Left Ventricular End-diastolic Wall Thickness Research Articles

Prevalence of cardiomyopathy and cardiac mortality in a colony of non-purebred cats in New Zealand

ABSTRACT Aims To evaluate the prevalence of subclinical cardiomyopathy and cardiac mortality in a research colony of non-purebred cats, established as a model of the wider cat population in New Zealand. Methods All apparently healthy, compliant, non-pregnant, non-neonatal cats in the colony at the Centre for Feline Nutrition (Massey University, Palmerston North, NZ) underwent physical examination and echocardiography using a 4.4–6.2-MHz probe by a board-certified veterinary cardiologist. Cardiac phenotype was classified following current guidelines. Hypertrophic cardiomyopathy (HCM) phenotype was defined as an end-diastolic left ventricular wall thickness ≥ 6 mm. Colony mortality data from February 2012 to February 2022 was reviewed to determine cardiac mortality. Results Cats (n = 132; 65 females and 67 males) included in the study had a median age of 4.1 (IQR 3.0–8.0) years. Thirty-two (24%) cats had a heart murmur, and three (2%) cats had an arrhythmia. Echocardiography revealed heart disease in 24 (18.2%) cats, including 23 with an HCM phenotype and one with a restrictive cardiomyopathy phenotype. Of the cats with the HCM phenotype, 3/23 had systemic hypertension or hyperthyroidism or both, and these cats were excluded from the final diagnosis of HCM (20/132; 15.2 (95% CI = 9.5–22.4)%). Between 2012 and 2022, 168 colony cats died, with 132 undergoing post-mortem examination. Heart disease was considered the cause of death in 7/132 (5.3%; 95% CI = 2.2–10.6%) cats; five had HCM, one a congenital heart defect, and one myocarditis. The overall prevalence of death related to HCM in the colony during this period was 3.8% (95% CI = 1.2–8.6%). Three cats with HCM and the cat with a congenital heart defect died unexpectedly without prior clinical signs, while congestive heart failure was observed prior to death in two cats with HCM and the cat with myocarditis. Additionally, 30/132 (22.7%) cats had cardiac abnormalities but died for non-cardiac reasons. Conclusions Subclinical cardiomyopathy, specifically HCM, was common in cats in the colony. Given that the colony originated as a convenience selection of non-purebred cats in New Zealand, the true prevalence of HCM in the wider New Zealand population is likely to fall within the 95% CI (9.5–22%). The proportion of deaths of colony cats due to HCM was lower (3.8%) supporting the conclusion that subclinical cardiomyopathy may not progress to clinical disease causing death. Clinical relevance Veterinarians should be aware of the high prevalence of subclinical HCM when treating cats. Abbreviations CAM: Systolic anterior motion of the chordae tendineae; CFN: Centre for Feline Nutrition; HCM: Hypertrophic cardiomyopathy; LA/Ao: Left atrial to aortic ratio; LV FS: Left ventricular fractional shortening; LVIDd: Left ventricular internal diameters in end-diastole; LVIDs: Left ventricular internal diameter in end-systole; LVWT: Max Maximum left ventricular wall thickness; SAM: Systolic anterior motion of the mitral valve; 2D: Two-dimensional

Prevalence and characteristics of transthyretin amyloid cardiomyopathy in hypertrophic cardiomyopathy.

Recognition of transthyretin amyloid cardiomyopathy is increasing due to advances in cardiac imaging and diagnostic strategies, but questions remain regarding disease frequency and characteristics. We examined the prevalence and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy of unascertained aetiology. TTRACK was a multicentre, non-interventional, cross-sectional epidemiologic study funded by Pfizer and conducted in 20 hospitals and medical centres in 11 countries (NCT03842163). Eligible patients were aged ≥50years, had hypertrophic cardiomyopathy (maximal end-diastolic left ventricular wall thickness ≥15mm on echocardiogram) without an identified genetic or alternative origin at study enrolment, and underwent 99mTechnetium bone scintigraphy, with or without single photon emission computed tomography (SPECT). Cardiac-versus-bone uptake on scans was visually scored from 0 to 3 (Perugini scoring). Patients with grades 1-3 underwent monoclonal protein and laboratory testing and transthyretin (TTR) gene sequencing. Of 766 eligible patients, 691 (90.2%) had scintigraphy alone and 75 (9.8%) scintigraphy plus SPECT. Two hundred and eight patients (27.2%) had grade 2 or 3 cardiac uptake on scintigraphy; 144 (18.8%) had grade 2 or 3 cardiac uptake and no evidence of plasma cell dyscrasia and were diagnosed with transthyretin amyloid cardiomyopathy. Of patients with transthyretin amyloid cardiomyopathy, 11 (7.6%) had a pathogenic TTR gene variant and 34 (23.8%), 74 (51.7%), and 35 (24.5%) had New York Heart Association class I, II, and III/IV heart failure (HF) symptoms, respectively. Clinical and laboratory diagnostic characteristics were observed in ≥90% of patients with transthyretin amyloid cardiomyopathy. The characteristics most strongly associated with transthyretin amyloid cardiomyopathy on multivariable analysis were carpal tunnel syndrome (odds ratio [OR] 54.3; P<0.0001) and male sex (OR 7.9; P<0.0001). In the TTRACK study, almost one in five patients ≥50years of age with hypertrophic cardiomyopathy had transthyretin amyloid cardiomyopathy. Greater awareness of the frequency and characteristics of transthyretin amyloid cardiomyopathy in older patients with hypertrophic cardiomyopathy are needed to help improve early detection of this debilitating but treatable disease.

Abstract Tu052: RPN6-Serine14 Phosphorylation by PKA Protects Against Systolic Overload-Induced Cardiac Remodeling and Heart Failure

The ubiquitin-proteasome system is the main proteolytic pathway for quality control (PQC) and regulatory degradation of proteins in living cells. Systolic overload, as seen in hypertension and aortic stenosis, is a leading cause of heart failure (HF). Proteasome functional insufficiency is implicated in HF caused by systolic overload. Previous studies have established that Ser14-RPN6 phosphorylation (pS14-RPN6) mediates the activation of 26S proteasomes by protein kinase A. However, the pathophysiological significance of pS14-RPN6 in systolic overload remains to be established. We hypothesize that pS14-RPN6 helps maintain proteostasis and protects the heart during systolic overload. We observed a significant increase in myocardial pS14-RPN6 and ubiquitin conjugates in human HF of ischemic or non-ischemic etiologies (p=0.020, p=0.034) and similarly in wild type (WT) mice after 2 weeks of transverse aortic constriction (TAC) (p&lt;0.0001, p=0.001). To investigate the role of pS14-RPN6 in vivo, our lab created Rpn6 S14A (S14A) knock-in mice where Ser14-Rpn6 phosphorylation is blocked. Here we have compared the responses to TAC between WT and S14A mice. We found that TAC-induced increases in myocardial proteasome peptidase activities were significantly attenuated, and accumulation of ubiquitin conjugates exacerbated in S14A mice (p&lt;0.0001; p&lt;0.0005). Serial echocardiography revealed that S14A mice displayed significantly greater left ventricular (LV) end-diastolic posterior wall thickness and LV mass to body weight ratios at 1- and 12-week post-TAC (p=0.024, 0.0003; p=0.005, 0.01), and lower ejection fraction at 12-week post-TAC than WT mice (p=0.035). S14A mice also showed greater heart weight to tibial length (TL) and ventricular weight to TL ratios at 1 and 12-week post-TAC (1-week, p=0.043, 0.039; 12-week, p=0.007, 0.006). Wheat germ agglutinin and picrosirius red staining indicated a greater cardiomyocyte cross-sectional area and cardiac fibrosis in 12-week post-TAC S14A mice vs. WT mice (p&lt;0.0001; p=0.005). These novel findings demonstrate compellingly that myocardial pS14-RPN6 helps maintain proteostasis, curtails cardiac hypertrophy and delays heart failure occurrence during systolic overload

Discrimination models with radiomics features derived from cardiovascular magnetic resonance images for distinguishing hypertensive heart disease from hypertrophic cardiomyopathy.

Discriminating hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) is challenging, because both are characterized by left ventricular hypertrophy (LVH). Radiomics might be effective to differentiate HHD from HCM. Therefore, this study aimed to investigate discriminators and build discrimination models between HHD and HCM using multiparametric cardiac magnetic resonance (CMR) findings and radiomics score (radscore) derived from late gadolinium enhancement (LGE) and cine images. In this single center, retrospective study, 421 HCM patients [median and interquartile range (IQR), 50.0 (38.0-59.0) years; male, 70.5%] from January 2017 to September 2021 and 200 HHD patients [median and IQR, 44.5 (35.0-57.0) years; male, 88.5%] from September 2015 to July 2022 were consecutively included and randomly stratified into a training group and a validation group at a ratio of 6:4. Multiparametric CMR findings were obtained using cvi42 software and radiomics features using Python software. After dimensional reduction, the radscore was calculated by summing the remaining radiomics features weighted by their coefficients. Multiparametric CMR findings and radscore that were statistically significant in univariate logistic regression were used to build combined discrimination models via multivariate logistic regression. After multivariate logistic regression, the maximal left ventricular end diastolic wall thickness (LVEDWT), left ventricular ejection fraction (LVEF), presence of LGE, cine radscore and LGE radscore were identified as significant characteristics and used to build a combined discrimination model. This model achieved an area under the receiver operator characteristic curve (AUC) of 0.979 (0.968-0.990) in the training group and 0.981 (0.967-0.995) in the validation group, significantly better than the model using multiparametric CMR findings alone (P<0.001). Radiomics features derived from cardiac cine and LGE images can effectively discriminate HHD from HCM.

Cardiac remodelling in non-alcoholic fatty liver disease in the general population.

Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk for cardiovascular disease. Our study investigates the contribution of NAFLD to changes in cardiac structure and function in a general population. One thousand ninety-six adults (49.3% female) from the Study of Health in Pomerania underwent magnetic resonance imaging including cardiac and liver imaging. The presence of NAFLD by proton density fat fraction was related to left cardiac structure and function. Results were adjusted for clinical confounders using multivariable linear regression model. The prevalence for NAFLD was 35.9%. In adjusted multivariable linear regression models, NAFLD was positively associated with higher left ventricular mass index (β = 0.95; 95% confidence interval (CI): 0.45; 1.45), left ventricular concentricity (β = 0.043; 95% CI: 0.031; 0.056), left ventricular end-diastolic wall thickness (β = 0.29; 95% CI: 0.20; 0.38), left atrial end-diastolic volume index (β = 0.67; 95% CI: 0.01; 1.32) and inversely associated with left ventricular end-diastolic volume index (β = -0.78; 95% CI: -1.51; -0.05). When stratified by sex, we only found significant positive associations of NAFLD with left ventricular mass index, left atrial end-diastolic volume index, left ventricular cardiac output and an inverse association with global longitudinal strain in women. In contrast, men had an inverse association with left ventricular end-diastolic volume index and left ventricular stroke volume. Higher liver fat content was stronger associated with higher left ventricular mass index, left ventricular concentricity and left ventricular end-diastolic wall thickness. NAFLD is associated with cardiac remodelling in the general population showing sex specific patterns in cardiac structure and function.

Regulation of BACH1 expression by hemin improves cardiac function and revascularisation in a mouse model of myocardial infarction

Abstract Therapies to induce mature neovascularization formation and moderate oxidative stress after myocardial infarction (MI) are urgently needed. The BACH1 transcription factor is known as a repressor of genes involved in the antioxidant response (1). We have demonstrated BACH1 can regulate neovascularization through modulation of pro-angiogenic genes, particularly angiopoietin-1 (2). We hypothesise expression of BACH1 after MI contributes to suppression of genes which promote reparative angiogenesis. We propose treatment with hemin (a therapeutic compound known to degrade BACH1) will prevent BACH1 repression of target genes, leading to increased expression of proangiogenic factors and increased neovascularisation and cardiac repair in a mouse MI model. MI was induced in 8-week old C57/Bl6 male mice by permanent ligation of the left anterior descending coronary artery, n=10-14. Expression of Bach1 and the antioxidant Hmox1 in heart tissue was determined by Western blot at day 3 and 10 post MI, whilst a second group were randomized to receive vehicle, 12.5, 25 or 50mg/kg hemin intraperitoneally every 3 days until 28 days post-MI. On day 28, following echocardiography, mice were euthanised and ventricular tissue collected for histological analysis. Data was analysed by 2-way ANOVA with post-test multiple comparisons. Compared to sham mice, Bach1 expression significantly increased at both day 3 and 10 post MI (P&amp;lt;0.0001 and P&amp;lt;0.01 respectively). Bach1 expression at day 10 was significantly lower compared to day 3, suggesting a transient effect (P&amp;lt;0.01). Hmox1 expression was significantly decreased at both timepoints (both P&amp;lt;0.001 vs. sham) suggesting in the initial period after MI the antioxidant and angiogenic responses are suboptimal. Treatment of mice with 25mg/kg hemin for 28 days post MI caused significant increases in capillary and arteriole density in the peri-infarct zone (P&amp;lt;0.0002 and P&amp;lt;0.0008 vs. vehicle respectively). There was no effect on capillary or arteriole density in the remote zone. In vehicle-treated mice there was thinning of the left ventricular end-diastolic anterior wall thickness (LVAW) corresponding to the infarct area. Interestingly, a significant increase in the thickness of the LVAW was observed after 25mg/kg hemin treatment (P&amp;lt;0.0001 vs. vehicle), whilst LV internal diameter significantly decreased (P&amp;lt;0.0001 vs. vehicle). Ejection fraction (P&amp;lt;0.0001), fractional shortening (P&amp;lt;0.0009) and stroke volume (P&amp;lt;0.0001) all significantly increased in mice treated with hemin compared to vehicle. Treatment of mice with 25mg/kg hemin for 28 days post MI was sufficient to induce significantly increased capillary and arteriole density in the peri-infarct region. We also observed hemin exerted benefits on volumetric and contractility indexes. This data suggests hemin has potential to be used therapeutically post MI to improve revascularisation and cardiac function.

Transient myocardial thickening: a retrospective analysis on etiological, clinical, laboratory, therapeutic, and outcome findings in 27 cats

Introduction/objectiveTransient myocardial thickening (TMT) in cats is a poorly characterized clinical entity. Therefore, this study aimed to provide descriptions of additional cats diagnosed with this clinical phenomenon. Animals, materials, and methodsFor this multicenter observational retrospective study, cats diagnosed with TMT were searched in three medical databases. TMT was defined for cats with at least two echocardiograms showing an increased end-diastolic left ventricular wall thickness (LVWTd; i.e. ≥6 mm) at presentation and subsequent echocardiographic normalization (i.e. LVWTd <5.5 mm). Signalment, history, clinical, laboratory, therapeutic, and outcome data were retrieved. ResultsTwenty seven cats were included. The median age was 3 years. In 9/27 cats, an antecedent event was documented. At admission, 27/27 cats had evidence of myocardial injury (median value of cardiac troponin I 5.5 ng/mL), 25/27 cats had congestive heart failure, 13/27 cats had hypothermia, 8/27 cats had systemic hypotension, 7/27 cats had bradycardia, and 7/27 cats had electrocardiographic evidence of an arrhythmia. The median LVWTd was 6.4 mm. A potential cause of myocardial injury was identified in 14/27 cats. The median time from diagnosis to a significant reduction in LVWTd was 43 days. DiscussionTMT can be diagnosed in a wide range of cats, including young subjects. An antecedent predisposing event and/or a possible causative trigger can be identified in some. The reduction in LVWTd that defines this phenomenon usually occurs over a variable time frame. ConclusionsThis study represents the largest investigation of TMT in cats and provides additional information on this uncommon clinical entity.

Use of Echocardiography to Diagnose Obstructive Hypertrophic Cardiomyopathy

Fabian Knebel, Sana Klinikum, Berlin, Germany, and Department of Cardiology and Angiology, Charité Campus Mitte, Berlin, Germany, opened the podcast with a definition of hypertrophic cardiomyopathy (HCM), which is characterised by left ventricular hypertrophy. Knebel then described the symptoms of the condition, such as shortness of breath and syncope after physical exertion. Up to one in 400 persons carry the genetic mutations that can lead to HCM, which is a dangerous condition if left undiagnosed, potentially leading to ventricular tachyarrhythmias and sudden cardiac death, or end-stage heart failure. HCM is a genetic condition, and genetic testing should be performed in cases of unexplained death so that families can be tested if HCM is diagnosed. Echocardiography is the first imaging method of choice for patients with HCM due to its relatively low cost and wide availability, but cardiac MRI may also be performed to measure left ventricular wall thickness, fibrosis, and left ventricular outflow tract (LVOT) obstruction, and to evaluate the success of therapies such as septal myectomy. When using echocardiography, the first obvious finding to indicate HCM is a thickened left ventricular wall, usually in the interventricular septum. European and American guidelines agree that an end-diastolic left ventricular wall thickness of ≥15 mm should be considered HCM. Knebel provided advice on how to effectively perform echocardiography, including using apical cut planes, and measuring the pressure gradient in the LVOT during the Valsalva manoeuvre. A case study was presented of a patient presenting with signs and symptoms suggestive of myocardial infarction, demonstrating the potential complexity of diagnosing HCM. Knebel concluded with a summary of current therapeutic options, such as septal reduction surgery and septal branch ablation, and pointed out that in the near future there will be medications to reduce LVOT obstruction and alleviate symptoms.

Assessment of cardiac dimensions in children diagnosed with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant heart disease, characterized by increased left ventricular wall thickness and abnormal loading conditions. Imaging modalities are the first choice for diagnosis and risk stratification. Although heart dimensions have been characterized widely in HCM adults from cardiac imaging, there is limited information about children affected by HCM. The aim of this study is to evaluate left ventricular function and left heart dimensions in a small population of children diagnosed with HCM. A total of 16 (seven male, nine female) pediatric patients with an average age of 14.0±2.5 years diagnosed with HCM at Great Ormond Street Hospital for Children were included in this study. Cardiac magnetic resonance (CMR) images were used to measure left and right ventricular dimensions, and septal and left ventricular free wall thicknesses in Simpleware ScanIP. The gender groups were compared using student t-test or non-parametric Mann-Whitney U-test depending on the sample distribution. Differences in heart rate, left ventricular end-diastolic volume and end-diastolic volume index, left ventricular stroke volume and stroke volume index, left ventricular end-systolic long axis length, left ventricular end-systolic long axis length index, left ventricular end-diastolic mid-cavity diameter, left ventricular end-diastolic free wall thickness, left ventricular end-diastolic free wall thickness index, right ventricular end-diastolic long axis length were statistically significant in males and females. Left ventricular wall and intraventricular septal thickness increase affecting left ventricle cavity dimensions and there may be differences in anatomical and physiological parameters in males and females affected by HCM.

Acute effects of high intensity training on cardiac function: a pilot study comparing subjects with type 2 diabetes to healthy controls

This study evaluated acute cardiac stress after a high-intensity interval training session in patients with type 2 diabetes (T2D) versus healthy controls. High intensity aerobic exercise was performed by 4 × 4-min intervals (90–95% of maximal heart rate), followed by a ramp protocol to peak oxygen uptake. Echocardiography was performed before and 30 min after exercise. Holter electrocardiography monitored heart rhythms 24 h before, during, and 24 h after the exercise. Left atrial end-systolic volume, peak early diastolic mitral annular velocity, and the ratio of peak early to late diastolic mitral inflow velocity were reduced by approximately 18%, 15%, and 31%, respectively, after exercise across groups. Left ventricular end-diastolic wall thickness was the only echo parameter that significantly differed between groups in response to exercise. The T2D group had a rate of supraventricular extrasystoles per hour that was 265% greater than that of the controls before exercise, which remained higher after exercise. A single exhaustive exercise session impaired left ventricular diastolic function in both groups. The findings also indicated impaired right ventricular function in patients with T2D after exercise.ClinicalTrials.gov Identifier: NCT02998008.

Lowering the Recommended Maximal Wall Thickness Threshold Improves Diagnostic Sensitivity in Asians With Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is defined as left ventricular end-diastolic maximal wall thickness (WTMax)≥15.0mm, without accounting for ethnicity, sex, and body size. It is well-established that Asians have smaller hearts than do Caucasians. This study aims to examine the implications of this single absolute WTMax threshold on the diagnosis of HCM in Asians. The study consisted of 360 healthy volunteers (male: n=174; age: 50 ± 12 years) and 114 genetically characterized patients with HCM (male: n=83; age: 52 ± 13 years; genotype-positive, n=39). All participants underwent cardiovascular magnetic resonance. WTMax was measured semiautomatically at end-diastole according to the standard 16 myocardial segments. Healthy male volunteers had increased WTMax compared with that of female volunteers (8.4 ± 1.2mm vs 6.6± 1.1mm, respectively; P< 0.001). Conversely, WTMax was similar between male and female patients with HCM (15.2 ± 3.4mm vs 14.7 ± 3.0mm, respectively; P = 0.484) and between those with and without a pathogenic gene variant (P= 0.828). Using the recommended diagnostic threshold of 15.0mm, 56 patients with HCM had WTMax<15.0mm and no healthy volunteers had WTMax >15.0mm (specificity of 100% and sensitivity of 51%). Lowering WTMax thresholds to 10.0mm in female patients and 12.0mm in male patients did not affect specificity (100%) but significantly improved sensitivity (84%). Despite lower left ventricular mass, female patients with HCM demonstrated more features of adverse cardiac remodeling than did male patients: increased myocardial fibrosis, higher asymmetric ratio, and disproportionately worse myocardial strain. The study highlights cautious application of guideline-recommended WTMax to diagnose HCM in Asians. Lowering WTMax to account for ethnicity and sex improves diagnostic sensitivity without compromising specificity.

The regulatory mechanism of Raf/MEK/ERK pathway on the rat cardiac hypertrophy induced by transverse aortic constriction

To investigate the mRNA, protein expression levels and the phosphorylation levels of key factors in rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases (Raf/MEK/ERK) pathway, and to clarify the regulatory function of Raf/MEK/ERK pathway in myocardial hypertrophy. Twenty SD rats were divided into sham-operated group and model group. The myocardial hypertrophy model was established by transverse aortic constriction (TAC). At 12 weeks after TAC, blood samples were collected from the submandibular vein, and the serum was separated to detect the content of N terminal pro B type natriuretic peptide (NT-proBNP). After that, the rats were subjected to echocardiography and hemodynamic measurement. Then the pathological changes of myocardial tissue were observed. And the levels of mRNA, protein expression and the phosphorylation of key factors in Raf/MEK/ERK pathway were detected in myocardial tissue. Compared with sham-operated group, left ventricular end-diastolic interventricular septal thickness (IVSd), left ventricular end-systolic interventricular septal thickness (IVSs), left ventricular end-diastolic posterior wall thickness (LVPWd) and left vebtricular end-systolic posterior wall thickness (LVPWs) in TAC model group were increased significantly (P＜0.05,P＜0.01), left ventricular end-systolic diameter (LVIDs) was decreased significantly (P＜0.01), LV Mass and LW(LV Mass/Weight)were increased significantly (P＜0.05, P＜0.01). The levels of heart rate (HR), left ventricular pressure maximal rate of rise (+dp/dtmax), left ventricular pressure maximal rate of fall (-dp/dtmax) were decreased significantly (P＜0.01). The serum level of NT-proBNP in TAC rat was increased significantly (P＜0.01). The myocardial cells in TAC model group were arranged disorderly, myocardial cell hypertrophy, cytoplasm were increased significantly, and inflammatory cells infiltrated. A large amount of collagen fibers were deposited and large area of myocardial cells were stained blue in TAC rat. The expression levels of phospho-c-Raf (Ser259) and phospho-c-Raf (Ser338) in myocardial tissue were significantly increased (P＜0.01), meanwhile the expression levels of phospho- MEK1/2(Ser217/Ser221) and phospho-ERK1/2 (Thr202/Tyr204) were also significantly increased (P＜0.01). The regulatory role of Raf / MEK / ERK pathway in cardiac hypertrophy may be through the activation of phosphorylation of c-raf, MEK1, Mek2, ERK1 and ERK2 at specific sites.

The Observation of Liver and Kidney Injury and the Activation of Macrophages in the Overload Pressure Induced Cardiac Hypertrophy/Heart Failure Mouse Model

The purpose of this study is to investigate the injury of liver and kidney tissues in overload pressure induced cardiac hypertrophy/heart failure mice model and the changes of macrophage activation level. 6-8 week-old C57BL/6 mice were subjected to transverse aortic constriction (TAC) surgery to establish the cardiac hypertrophy/heart failure mouse model induced by pressure overload, while the aortic was not ligated in the Sham group. At 4 weeks and 8 weeks after TAC, the mice of each group were subjected to echocardiography and blood collection. And mice were sacrificed to collect samples of the heart, liver, and kidney tissues. The contents of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and serum creatinine (Scr) in Sham group and two operation groups were determined. The histological changes of liver, heart and kidney tissues were observed by HE staining, and the expression of the marker of macrophage activation, F4/80 protein, was detected in the heart, liver and kidney tissue by immunohistochemical staining. Cardiac hypertrophy occurred at 4 weeks after TAC operation in C57BL/6 mice and developed into heart failure at 8 weeks after TAC. The echocardiography showed that, compared with the Sham group, the left ventricular end-diastolic posterior wall thickness (LVPWd) and the left ventricular internal diameter in diastole (LVIDd) were significantly increased, while the left ventricular ejection fraction (EF) and the left ventricular fractional shortening (FS) were significantly decreased ( P<0.05) in the 4-week-TAC group and 8-week-TAC group. The plasma content of ALT, AST, TBil and Scr in the 4-week-TAC group and 8-week-TAC group were significantly higher than those in the Sham group ( P<0.05). HE staining showed obvious liver pathological changes in TAC mice, such as vacuolation, mild hepatic sinusoid congestion and inflammatory infiltration in mice post 4 weeks after surgery, and such liver injury was worse in mice post 8 weeks after surgery. Besides, there was a slight damage in renal tissue shown by HE staining, such as slight glomerular injury and slight bleeding. F4/80 protein immunohistochemical staining results demonstrated that the activation of macrophages in the heart and liver in the 4-week-TAC group and 8-week-TAC group was significantly increased than that in the sham group ( P<0.05), but there was no significant difference in kidney tissues in groups. Macrophages are involved in the process of liver and kidney injury in cardiac hypertrophy/heart failure.

Valsartan Reduces Left Ventricular Hypertrophy in Ovariectomized Spontaneous Hypertensive Rats

Abstract Objective To investigate the effects of valsartan on left ventricular mass, function, and oxidative stress in ovariectomized spontaneous hypertensive rats (SHR). Methods Twelve-week-old female SHRs were randomly divided into ovariectomy (OVX) control (n = 12), OVX + valsartan (n = 12), sham control (Sham, n = 13), and Sham + valsartan (n = 14) groups. Valsartan (30 mg/kg/day) or double-distilled water was given by oral gavage. After 12 weeks of valsartan or water treatment, left ventricular wall thickness and function, superoxide dismutase (SOD), glutathione peroxidase (GSH), and 8-hydroxydeoxyguanosine (8-OHdG) were assessed. Results There was a significant interaction between ovariectomy and valsartan on interventricular end-diastolic septum thickness (IVSTd), end-systolic interventricular septum thickness (IVSTs), left ventricular end-diastolic posterior wall thickness (LVPWTd), and left ventricular end diastolic diameter (LVEDD) (P &amp;lt; 0.05). Valsartan treatment in OVX rats decreased IVSTd, IVSTs, LVPWTd, and LVPWTs compared to OVX control (P &amp;lt; 0.05). Compared with Sham + control group, LVESP and ±dP/dt of LV were decreased while LVEDP was increased in OVX + control group (all P &amp;lt; 0.05). After valsartan treatment, LVESP and ±dP/dt of LV were increased and LVEDP was decreased in ovariectomized rats (all P &amp;lt; 0.05). Ovariectomy decreased GSH and SOD levels and increased 8-OHdG levels, which were reversed by valsartan treatment (all P &amp;lt; 0.05). Conclusion Valsartan treatment decreases oxidative stress, reduces LV hypertrophy, and improves cardiac function in overiectomized SHR.

Effects of simulated high-altitude hypobaric hypoxia on cardiac structure and function in rats

To investigate the effects of simulated hypobaric hypoxia environment at 7 000 m above sea level on cardiac structure and function in rats. A total of 96 male SD rats were randomly divided into high-altitude hypobaric hypoxia group (hypoxia group) and normobaric normoxia group (control group). Rats of hypoxia group were placed in a large cabin simulated 7 000 m high-altitude hypobaric hypoxia environment. Operating time 23 h / d, the control circadian ratio of approximately 12 h:12 h. The rats in control group were bred under normobaric normoxia. The hypoxic group was divided into 3 d, 7 d, 14 d, 28 d groups according to hypoxic time, 12 rats in each group. Changes of structure and function of heart due to hypoxia were evaluated by echocardiography and electrocardiogram. Myocardial pathological changes were analyzed by hematoxylin-eosin staining(HE). Compared with the control group at the same time point ①With prolonged exposure to hypobaric hypoxia, the growth ratio of body mass in rats is slower. Arterial oxygen saturation was significantly lower in both 14 d and 28 d (P＜0.05). ② Left ventricular end-diastolic anterior wall thickness (LVAWD) and left ventricular end-diastolic posterior wall thickness (LVPWD) of rats in 28 d were increased significantly (P＜0.05). Left ventricular end-diastolic diameter (LVIDD) and left ventricular internal dimension systole (LVIDS) of rats in 28 d were decreased significantly (P＜0.05, P＜0.01). Left ventricular ejection fraction (EF), fractional shortening of left ventricle (FS), pulmonary vein (PV) peak velocity and PV peak gradient of rats in 7 d were decreased significantly (P＜0.05, P＜0.01). ③The QRS and QT interval period were significantly prolonged in 14 d and 28 d (P＜0.05, P＜0.01). The ST was significantly lower in 3 d and 7 d (P＜0.05, P＜0.01). The amplitude of R wave gradually shifted downward in 7 d, 14 d, 28 d (P＜0.05, P＜0.01). ④The red blood cell (RBC), hemoglobin (HGB), red blood cell distribution width (RDW) in hypoxic group were increased significantly (P＜0.01). The platelet count (PLT) count was decreased significantly in 14 d and 28 d (P＜0.01). The serum creatinine (CR) was increased significantly in 14 d and 28 d (P＜0.05). ⑤Pathological changes such as myocardial edema, sarcolemma condensate, focal degeneration and necrosis with inflammatory cell infiltration could be found at early stage of hypoxia. Myocardial compensatory repair such as myocardial fibroblasts proliferation was significant at end stage of hypoxia. Left ventricular systolic functions of rats were decreased significantly after exposure to high altitude hypoxia hypobaric. The left ventricular systolic functions would recovery compensatory after one week exposed to high altitude hypoxia hypobaric.

Early myocardial changes in normotensive children of hypertensive parents: a tissue Doppler study.

The aim of this study was to examine early left ventricular systolic and diastolic changes using tissue Doppler imaging (TDI) in normotensive children of hypertensive parents (NCHP), a risk group for cardiovascular diseases. Ninety-two children characterized as NCHP (age range: 6-18 years) and 90 age-, gender-, height-, weight-, and body mass index-matched children characterized as normotensive children of normotensive parents (NCNP) were included in the study. Left ventricular diastolic parameters were assessed using transmitral flow pulse wave Doppler echocardiography and mitral septal and lateral annular TDI. Left ventricular systolic and diastolic function was evaluated globally using the TDI-derived myocardial performance index (MPI'). Mean systolic, diastolic, and average blood pressure values were found to be higher in the NCHP group than in the NCNP group. Echocardiographic parameters in the NCHP group showed statistically significant differences, including increased interventricular septum end-diastolic wall thickness (p = 0.039), left ventricular end-diastolic posterior wall thickness (p = 0.011), relative wall thickness (p = 0.013), and transmitral flow A velocity (p = 0.003); parameters determined by TDI included a prolonged isovolumetric relaxation time (p < 0.001) and isovolumetric contraction time (p = 0.002), shortened ejection time (p = 0.001), and increased MPI' (p < 0.001) in the NCHP group. Early alterations in myocardial function, indicated by increased MPI' values, had a positive correlation with systolic blood pressure and myocardial thickness. Conversely, they were negatively correlated with the ejection fraction and E/A ratio, which decreases with diastolic dysfunction. The MPI' is considered a repeatable, non-invasive, and low-cost assessment method that can surpass conventional methods in the detection of early left ventricular systolic and diastolic functional changes in the subclinical period of hypertension in children with familial risk.

Low-Dose 4-Hydroxy-2-Nonenal (HNE) Reperfusion Therapy Displays Cardioprotective Effects in Mice After Myocardial Infarction That Are Abrogated by Genipin.

BackgroundRevascularization is a successful therapeutic strategy for myocardial infarction. However, restoring coronary blood flow can lead to ischemia-reperfusion (I/R) injury. Low-dose 4-hydroxy-2-nonenal (HNE) therapy appears to play a key role in myocardial tolerance to I/R injury. We hypothesized that the positive effects of HNE on myocardial I/R injury may be UCP3-dependent.Material/MethodsAdult male wild-type (WT) or UCP3 knockout (UCP3−/−) mice were pre-treated with the UCP inhibitor genipin or saline 1 h before ischemia and underwent 30-min coronary artery ligation followed by 24-h reperfusion. Mice were treated with intravenous HNE (4 mg/kg) or saline 5 min before reperfusion. Echocardiography was conducted to measure left ventricular end-diastolic posterior wall thickness (LVPWd), end-diastolic diameter (LVEDD), and fractional shortening (FS). Infarct size was measured by TTC staining. qRT-PCR and Western blotting were used to assess the expression of UCP3, UCP2, and the apoptosis markers cytochrome C and cleaved caspase-3.ResultsHNE improved survival at 24 h post-MI in wild-type mice (p<0.05) but not in UCP3−/− mice. HNE preserved LVEDD and FS in WT mice (p<0.05) but not in UCP3−/− mice. HNE reduced infarct size in WT mice (p<0.05) but not in UCP3−/− mice. HNE upregulated UCP3 expression (p<0.05) but did not affect UCP2 expression. HNE reduced apoptosis marker expression in WT mice (p<0.05) but not in UCP3−/− mice. HNE’s positive effects were abrogated by genipin in an UCP3-dependent manner.ConclusionsLow-dose HNE reperfusion therapy attenuates murine myocardial I/R injury in an UCP3-dependent manner. These effects are abrogated by genipin in an UCP3-dependent manner.

Prognostic value of mitral annular systolic plane excursion and tricuspid annular plane systolic excursion in cats with hypertrophic cardiomyopathy

IntroductionHypertrophic cardiomyopathy (HCM) has a variable prognosis; left atrial size, presence of clinical signs and left ventricular systolic function have been shown to predict outcomes. Mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) assess longitudinal ventricular systolic function and are decreased in cats with HCM. The aim of the study was to ascertain whether MAPSE and TAPSE have prognostic value in HCM and if cats with pleural effusion have lower MAPSE and TAPSE than cats with pulmonary oedema. AnimalsOne hundred eighty-four client-owned cats diagnosed with HCM. MethodsThis is a retrospective study. Echocardiography was used to diagnose HCM (end-diastolic left ventricular wall thickness ≥ 6 mm) and to measure MAPSE and TAPSE. Survival information was obtained. ResultsNo multivariable model including MAPSE or TAPSE could be generated in this population. Cats with pleural effusion ± pulmonary oedema had lower MAPSE measured at the interventricular septum (MAPSE IVS) and TAPSE, compared with cats with pulmonary oedema only. MAPSE IVS was the only factor predicting pleural effusion on multivariable regression model. ConclusionsLower MAPSE and TAPSE were not independently associated with outcomes on multivariable analysis. Cats with pleural effusion ± pulmonary oedema had lower TAPSE and MAPSE IVS than cats with pulmonary oedema, and MAPSE IVS was the only predictive factor associated with the development of pleural effusion in this population.

Assessment of left ventricular hypertrophy using non-contrast T1 mapping

Objective To study the diagnostic value of non-contrast T1 mapping in left ventricular hypertrophy (LVH). Methods Forty LVH patients (LVH group) including 11 cardiac amyloidosis (CA), 19 hypertrophic cardiomyopathy (HCM) and 10 hypertensive heart disease (HHD) patients, and 14 healthy volunteers (control group) were enrolled in this retrospective study between November 2015 and October 2016. All subjects underwent cardiac magnetic resonance (CMR) on a 3 T scanner. The CMR scan protocol included cine sequences, first-pass perfusion, late Gadolinium enhancement (LGE) and non-contrast T1 mapping (MOLLI) prototype sequences. The cardiac morphology was assessed by cine, first-pass perfusion as well as LGE. Left-ventricular end-diastolic wall thickness (EDTH) was assessed for 16 segments, native T1 values were measured in hypertrophic segments. The differences in EDTH and native T1 values between LVH group and control group were evaluated using t test. The ANOVA and LSD were used in the comparison of differences among four sub-groups. Sensitivity, specificity, cut-off values and area under the curve (AUC) were derived using receiver-operating characteristics curve (ROC) analysis. Results The EDTH and native T1 values in LVH group were significantly higher than those of control group [ (16.5±5.2) mm vs. (6.3±1.8) mm, (1 388.6±119.8) ms vs. (1 248.4±58.1) ms, t=28.8 16.4, both P<0.01]. Moreover, CA showed significantly higher T1 value [(1 495.5±100.9)ms] than that of HCM [(1 342.0±69.2)ms] and HDD [(1 290.7±45.5)ms] (F=300.5, P<0.01), and T1 values in HCM were also higher than HDD (P<0.01). HCM showed significantly higher EDTH than that of CA and HDD (P<0.01), and EDTH in CA was also higher than HDD (P<0.01). The native T1 showed good diagnostic performance between CA and HCM with AUC 0.914, sensitivity 90.1%%, and specificity 84.3%, and cutoff value 1 382.8 ms, between CA and HHD with AUC 0.989, sensitivity 97.0%, specificity 93.5% and cutoff value 1 359.5 ms. Conclusion The elevated native T1 values were useful for quantitatively differential diagnosis of LVH. Key words: Magnetic resonance imaging; Cardiac amyloidosis; Cardiomyopathy, hypertrophic; Hypertensive heart disease

Inter-observer variability for cardiac ultrasound measurements in cats repeated at different time points in early adult life

A high degree of accuracy is required when using echocardiography to diagnose hypertrophic cardiomyopathy (HCM) in cats, as variation in measurements of 0.5 mm may affect classification of individuals as ‘abnormal’. This study in adult cats examined at different time points inter-observer variability between two Board certified echocardiographers in veterinary cardiology.Twenty-four female European shorthair cats were examined at 12, 18 and 24 months of age by observer 1. Two dimensional (2D) echocardiographic images were collected in conscious cats to measure left ventricular, aortic and left atrial dimensions. Measurements were repeated by observer 2 on stored images, and analysed for effect of time, observer and time-observer interaction. Based on end-diastolic left ventricular wall thickness, cats were diagnosed as ‘normal’ or 'abnormal'. Linear mixed models (generalized when appropriate) were performed.A significant difference between observers was found for all septal (IVSd) and free wall (LVFWd) thickness measurements and left ventricular internal diameters but not for aortic or left atrial measurements. All measurement coefficients of variation (CV) were < 10%. The CV for IVSd was higher than the CV for LVFWd. There was a significant effect of time on IVSd, aortic measurements and left ventricular internal diameter measurements. No significant time-observer interaction was found for any parameter. Diagnosis of cats as ‘abnormal’ (>5 mm in cats > 6 kg bodyweight) was significantly different between observers for IVSd but not LVFWd.Caution is warranted when diagnosing as ‘abnormal’ or interpreting small changes based on IVSd, due to significant inter-observer differences in this measurement.