bundle branch block (LBBB), were enrolled. Activation imaging studies were performed with a three-dimensional speckle-tracking echocardiographic system, which allowed visualization of LV activation propagation and measurement of the time from the QRS complex to activation onset. A CRT volume responder was defined as a patient with ≥15% reduction of LV end-systolic volume at 6 months after CRT. Clinical outcomes were assessed with the composite end point of death due to cardiac causes or unplanned hospitalization for cardiac diseases. RESULTS: In patients with LBBB, the main activation pattern (74%) was a U-shaped propagation pattern, which was characterized as propagation from the midseptum to the lateral or posterior wall through the apex. In patients without LBBB, various non-U-shaped propagation patterns were observed in the majority of patients (97%). Among the 41 CRT responders, almost all (87.8%) had the U-shaped propagation pattern. During follow-up (median, 20 months), 29 patients (35.8%) reached the clinical end points. In a multivariate Cox proportional hazards model, a U-shaped propagation pattern was associated with the end points independently of LBBB or LV end-diastolic volume. CONCLUSIONS: The U-shaped propagation pattern on three-dimensional speckle-tracking echocardiography was significantly associated with a favorable CRT response. Activation pattern analysis may provide additional information to predict response to CRT.

Age-associated alterations in the micromechanical properties of chromosomes in the mammalian egg.

PURPOSE: The incidence of aneuploidy in eggs from women of advanced reproductive age can exceed 60%, making the mammalian egg a unique model system to study the mechanisms of chromosome segregation errors. METHODS: Here we applied a novel biophysical chromosome stretching approach to quantify mechanical stiffness of meiotic chromosomes in the mammalian egg and then documented how these properties changed in a mouse model of physiologic reproductive aging. RESULTS: We found significant differences in chromosome micromechanics, and thus in higher order chromosome structure, coincident with advanced reproductive age, a time that is also unequivocally associated with an increase in egg aneuploidy. CONCLUSIONS: These findings have important implications for both reproductive and cancer biology where aneuploidy plays a central role in aging related disease states.

Three-dimensional speckle tracking echocardiography.

Speckle tracking echocardiography (STE) was popularized in the first decade of this century. Analysis of cardiac mechanics has been the focus of ultrasonics, and the breakthrough came with STE. Beyond analysis solely of left ventricular ejection fraction, STE allows the assessment of various pathophysiologies, including myocardial layer-specific myocardial function, twist and rotation, and dyssynchrony. Recent developments in the technology have resulted in commercially available 3-dimensional (D)-STE systems. Through experimental studies and clinical investigations, the reliability and feasibility of 3D-STE-derived data have been validated, and the advantages of 3D-STE over 2D-STE have been revealed. In addition, because of the 3D nature of the technology, 3D-STE provides novel deformation parameters (ie, 3D-strain and area change ratio) that have the potential for more accurate assessment of overall and regional myocardial function. Recently, various preliminary studies using 3D-STE have reported on myocardial characteristics, novel mechanics in the left ventricle, prediction of therapeutic effects, observations of cardiac function through interventions, and challenges for left atrial and right ventricular functions. In this review, we focus on the features of the methodology, validation, and clinical application of 3D-ST.

Novel dyssynchrony evaluation by M-mode imaging in left bundle branch block and the application to predict responses for cardiac resynchronization therapy.

BACKGROUND: To determine an appropriate M-mode method in assessing left ventricular (LV) dyssynchrony in left bundle branch block (LBBB), and to assess feasibility of the method to predict cardiac resynchronization therapy (CRT) responses. METHODS AND RESULTS: Fifty-one patients with LBBB were enrolled. Among them 31 patients underwent CRT. In addition to original septal to posterior wall motion delay (SPWMD), first peak-SPWMD was proposed as time of difference between the first septal displacement and the maximum displacement of the posterior. If an early septal point was not present, anatomical M-mode was used to visualize an early septal displacement spreading scan-area until inferoseptal wall. CRT responders were defined as LV end-systolic volume reduction (>15%) at 6 months after CRT. Twenty patients (65%) were identified as CRT responders. First peak-SPWMD in responders was significantly higher than those in nonresponders, although SPWMD did not differ between groups. Strong predicting ability of first peak-SPWMD was revealed (first peak-SPWMD: 80/90/83%; SPWMD: 35/100/58%), and area under the curve in receiver operating characteristic analysis of first peak-SPWMD (0.88) was significantly higher than that of SPWMD (0.61) (p<0.05). CONCLUSION: In patients with LBBB, time differences between early septal and delayed displacement of posterolateral wall on M-mode images were the appropriate dyssynchrony parameter, and could improve the predictive ability for CRT responses.

Diastolic suction in heart failure: impact of left ventricular geometry, untwist, and flow mechanics.

AIMS: Vector flow mapping (VFM) can be used to assess intraventricular hemodynamics quantitatively. This study assessed the magnitude of the suction flow kinetic energy with VFM and investigated the relation between left ventricular (LV) function and geometry in patients with an estimated elevated LV filling pressure. MATERIALS AND METHODS: We studied 24 subjects with an elevated LV filling pressure (EFP group) and 36 normal subjects (normal group). Suction was defined as flow directed toward the apex during the period from soon after systolic ejection to before mitral inflow. The flow kinetic energy index was quantified as the sum of the product of the blood mass and velocity vector and its magnitude to the peak value was measured. KEY FINDINGS: Suction flow was observed in 12 (50%) EFP-group patients and 36 (100%) normal-group subjects. The magnitude of the suction kinetic energy index was significantly smaller in EFP versus normal group (2.7 ± 3.8 vs. 5.7 ± 4.4 g/s/cm(2), P<0.01). The EFP-group patients with suction had a smaller LV end-systolic volume (ESV) (P<0.01), greater ellipsoidal geometry (P<0.05) and untwisting rate (P<0.01) than the EFP-group patients without suction. A regression analysis indicated a significant linear relation between the suction kinetic energy index and LVEF (r=0.43, P=0.04), ESV (r=-0.40, P=0.05), eccentricity index (r=0.44, P=0.04), and untwisting rate (r=0.51, P=0.04). SIGNIFICANCE: The magnitude of the suction flow kinetic energy index derived from VFM may allow the quantitative assessment of the suction flow, which correlates with LV systolic function, geometry, and untwisting mechanics.

Complex left atrial appendage morphology and left atrial appendage thrombus formation in patients with atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation (AF), most thrombus forms in the left atrial appendage (LAA). However, the relation of LAA morphology with LAA thrombus is unknown. METHODS AND RESULTS: We prospectively enrolled 633 consecutive patients who were candidates for catheter ablation for symptomatic drug-resistant AF. Transesophageal echocardiography (TEE) was performed to assess LAA thrombus. LAA structure was assessed by 3-dimensional TEE. LAA orifice area, depth, volume, and number of lobes were measured on reconstructed 3-dimensional images. Clinical characteristics and echocardiographic measures were compared to determine variables predicting LAA thrombus. Excluded were 69 (10.9%) patients who met the exclusion criteria. Finally, this study comprised 564 patients, of whom LAA thrombus was observed in 36 (6.4%) patients. Multivariate analysis revealed CHADS2 (Congestive heart failure, Hypertension Age>75, Diabetes mellitus and prior Stroke or transient ischemic attack) score (P=0.002), left ventricular ejection fraction (P=0.01), degree of spontaneous echo contrast (P=0.02), left atrial volume (P=0.02), and number of LAA lobes (P<0.001) to be independently associated with thrombus formation. Most patients with LAA thrombus (32/34, 94.4%) had ≥3 LAA lobes, whereas LAA thrombus was observed in only 2 (0.7%) of 296 patients with 1 or 2 lobes. LAA volume significantly decreased in patients maintaining sinus rhythm after catheter ablation (P=0.0009). Number of LAA lobes did not change in any patient. CONCLUSIONS: Complex LAA morphology characterized by an increased number of LAA lobes was associated with the presence of LAA thrombus independently of clinical risk and blood stasis. This study suggests that LAA morphology might be a congenital risk factor for LAA thrombus formation in patients with AF.

Left ventricular strain and transmural distribution of structural remodeling in hypertensive heart disease.

Left ventricular (LV) systolic wall strain is a new candidate for prognostic indicator of hypertensive heart failure. It remains unclear how underlying transmural structural remodeling corresponds to LV wall systolic deformation as hypertensive hypertrophy progresses. We fed 68 Dahl salt-sensitive rats a high-salt (hypertensive group) or low-salt diet (control group) from 6 weeks old. At 10, 14, and 18 weeks, pressure-volume relation, transmural distribution of LV fibrosis, and myocyte hypertrophy were evaluated. LV global longitudinal and circumferential strain was measured with speckle tracking echocardiography. Emax was preserved throughout the study period, whereas τ and end-diastolic pressure-volume relation progressively deteriorated from 14 weeks (diastolic dysfunction stage). Lung weight increased significantly at 18 weeks (decompensated stage). Histological percentage area fibrosis and collagen type I/III, myocyte hypertrophy, and α-myosin heavy chain isoform increased in the subendocardial layer at 14 weeks and progressed into the midlayer at 18 weeks. Longitudinal strain progressively deteriorated in the hypertensive group versus control group at 14 weeks (hypertensive group: -17±3%, control: -27±4%; P<0.001), and circumferential strain decreased at 18 weeks (hypertensive group: -17±2%, control: -27±3%; P=0.002). After adjustment for systolic wall stress, subendocardial percentage area fibrosis was selected as the independent determinant of longitudinal strain. This study showed that LV wall strain alternations were accompanied by fibrosis and myocyte hypertrophy from subendocardium to epicardium, and longitudinal strain related significantly to subendocardial layer fibrosis. Longitudinal strain could be a surrogate of subendocardial fibrotic changes and may be useful for risk stratification of hypertensive heart failure.

Feasibility of left ventricular volume measurements by three-dimensional speckle tracking echocardiography depends on image quality and degree of left ventricular enlargement: validation study with cardiac magnetic resonance imaging.

BACKGROUND: Novel 3-dimensional echocardiography with speckle tracking imaging (3D-STE) may have advantages in assessing left ventricular (LV) volume through a cardiac cycle. The feasibility of 3D-STE may be affected by image quality and LV morphology. METHODS AND RESULTS: We studied 64 patients (38 men, age 55±12 years) who underwent cardiac magnetic resonance imaging (CMRI) and 3D-STE on the same day. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured by both modalities. Imaging qualities were quantified in each of 6 LV segments by an imaging quality score (IQS) of 1-3, and scores were averaged (mean IQS) at end-diastole and end-systole. Compared to CMRI, 3D-STE showed a tendency to underestimate LV volume measurements, but not significantly (EDV: bias=-18±37ml; ESV: bias=-10±34ml), and measurements correlated well with those by CMRI (EDV: R=0.80, ESV: R=0.86, ejection fraction: R=0.75, p<0.001). The absolute differences of LVEDV and ESV between 3D-STE and CMRI correlated significantly with mean IQS (LVEDV, R=-0.35, p=0.005; LVESV, R=-0.30, p=0.02). Based on the medium value of LVEDV by CMRI (127ml), subjects were classified into the small (<127ml) and large LVEDV (≧127ml) groups. In the large LVEDV group, mean IQS significantly correlated with the absolute differences of LVEDV (mean IQS, r=-0.45, p=0.01), despite no significant correlation in the small LVEDV group. CONCLUSION: 3D-STE could measure LV volume as well as CMRI, however, its accuracy depends on the quality of the acquired image and particularly on enlargement of the left ventricle.

Efficacy, safety, and outcomes of catheter ablation of atrial fibrillation in patients with heart failure with preserved ejection fraction.

OBJECTIVES: This study sought to investigate the efficacy and safety of catheter ablation for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFPEF). BACKGROUND: AF is a precipitating factor for clinical deterioration of HFPEF. METHODS: Catheter ablation for AF was performed in a consecutive 74 patients with compensated HFPEF (left ventricular [LV] ejection fraction >50%). AF-free probability after catheter ablation and factors relating to maintenance of sinus rhythm were investigated. LV strain and strain rate were assessed by echocardiography at baseline and over 12 months after ablation. RESULTS: During a 34 ± 16-month follow-up period, single- and multiple-procedure drug-free success rates were 27% (n = 20) and 45% (n = 33), respectively. Multiple procedures and pharmaceutically assisted success rate was 73% (n = 54). No major complications occurred during follow-up. Multivariate Cox regression analyses revealed that AF type (other than long-standing persistent AF) and lack of hypertension were independently associated with maintenance of sinus rhythm (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.03 to 3.17, p = 0.04; HR: 0.49, 95% CI: 0.24 to 0.96, p = 0.04, respectively). LV systolic indices (LV ejection fraction, LV strain/strain rate at systole) and diastolic indices (E/E', ratio of LV strain rate at diastole with early transmitral flow) were improved only in patients maintaining sinus rhythm at follow-up. CONCLUSIONS: Our results suggest that AF can be effectively and safely treated with a composite of repeat procedures and pharmaceuticals in patients with HFPEF. However, the current study was a single-arm analysis; therefore, larger randomized control studies are needed to verify the benefit of AF ablation in this cohort.

Left ventricular activation imaging by 3-dimensional speckle-tracking echocardiography. Comparison with electrical activation mapping.

BACKGROUND: Activation imaging with 3-dimensional speckle-tracking echocardiography (3D-STE) aims to visualize the time required for the onset of regional contraction from QRS onset. We hypothesized that the optimal setting of activation imaging was associated with electrical activation. This study was designed to determine an optimal setting of activation imaging with 3D-STE in comparison with that of a voltage mapping system and to assess the feasibility of this imaging method. METHODS AND RESULTS: We enrolled 7 patients who underwent electrical voltage mapping. Regional deformation was measured by area change ratio (ACR) with 3D-STE. Activation imaging data were obtained at 10%, 25%, 50%, and 100% of maximal ACR values as the threshold for onset of regional contraction. Duration of LV electrical intraventricular activation time (IVAT(electrical)) by voltage mapping and mechanical IVAT (IVAT(mechanical)) by activation imaging was defined as the time difference between the first and latest endocardial activation sites. We obtained 21 data sets under various conduction patterns and pacing configurations. The strongest correlation between IVAT(mechanical) and IVAT(electrical) was observed at 25% of maximal ACR values (IVAT(electrical)=0.47 * IVAT(mechanical)+20, R=0.80, P<0.001). Concordance of the first and latest activated segments between activation imaging and voltage mapping was 90.5% at this setting (19 studies). CONCLUSIONS: Activation imaging with 3D-STE may be a feasible noninvasive method of dyssynchrony imaging based on electromechanical coupling.

Application of 3-dimensional speckle tracking imaging to the assessment of right ventricular regional deformation.

BACKGROUND: The aim of this study was to carry out 3-dimensional speckle tracking imaging (3DSTI) of the right ventricle (RV) and evaluate RV regional wall deformation. METHODS AND RESULTS: 3DSTI of the RV was performed in 35 normal subjects, 8 patients with arrhythmogenic right ventricular cardiomyopathy, and 8 patients with pulmonary arterial hypertension. Peak systolic area change ratio and regional contraction timing relative to global systolic time (time to peak strain/time to end-systole×100) were measured in each segment. Good-quality images were acquired of the inflow segment in 87%, apex in 87%, outflow in 57%, and septum in 94% of the 35 normal subjects. In normal subjects, peak systolic area change ratio of the inflow anterior wall was -41±14%; inflow inferior wall, -35±9%; apical anterior wall, -41±10%; apical inferior wall, -31±11%; outflow, -31±9%; and septum wall, -36±11%. Contraction timing of the apical anterior wall and septum wall were earlier than those of other segments. In patients with RV dysfunction, 3DSTI indicated low peak systolic area change ratio in the damaged area. CONCLUSIONS: RV 3DSTI indicated segmental heterogeneity in magnitude and timing of RV contraction. 3DSTI may be a promising modality for providing precise quantitative information on complex RV wall motion.

Significant improvement of left atrial and left atrial appendage function after catheter ablation for persistent atrial fibrillation.

BACKGROUND: The long-term effects of catheter ablation (CA) on the left atrium and left atrial appendage (LAA) are unknown in persistent atrial fibrillation (AF). This study investigated left atrial (LA) reverse remodeling and evolution of LA/LAA function after successful CA for persistent AF and identified predictors for maintenance of sinus rhythm (SR) and LA reverse remodeling. METHODS AND RESULTS: CA was performed in 123 patients with persistent AF. LA volumes, LA strain and LAA wall velocity were assessed both at baseline and at 12 months after ablation. Patients who maintained SR were divided into 2 groups according to whether LA volume decreased by ≥15% at follow-up (responders) or not (non-responders). During a follow-up period of 18±2 months, AF recurred in 45 patients (37%). Of the remaining 78 patients (63%) without recurrent AF, 62 patients (79%) were classified as responders. LA/LAA function significantly improved and the prevalence of spontaneous echo contrast decreased only in responders at follow-up. LA systolic strain and LAA wall velocity were independent predictors of both maintenance of SR (odds ratio [OR], 2.57; P=0.003; OR, 3.02; P=0.002, respectively) and LA reverse remodeling (OR, 4.44; P=0.007; OR, 3.52; P=0.01, respectively). CONCLUSIONS: Successful CA is associated with LA reverse remodeling and LA/LAA functional recovery in patients with persistent AF. LA systolic strain and LAA wall velocity at baseline predicted both maintenance of SR and LA reverse remodeling.

Longitudinal strain impairment as a marker of the progression of heart failure with preserved ejection fraction in a rat model.

BACKGROUND: Recent advances in very high frame rate use of ultrasonography have enabled the application of two-dimensional speckle-tracking echocardiography (STE) to small animal cardiac functional assessments. In this study, two-dimensional STE was applied to a rat model of hypertensive heart failure with preserved ejection fraction to clarify consequences of left ventricular (LV) wall deformation in the progression of heart failure with preserved ejection fraction. METHODS: STE was performed every 2 weeks in Dahl salt-sensitive rats fed a 0.3% (control group) or 8% (hypertension [HT] group) sodium chloride diet from 6 to 14 weeks of age. Longitudinal, radial, and circumferential global strain and strain rate were measured, and the time courses of these parameters were observed. RESULTS: Deterioration of longitudinal strain occurred in the early phase of the progression of LV hypertrophy and continued to worsen until congestive heart failure developed (longitudinal strain in the HT group: 25 ± 3% at 10 weeks, 21 ± 4% at 12 weeks, and 18 ± 2% at 14 weeks; longitudinal strain in controls was preserved during the experimental period). At 12 weeks, radial strain (HT group, 35 ± 7%; controls, 41 ± 10%) had deteriorated at the late stage of manifest diastolic dysfunction. Throughout the experiments, circumferential strain was preserved (HT group, 35 ± 6%; control group, 35 ± 5%), and no significant increase in short-axis function was observed. CONCLUSIONS: STE is applicable to the small animal heart and detected LV wall long-axis dysfunction preceding short-axis dysfunction or overt congestive heart failure in the progression of hypertensive LV hypertrophy in a rat model.

Abnormal early diastolic intraventricular flow 'kinetic energy index' assessed by vector flow mapping in patients with elevated filling pressure.

AIMS: Recently developed vector flow mapping (VFM) enables evaluation of local flow dynamics without angle dependency. This study used VFM to evaluate quantitatively the index of intraventricular haemodynamic kinetic energy in patients with left ventricular (LV) diastolic dysfunction and to compare those with normal subjects. METHODS AND RESULTS: We studied 25 patients with estimated high left atrial (LA) pressure (pseudonormal: PN group) and 36 normal subjects (control group). Left ventricle was divided into basal, mid, and apical segments. Intraventricular haemodynamic energy was evaluated in the dimension of speed, and it was defined as the kinetic energy index. We calculated this index and created time-energy index curves. The time interval from electrocardiogram (ECG) R wave to peak index was measured, and time differences of the peak index between basal and other segments were defined as ΔT-mid and ΔT-apex. In both groups, early diastolic peak kinetic energy index in mid and apical segments was significantly lower than that in the basal segment. Time to peak index did not differ in apex, mid, and basal segments in the control group but was significantly longer in the apex than that in the basal segment in the PN group. ΔT-mid and ΔT-apex were significantly larger in the PN group than the control group. Multiple regression analysis showed sphericity index, E/E' to be significant independent variables determining ΔT apex. CONCLUSION: Retarded apical kinetic energy fluid dynamics were detected using VFM and were closely associated with LV spherical remodelling in patients with high LA pressure.