Heart Wall Thickness Research Articles

Histology slide is non-repeatable, non-reproducible and unreliable in estimating post-mortem heart wall thickness

ABSTRACT A routine measurement in heart examination is that of the heart wall thickness. This study investigated whether histology can be used to estimate heart wall thickness measured in a post-mortem examination, and therefore assess the utility of this method in the post-mortem report peer review process. This study compared 30 consecutive adult heart measurements (left and right free wall thickness and interventricular wall thickness). It showed that heart wall thickness measurements on histology slides were non-repeatable, non-reproducible, and unreliable, with overall poor to moderate intraclass correlation coefficient (<0.60, p < 0.05). The 95% confidence interval in the difference between histology and post-mortem examination was 1–3.5 mm for left ventricle and interventricular wall thickness, and −1–0.5 mm for the right ventricle. This study showed limited utility in using histology in estimating heart wall thickness. However, in instances where histology was the only modality available to estimate heart wall, marking where the measurements were taken, citing the confidence intervals, and noting the limitations thereof is recommended.

Isoproterenol induced cardiac hypertrophy: A comparison of three doses and two delivery methods in C57BL/6J mice.

Heart Failure (HF) continues to be a complex public health issue with increasing world population prevalence. Although overall mortality has decreased for HF and hypertrophic cardiomyopathy (HCM), a precursor for HF, their prevalence continues to increase annually. Because the etiology of HF and HCM is heterogeneous, it has been difficult to identify novel therapies to combat these diseases. Isoproterenol (ISP), a non-selective β-adrenoreceptor agonist, is commonly used to induce cardiotoxicity and cause acute and chronic HCM and HF in mice. However, the variability in dose and duration of ISP treatment used in studies has made it difficult to determine the optimal combination of ISP dose and delivery method to develop a reliable ISP-induced mouse model for disease. Here we examined cardiac effects induced by ISP via subcutaneous (SQ) and SQ-minipump (SMP) infusions across 3 doses (2, 4, and 10mg/kg/day) over 2 weeks to determine whether SQ and SMP ISP delivery induced comparable disease severity in C57BL/6J mice. To assess disease, we measured body and heart weight, surface electrocardiogram (ECG), and echocardiography recordings. We found all 3 ISP doses comparably increase heart weight, but these increases are more pronounced when ISP was administered via SMP. We also found that the combination of ISP treatment and delivery method induces contrasting heart rate, RR interval, and R and S amplitudes that may place SMP treated mice at higher risk for sustained disease burden. Mice treated via SMP also had increased heart wall thickness and LV Mass, but mice treated via SQ showed greater increase in gene markers for hypertrophy and fibrosis. Overall, these data suggest that at 2 weeks, mice treated with 2, 4, or 10mg/kg/day ISP via SQ and SMP routes cause similar pathological heart phenotypes but highlight the importance of drug delivery method to induce differing disease pathways.

Attention LSTM U-Net model for Drosophila melanogaster heart tube segmentation in optical coherence microscopy images.

Optical coherence microscopy (OCM) imaging of the Drosophila melanogaster (fruit fly) heart tube has enabled the non-invasive characterization of fly heart physiology in vivo. OCM generates large volumes of data, making it necessary to automate image analysis. Deep-learning-based neural network models have been developed to improve the efficiency of fly heart image segmentation. However, image artifacts caused by sample motion or reflections reduce the accuracy of the analysis. To improve the precision and efficiency of image data analysis, we developed an Attention LSTM U-Net model (FlyNet3.0), which incorporates an attention learning mechanism to track the beating fly heart in OCM images. The new model has improved the intersection over union (IOU) compared to FlyNet2.0 + with reflection artifacts from 86% to 89% and with movement from 81% to 89%. We also extended the capabilities of OCM analysis through the introduction of an automated, in vivo heart wall thickness measurement method, which has been validated on a Drosophila model of cardiac hypertrophy. This work will enable the comprehensive, non-invasive characterization of fly heart physiology in a high-throughput manner.

DETERMINANTS OF ADULT CARDIAC STRUCTURE: DEVELOPMENTAL INFLUENCE OF PHYSICAL ACTIVITY, SYSTOLIC BLOOD PRESSURE AND TV WATCHING

INTRODUCTION The impacts of health-related behaviours and risk factor exposures across childhood and adolescence on the adult heart are largely unexplored. We investigated whether early-life trajectories for physical activity (PA), sedentary behaviour and systolic blood pressure (SBP) are associated with cardiac structure in adulthood. METHODS Data collected throughout childhood and adolescence on PA, TV watching and SBP in a cohort study were used to develop antecedent trajectories. At age ∼29yrs, participants were invited to undergo an echocardiogram, to assess left ventricular mass (LVM), LV internal diameter (LVID) and LV wall thickness (LVWT). Analysis was performed between trajectories, separately by sex. RESULTS 723 participants were included. In males, LVM was greater in the antecedent High-PA trajectory (184.1±35.6g), compared to both Mid-PA (171.7±36.1g, P=0.014) and Low-PA (166.7±38.0g, P=0.021). This was related to greater LVID in High-PA compared to both Mid-PA (Δ1.3±0.5cm, P=0.018) and Low-PA (Δ1.3±0.8cm, P=0.087) groups; there were no differences in LVWT (all P&amp;gt;0.050). No differences were found in heart structure between PA trajectory groups in females (all P&amp;gt;0.050). For antecedent SBP, LVM was lower in both the Low-SBP (155.7±30.5g) and Normal-SBP groups (172.9±36.7g) compared to both High-normal (184.8±32.9g) and High-SBP (206.2±41.3g) in males (all P&amp;lt;0.001). This was primarily driven by larger LVWT in High-normal (Δ1.2±0.2g, P=0.001) and High-SBP groups (1.9±0.5g, P=0.001); no differences were observed for LVID (P=0.398). These findings for SBP were similar in females, with the highest SBP group having the greatest LVM and LVWT (all P&amp;lt;0.001). There were no significant impacts of antecedent TV trajectories on adult cardiac measures (all P&amp;gt;0.050). CONCLUSION Higher developmental SBP is associated with larger heart size and wall thickness in adulthood. Higher developmental PA levels are associated with larger cardiac chamber dimension in adult males, but not females. These findings suggest adult cardiac structure may be influenced by early-life risk factor exposures.

Semi-Supervised Gan for medical image segmentation

Echocardiography is a popular ultrasound imaging method used for the diagnosis of heart conditions. With the advent of numerous image processing algorithms, echocardiographic image segmentation has become more significant. This is a crucial stage since it offers a framework for evaluating numerous cardiac parameters, including LV volume and heart wall, valve motion, ejection fraction, thickness, etc. All these factors are crucial for determining a heart's health. The task of manual segmentation requires skilled operators and takes a lot of time. By requiring the discriminator network to output class labels, we extend Generative Adversarial Networks to the semi-supervised type. This paper examines image segmentation techniques for echocardiography to find the borders of the left ventricle. In this paper, we introduce a new convolution neural network model for the auto-segmentation of the left ventricle in echo images. The division of a picture into regions is known as image segmentation. Segments, that computer vision can use to automatically understand. This method makes it easier to simultaneously evaluate and diagnose echo pictures. The segmentation of echocardiographic images can be utilized to measure cardiac characteristics like heart wall thickness.

Effects of Breed, Exercise, and a Two-Month Training Period on NT-proBNP-Levels in Athletic Dogs.

N-terminal pro-b-type natriuretic peptide (NTproBNP) is a cardiac biomarker used to detect myocardial wall stress. Physical activity and cardiac disease can affect serum NTproBNP concentrations. In people, different types of physical activity have different effects on NTproBNP. Our hypothesis was that physical activity and training have an effect on NTproBNP concentrations depending on the type of exercise and the intensity. Seven German Shepherd dogs (GSD) under military training performing short bursts of fast-paced interval exercise and seven Eurohounds (EHs) training for racing competition with endurance exercise were included in the study. Blood samples were taken at enrollment (T0) and after a two-month (T2mth) training period; on both occasions, the samples were acquired before and after physical exercise. An echocardiographic evaluation was performed at T0. Echocardiographic heart size was larger in the EHs compared to the GSDs. The NTproBNP concentration was higher in the EHs than in the GSDs before and after exercise at T0 and T2mth. Echocardiographic parameters of heart size and wall thickness correlated with NTproBNP at T0 before and after exercise. Exercise induced an elevation of NTproBNP in the EHs at T0 and T2mth, while in the GSDs this was observed only at T0. In the EHs, post exercise was associated with higher NTproBNP at T2mth compared to T0, while in the GSDs the opposite pattern was noticed. From our study, the serum NTproBNP concentration differs between breeds. Intense physical activity causes an increase in NTproBNP. A two-month training period does not affect the NTproBNP concentration at rest. Intense physical activity may increase NTproBNP above the reference range in individual dogs.

Inducible over-expression of cardiac Nos1ap causes short QT syndrome in transgenic mice.

Recent evidence demonstrated that alterations in the QT interval duration on the ECG are not only determined by mutations in genes for ion channels, but also by modulators of ion channels. Changes in the QT interval duration beyond certain thresholds are pathological and can lead to sudden cardiac death. We here focus on the ion channel modulator nitric oxide synthase 1 adaptor protein (Nos1ap). Whole-cell patch-clamp measurements of a conditional transgenic mouse model exhibiting cardiac-specific Nos1ap over-expression revealed a Nos1ap-dependent increase of L-type calcium channel nitrosylation, which led to increased susceptibility to ventricular tachycardias associated with a decrease in QT duration and shortening of APD90 duration. Survival was significantly reduced (60% after 12 weeks vs. 100% in controls). Examination of the structural features of the hearts of transgenic mice revealed constant heart dimensions and wall thickness without abnormal fibrosis content or BNP production after 3 months of Nos1ap over-expression compared to controls. Nos1ap over-expression did not alter cGMP production or ROS concentration. Our study showed that myocardial over-expression of Nos1ap leads to the shortening of the QT interval and reduces the survival rate of transgenic animals, perhaps via the development of ventricular arrhythmias. We conclude that Nos1ap overexpression causes targeted subcellular localization of Nos1 to the CaV1.2 with a subsequent decrease of ADP90 and the QT interval. This causes detrimental cardiac arrhythmias in transgenic mice.

Abstract P2034: Photobiomodulation Accelerates Wound Healing In Heart Tissue

Cardiovascular diseases and aging induce stress on the heart, resulting in heart wall thickness and stiffness associated with increased fibrosis. The sinoatrial node (SAN) is the heart’s natural pacemaker composed of a fibrous tissue matrix with a heterogenous cellular population. With aging, activated fibroblasts can create scar tissue, thus commonly resulting in sick sinus syndrome (SSS) and arrhythmias. SSS is produced by idiopathic degeneration of the SAN, requiring implantation of electronic pacemakers. Phototherapy or photobiomodulation (PBM) is a technique with many therapeutic properties that has been applied clinically to treat various forms of tissue pathology. Although there has been evidence that PBM has positive effects on the heart to improve cardiac function and prevent infarction, its age associated changes during wound healing are unknown. This study uses timelapse microscopy and red light (630 nm) or near-infrared (NIR, 810 nm) PBM on SAN support cells (SANspc) isolated from 2 months (2mo) and 2 years (2y) old mice during in vitro wound healing. With an average initial gap width of 540 μm, the kinetics and extent of wound closure are measured for each of the SANspc age and treatment groups. Nonirradiated SANspc served as controls. Aging slowed kinetics and increased the extent of wound healing by an average of 1.87 hours earlier than that of the 2mo-SANspc (p &lt; 0.05). Irradiation with red light induces a significantly faster scale of closure for the gap width to close between ½ and ¾ by 0.25 and 0.68 hours, in 2mo- and 2y-SANspc respectively, compared to their corresponding age control. With red irradiation, 2y-SANspc resulted in a significantly faster scale of closure of 0.52 hours compared to 2mo-SANspc. Irradiation with NIR resulted in the opposite effect in both age groups, in which the scale of closure for the wound slowed significantly (0.19 and 0.71 hours in the 2mo- and 2y-SANspc, respectively). In conclusion, these data suggests that SANspc migration and proliferation capacity is faster with aging and red irradiation increases wound closing effect in both age groups. Thus, the enhanced wound healing induced by PBM may be an attractive therapeutic approach to target cardiac fibrosis and promote cardiac remodeling in the aging heart.

Bariatric Surgery Improves Heart Geometry and Plasticity.

Obesity is commonly associated with increased sympathetic tone, changes in heart geometry, and mortality. The aforementioned translates into a higher and potentially modifiable mortality risk for this specific population. The aim of the study was to analyze the extent of changes in the heart ventricular structure following rapid weight loss after bariatric surgery. Academic, university-affiliated hospital. We retrospectively reviewed all the patients that underwent bariatric surgery at our institution between 2010 and 2015. Data analyzed included demographics, BMI, and associated medical problems. Preoperative and postoperative echography readings were compared looking at the heart geometry, cardiac volumes, and wall thickness. Fifty-one patients who had bariatric surgery and had echocardiography before and after the surgery were identified. There were 33 females (64.7%). The mean age was 63.4 ± 12.0 years with an average BMI of 40.3 ± 6.3. The mean follow-up was 1.2 years after the procedure. At 1 year follow-up 25 patients (49%, p = 0.01) showed normal left ventricular geometry. The left ventricular mass (229 ± 82.1 vs 193.2 ± 42.5, p<0.01) and the left ventricular end diastolic volume (129.4 ± 53 vs 96.4 ± 36.5, p = 0.01) showed a significant modification following the procedure. There was a significant improvement in the interventricular septal thickness (p = 0.01) and relative wall thickness (p < 0.01) following surgery. The patients with obesity present a significant cardiac remodeling from concentric remodeling to normal geometry after bariatric surgery. The decrease in BMI has a direct effect on improvement of the left ventricular structure. Further studies must be carried out to define the damage of obesity to diastolic function.

The Effect of Black Garlic (Allium sativum Linn) on Cardiac and Aortic Histopathology in Experimental Studies in Obesity Rats

ABSTRACTBackground: Obesity is a disorder or disease characterized by the accumulation of excess fat in the body due to an imbalance in energy intake that is used for a long time. Accumulation of fat can reduce adiponectin, causing cardiac hypertrophy, endothelial vasodilation, and other cardiovascular diseases. Black garlic have high antioxidants in the form of S-Allylcysteine(SAC) which functions to increase adiponectin. Objective: To determine the effect of Black garlic on the histopathological picture of the heart and aorta of obese rats. Methods: This study was an experimental study with a randomized post-test only design with control group design with 5 groups of male white rats Sprague Dawley (Rattus novergicus) fed High Fat Fructose. Diet (HFFD) enriched with 1.25% cholesterol and 0.5% cholic acid for 8 weeks and was given black garlic intervention at doses of 450 mg / 200BW, 900mg / 200BW and 1350mg200 / BW for 4 weeks. Results: Giving black garlic significantly reduced body weight of rats (p = 0.001), and the results did not significantly reduce heart weight (p = 0.147), aortic weight (p = 0.061), histopathological changes in heart wall thickness (p = 0.423) and aortic wall thickness (p = 0.802). The effective doses of black garlic in this study were 450 mg / 200 grams BW, 900 mg / 200 grams rat BW and 1350 mg / 200 grams BW of rats. The optimal dose is 900 mg / 200 grams BW. Conclusion: Black garlic gave a significant reduction in body weight of rats and no significant reduction in heart weight, aortic weight, cardiac and aortic histopathological features.

Pentamethylquercetin Attenuates Cardiac Remodeling via Activation of the Sestrins/Keap1/Nrf2 Pathway in MSG-Induced Obese Mice.

Objective Obesity causes a variety of metabolic alterations that may contribute to abnormalities of the cardiac structure and function (obesity cardiomyopathy). In previous works, we have shown that pentamethylquercetin (PMQ) significantly improved metabolic disorders in obese mice and it inhibited pressure overload-induced cardiac remodeling in mice. However, its potential benefit in obesity cardiomyopathy remains unclear. The aim of this study was to investigate the effects of PMQ on cardiac remodeling in obese mice. Methods We generated a monosodium glutamate-induced obese (MSG-IO) model in mice, which were treated with PMQ (5, 10, and 20 mg/kg) for 16 weeks consecutively. We examined the metabolic parameters and observed cardiac remodeling by performing cardiac echocardiography and Masson's staining. The expression levels of molecules associated with the endogenous antioxidant system, including the sestrins/kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, were analyzed by western blotting and immunofluorescent staining. Results We found that PMQ treatment significantly ameliorated obesity phenotypes and improved metabolic disorders in MSG-IO mice. PMQ decreased the heart wall thickness and attenuated cardiac fibrosis. Further study revealed that the protective effects of PMQ might be mediated by promoting Keap1 degradation and augmenting sestrins expression and Nrf2 nuclear translocation. Conclusion Our findings indicated that PMQ ameliorated cardiac remodeling in obese mice by targeting the sestrins/Keap1/Nrf2 signaling pathway.

Multiparametric Echocardiography Scores for the Diagnosis of Cardiac Amyloidosis

ObjectivesThis study aimed to investigate the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness who had amyloid was suspected. We also aimed to further characterize the structural and functional changes associated with amyloid infiltration. BackgroundCardiac amyloidosis (CA) is a serious but increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool. MethodsWe studied 1,187 consecutive patients evaluated at 3 referral centers for CA and analyzed morphological, functional, and strain-derived echocardiogram parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified by using extracellular volume measurements at cardiac magnetic resonance. ResultsA total of 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin CA. Concentric remodeling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E wave/e′ wave ratio, longitudinal strain, and tricuspid annular plane systolic excursion had the greatest diagnostic performance in AL amyloidosis (area under the curve: 0.90; 95% confidence interval: 0.87 to 0.92), whereas the addition of septal apical–to–base ratio yielded the best diagnostic accuracy in the increased heart wall thickness group (area under the curve: 0.80; 95% confidence interval: 0.85 to 0.90). ConclusionsSpecific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances and enable the definition of 2 scores that are sensitive and specific tools with which diagnose or exclude CA.

Soluble epoxide hydrolase inhibitor, TUPS, attenuates isoproterenol/angiotensin II-induced cardiac hypertrophy through mammalian target of rapamycin-mediated autophagy inhibition.

To investigate the potential role and mechanism of TUPS, a soluble epoxide hydrolase inhibitor, in cardiac hypertrophy. Rat and H9C2 cell models of cardiac hypertrophy were induced by isoproterenol and angiotensin II, respectively, followed by TUPS treatment. The expression of hypertrophic markers, ANP and BNP, was determined by quantitative real-time PCR. The abundance of Beclin-1, LC3, p-AMPK and phosphorylated-mammalian target of rapamycin (p-mTOR) proteins was analysed by Western blot and immunohistocytology. Cell morphology and viability were evaluated by F-actin staining and MTS. H9C2 cells were transfected with GFP-LC3 to evaluate autophagy flux. TUPS significantly inhibited rat heart size, heart weight-to-body weight ratio, heart wall thickness, hypertrophic H9C2 cell swelling and viability suppression as well as the expression of ANP and BNP genes in hypertrophic models. In addition, autophagic markers Beclin-1 and LC3 were elevated in both cellular and animal models, which were suppressed by TUPS, with corresponding changes of autophagy flux. The abundance of p-AMPK was increased, while p-mTOR was decreased in hypertrophic cells, which were abolished by TUPS. Rapamycin decreased p-mTOR level, increased Beclin-1 and LC3 expression and induced cell size enlargement and cell viability inhibition in hypertrophic H9C2 cells treated with TUPS. TUPS inhibits cardiac hypertrophy by regulating mTOR/autophagy axis.

Escherichia coli outer membrane vesicles can contribute to sepsis induced cardiac dysfunction

Sepsis induced cardiac dysfunction (SIC) is a severe complication to sepsis which significantly worsens patient outcomes. It is known that bacteria have the capacity to release outer membrane vesicles (OMVs), which are nano-sized bilayered vesicles composed of lipids and proteins, that can induce a fatal inflammatory response. The aim of this study was to determine whether OMVs from a uropathogenic Escherichia coli strain can induce cardiac dysfunction, and to elucidate any mechanisms involved. OMVs induced irregular Ca2+ oscillations with a decreased frequency in cardiomyocytes through recordings of intracellular Ca2+ dynamics. Mice were intraperitoneally injected with bacteria-free OMVs, which resulted in increased concentration of pro-inflammatory cytokine levels in blood. Cytokines were increased in heart lysates, and OMVs could be detected in the heart after OMVs injection. Troponin T was significantly increased in blood, and echocardiography showed increased heart wall thickness as well as increased heart rate. This study shows that E. coli OMVs induce cardiac injury in vitro and in vivo, in the absence of bacteria, and may be a causative microbial signal in SIC. The role of OMVs in clinical disease warrant further studies, as bacterial OMVs in addition to live bacteria may be good therapeutic targets to control sepsis.

Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: role of Sirt1-mediated autophagy regulation.

SummaryAging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca2+ properties were evaluated using echocardiography, IonOptix® edge‐detection and fura‐2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot. Our results revealed that Akt2 ablation prolonged life span (by 9.1%) and alleviated aging (24 months)‐induced unfavorable changes in myocardial function and intracellular Ca2+ handling (SERCA2a oxidation) albeit with more pronounced cardiac hypertrophy (58.1%, 47.8%, and 14.5% rises in heart weight, wall thickness, and cardiomyocyte cross‐sectional area). Aging downregulated levels of Sirt1, increased phosphorylation of Akt, and the nuclear transcriptional factor Foxo1, as well as facilitated acetylation of Foxo1, the effects of which (except Sirt1 and Foxo1 acetylation) were significantly attenuated or negated by Akt2 ablation. Advanced aging disturbed autophagy, mitophagy, and mitochondrial integrity as evidenced by increased p62, decreased levels of beclin‐1, Atg7, LC3B, BNIP3, PTEN‐induced putative kinase 1 (PINK1), Parkin, UCP‐2, PGC‐1α, and aconitase activity, the effects of which were reversed by Akt2 ablation. Aging‐induced cardiomyocyte contractile dysfunction and loss of mitophagy were improved by rapamycin and the Sirt1 activator SRT1720. Activation of Akt using insulin or Parkin deficiency prevented SRT1720‐induced beneficial effects against aging. In conclusion, our data indicate that Akt2 ablation protects against cardiac aging through restored Foxo1‐related autophagy and mitochondrial integrity.

APPLICATION OF NEW ECHOCARDIOGRAPHIC TECHNOLOGIES OF NON-DOPPLER MYOCARDIAL IMAGES IN 2D AND 3D MODES IN PATIENTS WITH CHRONIC HEART FAILURE WITH PRESERVED AND REDUCED EJECTION FRACTION

According to the recommendations of the European Society of Cardiologists, transthoracic echocardiography (TTE) is the most informative diagnostic method in patients with chronic heart failure (CHF) [3]. Echocardiography provides accurate information on the size of heart chambers, wall thickness and indices of systolic and diastolic function. Nowadays, in view of the new technological development, the most perspective technologies for the integrated assessment of the functional condition of the myocardium of the left ventricle (LV) are the ones that assess not only the ejection fraction (EF), but also the deformation parameters and rotational properties of the LV myocardium, including technologies of nonDoppler myocardial images in 2D and 3D modes (2D and 3D Speckle Tracking Echocardiography or STE). Based on the 2D Speckle Tracking Echocardiography data, reduction of the global longitudinal deformation has more prognostic significance in risk of death assessment in patients with heart failure than the EF of LV and the index breach of the local contractility of LV. However, the method of evaluating myocardial deformation in 3D mode STE and its advantages over the 2D mode STE is insufficiently explored. Thus, for the assessment of LV systolic and diastolic dysfunctions in patients with CHF with preserved and reduced EF of LV, a great interest represents the application of the new echocardiographic technologies, such as the 2D and 3D Speckle Tracking Echocardiography.

Early Changes in Cytochrome P450s and Their Associated Arachidonic Acid Metabolites Play a Crucial Role in the Initiation of Cardiac Hypertrophy Induced by Isoproterenol.

Cytochrome P450 enzymes (P450s), along with their cardioprotective metabolites the epoxyeicosatrienoic acids (EETs) and cardiotoxic metabolite 20-hydroxyeicosatetraeonic acid (20-HETE), were found to be altered in cardiac hypertrophy; however, it is unclear whether these changes are causal or epiphenomenon. Therefore, we hypothesized that P450s and their metabolites play a crucial role in the initiation of cardiac hypertrophy. To test our hypothesis, rats and RL-14 cells were treated with the hypertrophic agonist isoproterenol for different time periods. Thereafter, in vivo heart function and wall thickness were assessed using echocardiography. Moreover, the role of P450 epoxygenases, ω-hydroxylases, and soluble epoxide hydrolase (sEH) were determined at mRNA, protein, and activity levels using real-time polymerase chain reaction, Western blot, and liquid chromatography-mass spectrometry, respectively. Our results show that in vivo and in vitro hypertrophy was initiated after 72 hours and 6 hours of isoproterenol treatment, respectively. Studies performed at the prehypertrophy phase showed a significant decrease in P450 epoxygenases along with a significant induction of sEH activity. Consequently, lower EET and higher dihydroxyeicosatrienoic acid levels were observed during this phase. However, significant increases in P450 ω-hydroxylase along with its associated metabolite, 20-HETE, were detected only in vivo. Interestingly, increasing EET levels by P450 epoxygenase induction, sEH inhibition, or exogenous administration of EET prevented the initiation of cardiac hypertrophy through a nuclear factor-κB-mediated mechanism. Taken together, these findings reveal a crucial role of P450 epoxygenases and EETs in the development of cardiac hypertrophy, which could uncover novel targets for prevention of heart failure at early stages.

Retrospective analysis of liver cirrhosis influence on heart walls thickness

ObjectiveCirrhotic cardiomyopathy is a chronic cardiac dysfunction in patients with liver cirrhosis. It is mostly characterized by impaired cardiac function, but some myocardial anatomical changes have also been described. The aim of this study was to assess the influence of liver cirrhosis on heart wall thickness changes in a retrospective pathological analysis of cirrhotic patients without hypertension. Materials and methodsStatistical analysis of 11,860 autopsy protocols drawn up between 1981 and 2002 in the Department of Pathology Medical University of Warsaw was done. ResultsLiver cirrhosis was confirmed by autopsy in 802 patients (6.7%); in 697 patients, hypertension was excluded. Analysis of heart wall thickness showed pathological changes in 53.2% of patients – left ventricular thickening in 9.3%, right ventricular thinning in 31.0%, and both in 12.9%. In clinical assessment, the cause of death in 25.8% of patients was cardiocirculatory failure, significantly more in the group with selective left ventricular thickening. It was the most common cause of death among them. Vascular changes in the upper gastrointestinal tract, liver enlargement and hepatic coma were also significantly related to the heart wall thickness changes occurrence. ConclusionsBased on statistical analysis of autopsy material, we concluded that liver cirrhosis can lead to heart wall thickness changes (left ventricular thickening and/or right ventricular thinning). We revealed that patients with selective left ventricular thickening had significantly more cardiac related causes of death. In clinical practice, treatment of cirrhotic cardiomyopathy requires specialized diagnostics and appropriate cardiological procedures involving the participation of a hepatologist, especially in the group of patients with selective left ventricular hypertrophy.

Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila.

Activated/uninhibited calcineurin is both necessary and sufficient to induce cardiac hypertrophy, a condition that often leads to dilated cardiomyopathy, heart failure, and sudden cardiac death. We expressed constitutively active calcineurin in the adult heart of Drosophila melanogaster and identified enlarged cardiac chamber dimensions and reduced cardiac contractility. In addition, expressing constitutively active calcineurin in the fly heart using the Gal4/UAS system induced an increase in heart wall thickness. We performed a targeted genetic screen for modifiers of calcineurin-induced cardiac enlargement based on previous calcineurin studies in the fly and identified galactokinase as a novel modifier of calcineurin-induced cardiomyopathy. Genomic deficiencies spanning the galactokinase locus, transposable elements that disrupt galactokinase, and cardiac-specific RNAi knockdown of galactokinase suppressed constitutively active calcineurin-induced cardiomyopathy. In addition, in flies expressing constitutively active calcineurin using the Gal4/UAS system, a transposable element in galactokinase suppressed the increase in heart wall thickness. Finally, genetic disruption of galactokinase suppressed calcineurin-induced wing vein abnormalities. Collectively, we generated a model for discovering novel modifiers of calcineurin-induced cardiac enlargement in the fly and identified galactokinase as a previously unknown regulator of calcineurin-induced cardiomyopathy in adult Drosophila.

Heart Wall Is Thicker on Postmortem Computed Tomography Than on Ante Mortem Computed Tomography: The First Longitudinal Study

ObjectiveTo evaluate the postmortem changes of the heart wall on postmortem (PM) computed tomography (CT) in comparison with those on ante mortem CT (AMCT), and in comparison with the pathological findings, obtained in the same patients.Materials and MethodsWe studied 57 consecutive patients who had undergone AMCT, PMCT, and pathological autopsy in our tertiary care hospital between April 2009 and December 2010. PMCT was performed within 20 hours after death, followed by pathological autopsy. The cardiac chambers were measured at five sites on both AMCT and PMCT by two board-certified radiologists who were not provided with clinical information. The differences in heart wall thickness between AMCT with and without contrast medium, between AMCT and PMCT, and between PMCT and pathological anatomy were evaluated statistically. Confounding factors of postmortem change such as gender, presence of arteriosclerosis, the organ related to cause of death, age, and elapsed time since death were examined statistically.ResultsNo significant differences were observed on AMCT in comparison of contrasted and non-contrasted images. The heart wall was significantly thicker on PMCT than on AMCT (p < 0.0001) at all five measurement sites. The heart wall was significantly thicker on PMCT than on pathology specimens when measured in accordance with pathological standard mensuration. However, no significant difference was observed between PMCT measurements and those of pathology specimens at any site when the papillary muscles and epicardial fat were included. No significant association was found between postmortem change in heart wall thickness and gender, presence of arteriosclerosis, the organ related to cause of death, age, or elapsed time since death.ConclusionThis is the first longitudinal study to confirm greater thickness of heart wall on postmortem images compared with ante mortem images, in the same patients. Furthermore, the postmortem changes on CT were supported by the pathological findings.