Changes In Left Ventricular Dimensions Research Articles

Pathophysiological alterations of left ventricular myocardial systolic function during normal pregnancy assessed by speckle tracking echocardiography: a prospective cohort echocardiography study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pregnancy induces a variety of haemodynamic and morphological changes, leading to the amplification of cardiac pumping function. These changes do not cause any significant left ventricular (LV) dysfunction by using conventional echocardiographic indices, but it is not fully elucidated whether subclinical or/and reversible myocardial dysfunction is provoked during pregnancy. Two-dimensional speckle tracking echocardiography (2D-STE) can detect subclinical myocardial dysfunction even when conventional echocardiography reveal LV normal ejection fraction (LVEF).Purpose: The aim of this study was to evaluate whether LV systolic performance is impaired during normal low risk pregnancy by using both conventional 2D and 3D echo indices and 2D-STE. Materials and methods: One hundred and twelve consecutive pregnant women without any history of heart disease were prospectively recruited. They underwent serial echocardiographic evaluation in each pregnancy trimester (1st: 8th-12th week, 2nd: 22th-26th week, 3rd: 32-36th week) and 6 months after delivery (time indicated as 4). LV dimensions, relative wall thickness (RWT), 2D-LVEF, 3D-LVEF, systolic S wave from Tissue Doppler Imaging, LV global longitudinal strain (LVGLS), LV global circumferential strain (LVGCS) and LV-twist were measured and compared to 31 nulliparous women of similar age, who served as a control group (c).Results: Progressive eccentric LV hypertrophy was observed during pregnancy, which was subsided postpartum (p1-2 = 0.08, p2-3= 0.002, p3-4 = 0.001, p1-3 < 0.001, p1-4= 0.789), while no significant change in LV dimensions was found. 2D-LVEF, 3D-LVEF and S wave values were not significantly different among the three trimesters, postpartum and controls. LVGLS progressively decreased during pregnancy (1st:-21.71 ± 2.13%, 2nd: -21.20 ± 2.30%, 3rd: -19.82 ± 2.10%,4th: -21.81 ± 2.05%, c: -21.71 ± 2.2[E1]%,overall p < 0,001 ) and returned to normal during puerperium. No significant difference was noted in LVGCS (1st: -18.08 ± 5.54%, 2nd: -18.57 ± 3.41%, 3rd: -18.20 ± 3.33%,4th: -17.95 ± 3.39%,c: -18.8 ± 2.2% , p > 0.3). LV-Twist was significantly higher in the 1st trimester compared to controls (p= 0.04) and remained constantly high during the rest of the pregnancy and puerperium (1st:13.80 ± 5.09°, 2nd :13.46 ± 5.35°, 3rd:13.58 ± 4.32°, 4th:13.37 ± 4.26°, c: 11.5 ± 4.3°, ).Conclusion: Left ventricular subclinical dysfunction seems to occur in the longitudinal axis even in low risk individuals with normal pregnancy. Increased torsional movement of the heart seems to counterbalance the temporal impairment of longitudinal systolic function.

Trajectory of Left Ventricular Remodeling in Children With Valvar Aortic Stenosis Following Balloon Aortic Valvuloplasty

Aortic valve stenosis is the most common type of congenital left ventricular (LV) outflow tract obstruction. Balloon aortic valvuloplasty (BAV) has become the first-line treatment pathway in many centers. Our aim was to assess the trajectory of LV remodeling following BAV in children and its relationship to residual aortic stenosis (AS) and insufficiency (AI). Children <18 years of age who underwent BAV for isolated aortic stenosis from 2004 to 2012 were eligible for inclusion. Those with AI before BAV, other complex congenital heart lesions, or <2 accessible follow-up echocardiograms were excluded. Baseline and serial echocardiographic data pertaining to aortic valve and LV size and function were retrospectively collected through December 2017 or the first reintervention. Longitudinal data was assessed using per-patient time profiles with superimposed trend lines using locally estimated scatterplot smoothing. Associations with reintervention or death were also evaluated. Among the 98 enrolled children, the median (interquartile range) age at BAV was 2.8 months (0.2-75). The median (interquartile range) follow-up was 6.8 years (1.9-9.0). Children with predominantly residual AI (n=11) demonstrated progressive increases in their LV end-diastolic dimension Z score within the first 3 years after the BAV, followed by a plateau (P<0.001). Their mean LV circumferential and longitudinal strain values remained within the normal range but lower than in the non-AI group (P<0.001 and P=0.001, respectively). Children with predominantly residual aortic stenosis (n=44) had no changes in LV dimensions but had a rapid early increase in mean LV circumferential and longitudinal strain. The cumulative proportion (95% CI) of reintervention at 5 years following BAV was 33.7% (23.6%-42.4%). Our study demonstrates that LV remodeling occurs mainly during the first 3 years in children with predominantly residual AI after BAV, with no subsequent significant functional changes over the medium term. These data improve our understanding of expected patient trajectories and thus may inform decisions on the timing of reintervention.

Assessment of echocardiographic left ventricular dimensions with several clinical findings among healthy people

Background: The echocardiographic measurement of left ventricular dimensions and the changes of left ventricular dimensions may be important to assess cardiac as well as the cardiovascular conditions of patients. On the other hand, the QRS duration signifies the time for ventricular depolarization. Aim of the study: The aim of this study was to assess the echocardiographic left ventricular dimensions with several clinical findings among healthy people. Methods: This was an observational cross-sectional study which was conducted in the Department of Cardiology, University Cardiac Centre, Bangabandhu Sheikh Mujib Medical University, Dhaka over a period of 2 years from July 2008 to June 2010. In total 92 apparently healthy people without heart failure (HF) or myocardial infarction (MI) were included as the study population. Among them, 22 were in Referent (QRS duration &lt;100 ms), 40 in Incomplete BBB (QRS duration 100 – 119), and 30 in Complete BBB (≥ 120 ms) groups. Proper written consent was taken from all the participants and this study was approved by the ethical committee of the mentioned university. All data were processed, analyzed, and disseminated by MS Office and SPSS version as per need. Results: In this study, the left ventricular (LV) mass, left ventricular diastolic dimension, septal wall thickness, posterior wall thickness and left atrial size were significantly higher in complete BBB group than those in referent and incomplete BBB group (143.0 ± 30.2 vs. 182.6 ± 37.9 vs. 222.0 ± 61.0, p &lt; 0.001; 4.6 ± 0.3 vs. 4.9 ± 0.3 vs. 5.2±0.4, p&lt; 0.001; 0.9±0.1 vs. 1.0 ± 0.1 vs. 1.1± 0.1, p&lt;0.001; 0.9 ± 0.1 vs. 1.0 ± 0.1 vs. 1.1± 0.1, p&lt;0.001; and 3.3 ± 0.3 vs. 3.6±0.3 vs. 3.7±0.3, p&lt;0.001 respectively). However, fractional shortening and left ventricular ejection fraction were found to decrease significantly with the increase in QRS duration (p &lt; 0.001 and p &lt; 0.001 respectively). In this study the QRS duration was observed to be linearly correlated with LV mass, LV diastolic dimension, septal wall thickness, posterior wall thickness and left atrial size (r=0.577, p&lt;0.001; r=0.480, p&lt;0.001; r=0.583, p&lt;0.001; r=0.521, p&lt; 0.001 and r= 0.418, p&lt;0.001 respectively).&nbsp; However, QRS duration was found to maintain a negative correlation with fractional shortening and LVEF (r =- 0.637, p&lt;0.001 and r =- 0.701, p&lt;0.001 respectively). Conclusion: The present study revealed that longer electrocardiographic QRS duration was correlated with the increase in LV mass, LV diastolic dimensions, septal wall thickness, posterior wall thickness, and left atrial size. The association was most striking in individuals with complete BBB compared with a normal QRS duration. Meanwhile, the presence of prolonged QRS in a patient’s ECG can serve as a bedside clue to the presence of decreased fractional shortening and left ventricular ejection fraction.

Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction

Left ventricular remodeling following acute myocardial infarction results in progressive myocardial dysfunction and adversely affects prognosis. To investigate the efficacy of paroxetine-mediated G-protein-coupled receptor kinase 2 inhibition to mitigate adverse left ventricular remodeling in patients presenting with acute myocardial infarction. This double-blind, placebo-controlled randomized clinical trial was conducted at Bern University Hospital, Bern, Switzerland. Patients with acute anterior ST-segment elevation myocardial infarction with left ventricular ejection fraction (LVEF) of 45% or less were randomly allocated to 2 study arms between October 26, 2017, and September 21, 2020. Patients in the experimental arm received 20 mg of paroxetine daily; patients in the control group received a placebo daily. Both treatments were provided for 12 weeks. The primary end point was the difference in patient-level improvement of LVEF between baseline and 12 weeks as assessed by cardiac magnetic resonance tomography. Secondary end points were changes in left ventricular dimensions and late gadolinium enhancement between baseline and follow-up. Fifty patients (mean [SD] age, 62 [13] years; 41 men [82%]) with acute anterior myocardial infarction were randomly allocated to paroxetine or placebo, of whom 38 patients underwent cardiac magnetic resonance imaging both at baseline and 12 weeks. There was no difference in recovery of LVEF between the experimental group (mean [SD] change, 4.0% [7.0%]) and the control group (mean [SD] change, 6.3% [6.3%]; mean difference, -2.4% [95% CI, -6.8% to 2.1%]; P = .29) or changes in left ventricular end-diastolic volume (mean difference, 13.4 [95% CI, -12.3 to 39.0] mL; P = .30) and end-systolic volume (mean difference, 11.4 [95% CI, -3.6 to 26.4] mL; P = .13). Late gadolinium enhancement as a percentage of the total left ventricular mass decreased to a larger extent in the experimental group (mean [SD], -13.6% [12.9%]) compared with the control group (mean [SD], -4.5% [9.5%]; mean difference, -9.1% [95% CI, -16.6% to -1.6%]; P = .02). In this trial, treatment with paroxetine did not improve LVEF after myocardial infarction compared with placebo. ClinicalTrials.gov Identifier: NCT03274752.

Use of strain rate imaging for early detection of epirubicin-induced cardiotoxicity in patients with breast cancer.

e12531 Background: Although epirubicin has improved outcome in breast cancer (BC) patients, its application is limited by its cardiotoxicity . Assessment of left ventricular (LV) ejection fraction (EF) is performed to demonstrate cardiac dysfunction. Changes in cardiac function induced by this therapy, however, are difficult to quantitate by conventional echocacardiography. Tissue Doppler myocardial imaging (TDI) derived wall motion velocity, and strain rate (SR) have been shown to sensitively quantify abnormalities in cardiac function. The aim of this study was to determine if sensitive indices of LV dysfunction, would be useful for addressing the early detection of cardiotoxic side effects of epirubicin. Methods: BC patients (N = 45 median age 60.2years) without cardiovascular risk factors were prospectively included. All patients received epirubicin. Twenty patients received further trastuzumab. Conventional and TDI echocardiography were obtained at baseline , every 2cycles of treatment and 3 months after chemotherapy. Segmental peak systolic longitudinal and radial velocity, SR and strain, were measured. Results: at baseline, median LV-EF was &gt; 55 %. There was no overall change in LV dimensions, EF and peak systolic velocity. In contrast, a significant reduction in longitudinal and radial SR and strain was found after 3 cycles (longitudinal strain -10.2% +/- 1.3 % vs baseline 22 +/- 4.1 %, P = .001; radial strain 26.1% +/-4,2% vs baseline 47.3% +/- 9.2 %, P &lt; .001). Changes in radial strain appeared earlier and were more pronounced than longitudinal strain. Conclusions: In this study we confirm the clinical use of TDI parameters for early detection of epirubicin mediated cardiac dysfunction. TDI detected subtle changes of LV function after 3 cycles of therapy. Use of Strain Rate Imaging detects subclinical LV dysfunction and can predict further changes in EF ,therefore can be used to monitor epirubicin-induced cardiotoxicity.

Study of Cardiovascular Changes in Adolescents with Simple Obesity

Obesity is a risk factor for cardiovascular morbidity and mortality that has deleterious effects on cardiovascular function. The aim of this work was to screen early cardiovascular abnormalities in obese asymptomatic adolescents using Conventional Echocardiography and Electrocardiogram. Fifty asymptomatic obese adolescents selected from National Heart Institute were compared to fifty non-obese normal controls with mean age of (12.44 ± 1.91) and (11.99 ± 1.89) years respectively. All studied adolescents were subjected to: careful history taking, complete clinical examination, laboratory investigation: fasting blood glucose, lipid profile, fasting insulin, insulin resistance, echocardiography and ECG. Results: It revealed statistical significant differences between obese and non-obese groups regarding left ventricle septal wall in diastole (LVSd), posterior wall thickness in diastole (LVPWd), relative wall thickness (RWT), LV end diastolic and systolic diameter (LVEDD and LVESD) and LV mass (P-value: 0.000). The left atrial dimensions (LA) were also significantly higher in the obese subjects than in the control group (P-value: 0.000). For the Doppler measurements, the early and late mitral valve velocity and the ratio between them (MVE velocity, MVA velocity and MV E/A) were significantly higher in obese than control subjects (P-value: 0.000). A strong positive correlation was noted between BMI and left atrial size (P-value: 0.003), left ventricular septum in diastole (LVSd) (P-value: 0.000), LVEDD (P-value: 0.005) and LVESD (P-value: 0.000), posterior wall thickness in diastole (LVPWd) (P-value: 0.012), left ventricle septal wall in diastole (LVSd) (P-value: 0.000) and left ventricular mass (P-value: 0.010). Conclusion: This study demonstrated that asymptomatic obese adolescents had significant changes in left ventricular dimensions and early diastolic filling compared to non-obese subjects.

Abstract 439: Trajectory Analysis of Left Ventricular Dimensions From Biobank Data Uncovers Novel Genetic Associations

Background: Approximately 6 million adults in the United States have heart failure. The progression of heart failure is variable arising from differences in sex, age, genetic background including ancestry, and medication response. Many population-based genetic studies of heart failure have been cross-sectional in nature, failing to gain additional power from longitudinal analyses. As heart failure is known to change over time, using longitudinal data trajectories as a quantitative trait will increase power in genome wide association studies (GWAS). Methods: We used the electronic health record in a racially and ethnically diverse medical biobank from a single, metropolitan US center. We used whole genome data from 896 unrelated participants analyzed, including 494 who had at least 1 electrocardiogram and 324 who had more than 1 echocardiogram (average of 3 observations per person). A mixture model based semiparametric latent growth curve model was used to cluster outcome measures used for genome-wide analyses. Results: GWAS on the trajectory probability of QTc interval identified significant associations with variants in regulatory regions proximal to the WLS gene, which encodes Wntless, a Wnt ligand secretion mediator. WLS was previously associated with QTc and myocardial infarction, thus confirming the power of the method. GWAS on the trajectory probability of left ventricular diameter (LVIDd) identified significant associations with variants in regulatory regions near MYO10 , which encodes unconventional Myosin-10. MYO10 was previously associated with obesity and metabolic syndrome. Conclusions: This is the first study to show an association with variants in or near MYO10 and left ventricular dimension changes over time. Further, we found that using trajectory probabilities can provide increased power to find novel associations with longitudinal data. This reduces the need for larger cohorts, and increases yield from smaller, well-phenotyped cohorts, such as those found in biobanks. This approach should be useful in the study of rare diseases and underrepresented populations.

TCT-135 The Impact of Baseline Aortic Regurgitation on the Degree of Left Ventricular Remodeling After Transcatheter Aortic Valve Implantation

The effect of baseline aortic regurgitation (AI) on left ventricular (LV) geometry regression following transcatheter aortic valve replacement (TAVR) is not well defined. We aimed to assess the effect of native valve AI on LV mass regression and changes in LV dimensions at 1-year post-TAVR. We

Insulin resistance and dysglycemia are associated with left ventricular remodeling after myocardial infarction in non-diabetic patients

BackgroundAdverse cardiac remodeling after ST-segment elevation myocardial infarction (STEMI) is a major cause for poor cardiovascular outcomes such as heart failure. The predisposing factors and underlying mechanisms remain not fully understood. This study investigates the association of insulin resistance and dysglycemia with left ventricular (LV) remodeling after STEMI in non-diabetic patients.MethodsA total of 485 non-diabetic subjects with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for 12 months. Relation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and glucose levels to changes in echocardiography parameters was studied.ResultsLeft ventricular dilation was detected in 49.1% of subjects at 12-month follow-up after STEMI, and was more severe in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and high HOMA-IR levels. HOMA-IR remained correlated to changes in LV dimensions after adjusting for confounding risk factors. Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI. A significant interaction term was present between HOMA-IR and IGT in the model (P = 0.001).ConclusionsOur study reveals that insulin resistance and dysglycemia are prevalent in non-diabetic patients with STEMI and are predictors of the post-infarction LV dilation.Trial registration Trials number, NCT02089360; registered on March 17, 2014

THE IMPACT OF TRANSCATHETER AORTIC VALVE IMPLANTATION ON LEFT VENTRICULAR REMODELING AT ONE YEAR POST INTERVENTION

The effect of Transcatheter Aortic Valve Implantation (TAVI) on left ventricular (LV) geometry is not well defined. We aimed to assess the LV mass regression and changes in LV dimensions in patients with normal and reduced ejection fraction (EF) at 1 year post-TAVI. We queried our institutional

Do annuloplasty rings designed to treat ischemic/functional mitral regurgitation alter left-ventricular dimensions in the acutely ischemic ovine heart?

ObjectiveTo quantify the effects of annuloplasty rings designed to treat ischemic/functional mitral regurgitation on left ventricular septal-lateral (S-L) and commissure-commissure (C-C) dimensions. MethodsRadiopaque markers were placed as opposing pairs on the S-L and C-C aspects of the mitral annulus and the basal, equatorial, and apical level of the left ventricle (LV) in 30 sheep. Ten true-sized Carpentier-Edwards Physio (PHY), Edwards IMR ETlogix (ETL), and GeoForm (GEO; all from Edwards Lifesciences, Irvine, Calif) annuloplasty rings were inserted in a releasable fashion. After 90 seconds of left circumflex artery occlusion with the ring implanted (RING), 4-dimensional marker coordinates were obtained using biplane videofluoroscopy. After ring release, another data set was acquired after another 90 seconds of left circumflex artery occlusion (NO RING). S-L and C-C diameters were computed as the distances between the respective marker pairs at end-diastole. Percent change in diameters was calculated between RING versus NO RING as 100 × (diameter in centimeters [RING] − diameter in centimeters [NO RING])/diameter in centimeters [NO RING]). ResultsCompared with NO RING, all ring types (PHY, ETL, and GEO) reduced mitral annular S-L dimensions by −20.7 ± 5.6%, −26.8 ± 3.9%, and −34.5 ± 3.8%, respectively. GEO reduced the S-L dimensions of the LV at the basal level only by −2.3 ± 2.4%, whereas all other S-L dimensions of the LV remained unchanged with all 3 rings implanted. PHY, ETL, and GEO reduced mitral annular C-C dimensions by −17.5 ± 4.8%, −19.6 ± 2.5, and −8.3 ± 4.9%, respectively, but none of the rings altered the C-C dimensions of the LV. ConclusionsDespite radical reduction of mitral annular size, disease-specific ischemic/functional mitral regurgitation annuloplasty rings do not induce relevant changes of left ventricular dimensions in the acutely ischemic ovine heart.

Adaptive servo-ventilation for central sleep apnoea in systolic heart failure: results of the major substudy of SERVE-HF.

The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers. In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months. In secondary analyses, data for patients with baseline and 12-month values were evaluated; 312 patients participated in the substudy. The primary endpoint, change in echocardiographically determined left ventricular ejection fraction from baseline to 12 months, did not differ significantly between the ASV and the control groups. There were also no significant between-group differences for changes in left ventricular dimensions, wall thickness, diastolic function or right ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in small patient numbers). Plasma N-terminal pro B-type natriuretic peptide concentration decreased in both groups, and values were similar at 12 months. There were no significant between-group differences in changes in cardiac, renal and systemic inflammation biomarkers. In patients with systolic heart failure and CSA, addition of ASV to guideline-based medical management had no statistically significant effect on cardiac structure and function, or on cardiac biomarkers, renal function and systemic inflammation over 12 months. The increased cardiovascular mortality reported in SERVE-HF may not be related to adverse remodelling or worsening heart failure.

Reply to “Moving Beyond Linear Formulas for Left Ventricular Mass in Aortic Valve Replacement”

We thank Moneghetti and colleagues for acknowledging positively our investigative result related to a potential pitfall of the linear echocardiography method for calculating left ventricular (LV) mass. The Devereux LV mass formula is the most widely used echocardiographic method to estimate LV mass and it has been a reliable predictor of cardiovascular outcomes in various populations. The formula was originally derived from the cube function of the LV end-diastolic dimension, posterior wall thickness, and interventricular septal thickness. The LV mass estimated from this formula was validated against the anatomically measured LV mass in 34 patients. The main point of our paper was to provide an explanation for the paradoxical finding of a greater and faster LV mass reduction in patients with severe aortic stenosis after surgical aortic valve replacement (SAVR) compared to after transcatheter AVR (TAVR) despite better hemodynamics with transcatheter aortic prostheses. In evaluating the echocardiographic parameters used to calculate LV mass in the CoreValve high-risk trial, we found that LV end-diastolic dimension became significantly smaller soon after SAVR, but not after TAVR, while both posterior and ventricular septal wall thickness decreased in both groups over time and to a similar extent. The smaller LV end-diastolic dimension after SAVR was responsible for the paradoxical faster and greater regression of the calculated LV mass. The reduced LV dimension after SAVR appeared to be related to reduced stroke volume after SAVR which did not occur after TAVR. There are several other echocardiographic methods to calculate LV mass. The Area-length method has also been well-validated against LV mass calculated by cardiac magnetic resonance imaging (MRI). The Area-length method uses LV cavity long-axis dimension and short-axis area. However, the Area-length method would also be falsely reduced if stroke volume decreases immediately after SAVR. There are several alternative means to compare LV mass regression after SAVR and TAVR. As suggested by Moneghetti and colleagues, 3D echocardiography or other imaging techniques such as cardiac computed tomography (CT) or cardiac MRI should provide more accurate LV mass calculations without being affected by acute changes in LV dimensions. We are currently conducting a prospective study to compare LV mass after SAVR and TAVR using cardiac CT, and hope to share our data soon. Ana Kadkhodayan has nothing to disclose. Dr. Jae K. Oh has received research support for the echocardiographic core laboratory from Medtronic.

Assessment of subclinical left ventricular systolic function using strain imaging in the follow-up of patients with chronic mitral regurgitation.

Determining optimal timing for surgery in asymptomatic mitral regurgitation (MR) remains a challenge. The aim of this study was to evaluate subclinical changes in left ventricular (LV) systolic functions using velocity vector imaging (VVI) during follow-up of patients with chronic mitral regurgitation (MR). A total of 54 patients (mean age: 57.9±8 years; 55% male) with moderate-to-severe MR and normal LV ejection fraction (EF), and 30 healthy controls (mean age: 56±6.5 years; 55% male) were evaluated using conventional echocardiography and VVI at baseline. At the end of 12 months, measurements of 45 MR patients were repeated. There was no significant change in LV dimensions or EF on follow-up. LV peak systolic strain and strain rate (SR) were decreased in patients with MR compared with controls (strain: 16.29±3.30 to 23.4±1.9; p=0.0001 and SR: 0.93±0.39 to 4.9±0.6; p=0.0001) at baseline. Impairment was more significant on follow-up. (strain: 13.76±2.68 and SR: 0.27±0.14; p=0.0001). VVI-derived strain imaging might be used in the assessment of subclinical LV dysfunction and its progression during follow-up of patients with chronic MR especially in the decision of optimal timing for surgery.

Sestrin2 protects the myocardium against radiation-induced damage.

The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury.

Modeling of Longitudinal Changes in Left Ventricular Dimensions among Female Adolescent Runners.

PurposeLeft ventricular (LV) enlargement has been linked to sudden cardiac death among young athletes. This study aimed to model the effect of long-term incessant endurance training on LV dimensions in female adolescent runners.MethodsJapanese female adolescent competitive distance runners (n = 36, age: 15 years, height: 158.1 ± 4.6 cm, weight: 44.7 ± 6.1 kg, percent body fat: 17.0 ± 5.2%) underwent echocardiography and underwater weighing every 6 months for 3 years. Since the measurement occasions varied across subjects, multilevel analysis was used for curvilinear modeling of changes in running performance (velocities in 1500 m and 3000 m track race), maximal oxygen uptake (VO2max), body composition, and LV dimensions.ResultsInitially, LV end-diastolic dimension (LVEDd) and LV mass were 47.0 ± 3.0 mm and 122.6 ± 15.7 g, respectively. Running performance and VO2max improved along with the training duration. The trends of changes in fat-free mass (FFM) and LVEDd were similarly best described by quadratic polynomials. LVEDd did not change over time in the model including FFM as a covariate. Increases in LV wall thicknesses were minimal and independent of FFM. LV mass increased according to a quadratic polynomial trend even after adjusting for FFM.ConclusionsFFM was an important factor determining changes in LVEDd and LV mass. Although running performance and VO2max were improved by continued endurance training, further LV cavity enlargement hardly occurred beyond FFM gain in these adolescent female runners, who already demonstrated a large LVEDd.

Anemia and its association with clinical outcome in heart failure patients undergoing cardiac resynchronization therapy.

Although a substantial proportion of patients with heart failure (HF) have anemia, there is a paucity of data evaluating the impact of anemia on clinical outcome in CRT patients. Our goal was to examine the ability of baseline hemoglobin (Hb) level and change in Hb level over time to predict clinical 2-year outcome and echocardiographic response to CRT. Three hundred consecutive CRT patients (median 72 years [interquartile range (IQR) 16 years], 19% female) with baseline and follow-up hematological profiles available were examined. Baseline anemia was defined as Hb <12 g/dL in women and <13 g/dL in men, and patients were grouped into equal quartiles based on change in Hb. Two-year clinical outcome was determined using a composite endpoint that included HF hospitalization, left ventricular assist device (LVAD) placement, heart transplantation, and all-cause mortality. Echocardiographic reverse remodeling was examined at 6-month follow-up. One hundred fifty-one anemic patients were compared to 149 non-anemic patients. Changes in left ventricular dimensions and ejection fraction were similar for both groups. Univariate predictors of 2-year clinical outcome included baseline creatinine level, diuretic usage, and anemia; in multivariable regression, baseline anemia was an independent predictor for outcome (hazard ratio [HR] 1.79, 95% confidence interval [CI] [1.22-2.63], p = 0.003). The quartile with the most negative change in Hb concentration over time (≤-1.00 g/dL) had poorer event-free 2-year survival (HR 1.84, CI [1.13-3.00], p = 0.014). Baseline anemia and early postimplantation decline in Hb levels are associated with a worse 2-year prognosis in CRT patients, even though the magnitude of left ventricular reverse remodeling is similar compared to non-anemic patients.

Role of Interleukin-1 in Radiation-Induced Cardiomyopathy.

Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. Wild-type (wt) or IL-1R1 KO mice were treated with a single session of XRT (20 or 14 gray [Gy]). Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis and pericardial thickening. After 20 Gy, the contractile reserve was impaired in wt mice at d 3, and the LV ejection fraction (EF) was reduced after 4 months when compared with sham-XRT. IL-1R1 KO mice had preserved contractile reserve at 3 d and 4 months and LVEF at 4 months after XRT. Anakinra treatment for 1 d before and 7 d after XRT prevented the impairment in contractile reserve. A significant increase in LV end-diastolic pressure, associated with increased myocardial interstitial fibrosis and pericardial thickening, was observed in wt mice, as well as in IL-1R1 KO-or anakinra-treated mice. In conclusion, induction of IL-1 by XRT mediates the development of some, such as the contractile impairment, but not all aspects of the XRT-induced cardiomyopathy, such as myocardial fibrosis or pericardial thickening.

Response of right ventricular size to treatment with cardiac resynchronization therapy and the risk of ventricular tachyarrhythmias in MADIT-CRT

Cardiac resynchronization therapy (CRT) is increasingly recognized for its ability to reduce ventricular tachyarrhythmias, possibly associated with left ventricular reverse remodeling, but the role of the right ventricle (RV) in this process has not been examined. The purpose of this study was to investigate the relationship between ventricular tachyarrhythmias and change in RV dimensions in patients receiving CRT with a defibrillator (CRT-D). Multivariate Cox proportional hazards regression modeling was used to assess the risk for fast (≥180 bpm) ventricular tachycardia/ventricular fibrillation (VT/VF) or death by baseline and follow-up RV size (defined as right ventricular end-diastolic area [RVEDA]) among 1495 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Multivariate analysis showed that treatment with CRT-D was independently associated with a 27% (P = .003) reduction in the risk of VT/VF or death among patients with larger RVs (>first quartile RVEDA ≥13 mm(2)/m(2)) compared with implantable cardioverter-defibrillator (ICD)-only therapy, whereas in patients with smaller RVs there was no significant difference in the risk of VT/VF between the 2 treatment arms (hazard ratio = 1.00, P = .99). At 1-year follow-up, CRT-D patients displayed significantly greater reductions in RVEDA compared to ICD-only patients (P <.001), associated with a corresponding reduction in the risk of subsequent VT/VF or death (>first quartile reduction in RVEDA with CRT-D vs ICD-only: hazard ratio = 0.55, P <.001) independent of changes in left ventricular dimensions. Our findings suggest that the RV may have an important role in determining the antiarrhythmic effect of CRT independent of the effect of the device on the left ventricle.

The impact of anti-inflammatory cytokines provoked by CD163 positive macrophages on ventricular functional recovery after myocardial infarction

Present study aimed to investigate the impact of anti-inflammatory cytokines provoked by the hemoglobin scavenger receptor, CD163, on left ventricular (LV) functional recovery after successful reperfusion in patients with acute myocardial infarction (AMI). Intraplaque hemorrhage accelerates plaque destabilization. Extracellular hemoglobin is cleared by CD163, a macrophage scavenger receptor. This process provokes secretion of anti-inflammatory atheroprotective cytokine, interleukin (IL)-10. In 40 patients with the first AMI, coronary atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI), stained with antibodies to CD163 and IL-10. LV function was determined by echocardiography before PCI and 6months after PCI. %CD163 was defined as ratio of CD163 (+)-cells to whole cells. %IL-10 was expressed as the ratio of positively stained areas per total tissue. Patients were divided into two groups depending on the amount of CD163 (+)-cells: CD163>10% (CD163high, n=20) and CD163≤10% (CD163low, n=20). CD163high group had significantly higher %IL-10. Final thrombolysis in myocardial infarction (TIMI) flow grade was significantly lower in CD163high group. In subgroups with the final TIMI-3 flow (CD163high-Reflow, n=15 and CD163low-Reflow, n=20), the time to reperfusion, infarct size, LV dimensions and fractional shortening (%FS) before PCI were similar. Significant correlation was observed between %IL10 and changes in LV dimensions (diastole, r=-0.49, P=0.01; systole, r=-0.65, P<0.01) or %FS (r=0.51, P<0.01) at 6months after PCI. Plaque with CD163(+)-macrophages could impair distal flow after primary PCI. However, CD163(+)-macrophages enhance the anti-inflammatory cytokine expression that aids in ventricular functional recovery if distal flow can be achieved by successful reperfusion.