Transitioning disopyramide to mavacamten in obstructive hypertrophic cardiomyopathy: A case series and clinical guide.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disorder for which first-line treatments for obstructive HCM (oHCM) include beta-blockers, non-dihydropyridine calcium channel blockers, and disopyramide for refractory cases. Mavacamten, a selective cardiac myosin inhibitor, is indicated for symptomatic oHCM to improve functional capacity and symptoms. Use of disopyramide and mavacamten together is not recommended due to concerns of additive negative inotropic effects. Transitioning from disopyramide to mavacamten may be preferred to avoid adverse effects and frequent administration, however, the best approach for making the transition has not been established. CASES: We present a series of seven patients with oHCM who transitioned from disopyramide to mavacamten and underwent echocardiograms mandated by a Risk Evaluation and Mitigations Strategies program. Two methods were employed. The first approach, involving washout of disopyramide before starting mavacamten, resulted in worsening of heart failure symptoms in the first two cases. The second approach, involving tapering disopyramide when starting mavacamten, was successfully implemented in the last five cases, with no adverse effects or worsening of systolic dysfunction. CONCLUSION: Our method of tapering disopyramide when starting mavacamten using a stepwise approach is feasible and safe. Our report fulfills an unmet need by serving as a guide for other clinicians who seek to transition their patients from disopyramide to mavacamten.

Hypertrophic Cardiomyopathy and Atrial Fibrillation: A Systematic Review and Meta-analysis of Anticoagulation Strategy.

BACKGROUND: Atrial fibrillation (AF) frequently complicates hypertrophic cardiomyopathy (HCM), and anticoagulation significantly decreases the risk of stroke in this population. To date, no randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). The present study aimed to systematically compare the two anticoagulation strategies in terms of effectiveness and safety. METHOD: We performed a systematic literature search and meta-analysis in the PubMed, MEDLINE, and EMBASE databases for studies reporting all-cause mortality, major bleeding, or thromboembolic events (TEs). Since no RCTs were available, we included observational studies only. The overall hazard ratio (HR) and 95% confidence interval (CI) for each analyzed parameter were pooled using a random-effects model. RESULTS: Five observational studies including 6919 patients were eligible for inclusion. Compared with VKAs, DOACs were associated with statistically significant lower rates of all-cause mortality (HR 0.64, 95% CI 0.35-0.54; p < 0.00001), comparable major bleeding events (HR 0.64, 95% CI 0.40-1.03; p = 0.07), and TEs (HR 0.94, 95% CI 0.73-1.22; p = 0.65). CONCLUSIONS: Compared with VKAs, a DOAC-based strategy might represent an effective and safe strategy regarding all-cause mortality, major/life-threatening bleeding complications, and TEs in HCM patients with concomitant AF. However, further prospective studies are necessary to reinforce a DOAC-based anticoagulation strategy in this population.

Cardioprotective Effect of Polymyxin-B and Dantrolene Combination on Isoproterenol-Induced Hypertrophic Cardiomyopathy in Rats, via Attenuation of Calmodulin-Dependent Protein Kinase II.

Hypertrophic cardiomyopathy is a major cause of mortality worldwide. In this study, we hypothesized that the combination of Dantrolene and Polymyxin-B will provide cardioprotective action against isoproterenol-induced hypertrophic cardiomyopathy via attenuation of Calmodulin-dependent protein kinase II (CaMKII). Hypertrophic cardiomyopathy was induced in rats by subcutaneous administration of isoproterenol (5 mg/kg) for 14 days. Simultaneously, animals were treated with Polymyxin-B per se, Dantrolene per se, and Dantrolene and Polymyxin-B combination for 14 days. Hemodynamic parameters, biochemical parameters, and histological analysis were performed. Administration of isoproterenol for 14 days resulted in severe myocardial damage, characterized by cardiac hypertrophy and increase serum CK-MB, CK-Nac, LDH, AST, and ALT levels. It also caused alteration in electrocardiogram and blood pressure. A significant increase in CaMKII was observed in heart homogenate. Treatment with the Polymyxin-B and Dantrolene combination significantly ameliorated cardiac hypertrophy, biochemical parameters, ECG parameters, and heart histopathology. Further, significant attenuation in CaMKII levels was observed. The effect of the combination was more than per se treatment. Results of the current study showed that the combination of Polymyxin-B and Dantrolene prevented the development of isoproterenol-induced hypertrophic cardiomyopathy in rats via attenuation of the CaMKII.

Effects of Angiotensin II Receptor Blockers on Ventricular Hypertrophy in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Animal studies have suggested that angiotensin II receptor blockers (ARBs) can attenuate or reverse the progression of hypertrophic cardiomyopathy, while clinical studies yielded conflicting results. We sought to conduct a meta-analysis to investigate the effect of ARBs in patients with hypertrophic cardiomyopathy. METHODS: PubMed and EMBASE databases were searched through June 2020. Only randomized controlled trials (RCTs) were included, and each study's quality was assessed using the Jadad scale. The primary outcome was left ventricular mass reduction, and the secondary outcome was the change in left ventricular ejection fraction (LVEF). Data were pooled using the random effects model. RESULTS: A total of 1294 articles were screened. Five RCTs were included in the final analysis, enrolling 209 patients with hypertrophic cardiomyopathy (101 patients were in the ARB arm). ARB treatment was not associated with either significant left ventricular mass reduction (standardized mean difference: - 0.25; 95% CI: - 0.73, 0.22; p = 0.29) or change in LVEF (weighted mean difference: 0.73%; 95% CI: - 1.10%, 2.56%; p = 0.43). Subgroup analysis showed that losartan, one of the most investigated and commonly used ARBs, was also not associated with significant decreases of left ventricular mass (standardized mean difference: - 0.13; 95% CI: - 0.61, 0.36; p = 0.61). CONCLUSION: This meta-analysis showed that ARB treatment is not associated with reduced left ventricular mass nor remarkable LVEF change among patients with hypertrophic cardiomyopathy. Further studies with a larger number of patients will be required to confirm these findings.

Hypertrophic cardiomyopathy and nephrogenic diabetes insipidus associated with chronic lithium carbonate use.

Lithium carbonate is an effective mood stabilizer. We treated a patient for hypertrophic cardiomyopathy due to chronic unsupervised lithium carbonate use. We noted: a) a previously normal ECG; b) the absence of any familiarity for sudden cardiac death; c) the associated nephrogenic diabetes insipidus; d) probable exaggerated lithium plasma concentrations, which had not been monitored over the past few years; and e) the unusual traits of the right ventricle. We would like to stress the need for regular cardiologic follow-up in psychiatric patients treated with lithium carbonate, to minimize its potential cardiac untoward consequences.

Low doses of BPA induced abnormal mitochondrial fission and hypertrophy in human embryonic stem cell-derived cardiomyocytes via the calcineurin-DRP1 signaling pathway: A comparison between XX and XY cardiomyocytes.

Humans are inevitably exposed to bisphenol A (BPA) via multiple exposure ways. Thus, attention should be raised to the possible adverse effects related to low doses of BPA. Epidemiological studies have outlined BPA exposure and the increased risk of cardiovascular diseases (such as cardiac hypertrophy), which has been confirmed to be sex-specific in rodent animals and present in few in vitro studies, although the molecular mechanism is still unclear. However, whether BPA at low doses equivalent to human internal exposure level could induce cardiac hypertrophy via the calcineurin-DRP1 signaling pathway by disrupting calcium homeostasis is unknown. To address this, human embryonic stem cell (H1, XY karyotype and H9, XX karyotype)-derived cardiomyocytes (CM) were purified and applied to study the low-dose effects of BPA on cardiomyocyte hypertrophy. In our study, when H1- and H9-CM were exposed to noncytotoxic BPA (8 ng/ml), markedly elevated hypertrophic-related mRNA expression levels (such as NPPA and NPPB), enhanced cellular area and reduced ATP supplementation, demonstrated the hypertrophic cardiomyocyte phenotype in vitro. The excessive fission produced by BPA was promoted by CnAß-mediated dephosphorylation of DRP1. At the molecular level, the increase in cytosolic Ca2+ levels by low doses of BPA could discriminate between H1- and H9-CM, which may suggest a potential sex-specific hypertrophic risk in cardiomyocytes in terms of abnormal mitochondrial fission and ATP production by impairing CnAß-DRP1 signaling. In CnAß-knockdown cardiomyocytes, these changes were highly presented in XX-karyotyped cells, rather than in XY-karyotyped cells.

Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-ß/Smads pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. AIM OF THE STUDY: The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-ß/Smads pathway. MATERIALS AND METHODS: We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10 mg/kg/d) and Astragalus extract (AE) (4.35 g/kg/d, which contained about ASG 10 mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 µM) and treated with ASG (10 µM) simultaneously for 24 h. RESULTS: The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-ß/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-ß/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis. CONCLUSIONS: AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-ß/Smads pathway.

Transient hypertrophic cardiomyopathy and hypertension associated with hydrocortisone in preterm infant: A case report.

RATIONALE: Hypertrophic cardiomyopathy (HCM) is a heterogeneous, usually familial disorder of heart muscle. The hypertrophic form of cardiomyopathy is frequently genetic, or as part of several neuromuscular disorders. In neonates, especially prematurity, HCM could also be secondary to corticosteroid treatment. PATIENT CONCERNS: We reported here a 34 weeks gestational age preterm infant presented with profound cardiomegaly after multiple doses of hydrocortisone used to treat blood pressure instability associated with septic shock and persistent pulmonary hypertension (PPHN). DIAGNOSIS: Patient presented auscultation of a grade III/IV harsh systolic ejection murmur from day 14, which was absent before. Profound cardiomegaly was indicated at chest film at day 30. Echocardiography showed severe thickening of the IVS (13.8 mm, z score = 8.29) and mild thickening of the posterior left ventricular wall (LVPW, 6 mm). INTERVENTIONS: Propranolol and captopril were started along with supportive care. The patient was also admitted to NICU for further treatment with 24-hour Holter electrocardiographic monitoring. OUTCOMES: A reversible course was observed without left ventricular outflow tract obstruction nor arrhythmias within 4 weeks. LESSONS: The risk/benefit ratio must be carefully considered when corticosteroids are used in prematurity. Monitors such as echocardiography and electrocardiograph should be conducted in order to guide cardiovascular management. Systematic surveys of the incidence of cardiac complications in a larger population of preterm infant treated with corticosteroid are needed in the future.

Effects of Long-Term Calcium Supplementation on Rats Bone Mineral Density and Cardiovascular Based on Metabonomics.

Calcium supplements were necessary for those people with low calcium intake and high risk of osteoporosis. Recent cohort studies have shown that long-term calcium supplements may raise the risk of cardiovascular disease, but its mechanism is still unclear. In this study, metabonomics were employed to evaluate the changes of metabolism in rats with long-term calcium supplementation and further seek the potential markers of cardiovascular risk. SD rats were divided into two groups including normal control group (calcium intake, 0.50 g/kg bw) and high calcium supplement group (calcium intake, 2.50 g/kg bw). After 6 mo, the cardiovascular system and bone mineral density were observed. UPLC-MS was used to analyze serum metabonomics in rats. The results showed that the contents of total cholesterol and low-density lipoprotein cholesterol in the high calcium group were significantly higher than those in normal control group (p<0.05). The interventricular septum thickness (IVS), left ventricular mass (LVM), left ventricular posterior wall thickness (LVPW) in the high calcium group were higher than those in normal control group (p<0.05). Serum metabonomics analysis showed that there were persistent changes in many metabolites such as sphingosine and its derivatives (p<0.01) in the comparison between the high calcium group and the normal group. These results indicated that long term calcium supplementation can lead to dyslipidemia in rats, such as the rise of cholesterol and low-density lipoprotein, which might induce myocardial hypertrophy. Long-term calcium supplementation can cause the changes of the amount of sphingosine and its derivatives in the body, which many have potential risk to cardiovascular diseases such as myocardial hypertrophy and atherosclerosis.

Miocardiopatía hipertrófica en un recién nacido pretérmino con madre trasplantada renal / Hypertrophic cardiomyopathy in preterm newborn with kidney transplanted mother

La miocardiopatía hipertrófica en el recién nacido es una entidad poco frecuente y de etiología heterogénea. Se han descrito formas transitorias en hijos de madres con diabetes gestacional y en recién nacidos pretérminos expuestos a corticoides tanto prenatal como posnatalmente. Se presenta un caso de un recién nacido pretérmino, hijo de madre trasplantada renal al que se le detectó una miocardiopatía hipertrófica y que había estado expuesto prenatalmente a corticoides y tacrolimus que recibía la madre como tratamiento inmunosupresor. Ambos fármacos cruzan la barrera placentaria y, al llegar al feto, podrían haber favorecido su desarrollo. La miocardiopatía hipertrófica puede ser un efecto secundario poco común del tratamiento con tacrolimus en adultos y niños, y es reversible al retirarlo. En nuestro conocimiento, es el primer caso publicado de miocardiopatía hipertrófica transitoria tras la exposición fetal tanto a corticoides como a tacrolimus en un hijo de madre trasplantada renal.

Hypertrophic cardiomyopathy in the newborn is a rare entity with heterogeneous etiology. Transient forms have been described in children of mothers with gestational diabetes and in preterm infants exposed both to prenatal and postnatal corticosteroids. We report a case of a preterm infant son of a mother who received renal transplant in whom hypertrophic cardiomyopathy was detected. He had been prenatally exposed to corticosteroids and tacrolimus that received the mother as immunosuppressive therapy. Both drugs cross the placental barrier and, on reaching the fetus, could have favored its development. Hypertrophic cardiomyopathy may be an uncommon side effect of treatment with tacrolimus in adults and children and it is reversible upon withdrawal. To our knowledge, it is the first published case of transient hypertrophic cardiomyopathy after fetal exposure to both corticosteroids and tacrolimus in the son of a renal transplanted mother.

[Hypertrophic cardiomyopathy in preterm newborn with kidney transplanted mother]. / Miocardiopatía hipertrófica en un recién nacido pretérmino con madre trasplantada renal.

Hypertrophic cardiomyopathy in the newborn is a rare entity with heterogeneous etiology. Transient forms have been described in children of mothers with gestational diabetes and in preterm infants exposed both to prenatal and postnatal corticosteroids. We report a case of a preterm infant son of a mother who received renal transplant in whom hypertrophic cardiomyopathy was detected. He had been prenatally exposed to corticosteroids and tacrolimus that received the mother as immunosuppressive therapy. Both drugs cross the placental barrier and, on reaching the fetus, could have favored its development. Hypertrophic cardiomyopathy may be an uncommon side effect of treatment with tacrolimus in adults and children and it is reversible upon withdrawal. To our knowledge, it is the first published case of transient hypertrophic cardiomyopathy after fetal exposure to both corticosteroids and tacrolimus in the son of a renal transplanted mother.

La miocardiopatía hipertrófica en el recién nacido es una entidad poco frecuente y de etiología heterogénea. Se han descrito formas transitorias en hijos de madres con diabetes gestacional y en recién nacidos pretérminos expuestos a corticoides tanto prenatal como posnatalmente. Se presenta un caso de un recién nacido pretérmino, hijo de madre trasplantada renal al que se le detectó una miocardiopatía hipertrófica y que había estado expuesto prenatalmente a corticoides y tacrolimus que recibía la madre como tratamiento inmunosupresor. Ambos fármacos cruzan la barrera placentaria y, al llegar al feto, podrían haber favorecido su desarrollo. La miocardiopatía hipertrófica puede ser un efecto secundario poco común del tratamiento con tacrolimus en adultos y niños, y es reversible al retirarlo. En nuestro conocimiento, es el primer caso publicado de miocardiopatía hipertrófica transitoria tras la exposición fetal tanto a corticoides como a tacrolimus en un hijo de madre trasplantada renal.

Lethal endomyocarditis caused by chronic "Krokodil" intoxication.

"Krokodil" is a home-made opioid drug obtained by synthesizing desomorphine from codeine and combining it with other low-cost additives. Initially introduced in the former Soviet countries, it was then imported to Western Europe as a heroin substitute. To our knowledge, this is the first report of an Italian case of lethal krokodil abuse, that occurred in a 39-year-old man, who died suddenly after transportation to the Emergency Department (ED) for hyperthermia associated with sweating, dyspnoea and tachycardia. Post-mortem examination revealed extensive necrotic ulcerative lesions on the forearms, and autopsy showed a hypertrophic heart with ample endocardial vegetation on the aortic valve and patency of the foramen ovale. Histopathological examination of the heart showed ulcero-vegetative lesions of the aortic valve with an abscess on the annulus and extension to the periaortic adipose tissue, as well as diffuse myocardial interstitial inflammatory neutrophilic infiltrates. Toxicological analysis demonstrated a desomorphine metabolite in urine. On the basis of all these findings the cause of death was ruled to be congestive heart failure caused by endocarditis and myocarditis, correlated with chronic abuse of krokodil.

The endoplasmic reticulum stress-autophagy pathway is involved in apelin-13-induced cardiomyocyte hypertrophy in vitro.

Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001-2 µmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4). Knockdown of Nox4 with siRNAs effectively prevented the reduction of GSH/GSSG ratio in apelin-13-treated cells. Furthermore, apelin-13 treatment dose-dependently increased the expression of Bip and CHOP, two ER stress markers, in the cells. Knockdown of APJ or Nox4 with the corresponding siRNAs, or application of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP expression. Moreover, apelin-13 treatment increased the formation of autophagosome and ER fragments and the LC3 puncta in the ER of the cells. Knockdown of APJ, Nox4, Bip or CHOP with the corresponding siRNAs, or application of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-II/I and beclin 1. Finally, knockdown of Nox4, Bip or CHOP with the corresponding siRNAs, or application of salubrinal significantly suppressed apelin-13-induced increases in the cell diameter, volume and protein contents. Our results demonstrate that ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.

Original Research: Atorvastatin prevents rat cardiomyocyte hypertrophy induced by parathyroid hormone 1-34 associated with the Ras-ERK signaling.

We investigated the effects of atorvastatin (Ator) on cardiomyocyte hypertrophy (CMH) induced by rat parathyroid hormone 1-34 (PTH1-34) and Ras-extracellular signal regulated protein kinases 1/2 (ERK1/2) signaling. Rat cardiomyocytes were randomly divided into seven groups: normal controls (NC), PTH1-34 (10(-7) mol/L), Ator (10(-5) mol/L), farnesyl transferase inhibitors-276 (FTI-276, 4 × 10(-5) mol/L), PTH1-34 + Ator, PTH1-34 + FTI-276 and PTH1-34 + Ator + mevalonic acid (MVA, 10(-4) mol/L). After treatment, the hypertrophic responses of cardiomyocytes were assessed by measuring cell diameter, detecting protein synthesis, and single-cell protein content. The concentrations of hypertrophic markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured by ELISA. Protein expressions of ERK1/2, p-ERK1/2 and Ras were detected by western blotting. The results showed that compared with the PTH1-34 group, cellular diameter, 3H-leucine incorporation, single-cell protein content, ANP and BNP concentration decreased by 12.07 µm, 1622 cpm/well, 84.34 pg, 7.13 ng/L and 20.04 µg/L, respectively, and the expressions of Ras and p-ERK1/2 were downregulated in PTH1-34 + Ator group (P < 0.05). Compared to the PTH1-34 + Ator group, the corresponding hypertrophic responses and hypertrophic markers increased by 4.95 µm, 750 cpm/well, 49.08 pg, 3.12 ng/L and 9.35 µg/L, respectively, and the expressions of Ras and p-ERK1/2 were upregulated in the PTH1-34 + Ator + MVA group (P < 0.05). In conclusion, Ator prevents neonatal rat CMH induced by PTH1-34 and Ras-ERK signaling may be involved in this process.

Neutrophil Gelatinase-Associated Lipocalin, a Novel Mineralocorticoid Biotarget, Mediates Vascular Profibrotic Effects of Mineralocorticoids.

Activation of the mineralocorticoid receptor has been shown to be deleterious in cardiovascular diseases (CVDs). We have recently shown that lipocalin 2 (Lcn2), or neutrophil gelatinase-associated lipocalin (NGAL), is a primary target of aldosterone/mineralocorticoid receptor in the cardiovascular system. Lcn2 is a circulating protein, which binds matrix metalloproteinase 9 and modulates its stability. We hypothesized that Lcn2 could be a mediator of aldosterone/mineralocorticoid receptor profibrotic effects in the cardiovascular system. Correlations between aldosterone and profibrotic markers, such as procollagen type I N-terminal peptide, were investigated in healthy subjects and subjects with abdominal obesity. The implication of Lcn2 in the mineralocorticoid pathway was studied using Lcn2 knockout mice subjected to a nephrectomy/aldosterone/salt (NAS) challenge for 4 weeks. In human subjects, NGAL/matrix metalloproteinase 9 was positively correlated with plasma aldosterone and fibrosis biomarkers. In mice, loss of Lcn2 prevented the NAS-induced increase of plasma procollagen type I N-terminal peptide, as well as the increase of collagen fibers deposition and collagen I expression in the coronary vessels and the aorta. The lack of Lcn2 also blunted the NAS-induced increase in systolic blood pressure. Ex vivo, treatment of human fibroblasts with recombinant Lcn2 induced the expression of collagen I and the profibrotic galectin-3 and cardiotrophin-1 molecules. Our results showed that Lcn2 plays a key role in aldosterone/mineralocorticoid receptor-mediated vascular fibrosis. The clinical data indicate that this may translate in human patients. Lcn2 is, therefore, a new biotarget in cardiovascular fibrosis induced by mineralocorticoid activation.

Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant.

Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM) is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg) used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

H2O 2 induces myocardial hypertrophy in H9c2 cells: a potential role of Ube3a.

Myocardial hypertrophy that often leads to eventual heart failure is a leading cause of mortality worldwide. While both apoptosis and cell proliferation have been reported to play an important part in heart failure, its exact triggering mechanism is still unclear. Reports have shown that low concentrations of H2O2 (10-30 µM) can induce myocardial hypertrophy without affecting survival. The ubiquitin ligase Ube3a has been reported to have a close affiliation with Angelman syndrome; but many ubiquitin ligases have been reported in a variety of cardiovascular conditions including myocardial hypertrophy. However, the relationship between Ube3a and myocardial hypertrophy has never been reported in literature. The rat cardiac myoblast cell line H9c2 and primary neonatal cardiomyocytes showed similar hypertrophic responses in vitro. In this report, we utilized H2O2 treatment on H9c2 cells to induce myocardial hypertrophy and determined the relationship between Ube3a and myocardial hypertrophy. Our results showed that 10-20 µM H2O2 can induce myocardial hypertrophy without affecting cell viability and inducing cell apoptosis, while the corresponding transcription and translation levels of Ube3a are significantly increased during the process. Therefore, these findings underline that Ube3a may play an important role in myocardial hypertrophy.

Prednisone induced two-way myocardial development in a patient with systemic lupus erythematosus.

We present a series of echocardiography images to demonstrate the myocardial response to a high dose of prednisone. A young woman with systemic lupus erythematosus (SLE) associated with interventricular septal hypertrophy exhibited a high pressure gradient between the ascending aorta and left ventricular outflow tract as well as significant systolic anterior motion (SAM) and mitral regurgitation (MR) during high-dose prednisone treatment. However, the pressure gradient decreased dramatically and the MR disappeared rapidly when the dose of prednisone was reduced. To the best of our knowledge, this is the only adult case of myocardial hypertrophy that is assumed to be related to prednisone use.