Cardiomegaly

Introduction. Rapidly vanishing lung pseudotumor (phantom tumor) refers to the transient well-demarcated accumulation of pleural fluid in the interlobar pulmonary fissures. Most frequently their appearance is associated with congestive heart failure, but also other disorders like hypoalbuminemia, renal insufficiency or pleuritis. Its rapid disappearance in response to the treatment of the underlying disorder is a classical feature of this clinical entity. Case report. A 47-yearold woman, chronic smoker with symptoms of shortness of breath, orthopnea, chills, cough, weakness and the temperature of 39.2?C was admitted to our hospital. A posteroanterior chest X-ray revealed cardiomegaly with the cardiothoracic ratio of > 0.5, blunting of both costophrenic angles and an adjacent 6 x 5 cm well-defined, rounded opacity in the right interlobar fissure. Transthoracic 2-dimensional echocardiography demonstrated left ventricular hyperthrophy with a systolic ejection fraction of 25% and mod...

The role of angiotensin II (ANG II) in the development of isoproterenol (Iso)-induced cardiac hypertrophy was examined in rats. Iso increased cardiac mass, left ventricular RNA-to-DNA ratio, and the cardiac content of both myosin heavy chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced cardiac hypertrophy involves growth of both muscle and connective tissue. Cardiac hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol prevented development of Iso-induced cardiac hypertrophy but did not affect the rate of its reversal. The ANG II receptor blocker losartan (Los) did not significantly decrease the hypertrophic response to Iso. Los injected after cessation of Iso dramatically enhanced the reversal of cardiac hypertrophy, even in rats that received Los with Iso during the induction of Iso-induced cardiac hypertrophy. ANG II, injected continuously at a subpressor dose that did not affect heart weight when given alone, inhibited reversal of cardiac hypertrophy when given after cessation of Iso. Los did not significantly affect the induction of the protooncogene c-fos by Iso. We conclude that endogenous ANG II has a major function in maintaining Iso-induced cardiac hypertrophy but does not mediate its induction. This suggests that different interactive stimuli may be required for development of cardiac hypertrophy, i.e., for initiation and for maintenance.

Autophagy is an evolutionarily conserved process used by the cell to degrade cytoplasmic contents for quality control, survival for temporal energy crisis, and catabolism and recycling. Rapidly increasing evidence has revealed an important pathogenic role of altered activity of the autophagosome-lysosome pathway (ALP) in cardiac hypertrophy and heart failure. Although an early study suggested that cardiac autophagy is increased and that this increase is maladaptive to the heart subject to pressure overload, more recent reports have overwhelmingly supported that myocardial ALP insufficiency results from chronic pressure overload and contributes to maladaptive cardiac remodeling and heart failure. This review examines multiple lines of preclinical evidence derived from recent studies regarding the role of autophagic dysfunction in pressure-overloaded hearts, attempts to reconcile the discrepancies, and proposes that resuming or improving ALP flux through coordinated enhancement of bot...

Cardiac hypertrophy is often associated with an increased sympathetic drive, and both in vitro and in vivo studies have demonstrated the development of cardiomyocyte hypertrophy in response to either α- or β-adrenergic stimulation. Because an association between the Na + /H + exchanger and cellular growth has been proposed, this study aimed to analyze the possible role of the antiporter in isoproterenol-induced cardiac hypertrophy. Isoproterenol alone (5 mg/kg IP once daily) or combined with a selective inhibitor of the Na + /H + exchanger activity (3 mg · kg −1 · d −1 BIIB723) was given to male Wistar rats for 30 days. Sex- and age-matched rats that received 0.9% saline IP daily served as controls. Echocardiographic follow-up showed a 33% increase in left ventricular mass in the isoproterenol-treated group, whereas it did not increase in the isoproterenol+BIIB723-treated group. Heart weight–to–body weight ratio at necropsy was 2.44±0.11 in controls and increased to 3.35±0.10 ( P &l...

Intracellular MAPK (mitogen-activated protein kinase) signalling cascades probably play an important role in the pathogenesis of cardiac and vascular disease. A substantial amount of basic science research has defined many of the details of MAPK pathway organization and activation, but the role of individual signalling proteins in the pathogenesis of various cardiovascular diseases is still being elucidated. In the present review, the role of the MAPKs ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 MAPK in cardiac hypertrophy, cardiac remodelling after myocardial infarction, atherosclerosis and vascular restenosis will be examined, with attention paid to genetically modified murine model systems and to the use of pharmacological inhibitors of protein kinases. Despite the complexities of this field of research, attractive targets for pharmacological therapy are emerging.

Background Despite the accumulating genetic and molecular investigations into hypertrophic cardiomyopathy (HCM), it remains unclear how this condition develops and worsens pathologically and clinically in terms of the genetic–environmental interactions. Establishing a human disease model for HCM would help to elucidate these disease mechanisms; however, cardiomyocytes from patients are not easily obtained for basic research. Patient‐specific induced pluripotent stem cells ( iPSCs ) potentially hold much promise for deciphering the pathogenesis of HCM. The purpose of this study is to elucidate the interactions between genetic backgrounds and environmental factors involved in the disease progression of HCM. Methods and Results We generated iPSC s from 3 patients with HCM and 3 healthy control subjects, and cardiomyocytes were differentiated. The HCM pathological phenotypes were characterized based on morphological properties and high‐speed video imaging. The differences between contro...

Methods and Results— To elucidate the molecular basis for the phenotype, transgenic mice were generated by cardiac-restricted expression of the wild-type (TG WT ) and mutant(TG R302Q ) PRKAG2 gene with the cardiac-specific promoter -myosin heavy chain. ECG recordings ...

Recent studies highlighted long noncoding RNAs (lncRNAs) to play an important role in cardiac development. However, understanding of lncRNAs in cardiac diseases is still limited. Global lncRNA expression profiling indicated that several lncRNA transcripts are deregulated during pressure overload-induced cardiac hypertrophy in mice. Using stringent selection criteria, we identified Chast (cardiac hypertrophy-associated transcript) as a potential lncRNA candidate that influences cardiomyocyte hypertrophy. Cell fractionation experiments indicated that Chast is specifically up-regulated in cardiomyocytes in vivo in transverse aortic constriction (TAC)-operated mice. In accordance, CHAST homolog in humans was significantly up-regulated in hypertrophic heart tissue from aortic stenosis patients and in human embryonic stem cell-derived cardiomyocytes upon hypertrophic stimuli. Viral-based overexpression of Chast was sufficient to induce cardiomyocyte hypertrophy in vitro and in vivo. Gapme...

An increasing amount of evidence demonstrates the beneficial role of oxytocin (OT) in the cardiovascular system. Similar actions are attributed to genistein, an isoflavonic phytoestrogen. The treatment with genistein activates the OT system in the aorta of ovariectomized (OVX) Sprague-Dawley (SD) rats. The objective of this study was to determine the effects of low doses of genistein on the OT-induced effects in rat hypertension. The hypothesis tested was that treatment of OVX spontaneously hypertensive rats (SHRs) with genistein improves heart structure and heart work through a mechanism involving the specific OT receptor (OTR). OVX SHRs or SD rats were treated with genistein (in μg/g body wt sc, 10 days) in the presence or absence of an OT antagonist (OTA) [d(CH2)5, Tyr(Me)2, Orn8]-vasotocin or a nonspecific estrogen receptor antagonist (ICI-182780). Vehicle-treated OVX rats served as controls. RT-PCR and Western blot analysis demonstrated that left ventricular (LV) OTR, downregul...

Angiotensin-(1-7) improves cardiac function and remodeling after myocardial infarction (MI). This may involve recruitment of hematopoietic progenitor cells that support angiogenesis. However, angiotensin-(1-7) is rapidly metabolized in plasma and tissue. The authors investigated in mice the effect of a metabolically stable angiotensin-(1-7) analogue, cyclic angiotensin-(1-7), on progenitor cell recruitment and on the heart post MI, when given in the angiogenesis phase of remodeling. Angiogenic progenitor cell recruitment was measured by using flow cytometry 24 and 72 hours after a daily bolus injection of cyclic angiotensin-(1-7) in healthy C57BL/6 mice. Further, mice underwent MI or sham surgery and subsequently received saline or 2 different doses of cyclic angiotensin-(1-7) for 3 or 9 weeks. Cyclic angiotensin-(1-7) increased circulating hematopoietic progenitor cells at 24 hours but not 72 hours. Post MI, cyclic angiotensin-(1-7) diminished cardiomyocyte hypertrophy and reduced ...

ADAMTS2 (A Disintegrin and Metalloproteinase With Thrombospondin Motifs 2) is recognized as a metalloproteinase that promotes the cleavage of amino propeptides of types I, II, III, and V procollagens. However, the role of ADAMTS2 in the heart has not yet been defined. Herein, we observed the upregulated expression of ADAMTS2 in failing human hearts and hypertrophic murine hearts. Mice lacking ADAMTS2 display exacerbated cardiac hypertrophy on pressure overload-induced hypertrophic response, whereas mice with cardiac-specific overexpression of ADAMTS2 display alleviation of this detrimental phenotype. Consistent with these results, in vitro loss or gain of function experiments in neonatal rat cardiomyocytes confirmed that ADAMTS2 negatively regulates cardiomyocyte hypertrophy in response to Ang II. Mechanistically, blockage of the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)-dependent signaling pathway with specific inhibitors both in vivo and in vitro could rescue the agg...

Mineralocorticoid receptor (MR) activation stimulates systemic vascular and left ventricular remodeling. We hypothesized that MR contributes to pulmonary vascular and right ventricular (RV) remodeling of pulmonary hypertension (PH). We evaluated the efficacy of MR antagonism by spironolactone in two experimental PH models; mouse chronic hypoxia-induced PH (prevention model) and rat monocrotaline-induced PH (prevention and treatment models). Last, the biological function of the MR was analyzed in cultured distal pulmonary artery smooth muscle cells (PASMCs). In hypoxic PH mice, spironolactone attenuated the increase in RV systolic pressure, pulmonary arterial muscularization, and RV fibrosis. In rat monocrotaline-induced PH (prevention arm), spironolactone attenuated pulmonary vascular resistance and pulmonary vascular remodeling. In the established disease (treatment arm), spironolactone decreased RV systolic pressure and pulmonary vascular resistance with no significant effect on h...

Proper assessment of COVID-19 patients has become critical to mitigating and halting the disease's rapid expansion during the present COVID-19 epidemic across the nations. Due to the presence of chronic lung/pulmonary diseases, the intensity and demise rates of COVID-19 patients were increased. This study will analyze radiography utilizing chest X-ray images (CXI), one of the most successful testing methods for COVID-19 case identification. Given that deep learning (DL) is a useful method and technique for image processing, there have been several research on COVID-19 case identification using CXI to train DL models. While few of the study claims outstanding predictive outcomes, their suggested models may struggle with overfitting, excessive variance, and generalization mistakes due to noise, a limited number of datasets and could not be deployed to IoT devices due to heavy network size. Considering deep Convolutional Neural Network (CNN) can conquer the weaknesses by getting predictions with several diseases using a single model deployed on a real-time IoT device. We propose a lightweight Deep Learning model (LDC-Net) that has spearheaded an open-sourced COVID-19 case identification technique using CNN-generated CXI by utilizing a suggested strategy aware of distinct features learning of different classes. Experimental results on Raspberry Pi show that LDC-Net provides encouraging outputs for detecting COVID-19 cases with an overall 96.86% precision, 96.78% recall, 96.77% F1-score, and 99.28% accuracy, better than other state-of-the-art models. By empowering the Internet of Things-IoT and IoMT devices, this suggested framework can identify COVID-19 from CXI and other seven lung diseases with healthy labels.

Doxorubicin (DOX) is a highly effective anti-neoplastic agent; however its cumulative dosing schedules are clinically limited by the development of cardiotoxicity. Previous studies have attributed the cause of DOX mediated cardiotoxicity to mitochondrial iron accumulation and the ensuing reactive oxygen species (ROS) formation. The present study investigates the role of frataxin (FXN), a mitochondrial iron-sulfur biogenesis protein, and its role in development of DOX mediated mitochondrial dysfunction. Athymic mice treated with DOX (5mg/kg, 1 dose per week with treatments, followed by 2 weeks recovery) treated and displayed left ventricular hypertrophy as observed by impaired cardiac hemodynamic performance parameters. Further, we also observed significant reduction in FXN expression in DOX treated animals and H9C2 cardiomyoblast cell lines resulting in increased mitochondrial iron accumulation and the ensuing ROS formation. This observation was paralleled in DOX treated H9C2 cells ...

Although frequently asymptomatic, left ventricular hypertrophy (LVH) is an independent predictor of sudden cardiac death (SCD). We hypothesized that diving may increase the propensity for pre-existent LVH to cause a lethal arrhythmia (and SCD) and therefore the prevalence of LVH may be greater among scuba fatalities than among traffic fatalities. We compared autopsy data for 100 scuba fatalities with 178 traffic fatalities. Extracted data contained information on age, sex, height, body mass, heart mass (HM), left ventricular wall thickness (LVWT), interventricular wall thickness (IVWT), and degree of coronary artery stenosis. A case was classified as LVH if the LVWT was > 15 mm. Log risk models were used to compare HM and LVWT in two groups while controlling for body mass, body length, age and sex. The prevalence of LVH was compared using Pearson's test. The mean HM was 428.3 +/- 100 for divers and 387 +/- 87 for controls. The crude HM ratio for scuba fatalities vs. controls ...

Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in...

Pericardial effusion is a recognized consequences of myxedema. Its incidence is unknown, primarily because of past difficulties in establishing the diagnosis. We studied 33 hypothyroid patients by echocardiography. Ten of the 33 patients (30%) had positive echoes for pericardial effusion. Seven of these ten patients had enlarged hearts on chest X-ray. Five patients had cardiac enlargement but no echo evidence of pericardial effusion. Serum concentrations of thyroxine, 1.8+/-0.3 vs 1.5+/-0.1 mcg/dl and of thyroid stimulating hormone, 34+/-4 vs 38+/-5 muU/ml did not differ in the groups with and without pericardial effusion, respectively. However, the pericardial effusion group had significantly slower heart rates on ECG than those without pericardial effusion: 53+/-8 vs 68+/-2 beats/min, P less than 0.05. Low voltage was present in five of the ten patients with pericardial effusion and five of the 23 nonpericardial effusion patients. None of the patients with pericardial effusion dev...

To determine the relevance of the transverse aortic arch diameter in the evaluation of early aortic and cardiac enlargements. A total of 1818 chest radiographs of male and female normotensive and hypertensive Nigerians of age range 4-80 and 10-80 years respectively were used for this study. Ages of subjects were obtained and transverse aortic arch, chest and heart diameters were determined. Mean aortic arch diameter for the normotensive groups were noted to be 5.0 +/- 0.5cm, 4.5 +/- 0.4cm and 4.7 +/- 0.5cm for males, females and both sexes respectively while 5.9 +/- 0.9cm, 5.4 +/- 0.6cm and 5.6 +/- 0.8cm for males, females and both sexes respectively were noted in the hypertensive group. Mean values were also generated for the chest and heart diameters. The study reports a mean difference in the aortic arch, heart and cardiothoracic ratio of 15% between the two groups. Relationship between aortic arch and heart diameter was established and aortic arch diameter was noted to be signif...

In pressure or volume overload, hypertrophic growth of the myocardium is associated with myofibroblast differentiation, a process in which cardiac fibroblasts express smooth muscle α-actin (SMA). The signaling mechanisms that mediate force-induced myofibroblast differentiation and SMA expression are not defined. We examined the role of the Rho–Rho-kinase pathway in force-induced SMA expression in fibroblasts using an in vitro model system that applies static tensile forces (0.65 pN/μm2) to integrins via collagen-coated magnetite beads. Force maximally induced RhoA activation at 10 minutes that was localized to force application sites and required intact actin filaments. Force application induced phosphorylation of LIM kinase (5-10 minutes) and an early dephosphorylation of cofilin (5 minutes) that was followed by prolonged cofilin phosphorylation. These responses were blocked by Y27632, an inhibitor of Rho kinase. Force promoted actin filament assembly at force application sites (10...