Left Ventricle Peak Research Articles

Echocardiographic Assessment of Left Ventricular Twisting and Untwisting Rate in Normal Subjects by Tissue Doppler and Velocity Vector Imaging: Comparison of Two Methods

Background: The torsional parameters of the left ventricle (LV) are sensitive indicators of the cardiac performance. The torsion/twist of the LV is the wringing motion of the heart around its long axis created by oppositely directed apical and basal rotations and is determined by contracting myofibers in the LV wall which are arranged in opposite directions between the subendocardial and subepicardial layers. This motion is essential for regulating the LV systolic and diastolic functions. Objectives: Recent advances in echocardiography techniques have allowed for quantification of LV mechanics. The aim of the present study was to compare various LV twisting and untwisting parameters in healthy human subjects determined by velocity vector imaging (VVI) and tissue Doppler imaging (TDI) at rest. Patients and Methods: All volunteers (47 healthy subjects in two groups: 24 subjects in VVI group and 23 subjects in TDI group) underwent complete echocardiographic study, and LV torsional parameters were assessed by VVI or TDI methods. In addition, LV torsion and LV twisting/untwisting rate profiles were calculated throughout cardiac cycle. Results: Twist degree was significantly lower in the VVI group than in the TDI group (P = 0.008, r = 0.56). LV torsion was lower in the VVI group but was not significant. (P = 0.13, r = 0.38). Twisting rate (P = 0.004, r = 0.66) and untwisting rate (P = 0.0001, r = 0.61) were lower in the VVI group, but when timing of untwisting rate was normalized by systolic duration, there was no significant difference between the two groups (P = 0.41, r = 0.59). Similarly, when peak untwisting rate was normalized by LV length, there was a significant decline in normalized peak untwisting rate in the VVI group (P = 0.004, r = 0.62), but not in peak twisting rate normalized by LV length (P = 0.12, r = 0.42). Peak untwisting rate normalized by LV torsion was not statistically different between the two groups (P = 0.05, r = 0.53). Conclusions: Results suggest that these methods cannot be interchanged, and VVI showed significantly lower LV peak twist, peak twisting rate and peak untwisting rate. However, when LV twist and LV twisting rates were normalized to LV length, values were comparable for both imaging techniques.

Cardiac phase-targeted dynamic load on left ventricle differentially regulates phase-sensitive gene expressions and pathway activation

The heart has remarkable capacity to adapt to mechanical load and to dramatically change its phenotype. The mechanism underlying such diverse phenotypic adaptations remains unknown. Since systolic overload induces wall thickening, while diastolic overload induces chamber enlargement, we hypothesized that cardiac phase-sensitive mechanisms govern the adaptation. We inserted a balloon into the left ventricle (LV) of a Langendorff perfused rat heart, and controlled LV volume (LVV) using a high performance servo-pump. We created isolated phasic systolic overload (SO) by isovolumic contraction (peak LV pressure >170mmHg) at unstressed diastolic LVV [end-diastolic pressure (EDP)=0mmHg]. We also created pure phasic diastolic overload (DO) by increasing diastolic LVV until EDP >40mmHg and unloading completely in systole. After 3hours under each condition, the myocardium was analyzed using DNA microarray. Gene expressions under SO and DO conditions were compared against unloaded control condition using gene ontology and pathway analysis (n=4 each). SO upregulated proliferation-related genes, whereas DO upregulated fibrosis-related genes (P<10−5). Both SO and DO upregulated genes related functionally to cardiac hypertrophy, although the gene profiles were totally different. Upstream regulators confirmed by Western blot indicated that SO activated extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase, and Ca2+/calmodulin-dependent protein kinase II (3.2-, 2.0-, and 4.7-fold versus control, P<0.05, n=5), whereas DO activated p38 (2.9-fold, P<0.01), which was consistent with the downstream gene expressions. In conclusion, pure isolated systolic and diastolic overload permits elucidation of cardiac phase-sensitive gene regulation. The genomic responses indicate that mechanisms governing the cardiac phase-sensitive adaptations are different.

Association between aortic stenosis severity and contractile reserve measured by two-dimensional strain under low-dose dobutamine testing

Early detection of left ventricle (LV) systolic dysfunction could be a clue for surgical treatment in patients with significant aortic stenosis (AS). Therefore, we evaluated LV peak of global longitudinal strain (PGLS) using speckle tracking imaging at rest and during low-dose dobutamine infusion in asymptomatic patients with moderate and severe AS and preserved LV ejection fraction (EF). All the patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis greater than 50% in diameter). The patients were divided into two groups: above and below median of 0.785 cm2 aortic valve area (AVA). PGLS was measured from acquired apical 4-chamber and 2-chamber cine loops using a EchoPac PC-workstation at rest and during 5 microg/kg/min, 10 microg/kg/min, and 20 microg/kg/min dobutamine infusion, respectively. The global strain was the average of segment strains from the apical views. A total of 62 patients with moderate and severe AS (AVA < = 1.5 cm2), the mean age 66.12 +/- 9.91, (57.14% males), were enrolled in this prospective study. At rest, mean gradient was 43.57 +/- 0.29 mmHg and mean EF was 72.24 +/- 0.45%. When divided according to median AVA, both groups had decreased average PGLS at rest (-9.33 +/- 4.46% vs -8.95 +/- 3.08%; p = ns). During dobutamine both groups increased their average PGLS, but only the group with AVA > median reached the statistical significance (- 8.71 +/- 2.68% vs -11.93 +/- 3.74%, p = 0.002). In addition, PGLS increase was also significant in 4-chamber view in the patients with AVA above median, but only when comparing baseline to peak 20 microg/kg/min (-10.72 +/- 3.07% vs -13.14 +/- 4.79%; p = 0.034). Conversely, in both groups the increase of PGLS in 2-chamber view did not reach significance. Two-dimensional strain speckle tracking analysis of myocardial deformation with measurement of peak systolic strain during dobutamine infusion is a feasible and accurate method to determine myocardial longitudinal systolic function and contractile reserve and may contribute to clinical decision making in patients with significant AS.

Extraction of left-ventricular torsion angle from the long-axis view by block-matching algorithm: Comparison with the short-axis view

IntroductionDue to limitations in measuring the torsion angle in the short-axis view when studying through-plane motion and so it is dependent on reference levels, in this study, we follow myocardial movement along the long-axis of the left ventricle (LV). Then, LV torsion is estimated in the long-axis view and compared with LV torsion in the short-axis view. Materials and methodsTwo dimensional echocardiographic images of healthy persons were recorded in cine loop format position throughout four cardiac cycles at basal and apical levels in the long- and short-axis views. The motion vectors for reign of interest in the horizontal and vertical directions were obtained by block matching algorithm. Correlation between the values of automated analysis and manual tracing was performed by Pearson correlation analysis. Then, the maximum rotation angles of the short- and long-axis views at basal and apical levels were assessed. Left-ventricular torsion angles in short-axis and long-axis views were calculated and compared based on rotation angles. ResultsThere was a high correlation between the measured myocardial wall displacement of automated analysis (BM algorithm) and manual tracing (R=0.96, p<0.05). The maximum rotation angles of basal and apical levels in the short-axis view are 7.96±1.57° and 9.49±1.72° and so in the long-axis view are 18.51±3.41° and 14.74±2.91°, respectively. The LV torsion angles and the time to reach peak LV torsion angles in the short-axis views are 17.26±2.53°, 293±26ms and in the long-axis view are 32.26±5.60° and 290±22ms respectively. There was a high correlation between the left-ventricular torsion angle in the short-axis view and the long-axis view (R=0.92, p<0.05). There was also a high correlation between the time to reach peak left-ventricular torsion angle in the short-axis view as compared to the long-axis view (R=0.97, p<0.05). ConclusionThis study suggested that the LVtorsion angles in the short- and long-axis views were significantly correlated. It is concluded that torsion and rotation angles in the long-axis view are similar to those determined using the short-axis view.

Cardiovascular and Systemic MicrovascularEffects of Anti-Vascular Endothelial Growth Factor Therapy for Cancer

This study sought to evaluate the contribution of microvascular functional rarefaction and changes in vascular mechanical properties to the development of hypertension and secondary ventricular remodeling that occurs with anti-vascular endothelial growth factor (VEGF) therapy. Hypertension is a common side effect of VEGF inhibitors used in cancer medicine. Mice were treated for 5 weeks with an anti-murine VEGF-A monoclonal antibody, antibody plus ramipril, or sham treatment. Microvascular blood flow (MBF) and blood volume (MBV) were quantified by contrast-enhanced ultrasound in skeletal muscle, left ventricle (LV), and kidney. Echocardiography and invasive hemodynamics were used to assess ventricular function, dimensions and vascular mechanical properties. Ambulatory blood pressure increased gradually over the first 3 weeks of anti-VEGF therapy. Compared with controls, anti-VEGF-treated mice had similar aortic elastic modulus and histological appearance, but a marked increase in arterial elastance, indicating increased afterload, and elevated plasma angiotensin II. Increased afterload in treated mice led to concentric LV remodeling and reduced stroke volume without impaired LV contractility determined by LV peak change in pressure over time (dp/dt) and the end-systolic dimension-pressure relation. Anti-VEGF therapy did not alter MBF or MBV in skeletal muscle, myocardium, or kidney; but did produce cortical mesangial glomerulosclerosis. Ramipril therapy almost entirely prevented the adverse hemodynamic effects, increased afterload, and LV remodeling in anti-VEGF-treated mice. Neither reduced functional microvascular density nor major alterations in arterial mechanical properties are primary causes of hypertension during anti-VEGF therapy. Inhibition of VEGF leads to an afterload mismatch state, increased angiotensin II, and LV remodeling, which are all ameliorated by angiotensin-converting enzyme inhibition.

008 Left ventricular hypertrophy is associated with intramural dyssynchrony on exercise in patients with heart failure and normal ejection fraction: Abstract 008 Table 1

<h3>Background</h3> The pathophysiology of heart failure with normal ejection fraction (HFNEF) is complex and not fully understood. We hypothesised that left ventricular hypertrophy (LVH) which is found in most patients with HFNEF might lead to intramural dyssynchrony and uncoupling of the complex 3-dimensional motion of the left ventricle (LV) particularly on exercise. <h3>Method</h3> 33 patients with the clinical diagnosis of HFNEF (age 69±11 years, 19 female, EF 60±7%) and LVH (according to American Society of Cardiology, female &gt;95 g/m², male 115 g/m²) underwent detailed 2D-echocardiography at rest and on supine exercise. They were compared to 41 clinically diagnosed HFNEF patients without LVH (age 73±8 years, 26 females, EF 61±7%) and 35 age-matched control subjects (age 71±7 years, 27 females, EF 63±7). All subjects underwent cardiopulmonary exercise test to assess peak oxygen consumption (peak VO2). Echocardiographic images were analysed off-line. Apical and basal rotation and radial displacement were measured by speckle tracking. Longitudinal displacement was assessed by colour tissue Doppler imaging. Raw data and timing of events were analysed using a custom-written interpolation algorithm. SDSM (SD of four LV peak systolic motions: basal and apical rotation, longitudinal and radial displacement) was calculated. <h3>Results</h3> SDSM was comparable at rest for all three groups but controls showed the highest reduction in SDSM compared to both groups of patients on exercise. Patients with LVH had the smallest reduction in SDSM implying greater dyssynchrony in LV motions on exercise. SDSM on exercise correlated with left ventricular mass index (r=0.362, p=0.002) and VO₂max (r=−0.319, p=0.011). <h3>Conclusion</h3> LVH in patients with HFNEF is associated with intramural dyssynchrony and uncoupling of the complex 3-dimensional LV motions on exercise. This might contribute to their exertional symptoms.

Abstract 8779: Effect of Cathepsin a Inhibition on Cardiac Function and Remodeling in Rats with Heart Failure Induced by Ischemia and Long-Term Reperfusion

Introduction: Cathepsin A (CathA) is a lysosomal carboxypeptidase involved in the cardiac metabolism of various peptide hormones. Its expression is significantly upregulated in the border zone after myocardial infarction (MI) in rats. Affymetrix profiling in MI patients revealed a similar regulation. Method: Male Wistar rats were randomized in: (1) Sham-OP, (2) I/R-Placebo (I/R=30min ischemia/reperfusion of the left coronary artery), (3) I/R-ramipril (RA 1 mg/kg/d p.o.), (4) I/R - CathA Inhibitor SAR1 (SAR1 30 mg/kg/d p.o.). After 9 weeks of treatment a magnetic resonance imaging (MRI)-investigation was done. Thereafter, left ventricles (LV) were fixed for histological evaluation and gene expression analysis by Taqman PCR. Brain natriuretic peptide (BNP) was measured in serum by ELISA. Results: Inhibition of CathA with SAR1 attenuated left ventricular (LV) remodeling observed after I/R without altering blood pressure. MRI analysis revealed preserved ventricular wall geometry in infarcted and non-infarcted regions. Global parameters such as ejection fraction, cardiac output, stroke volume, end-diastolic volume, end-systolic volume and left ventricle peak filling rate were significantly improved during dobutamin stress when compared to placebo treated I/R-rats. Especially the regional parameters such as wall motion and systolic wall thickness were improved in the infarcted area and even normalized in the non-infarcted area in SAR-treated I/R-rats. In contrast, RA treatment did not prevent the adverse remodeling. In all parameters SAR1 was clearly superior to RA. Histological investigations confirmed the beneficial effects of SAR1 treatment and serum levels of BNP were significantly reduced in SAR1 treated animals. LV gene expression of TGFβ, ANP, collagen type III and CD14 was decreased by ramipril and SAR1 treatment. Conclusion: We identified hitherto unknown functions of CathA in cardiac disease. Especially the dramatic improvement in LV wall geometry after inhibition of CathA with SAR1 makes this enzyme a highly promising target for the treatment of post-MI heart failure patients. SAR1 has the potential to introduce a new treatment option for patients with acute MI to further preserve myocardial function on top of standard treatment.

Modeling the impact of concomitant aortic stenosis and coarctation of the aorta on left ventricular workload

Coarctation of the aorta (COA) is an obstruction of the aorta and is usually associated with bicuspid and tricuspid aortic valve stenosis (AS). When COA coexists with AS, the left ventricle (LV) is facing a double hemodynamic load: a valvular load plus a vascular load. The objective of this study was to develop a lumped parameter model, solely based on non-invasive data, allowing the description of the interaction between LV, COA, AS and the arterial system. First, a formulation describing the instantaneous net pressure gradient through the COA was introduced and the predictions were compared to in vitro results. The model was then used to determine LV work induced by coexisting AS and COA with different severities. The results show that LV stroke work varies from 0.98 J (no-AS; no-COA) up to 2.15 J (AS: 0.61 cm 2+COA: 90%). Our results also show that the proportion of the total flow rate that will cross the COA is significantly reduced with the increasing COA severity (from 85% to 40%, for a variation of COA severity from 0% to 90%, respectively). Finally, we introduced simple formulations capable of, non-invasively, estimating both LV peak systolic pressure and workload. As a conclusion, this study allowed the development of a lumped parameter model, based on non-invasive measurements, capable of accurately investigating the impact of coexisting AS and COA on LV workload. This model can be used to optimize the management of patients with COA and AS in terms of the sequence of lesion repair.

114 Speckle tracking imaging assessment of left ventricular twist in heart transplant patients

Denervation, pericardiotomy and immunosuppressant drugs may affect mechanical properties of the left ventricle (LV). We aimed to assess LV twist in heart transplant patients with normal LV ejection fraction (LVEF), and without or with mild acute rejection on cardiac biopsy. Twenty biopsies and echocardiographic studies were performed in 10 heart transplant patients (mean age: 40 ± 17 years) a median of 6 months after transplantation (range: 1 to 120 months). No patients had evidence of cardiac allograft vasculopathy. The mean age of the donor heart at the time of echocardiography was 37 ± 14 years. Routine endomyocardial biopsy was performed 24 hours after echocardiography. Ten age-matched controls (43 ± 15 years) were also studied. Short axis views were analyzed using speckle tracking software. LV twist was defined as the difference between the apical and basal rotation. Eight biopsies were on grade 0 (no rejection) and 12 on grade 1 R (mild rejection). The transplant groups and the control group did not differ in terms of LVEF (Grade 0: 66 ± 7%, grade 1R: 67 ± 11% and controls: 66 ± 6%) and in systolic mitral annular velocities (8.5 ± 1.6 cm/s, 7.7 ± 2.1 cm/s and 8.4 ± 1.4 cm/s, respectively, p = NS). Peak LV twist was reduced in patients with grade 0 and grade 1 R (6.0 ± 3.3° and 7.1 ± 3.6°, respectively) as compared to controls (12.1 ± 2.9°, p < 0.005 for both comparison). A reduction in apical rotation accounted for most of this alteration (4.5 ± 2.7° for grade 0, 4.7 ± 3.3° for grade 1 R and 8.9 ± 3.1° for controls, p < 0.017). There was no difference in peak LV twist among the transplant groups. Early diastolic LV untwisting (at 5%, 10% and 15% of diastole) did not significantly differ between the three groups. Speckle tracking imaging allows to detect a reduced LV twist in the transplanted heart. A reduced apical rotation accounts for most this alteration. However, our data suggests that the assessment of LV twist does not allow to detect the early stage of rejection.

Right ventricular–left ventricular interaction in adults with Tetralogy of Fallot: A combined cardiac magnetic resonance and echocardiographic speckle tracking study

Objectives To assess ventricular dysfunction and ventricular interaction after repair of Tetralogy of Fallot (ToF) employing echocardiography speckle-tracking and cardiac magnetic resonance imaging (CMR). Background Severe pulmonary regurgitation and right ventricular (RV) dysfunction are common after repair of ToF and may also affect the shape and function of the left ventricle (LV). Recent studies suggest that LV dysfunction may be of particular prognostic value. Methods and results Twenty-one consecutive adults with repaired ToF (15 male, mean age 38 ± 11 years, 7 with severe PR) underwent a comprehensive echocardiographic exam including speckle-tracking analysis, CMR and cardiopulmonary exercise testing. Twenty-one subjects without relevant heart disease served as controls. Echocardiographically measured RV diameters correlated with RV volumes obtained from CMR ( r = 0.63; p = 0.006). In addition, a close correlation was found between RV and LV function on CMR ( r = 0.74, p = 0.002), speckle-tracking LV and RV peak longitudinal 2D strain ( r = 0.66, p = 0.003) and mitral and tricuspid annular plain systolic excursion ( r = 0.71, p = 0.0003). While LV ejection fraction was normal in the majority of patients and not different from controls, LV longitudinal strain was significantly reduced in ToF patients (− 16.5 ± 3.3 vs. -20.5 ± 2.7%, p = 0.0001). Conclusion Left and right ventricular function both by CMR and speckle-tracking is interrelated in adults with repaired ToF. Despite normal LV ejection fraction, 2D longitudinal strain is significantly reduced in ToF patients, suggesting subclinical LV myocardial damage. Considering the potential prognostic value of LV dysfunction in ToF, this measurement may gain importance and should be included in future outcome studies.

Hearts of Hypoxia-inducible Factor Prolyl 4-Hydroxylase-2 Hypomorphic Mice Show Protection against Acute Ischemia-Reperfusion Injury

Hypoxia-inducible factor (HIF) has a pivotal role in oxygen homeostasis and cardioprotection mediated by ischemic preconditioning. Its stability is regulated by HIF prolyl 4-hydroxylases (HIF-P4Hs), the inhibition of which is regarded as a promising strategy for treating diseases such as anemia and ischemia. We generated a viable Hif-p4h-2 hypomorph mouse line (Hif-p4h-2(gt/gt)) that expresses decreased amounts of wild-type Hif-p4h-2 mRNA: 8% in the heart; 15% in the skeletal muscle; 34-47% in the kidney, spleen, lung, and bladder; 60% in the brain; and 85% in the liver. These mice have no polycythemia and show no signs of the dilated cardiomyopathy or hyperactive angiogenesis observed in mice with broad spectrum conditional Hif-p4h-2 inactivation. We focused here on the effects of chronic Hif-p4h-2 deficiency in the heart. Hif-1 and Hif-2 were stabilized, and the mRNA levels of glucose transporter-1, several enzymes of glycolysis, pyruvate dehydrogenase kinase 1, angiopoietin-2, and adrenomedullin were increased in the Hif-p4h-2(gt/gt) hearts. When isolated Hif-p4h-2(gt/gt) hearts were subjected to ischemia-reperfusion, the recovery of mechanical function and coronary flow rate was significantly better than in wild type, while cumulative release of lactate dehydrogenase reflecting the infarct size was reduced. The preischemic amount of lactate was increased, and the ischemic versus preischemic [CrP]/[Cr] and [ATP] remained at higher levels in Hif-p4h-2(gt/gt) hearts, indicating enhanced glycolysis and an improved cellular energy state. Our data suggest that chronic stabilization of Hif-1alpha and Hif-2alpha by genetic knockdown of Hif-p4h-2 promotes cardioprotection by induction of many genes involved in glucose metabolism, cardiac function, and blood pressure.

Assessment of left ventricular endocardial and epicardial rotation before and after revascularization by speckle tracking echocardiography in patients with ST-segment elevation acute myocardial infarction

Objective To differentiate the transmural extent of myocardial necrosis by assessment of endocardial and epicardial rotation using speckle tracking imaging(STI)between ST-segment elevation acute myocardial infarction(STEAMI)and non-ST-elevation acute myocardial infarction(NSTEAMI).Methods The study comprised 20 controls(group A),26 patients with STEAMI(group B)and 22 patients with NSTEAMI(group C).Conventional echocardiography and STl were done in controls and in patients before and one month after percutaneous coronary intervention(PCI).Results In the apex,base of left ventricle (LV),peak rotation and torsion of the endocardium(endo)and epicardium(epi)in groups B and C were both significantly reduced relative to those of group A before PCI(all P<0.01).One month after PCI,there were no significant changes except peak apical epi-rotation and peak LV epi-torsion in group C(all P<0.01).Peak LV epi-torsion was positively correlated with LV ejection fraction(LVEF)(r=0.63,P<0.05)and inversely correlated with wall motion score index(r=-0.85,P<0.01).Conclusions Peak endo-and epi-rotation can contribute to estimation of transmural extent of necrosis between STEAMI and NSTEAMl using STI.Significant correlation is noted between peak LV torsion and myocardial contractile performance. Key words: Echocardiography; Myocardial infarction; Rotation; Torsion; Speckle tracking imaging

MRI assessment of pacing induced ventricular dyssynchrony in an isolated human heart

This study demonstrates the capabilities of MRI in the assessment of cardiac pacing induced ventricular dyssynchrony, and the findings support the need for employing more physiological pacing. A human donor heart deemed non-viable for transplantation, was reanimated using an MR compatible, four-chamber working perfusion system. The heart was imaged using a 1.5T MR scanner while being paced from the right ventricular apex (RVA) via an epicardial placed lead. Four-chamber, short-axis, and tagged short-axis cines were acquired in order to track wall motion and intramyocardial strain during pacing. The results of this study revealed that the activation patterns of the left ventricle (LV) during RVA pacing demonstrated intraventricular dyssynchrony; as the left ventricular mechanical activation proceeded from the septum and anterior wall to the lateral wall, with the posterior wall being activated last. As such, the time difference to peak contraction between the septum and lateral wall was approximately 125 msec. Likewise, interventricular dyssynchrony was demonstrated from the four-chamber cine as the time difference between the peak LV and RV free wall motion was 180 msec. With the ongoing development of MR safe and MR compatible pacing systems, we can expect MRI to be added to the list of imaging modalities used to optimize cardiac resynchronization therapy (CRT) and/or alternate site pacing.

Influence of cardiac shape on left ventricular twist

The dynamic interaction between subendocardial and subepicardial fibre helices in the left ventricle (LV) leads to a twisting deformation, which has an important role in LV function. This study sought to assess the influence of cardiac shape on LV twist in the normal and dilated human heart. The study comprised 45 dilated cardiomyopathy (DCM) patients and 60 for age- and gender-matched healthy volunteers. Speckle tracking echocardiography was used to determine basal and apical LV peak systolic rotation (Rot(max)) and instantaneous LV peak systolic twist (Twist(max)). LV sphericity index was calculated by dividing the LV maximal long-axis internal dimension by the maximal short-axis internal dimension at end-diastole. A parabolic relation between the sphericity index and apical Rot(max) or Twist(max) was identified in the total study population (R(2) = 0.56 and R(2) = 0.54, respectively; both P < 0.001) and healthy volunteers (R(2) = 0.39 and R(2) = 0.25, respectively; both P < 0.001), whereas these relations were linear in DCM patients (R(2) = 0.40 and R(2) = 0.43, respectively; both P < 0.001). In a multivariate analysis, LV sphericity index was the strongest independent predictor of apical Rot(max) and Twist(max). In conclusion, LV apical rotation and twist are significantly influenced by LV configuration. Taking the important function of LV twist into account, this finding highlights the vital influence of cardiac shape on LV systolic function.

Noncontact Mapping of Left Ventricle during CRT Implant

Not all candidates for cardiac resynchronization therapy (CRT) are responders at follow-up. Echocardiographic parameters of dyssynchrony do not predict the response. Analysis of electrical properties of left ventricle (LV) by noncontact mapping (NCM) could be useful to better identify candidates for CRT. We studied nine consecutive patients undergoing CRT. An NCM was positioned in the LV via atrial transeptal puncture. LV activation was recorded during sinus rhythm (SR), pacing from RV, from different LV epicardial locations, and in biventricular (BIV) pacing. The corresponding invasive pressure was determined. Heparin, administered during NCM, was reversed and CRT implant was completed. An offline analysis of the data was performed in order to measure transeptal and total LV activation time, to evaluate the site of earliest and latest LV activation, and the pattern of activation. No complications occurred. Mean time of total NCM procedures was 24 + or - 7 minutes. During SR, RV, LV, and BIV pacing, respectively, a "U"-shaped LV activation pattern was found in three, seven, four, and and two patients; mean LV activation time was 58.1 + or - 7.0, 81.7 + or - 15.8, 71.1 + or - 12.4, and 65.6 + or - 7.7 ms; and mean systolic LV peak pressure was 114 + or - 21, 97 + or - 18, 103 + or - 17 and 110 + or - 15 mmHg, respectively. LV activation was influenced by a slow conduction area at the pacing site and by the duration of transeptal time. An NCM during CRT is safe and feasible. It provides an additional information on electrical activation in SR and in various modality of pacing. Further studies with larger populations are needed in order to correlate electrical to clinical outcomes.

Central infusion of aldosterone synthase inhibitor attenuates left ventricular dysfunction and remodelling in rats after myocardial infarction

Blockade of mineralocorticoid receptors in the central nervous system (CNS) prevents sympathetic hyperactivity and improves left ventricle (LV) function in rats post-myocardial infarction (MI). We examined whether aldosterone produced locally in the brain may contribute to the activation of mineralocorticoid receptors in the CNS. Two days after coronary artery ligation, Wistar rats received an intra-cerebroventricular (icv) infusion via osmotic mini-pumps of the aldosterone synthase inhibitor FAD286 at 100 microg/kg/day or vehicle for 4 weeks. LV function was assessed by echocardiography at 2 and 4 weeks, and by Millar catheter at 4 weeks. At 4 weeks post-MI, aldosterone in the hippocampus was increased by 70% and tended to increase in the hypothalamus by 20%. These increases were prevented by FAD286. Across groups, aldosterone in the hippocampus and hypothalamus showed a high correlation. There were no differences in brain corticosterone levels. Compared to sham rats, at both 2 and 4 weeks post-MI rats treated with vehicle showed increased LV dimensions and decreased LV ejection fraction. Icv infusion of FAD286 attenuated these changes in LV dimensions and ejection fraction by approximately 30%. At 4 weeks post-MI, LV peak systolic pressure (LVPSP) and dP/dt(max/min) were decreased and LV end-diastolic pressure (LVEDP) was increased. In rats treated with icv FAD286, LVPSP and dP/dt(min) remained normal and LVEDP and dP/dt(max) were markedly improved. Post-MI increases in cardiac fibrosis and cardiomyocyte diameter were substantially attenuated by icv FAD286. These data suggest that aldosterone produced locally in the brain acts as the main agonist of mineralocorticoid receptors in the CNS and contributes substantially to the progressive heart failure post MI.

STUDY OF LEFT VENTRICULAR DIASTOLIC DIAMETER–PEAK STRESS RELATIONSHIP BEFORE AND AFTER VALVE REPLACEMENT OPERATION FOR PATIENTS WITH CHRONIC AORTIC REGURGITATION

Background: Patients with chronic aortic regurgitation (AR) usually have dilated left ventricle due to volume overload. Some of them will reduce in size after elimination of regurgitation, but others not. The present study evaluated the hypothesis that left ventricle end-diastolic diameter (LVEDD), left ventricle end-systolic diameter (LVESD) are related to left ventricle's peak stress (σ) both before and after operation. Methods: Sixty-eight patients with chronic aortic regurgitation receiving valve replacement were included in the study. LVEDD, LVESD, and σ were determined by echocardiography and cuff sphygmomanometer measurement before and beyond 6 months after operation. Results: The results showed that LVEDD, LVESD, and σ were decreased after the operation. In addition, σ and LVEDD had good linear correlation (for pre-operative data, σ = -3.02 + 0.286* LVEDD , R = 0.556, P &lt; 0.001; for post-operative data, σ = -11.4 + 0.474* LVEDD , R = 0.736, P &lt; 0.001). Conclusion: LVEDD and σ had a linear relationship before and after valve replacement operation for AR patients. The higher slope in linear regression equation for post-operative σ–LVEDD relationship than that for pre-operative data may indicate improved myocardial contractile efficiency after the operation.

Dysregulation of matrix metalloproteinases and their tissue inhibitors is related to abnormality of left ventricular geometry and function in streptozotocin‐induced diabetic minipigs

This study aimed to characterize matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in relation to changes in left ventricle (LV) geometry and function in a porcine model with streptozotocin (STZ)-induced diabetes. In 15 Chinese Guizhou minipigs with STZ-induced diabetes (diabetic group) and 15 age-matched normal controls (control group), Doppler tissue imaging was performed at 6 months of diabetes. Serum MMP-2, -9, TIMP-1, -4 and B-type natriuretic peptide (BNP) were determined. Expression of MMPs, TIMPs, urokinase type-plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in aortic intima and LV myocardium was evaluated, with gelatinolytic activities of tissue MMP-2, -9 accessed by zymography. Left ventricle end-diastolic septum thickness (P < 0.05) and mass (P < 0.05) were increased, whereas peak systolic mitral annulus velocity (Sm, P < 0.001), LV systolic (P = 0.01) and diastolic strain (P < 0.001) were significantly decreased in diabetic group than in controls. Diabetic group showed higher expression of TIMP-1, -4 in aortic intima and LV myocardium (P < 0.01 or P < 0.05), with increased collagen content and elevated serum BNP level (P = 0.004) and lower gelatinolytic activities of tissue MMP-2, -9 (all P < 0.05). Semi-quantitative RT-PCR of those diabetic tissues revealed elevated mRNA levels of major TIMPs, uPA, uPAR and PAI-1. Reduction of serum MMP-2 and -9 levels was observed in diabetic group vs. control group (both P < 0.05). This study features elevated levels of TIMP-1, -4, uPA, uPAR and PAI-1, and decreased activities of MMP-2, -9 in aorta and myocardium in STZ-induced diabetic minipigs, indicating that MMP-TIMP dysregulation is associated with LV hypertrophy, cardiac dysfunction and increased cardiovascular fibrosis in diabetes.

Assessment of left ventricular global twist in essential hypertensive heart by speckle tracking imaging

The left ventricular twist was evaluated by 2-dimensional ultrasound speckle-tracking imaging (STI) in 50 patients with hypertension with normal geometric left ventricle (LV) and 45 normal subjects as control group. The mean value of LV rotation was obtained at each plane using STI. LV twist and twist velocity were defined as apical rotation/rotation rate relative to the base respectively. To adjust the intersubject differences in heart rates, the time sequence were normalized. The results showed that peak twist developed near the end of systole. Peak LV twist was significantly higher in patients with hypertension than normal controls (P<0.001). The diastolic untwisting mainly occurred in early diastole ( approximately 38%). Compared with normal controls, untwisting rate (Untw R) in patients with hypertension was significantly reduced (P<0.001), and untwisting half-time (UHT) was significantly delayed (P<0.05). This study demonstrated that STI has a potential ability to evaluate the early change of heart function in patients with hypertension by measuring the twist of LV.

Global Circumferential Strain by 2-Dimensional Speckle Tracking Method for the Evaluation of the Left Ventricular Function

Background and Objectives: The speckle tracking method using 2-dimensional (2D) echocardiography is not affected by the tethering of neighboring segments and angulation. Global circumferential strain (GCS) of the left ventricle (LV) has been suggested as a systolic index and correlated with LV contractility. The purpose of this study was to investigate whether acute changes in preload affect global circumferential strain and to evaluate the usefulness of GCS by the speckle tracking method. Subjects and Methods: 2D echocardiography was performed in 69 patients with end-stage renal disease before and after hemodialysis to measure the LV end-diastolic volume and LV ejection fraction. 2D images were acquired from the short-axis view of the mid-LV for the evaluation of GCS. Results: Mean LV end-diastolic volume significantly decreased from 91.2±33.3 mL to 72.3±32.0 mL (p< 0.05), and LV ejection fraction decreased from 63.6±13.1% to 60.0±11.2% (p=0.006) after hemodialysis. However, mean GCS showed no significant change after hemodialysis (17.2±5.3% vs. 16.6±4.7%, p=0.13). GCS was found to be well correlated with LV ejection fraction (r=0.54, p<0.05) and peak systolic mitral annular velocity (r=0.46, p=0.000), but not with LV preload (r=0.06, p=0.622). Conclusion: GCS using the speckle tracking method is a useful index for the evaluation of LV systolic function because it is not affected by acute preload change and is correlated with LV ejection fraction and peak systolic mitral annular velocity. (Korean Circ J 2008;38:379-386)