Left Ventricular Cavity Area Research Articles

Assessment of Right Ventricular Function With CT and Echocardiography in Patients With Severe Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation.

Changes in right ventricular size and function are frequently observed in patients with severe acute respiratory distress syndrome. The majority of patients who receive venovenous extracorporeal membrane oxygenation undergo chest CT and transthoracic echocardiography. The aims of this study were to compare the use of CT and transthoracic echocardiography to evaluate the right ventricular function and to determine the prevalence of acute cor pulmonale in this patient population. Observational, retrospective, single-center, cohort study. Severe respiratory failure and extracorporeal membrane oxygenation center. About 107 patients with severe acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation. Chest CT to evaluate right ventricular size and transthoracic echocardiography to evaluate right ventricular size and function. All 107 patients had a qualitative assessment of right ventricular size and function on transthoracic echocardiography. Quantitative measurements were available in 54 patients (50%) who underwent transthoracic echocardiography and in 107 of patients (100%) who received CT. Right ventricular dilatation was defined as a right ventricle end-diastolic diameter greater than left ventricular end-diastolic diameter upon visual assessment or an right ventricle end-diastolic diameter/left ventricular end-diastolic diameter and/or right ventricle cavity area/left ventricular cavity area of greater than 0.9. Right ventricle systolic function was visually estimated as being normal or impaired (visual right ventricular systolic impairment). The right ventricle was found to be dilated in 38/107 patients (36%) and in 58/107 patients (54%), using transthoracic echocardiography or CT right ventricle end-diastolic diameter/left ventricular end-diastolic diameter, respectively. When the CT right ventricle cavity/left ventricular cavity area criterion was used, the right ventricle was dilated in 19/107 patients (18%). About 33/107 patients (31%) exhibited visual right ventricular systolic impairment. Transthoracic echocardiography right ventricle end-diastolic diameter/left ventricular end-diastolic diameter showed good agreement with CT right ventricle cavity/left ventricular cavity area (R 2 = 0.57; p < 0.01). A CT right ventricle cavity/left ventricular cavity area greater than 0.9 provided the optimal cutoff for acute cor pulmonale on transthoracic echocardiography with an AUC of 0.78. Acute cor pulmonale was defined by the presence of a right ventricle "D-shape" and quantitative right ventricle dilatation on transthoracic echocardiography or a right ventricle cavity/left ventricular cavity area greater than 0.9 on CT. A diagnosis of acute cor pulmonale was made in 9/54 (14% patients) on transthoracic echocardiography and in 19/107 (18%) on CT. Changes in right ventricular size and function are common in patients with severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation with up to 18% showing imaging evidence of acute cor pulmonale. A CT right ventricular cavity /left ventricular cavity area greater than 0.9 is indicative of impaired right ventricular systolic function.

Effect of Thermoresponsive Poly(L-lactic acid)-poly(ethylene glycol) Gel Injection on Left Ventricular Remodeling in a Rat Myocardial Infarction Model.

Some gel types have been reported to prevent left ventricular (LV) remodeling in myocardial infarction (MI) animal models. In this study, we tested biodegradable thermoresponsive gels. Poly(L-lactic acid)-poly(ethylene glycol) (PLLA-PEG) and poly(D-lactic acid)-poly(ethylene glycol) (PDLA-PEG) were synthesized by the polycondensation of l- and D-lactic acids in the presence of PEG and succinic acid. Each of these block copolymers was used to prepare particles dispersed in an aqueous medium and mixed together to obtain a PLLA-PEG/PDLA-PEG suspension, which was found to show a sol-to-gel transition around the body temperature by the stereocomplex formation of enantiomeric PLLA and PDLA sequences. In the present study, the G' of the PLLA-PEG/PDLA-PEG suspension in the rheological measurement remained as low as 1Pa at 20°C and increased 2kPa at 37°C. The sol-gel systems of PLLA-PEG/PDLA-PEG might be applicable to gel therapy. The effect of the PLLA-PEG/PDLA-PEG gel injection was compared with that of a calcium-crosslinked alginate gel and saline in a rat MI model. The percent fractional shortening improved in the PLLA-PEG/PDLA-PEG (20.8±4.1%) and alginate gel (21.1±4.8%) compared with the saline (14.2±2.8%) with regard to the echocardiograph 4weeks after the injection (p<0.05). There were reduced infarct sizes in both PLLA-PEG/PDLA-PEG gel and alginate gel compared with the saline injection (p<0.05). Moreover, a greater reduction in LV cavity area was observed with the PLLA-PEG/PDLA-PEG gel than with the alginate gel (p=0.06). These results suggest that the PLLA-PEG/PDLA-PEG gel should have high therapeutic potential in gel therapy for LV remodeling after MI.

Improved workflow for quantifying left ventricular function via cardiorespiratory-resolved analysis of free-breathing MR real-time cines.

To evaluate the feasibility of a proposed cardiorespiratory-resolved analysis in left ventricular (LV) function quantification from real-time cines in a cohort of cardiac patients. Electrocardiograph (ECG)-free free-breathing real-time cine imaging based on the balanced steady-state free precession technique was performed on short-axis slices of 20 cardiac patients at 3T. K-means cluster segmentation was used to delineate the endocardial contours, from which the LV centroid and cavity area were determined. Respiratory and cardiac signals were respectively resolved from the filtered LV centroid displacement and time-varied LV cavity area to identify end-expiratory end-diastolic (ED) and end-systolic (ES) images. The obtained LV cavity areas and derived volumetric function indices, including ED volume (EDV), ES volume (ESV), stroke volume (SV), and ejection fraction (EF), were compared with those measured from manual analysis using two-tailed paired Student's t-tests, linear regression analyses, and Bland-Altman plots. Interobserver variability was calculated. The LV cavity area was strongly correlated between the proposed and conventional manual methods (r > 0.87) for three representative slices at the base, middle ventricle, and apex. The average differences between the two methods were 0.66 ± 3.22 mL for EDV, -0.02 ± 2.68 mL for ESV, 0.67 ± 3.73 mL for SV, and 0.17 ± 2.30% for EF. All paired measures exhibited strong correlations (r > 0.96) without significant differences (P = 0.38-0.98). Acceptable interobserver variability (0.19-3.55%) and strong correlations (r > 0.96) were shown for all measures between the two observers. The proposed method is feasible for efficient measurement of LV function from real-time cines. 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:905-914.

Efficient method for analyzing MR real-time cines: Toward accurate quantification of left ventricular function.

To develop and assess an efficient method to identify end-expiratory end-diastolic (ED) and end-systolic (ES) images for accurate quantification of left ventricular (LV) function in real-time cine imaging. ECG-free free-breathing real-time cine imaging was performed on short-axis slices of thirteen healthy volunteers at 3 Tesla. K-means cluster segmentation was applied to delineate the endocardial contour, from which the LV centroid and cavity area were determined in each cine image. LV centroid displacement along the superior-inferior direction was filtered to extract respiratory motion in each slice. End-expiratory ED and ES images were then identified and used for LV function quantification. Accuracy was evaluated with that measured from the slice-matched standard ECG-gated breathhold segmented cines using two-tail paired Student's t-tests, linear regression analyses and Bland-Altman plots. Intra- and interobserver variability was calculated for each imaging technique. Qualitatively, end-expiratory ED and ES images identified with the proposed method agreed with those determined by frame-by-frame visual inspection in 97.5% of cases (P > 0.05). Quantitatively, good agreement of LV function indices between the real-time cine and the standard segmented cine was observed with averaged differences of 0.1 ± 0.9 g for myocardium mass, -0.3 ± 1.0 mL for ED volume, 0.2 ± 1.2 mL for ES volume, -0.2 ± 1.3 mL for stroke volume, and -0.3 ± 0.8% for ejection fraction. Paired LV function values exhibited strong correlation (r ≥ 0.96) and no significant difference (P > 0.05). The real-time cine and the standard segmented cine showed similar intra- (1.2-3.3% and 1.1-2.8%, respectively) and interobserver variability (2.6-6.9% and 1.8-4.8%, respectively) with all P-values > 0.05. All the variability was comparable with published results. Compared with the laborious frame-by-frame visual inspection, as conventionally adopted, the proposed method is efficient in analyzing real-time cines for the accurate quantification of LV function without excessively manual interactions.

Chronic hibernating myocardium in sheep can occur without degenerating events and is reversed after revascularization

Our goal was to show that blunting of myocardial flow reserve is mainly involved in adaptive chronic myocardial hibernation without apparent cardiomyocyte degeneration. Sheep chronically instrumented with critical multivessel stenosis and/or percutaneous transluminal coronary angioplasty (PTCA)-induced revascularization were allowed to run and feed in the open for 2 and 5 months, respectively. Regional myocardial blood flow (MBF) with colored microspheres, regional and global left ventricular function and dimensions (2D echocardiography), and myocardial structure were studied. In sheep with a critical stenosis, a progressive increase in left ventricular end-diastolic and end-systolic cavity area and a decrease in fractional area change were found. Fraction of wall thickness decreased in all left ventricular wall segments. MBF was slightly but not significantly decreased at rest at 2 months. Morphological quantification revealed a rather small but significant increase in diffusely distributed connective tissue, cardiomyocyte hypertrophy, and presence of viable myocardium of which almost 30 % of the myocytes showed depletion of sarcomeres and accumulation of glycogen. The extent of myolysis in the transmural layer correlated with the degree of left ventricular dilation. Structural degeneration of cardiomyocytes was not observed. Balloon dilatation (PTCA) of one of the coronary artery stenoses at 10 weeks revealed recovery of fraction of wall thickness and near normalization of global subcellular structure at 20 weeks. These data indicate that chronic reduction of coronary reserve by itself can induce ischemic cardiomyopathy characterized by left ventricular dilatation, depressed regional and global function, adaptive chronic myocardial hibernation, reactive fibrosis and cardiomyocyte hypertrophy in the absence of obvious degenerative phenomena. Reduction of myocardial flow reserve due to chronic coronary artery stenosis in sheep induces adaptive myocardial hibernation without involvement of degenerative phenomena.

Selective Homocysteine Lowering Gene Transfer Improves Infarct Healing, Attenuates Remodelling, and Enhances Diastolic Function after Myocardial Infarction in Mice

Background and aimsHomocysteine levels predict heart failure incidence in prospective epidemiological studies and correlate with severity of heart failure in cross-sectional surveys. The objective of this study was to evaluate whether a selective homocysteine lowering intervention beneficially affects cardiac remodelling and cardiac function after myocardial infarction (MI) in a murine model of combined hypercholesterolemia and hyperhomocysteinemia.Methodology and principal findingsA selective homocysteine lowering gene transfer strategy was evaluated in female C57BL/6 low density lipoprotein receptor (Ldlr)−/− cystathionine-ß-synthase (Cbs)+/− deficient mice fed a hyperhomocysteinemic and high saturated fat/high cholesterol diet using an E1E3E4-deleted hepatocyte-specific adenoviral vector expressing Cbs (AdCBS). MI was induced by permanent ligation of the left anterior descending coronary artery 14 days after saline injection or gene transfer. AdCBS gene transfer resulted in a persistent more than 5-fold (p<0.01) decrease of plasma homocysteine levels and significantly improved endothelial progenitor cell function. Selective homocysteine lowering enhanced infarct healing as indicated by a 21% (p<0.01) reduction of infarct length at day 28 after MI and by an increased number of capillaries and increased collagen content in the infarct zone. Adverse remodelling was attenuated in AdCBS MI mice as evidenced by a 29% (p<0.05) reduction of left ventricular cavity area at day 28, by an increased capillary density in the remote myocardium, and by reduced interstitial collagen. The peak rate of isovolumetric relaxation was increased by 19% (p<0.05) and the time constant of left ventricular relaxation was reduced by 21% (p<0.05) in AdCBS MI mice compared to control MI mice, indicating improved diastolic function.Conclusion/significanceSelective homocysteine lowering gene transfer improves infarct healing, attenuates remodelling, and significantly enhances diastolic function post-MI in female C57BL/6 Ldlr −/− Cbs +/− mice. The current study corroborates the view that hyperhomocysteinemia exerts direct effects on the myocardium and may potentiate the development of heart failure.

A comparison of left ventricular border detection techniques applied to 2D echocardiograms

INTRODUCTION: Cardiology has been one of the most important areas of medicine. For several applications to diagnose the heart functions diseases the measurement of left ventricular (LV) cavity area and LV fractional area change are of vital necessity. To achieve this task, it is necessary to trace the border of left ventricle, which manual tracing is a tedious and time-consuming work. To solve this problem, many techniques to automate this border detection have been developed using the specialist tracing as gold standard. METHODS: The purpose of this approach is to analyze the features of the main techniques applied to left ventricle border detection in medical imaging. To facilitate understanding, the left ventricle border detection techniques are divided into three categories: image-based techniques, model-based techniques and pixel-based techniques. For each of the category, a literature review was made to get examples of the techniques applied to left ventricle border detection and to describe them. The result of this review is a comparative tablewhere the main features of each technique is compared. CONCLUSION: From the comparative table we can conclude that the not mentioning of many features of the techniques by the authors and the lack of a standardization of the evaluation techniques hamper a more satisfactory comparison.

COMPARISON OF RECIPE FOR ACTIVATING BLOOD CIRCULATION AND BENEFITING VITAL ENERGY ON INHIBITING LEFT VENTRICULAR REMODELLING AND APOPTOSIS IN RATS WITH HEART FAILURE

ObjectivesTo compare the effective characteristic of recipe for activating blood circulation and benefiting vital energy on inhibiting left ventricular remodelling and apoptosis in rats with heart failure.MethodsLeft coronary artery occlusion...

Placement of an Elastic Biodegradable Cardiac Patch on a Subacute Infarcted Heart Leads to Cellularization With Early Developmental Cardiomyocyte Characteristics

BackgroundPlacement of an elastic biodegradable patch onto a subacute myocardial infarct (MI) provides temporary elastic support that may act to effectively alter adverse left ventricular (LV) remodeling processes. MethodsTwo weeks after permanent left coronary ligation in Lewis rats, the infarcted anterior wall was covered with polyester urethane urea (MI + PEUU; n = 15) or expanded polytetrafluoroethylene (MI + ePTFE; n = 15) patches, or had no implantation (MI + sham; n = 12). Eight weeks after surgery, cardiac function and histology were assessed. ResultsThe ventricular wall in the MI + ePTFE and MI + sham groups was composed of fibrous tissue, whereas PEUU implantation induced α-smooth muscle actin–positive muscle bundles coexpressing sarcomeric α-actinin and cardiac-specific troponin-T. This pattern of colocalization was also found in developing embryonic myocardium. Cardiac transcription factors Nkx-2.5 and GATA-4 were strongly expressed in the muscle bundles. In the MI + sham group, end-diastolic LV cavity area (EDA) increased and the percentage of fractional area change (%FAC) decreased. For ePTFE patched animals, both EDA and %FAC decreased. In contrast, with MI + PEUU patching, %FAC increased and EDA was maintained. With dobutamine-stress echocardiography, MI + PEUU patched LVs possessed contractile reserve significantly larger than the MI + sham group. ConclusionsMI + PEUU patch implantation onto subacute infarcted myocardium induced muscle cellularization with characteristics of early developmental cardiomyocytes as well as providing a functional reserve.

Critical infarct size to induce ventricular remodeling, cardiac dysfunction and heart failure in rats

Ventricular remodeling, decreased left ventricular systolic function, and heart failure have been associated with poor long-term outcomes after myocardial infarction [1,2]. Thus, it is critical to know the pathophysiological alterations involved in these processes for myocardial infarction management. A rat coronary artery ligation leads to a wide range of infarct size, cardiac remodeling and left ventricular dysfunction. In addition, it is accepted that the coronary occlusion consequences are closely related to infarction size, which is a powerful determinant of survival [3], ventricular remodeling [4], and cardiac systolic function [5]. In order to determine the association between infarct size and outcomes after coronary occlusion, the animals were divided into three groups (small, moderate or large infarct size), but this division was not homogeneous among the studies because the animals were randomly placed in the groups. Consequently, the infarct size that is necessary to determine morphological, functional, and clinical alterations after the coronary occlusion, still needs to be determined. The present study was carried out to determine the critical infarct size to induce ventricular remodeling, cardiac dysfunction, and heart failure in a rat model. Myocardial infarction was induced following the method described previously [6]. Six months after surgery, Sham (n=67) and infarcted animals (n=166) were subjected to transthoracic echocardiography, and euthanized the next day. The echocardiographic exams and morphometric analysis were performed as described previously [6,7]. The left ventricular remodeling was defined as the infarcted values of the left ventricular end-diastolic cavity areas with a difference of N2 and standard deviations above Sham group mean. The systolic dysfunction was defined as the infarcted values of posterior wall shortening velocity (PWSV) with a difference of b2 and standard deviations under Sham group mean. The diastolic dysfunction was defined as the infarcted values of E/A ratio with a difference of N2 and standard deviations above Sham group mean. The variables utilized to determine heart failure included pleuropericardial effusion, left atrial thrombi, ascites, or right ventricular hypertrophy (right ventricle weight-to-body weight ratio N0.8 mg/g) [8]. An infarct size cut-off valuewas derived from the receiver-operating characteristic (ROC) curve according to the infarct size value to maximize sensitivity, specificity, and predictivity values in order to anticipate remodeling, cardiac dysfunctions, and heart failure. The bias between histology and echocardiogram in the infarct size assessment was evaluated by Bland & Altman. After a six-month follow-up, the infarct size in the infarcted animals ranged from 18.5% to 57%, with an average of 40±9% assessed by histology, and 42±9% assessed by echocardiogram, and bias between the methods at −1.15%. The infarct size cut-off values were 36% (area under ROC curves (AUC): 0.70; 95% CI: 0.61-0.78; p=0.017) for ventricular remodeling; 38% (AUC: 0.72; 95% CI: 0.64-0.80; p=0.001) for PWSV; 44% (AUC: 0.72; 95% CI: 0.64–0.79; pb0.001) for E/A ratio and 40% (AUC: 0.65; 95% CI: 0.56-0.73; p=0.004) for heart failure. Among the infarcted rats, 93% presented ventricular remodeling; 86% showed systolic dysfunction; 47% presented diastolic dysfunction; and 66% had heart failure. The knowledge of the critical infarct size necessary to induce remodeling, cardiac dysfunction, and heart failure in this model can be extremely useful, since infarct size can be early estimated after the coronary occlusion by non invasive methods, such as echocardiogram. In the present study, the infarct size was determined by histology, even though this measurement had low bias when compared to infarct size measured by echocardiography. In conclusion, the identification of the critical infarct size to induce ventricular remodeling, cardiac dysfunction, and heart failure might be particularly useful in longitudinal studies about therapeutic and pathophysiological aspects following coronary occlusion. Our data indicate that the minimum infarct size to cause these morphological, functional and clinical abnormalities is 36%, 38%, and 40%, respectively. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1–2).

Viable Fibroblast Matrix Patch Induces Angiogenesis and Increases Myocardial Blood Flow in Heart Failure After Myocardial Infarction

This study examines a viable biodegradable three-dimensional fibroblast construct (3DFC) in a model of chronic heart failure. The viable fibroblasts, cultured on a vicryl mesh, secrete growth factors that stimulate angiogenesis. We ligated the left coronary artery of male Sprague-Dawley rats, implanted the 3DFC 3 weeks after myocardial infarction and obtained end point data 3 weeks later, that is, 6 weeks after myocardial infarction. Implanting the 3DFC increases (p<0.05) myocardial blood flow twofold, microvessel formation (0.02±0.01 vs. 0.07±0.03 vessels/μm2), and ventricular wall thickness (0.53±0.02 to 1.02±0.17mm). The 3DFC shifts the passive pressure volume loop toward the pressure axis but does not alter left ventricular (LV) ejection fraction, systolic displacement, LV end-diastolic pressure/dimension, or LV cavity area. The 3DFC stimulates selected cytokine activation with a decrease in the proinflammatory cascade and increased total protein content stimulated by strained 3DFC in vitro. The 3DFC functions as a cell delivery device providing matrix support for resident cell survival and integration into the heart. The imbedded fibroblasts of the 3DFC release a complex blend of cardioactive cytokines promoting increases in microvessel density and anterior wall blood flow but does not improve ejection fraction or alter LV remodeling.

Early predictors of cardiac decompensation in experimental volume overload

In humans, volume overload (VOL) increases the risk of sudden cardiac death, but there is also important inter-individual variability, presumably because of differences in genetic backgrounds. Although VOL has rapid effects on myocardial properties, it is not known to which extent the severity of these early responses correlate with the effect of sustained VOL on mortality. In order to test this question, we induced VOL in male rats from two genetically distinct strains [i.e., Sprague-Dawley (SD) and Wistar Kyoto-derived Hyperactive (WKHA) rats] by creating a surgical aorto-caval fistula (ACF). Only 36% of SD rats remained alive after 39 weeks of ACF, in contrast to 82% of the operated WKHA rats. We also monitored myocardial hemodynamic function, mitochondrial properties, left ventricular (LV) morphology and LV wall diastolic properties at different times ranging from 2 to 12 weeks after either ACF or sham surgery. ACF had a rapid impact on the LV walls of both rat strains, but the only variables that were affected to a greater extent in the mortality-prone SD strain were normalized LV weight, LV cavity area, and myocardial wall stiffness. In contrast, there were only marginal strain-related differences in the way ACF affected hemodynamic and mitochondrial functions. Thus, while early morphologic responses of LV walls to ACF (along with their downstream consequences on myocardial diastolic wall stress) correlated well with strain-dependent differences in late mortality, other functional changes showed no predictive effects. Close monitoring of early changes in cardiac geometry (as well as new methods to analyze myocardial diastolic strain) might, therefore, be helpful to further improve risk stratification in humans with volume overload cardiopathies.

Synthesis, characterization and therapeutic efficacy of a biodegradable, thermoresponsive hydrogel designed for application in chronic infarcted myocardium

Injection of a bulking material into the ventricular wall has been proposed as a therapy to prevent progressive adverse remodeling due to high wall stresses that develop after myocardial infarction. Our objective was to design, synthesize and characterize a biodegradable, thermoresponsive hydrogel for this application based on copolymerization of N-isopropylacrylamide (NIPAAm), acrylic acid (AAc) and hydroxyethyl methacrylate-poly(trimethylene carbonate) (HEMAPTMC). By evaluating a range of monomer ratios, poly(NIPAAm-co-AAc-co-HEMAPTMC) at a feed ratio of 86/4/10 was shown to be ideal since it formed a hydrogel at 37°C, and gradually became soluble over a 5 month period in vitro through hydrolytic cleavage of the PTMC residues. HEMAPTMC, copolymer and degradation product chemical structures were verified by NMR. No degradation product cytotoxicity was observed in vitro. In a rat chronic infarction model, the infarcted left ventricular (LV) wall was injected with the hydrogel or phosphate buffered saline (PBS). In the PBS group, LV cavity area increased and contractility decreased at 8 wk (p<0.05 versus pre-injection), while in the hydrogel group both parameters were preserved during this period. Tissue ingrowth was observed in the hydrogel injected area and a thicker LV wall and higher capillary density were found for the hydrogel versus PBS group. Smooth muscle cells with contractile phenotype were also identified in the hydrogel injected LV wall. The designed poly(NIPAAm-co-AAc-co-HEMAPTMC) hydrogel of this report may thus offer an attractive biomaterial-centered treatment option for ischemic cardiomyopathy.

Abstract 2821: Does End-systolic Stress Adequately Reflect Time-varying Left Ventricular Wall And Fiber Stress in Hypertension?: Influence Of The Components Of Arterial Pulsatile Load

Pulsatile hemodynamic abnormalities are key determinants of left ventricular (LV) afterload, which is commonly assessed by end-systolic wall and fiber stress. These important indices of afterload are highly sensitive to cavity size and wall thickness. Since cavity size, pressure and wall thickness all change markedly throughout systole, end-systolic stress may not adequately describe the contribution of different components of arterial load to time-varying stress, since these arterial components also vary markedly throughout systole. We studied 25 hypertensive adults (mean age: 58 yrs; 44% male). Central pressure (carotid tonometry) and flow (Doppler echocardiography) were measured simultaneously and the pressure wave was decomposed into its forward (Pf) and reflected (backward, Pb) components. Speckle-tracking echocardiography was used to measure instantaneous LV cavity and wall areas during systole, which were used to compute time-varying fiber (Arts method) and meridional wall (Janz method) stress. Peak fiber and wall stress values were, on average, 1.87- and 2.19-fold higher than end-systolic values, respectively. Peak fiber and wall stress occurred in early systole (97±7 and 81±4 msec after the onset of ejection, respectively), before important contributions of Pb to central pressure. Although end-systolic stress predicted a large proportion of the variability in peak fiber (76%; p&lt;0.0001) and wall (80%; p&lt;0.0001) stress, the ratio of peak/end-systolic stress decreased with increasing Pb/Pf amplitude ratio (fiber stress: R=−0.59, p=0.001; wall stress: R=−0.50; p=0.01). Similarly, the ratio of mean systolic/end-systolic stress decreased with increasing Pb/Pf amplitude ratio (fiber stress: R=−0.58, p=0.002; wall stress: R=−0.51; p=0.007). Adjustment for systemic vascular resistance did not affect these results. The relationship between end-systolic and time-varying LV fiber and wall stress is strongly biased by wave reflections. End-systolic stress does not adequately reflect the contribution of different components of arterial load on time-varying stress, which should be assessed with the combination of arterial tonometry and contemporary echocardiographic techniques.

Noninvasive Assessment of Diastolic Function in Subjects With Preserved Left Ventricular Ejection Fraction: Usefulness of Color Kinetic Imaging

Background Noninvasive assessment of left ventricular (LV) diastolic function is not established in patients with preserved ejection fraction. We investigated a relation between diastolic function and diastolic wall dynamics. Methods and Results In the animal study, data were collected in hypertensive Dahl salt-sensitive rats, a diastolic heart failure (DHF) model (n = 35), and normotensive Dahl rats (n = 26). In the clinical study, echocardiography was conducted in 26 diabetic patients with normal ejection fraction and 10 age-matched controls. The diastolic index of color-encoded images (color kinesis diastolic index [CK-DI]) was calculated as the ratio of LV cavity area expansion during the first 30% of diastolic filling time to that during the whole diastolic filling period. In the DHF model, the E/A ratio of the transmitral flow velocity curves was pseudonormalized with the development of heart failure, but CK-DI was not. CK-DI, not E/A, was significantly and inversely correlated with the time constant of LV relaxation. Angiotensin receptor blocker improved LV relaxation in the DHF model and increased CK-DI, but not E/A. The diabetic patients showed lower CK-DI than the controls, although E/A was not different. Conclusion Color-encoded imaging is useful in evaluating LV diastolic function. The prevalence of LV diastolic dysfunction may have been clinically underestimated by the transmitral flow velocity curves.

An Elastic, Biodegradable Cardiac Patch Induces Contractile Smooth Muscle and Improves Cardiac Remodeling and Function in Subacute Myocardial Infarction

Our objective in this study was to apply an elastic, biodegradable polyester urethane urea (PEUU) cardiac patch onto subacute infarcts and to examine the resulting cardiac ventricular remodeling and performance. Myocardial infarction induces loss of contractile mass and scar formation resulting in adverse left ventricular (LV) remodeling and subsequent severe dysfunction. Lewis rats underwent proximal left coronary ligation. Two weeks after coronary ligation, a 6-mm diameter microporous PEUU patch was implanted directly on the infarcted LV wall surface (PEUU patch group, n = 14). Sham surgery was performed as an infarction control (n = 12). The LV contractile function, regional myocardial wall compliance, and tissue histology were assessed 8 weeks after patch implantation. The end-diastolic LV cavity area (EDA) did not change, and the fractional area change (FAC) increased in the PEUU patch group (p < 0.05 vs. week 0), while EDA increased and FAC decreased in the infarction control group (p < 0.05). The PEUU patch was largely resorbed 8 weeks after implantation and the LV wall was thicker than infarction control (p < 0.05 vs. control group). Abundant smooth muscle bundles with mature contractile phenotype were found in the infarcted myocardium of the PEUU group. The myocardial compliance of the PEUU group was distributed between normal myocardium and infarction control (p < 0.001). Implantation of a novel biodegradable PEUU patch onto a subacute myocardial infarction promoted contractile phenotype smooth muscle tissue formation and improved cardiac remodeling and contractile function at the chronic stage. Our findings suggest a new therapeutic option against post-infarct cardiac failure.

Parametric harmonic-to-fundamental ratio contrast echocardiography: A novel approach to identification and accurate measurement of left ventricular area under variable levels of ultrasound signal attenuation

Objectives We introduced a harmonic-to-fundamental ratio (HFR) of the radiofrequency (RF) signals that reduces confounding effects of attenuation. We studied whether HFR analysis of RF signals received from contrast microbubbles allows accurate measurement of the left ventricular (LV) cavity area under varying levels of attenuation. Background Attenuation is a fundamental problem in ultrasound imaging and limits the use of clinical echocardiography. Methods RF data from short axis systolic and diastolic scans were obtained from 14 open-chest dogs following left-atrial bolus of Optison. Attenuation was induced by interposed silicone pads calibrated to induce 7 dB or 14 dB reductions of the backscattered RF signal. RF images were reconstructed from the RF signals, HFR values calculated for each image pixel for 0 dB, 7 dB and 14 dB attenuation conditions, and LV area obtained by summation of “LV cavity pixels”. A reference LV cavity area was obtained from endocardial border tracings in enhanced scans by experts. Results Correlation of the HFR-defined and reference areas at systole was R = 0.95, R = 0.94, and R = 0.91 for 0 dB, 7 dB and 14 dB levels of attenuation, respectively, and at diastole was R = 0.95 for 0 dB, 7 dB and 14 dB levels of attenuation. The mean difference from both systolic and diastolic values was <1.45 cm 2 (i.e. negligible) in all attenuation settings. Conclusion Our novel HFR method supports precise measurement of the LV cavity area in contrast images with simulated high attenuation of ultrasound signals.

Direct Effects of 3 Combinations of Enalapril, Metoprolol, and Spironolactone on Cardiac Remodeling in Dilated Cardiomyopathic Hamsters

In congestive heart failure, enalapril (E), metoprolol (M), and spironolactone (S) improve survival. Their direct effects on cardiac remodeling, when administered in combination, remain to be assessed. One hundred and five cardiomyopathic hamsters were divided into 5 groups (control, E, E-M, E-S, E-M-S) and treated from 150 to 240 days of age (E: 3 mg/kg, M: 1 mg/kg, S: 20 mg/kg). Cardiac and systemic hemodynamics, and cardiac remodeling were investigated. There was no difference between groups on blood pressure. Compared with C, both S-treated groups significantly increased cardiac index (E-S: +49%; E-M-S: +46%). Compared with C, E significantly decreased left ventricular (LV) cavity area (-10%). Compared with E, all combinations significantly decreased LV cavity area (E-M: -13%, E-S: -22%, E-M-S: -19%) and right ventricular (RV) collagen density (E-M: -18%, E-S: -30%, E-M-S: -34%), and the tri-therapy significantly decreased LV collagen density (-18%). Compared with bi-therapies, the tri-therapy significantly decreased LV (-19% vs. E-M, -16% vs. E-S) and RV (-20% vs. E-M) collagen densities. At subdepressor doses, both bi-therapies induced similar effects on myocardial remodeling, enhancing the effects of E on LV cavity area and reducing RV collagen density. Compared with bi-therapies, the tri-therapy induced additional effects on LV and RV collagen densities.

Prolonged strenuous exercise alters the cardiovascular response to dobutamine stimulation in male athletes

Prolonged strenuous exercise has been associated with transient impairment in left ventricular (LV) systolic and diastolic function that has been termed 'cardiac fatigue'. It has been postulated that cardiac beta-adrenoreceptor desensitization may play a central role; however, data are limited. Accordingly, we assessed the cardiovascular response to progressive dobutamine stimulation after prolonged strenuous exercise (2 km swim, 90 km bike, 21 km run). Nine experienced male athletes were studied: PRE (2-3 days before), POST (after) and REC (1-2 days later). The cardiovascular response to progressive continuous dobutamine stimulation (0, 5, 20, and 40 microg kg(-1) min(-1)) was assessed, including heart rate (HR), systolic blood pressure (SBP), LV cavity areas (two-dimensional echocardiography) and contractility (end-systolic elastance, SBP/end-systolic cavity area (ESCA)). POST there was limited evidence of myocardial necrosis (measured by troponin I), while catecholamines were elevated. HR was higher POST (mean +/-s.d.; PRE, 58 +/- 9; POST, 79 +/- 9; REC, 57 +/- 7 beats min(-1); P < 0.05), while SBP was lower (PRE, 127 +/- 15; POST, 116 +/- 9; REC, 121 +/- 12 mmHg; P < 0.05). A blunted HR, SBP and LV contractility (SBP/ESCA; PRE 29 +/- 6 versus POST 20 +/- 6 mmHg cm(-2); P < 0.05) response to dobutamine was demonstrated POST, with values returning towards baseline in REC. Following prolonged strenuous exercise, the chronotropic and inotropic response to dobutamine stimulation is blunted. This study supports the hypothesis that beta-receptor downregulation and/or desensitization may play a major role in prolonged-strenuous-exercise-mediated cardiac fatigue.

Administration of Erythropoietin Fails to Improve Long-Term Healing or Cardiac Function After Myocardial Infarction in the Rat

Erythropoietin (epo), initially recognized and used clinically to increase erythropoiesis, has been shown to have beneficial effects on various other tissues in the setting of hypoxia and ischemia. Epo has been shown to reduce apoptosis after myocardial infarction, but few studies have evaluated the long-term effects of epo treatment on left ventricular (LV) remodeling, cardiac function, and blood flow after healing of a permanent coronary artery occlusion. The aim of this study was to assess the effects of epo treatment on the healed heart 6 weeks after myocardial infarction. Anesthetized rats underwent coronary artery occlusion and were treated with erythropoietin (5000 units/kg/day, n=21) or saline (n=20) the day before surgery, the day of, then for 5 days. At 6 weeks LV ventriculography to assess LV volumes and ejection fractions and histologic assessment of infarct size and LV cavity and wall dimensions were performed. Overall epo had no effect on LV remodeling or cardiac function. There were no significant differences in infarct morphology, infarct size (44+/-3% of the LV circumference versus 39+/-3%), LV cavity area, scar thickness, LV systolic volume, or ejection fraction (44+/-3% versus 39+/-3%) between the epo and saline groups, respectively. However, for any given size of myocardial infarct, LV ejection fraction was significantly higher in erythropoietin hearts and LV systolic volumes lower. Thus, in our model, treatment with epo had no long-term beneficial effect on LV remodeling after myocardial infarction but may have exerted some positive effect on LV function.