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Within our multidisciplinary sarcoidosis program, we use advanced imaging that includes either CMR or FDG-PET to screen all patients with known extracardiac sarcoidosis (Figure). Keywords: Editorials; cardiac sarcoidosis; death, sudden, cardiac; implantable cardiac defibrillator; ventricular arrhythmias EN Editorials cardiac sarcoidosis death, sudden, cardiac implantable cardiac defibrillator ventricular arrhythmias 976 979 4 09/26/22 20220927 NES 220927 Recently, we were consulted on a 32-year-old man who had an out-of-hospital cardiac arrest. [Extracted from the article]

Parasympathetic stimulation of the heart, which provides protection from arrhythmias and sudden death, involves activation of the G protein--coupled inward rectifying [K.sup.+] channel GIRK1/4 and results in an acetylcholine-sensitive [K.sup.+] current, [I.sub.KACh]. We describe a unique relationship between lipid homeostasis, the lipid-sensitive transcription factor SREBP-1, regulation of the cardiac parasympathetic response, and the development of ventricular arrhythmia. In embryonic chick atrial myocytes, lipid lowering by culture in lipoprotein-depleted serum increased SREBP-1 levels, GIRK1 expression, and [I.sub.KACh] activation. Regulation of the GIRK1 promoter by SREBP-1 and lipid lowering was dependent on interaction with 2 tandem sterol response elements and an upstream E-box motif. Expression of dominant negative SREBP-1 (DN--SREBP-1) reversed the effect of lipid lowering on [I.sub.KACh] and GIRK1. In SREBP-1 knockout mice, both the response of the heart to parasympathetic stimulation and the expression of GIRK1 were reduced compared with WT. [I.sub.KACh], attenuated in atrial myocytes from SREBP-1 knockout mice, was stimulated by SREBP-1 expression. Following myocardial infarction, SREBP-1 knockout mice were twice as likely as WT mice to develop ventricular tachycardia in response to programmed ventricular stimulation. These results demonstrate a relationship between lipid metabolism and parasympathetic response that may play a role in arrhythmogenesis., Introduction The balance between the response of the heart to sympathetic and parasympathetic stimuli not only determines the rate and force of contraction but also plays a role in regulating [...]

Left ventricular (LV) remodeling after myocardial infarction (MI) results from hypertrophy of myocytes and activation of fibroblasts induced, in part, by ligand stimulation of the ANG II type 1 receptor (A[T.sub.1]R). The purpose of the present study was to explore the specific role for activation of the A[T.sub.1a]R subtype in post-MI remodeling and whether gender differences exist in the patterns of remodeling in wild-type and A[T.sub.1a]R knockout (KO) mice. A[T.sub.1a]R-KO mice and wild-type littermates underwent coronary ligation to induce MI or sham procedures; echocardiography and hemodynamic evaluation were performed 6 wk later, and LV tissue was harvested for infarct size determination, morphometric measurements, and gene expression analysis. Survival and infarct size were similar among all male and female wild-type and A[T.sub.1a]R-KO mice. Hemodynamic indexes were also similar except for lower systolic blood pressure in the A[T.sub.1a]R-KO mice compared with wild-type mice. Male and female wild-type and male A[T.sub.1a]R-KO mice developed similar increases in LV chamber size, LV mass corrected for body weight (LV/BW), and myocyte cross-sectional area (CSA). However, female A[T.sub.1a]R-KO mice demonstrated no increase in LV/BW and myocyte CSA post-MI compared with shams. Both male and female wild-type mice demonstrated higher atrial natriuretic peptide (ANP) levels after MI, with female wild types being significantly greater than males. However, male and female A[T.sub.1a]R-KO mice developed no increase in ANP gene expression with MI despite an increase in LV mass and myocyte size in males. These data support that gender-specific patterns of LV and myocyte hypertrophy exist after MI in mice with a disrupted A[T.sub.1a]R gene, and suggest that myocyte hypertrophy post-MI in females relies, in part, on activation of the A[T.sub.1a]R. Further work is necessary to explore the potential mechanisms underlying these gender-based differences. angiotensin II receptors; ventricular remodeling; myocyte; hypertrophy

Left ventricular remodeling, including the deposition of excess extracellular matrix, is key to the pathogenesis of heart failure. The stress-inducible transcriptional regulator p8 is increased in failing human hearts and is required both for agonist-stimulated cardiomyocyte hypertrophy and for cardiac fibroblasts matrix metalloprotease-9 (MMP9) induction. In the heart, upregulation of autophagy is an adaptive response to stress and plays a causative role in cardiomyopathies. We have recently shown that p8 ablation in cardiac cells upregulates autophagy and that, in vivo, loss of p8 results in a decrease of cardiac function. Here we investigated the effects of p8 genetic deletion in mediating adverse myocardial remodeling. Unstressed p8-/- mouse hearts manifested complex alterations in the expression of fibrosis markers. In addition, these mice displayed elevated autophagy and apoptosis compared with p8+/+ mice. Transverse aortic constriction (TAC) induced left ventricular p8 expression in p8+/+ mice. Pressure overload caused left ventricular remodeling in both genotypes, however, p8-/- mice showed less cardiac fibrosis induction. Consistent with this, although MMP9 induction was attenuated in the p8-/- mice, induction of MMP2 and MMP3 were strikingly upregulated while TIMP2 was downregulated. Left ventricular autophagy increased after TAC and was significantly higher in the p8-/- mice. Thus p8-deletion results in reduced collagen fibrosis after TAC, but in turn, is associated with a detrimental higher increase in autophagy. These findings suggest a role for p8 in regulating in vivo key signaling pathways involved in the pathogenesis of heart failure. [ABSTRACT FROM AUTHOR]

The article discusses the developments of small animal models and treatment for heart failure. The author states that heart failure models are created using rats since it bears high inherent potential, cost effective and maintain statistical power. It also cites the different models that already existed as well as the relevance of the model in developing new therapies and treatment for heart failure.

The article presents a study on the molecular mechanisms that underlies the inhibitory effects of estrogen replacement regarding pressure over-load-induced left ventricular (LV) hypertrophy in the mouse transverse aortic constriction (TAC) model. It provides further laboratory investigation on the influences of hypertrophy and calcineurin signaling. A demonstration of cellular ribonucleic acid (RNA) isolation from myocardial samples is also depicted.

The article reports on the result of the study on the increased expression of friend of GATA (FOG)-2 in failing myocardium disrupts thyroid hormone-dependents sarcoplasmic reticulum calcium ATPase (SERCA)2 gene transcription. The results revealed that SERCA2 is an important target of FOG-2 and that the increased FOG-2 expression may contribute to a decline in cardiac function in end-stage heat failure by an impaired signaling.

Left ventricular (LV) mass and other LV measures have been shown to be heritable. In this study we hypothesized that functional variation in the gene coding for estrogen receptor-alpha (ESR1), known for mediating the effect of estrogens on myocardium, is associated with age-related changes in LV structure. Four genetic markers (ESR1 TA repeat; rs2077647, or +30T>C; rs2234693, or PvuII; and rs9340799, or XbaI) were genotyped in 847 unrelated individuals (488 women) from the Framingham Offspring Study, who attended 2 examination cycles 16 years apart (mean ages at first examination: 43+/-9 years; at follow-up: 59+/-9 years). ANCOVA was used to assess the association of polymorphisms and their haplotypes with cross-sectional measurements and longitudinal changes in LV mass, wall thickness, end-diastolic and end-systolic internal diameter, and fractional shortening after adjustment for factors known to influence these variables. Changes over time were detected for all of the LV measurements (P ranging from <0.0001 to 0.02), except for fractional shortening in men. The SS genotype of the ESR1 TA repeat polymorphism in the promoter region was associated with longitudinal changes in LV mass and LV wall thickness (P ranging from 0.0006 to 0.01). Moreover, the TA[S]-+30[T]-PvuII[T]-XbaI[A] haplotype (frequency: 47.5%) was associated with greater LV changes as compared with the TA[L]-+30[C]-PvuII[C]-XbaI[G] haplotype (frequency: 31.8%). Our results are consistent with the hypothesis that common ESR1 polymorphisms are significantly associated with age-related changes in LV structure. Understanding the mechanisms predisposing to unfavorable LV remodeling of the heart with advancing age may aid in the discovery of new therapeutic targets for the prevention of heart failure. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) remodeling after myocardial infarction (MI) results from hypertrophy of myocytes and activation of fibroblasts induced, in part, by ligand stimulation of the ANG II type 1 receptor (AT1R). The purpose of the present study was to explore the specific role for activation of the AT1aR subtype in post-MI remodeling and whether gentler differences exist in the patterns of remodeling in wild-type and AT1aR knockout (KO) mice. AT1aR-KO mice and wild-type littermates underwent coronary ligation to induce MI or sham procedures; echocardiography and hemodynamic evaluation were performed 6 wk later, and LV tissue was harvested for infarct size determination, morphometric measurements, and gene expression analysis. Survival and infarct size were similar among all male and female wild-type and AT1aR-KO mice. Hemodynamic indexes were also similar except for lower systolic blood pressure in the AT1aR-KO mice compared with wild-type mice. Male and female wild-type and male AT1aR-KO mice developed similar increases in LV chamber size, LV mass corrected for body weight (LV/BW), and myocyte cross-sectional area (CSA). However, female AT1aR-KO mice demonstrated no increase in LV/BW and myocyte CSA post-MI compared with shams. Both male and female wild-type mice demonstrated higher atrial natriuretic peptide (ANP) levels after MI, with female wild types being significantly greater than males. However, male and female AT1aR-KO mice developed no increase in ANP gene expression with MI despite an increase in LV mass and myocyte size in males. These data support that gender-specific patterns of LV and myocyte hypertrophy exist after MI in mice with a disrupted AT1aR gene, and suggest that myocyte hypertrophy post-MI in females relies, in part, on activation of the AT1aR. Further work is necessary to explore the potential mechanisms underlying these gender-based differences. [ABSTRACT FROM AUTHOR]

Objectives: We examined the effect of mechanical unloading with ventricular assist device (VAD) therapy on myocardial inducible nitric oxide synthase (iNOS) expression and cardiomyocyte apoptosis in patients with end-stage heart failure (HF). Background: Despite advances in medical therapy, HF continues to be a progressive and ultimately fatal disorder. High levels of iNOS expression are present in the myocardium of failing hearts, suggesting a potential role for iNOS in HF progression. Methods: Inducible NOS protein expression was analyzed by Western blotting and cardiomyocyte apoptosis by terminal deoxynucleotidyltransferase dUTP nick end-labeling (TUNEL) in myocardial samples from failing hearts. Included in these analyses were tissues from 9 patients at the time of transplantation (HF-transplant group), 10 patients at the time of VAD insertion (pre-VAD group), and 11 patients undergoing transplant after VAD support (post-VAD group). Seven control samples were obtained at autopsy. Results: Low or undetectable levels of iNOS were present in controls (0.005 ± 0.002). The HF-transplant and pre-VAD myocardial specimens exhibited a marked increase in iNOS expression (1.48 ± 0.34 and 1.29 ± 0.26, respectively; p &#60; 0.01 for both vs. controls). The increase in iNOS expression was reversed in the post-VAD group (0.36 ± 0.16; p &#60; 0.01 vs. HF-transplant and pre-VAD groups). The rate of TUNEL-positive cardiomyocytes was high in the pre-VAD group and significantly lower in the post-VAD group (0.64 ± 0.15% in pre-VAD group and 0.16 ± 0.07% in post-VAD group; p &#60; 0.01). The iNOS levels correlated significantly with cardiomyocyte apoptosis (r = 0.66, p &#60; 0.01). Conclusions: Therapy with VAD normalizes iNOS expression in association with diminished cardiomyocyte apoptosis in the failing heart. Further work is required to define whether a causal relationship exists between iNOS and cardiomyocyte apoptosis. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after myocardial infarction (MI) in mice.: BackgroundObservational and clinical studies suggest that the cardiovascular effects of hormone replacement therapy can differ depending on the patient population studied. No prospective studies have examined the effect of estrogen on outcomes following MI. We now examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after MI in mice.: MethodsMyocardial infarction was induced by left coronary artery ligation in ovariectomized female mice treated with 17-beta-estradiol (E2) or placebo. At either one day or six weeks after MI, hemodynamic function was assessed, animals were euthanized, and infarct size was determined.: Results17-Beta-estradiol–treated mice had smaller infarcts than placebo-treated animals both one day (18% decrease; p < 0.01), and six weeks (14% decrease; p < 0.05) following MI. E2 reduced cardiomyocyte apoptosis as assessed by the terminal deoxynucleotidyl transferase uridine nucleotide end-labeling method (50% reduction, p < 0.05) and caspase 3 activation (33% reduction, p < 0.05). Despite having smaller infarcts, however, left ventricular mass increased more in the E2-treated animals (16% greater; p < 0.01). Left ventricular weight was positively correlated with infarct size in the estrogen-treated animals (R2 = 0.79, p = 0.0001). 17-Beta-estradiol treatment also significantly increased mortality in the infarcted animals (relative risk of death = 2.4; 95% confidence interval 1.2 to 5.3).: ConclusionsEstrogen replacement therapy reduces infarct size and cardiomyocyte apoptosis in mice. However, estrogen increased post-MI ventricular remodeling and mortality. Further studies will be necessary to elucidate the mechanisms underlying the complex effects of estrogen observed in the present study. [Copyright &y& Elsevier]

Presents information on a study on ventricular remodeling following myocardial infarction in a mouse. Importance of transgenic strains of mice as experimental species; Methods used in the study; Results of the study.

Cardiomyocyte hypertrophy and extracellular matrix remodeling, primarily mediated by inflammatory cytokine-stimulated cardiac fibroblasts, are critical cellular events in cardiac pathology. The molecular components governing these processes remain nebulous, and few genes have been linked to both hypertrophy and matrix remodeling. Here we show that p8, a small stress-inducible basic helix-loop-helix protein, is required for endothelin- and α-adrenergic agonist-induced cardiomyocyte hypertrophy and for tumor necrosis factor-stimulated induction, in cardiac fibroblasts, of matrix metalloproteases (MMPs) 9 and 13--MMPs linked to general inflammation and to adverse ventricular remodeling in heart failure. In a stimulus-dependent manner, p8 associates with chromatin containing c-Jun and with the cardiomyocyte atrial natriuretic factor (anf) promoter and the cardiac fibroblast mmp9 and mmp13 promoters, established activator protein 1 effectors. p8 is also induced strongly in the failing human heart by a process reversed upon therapeutic intervention. Our results identify an unexpectedly broad involvement for p8 in key cellular events linked to cardiomyocyte hypertrophy and cardiac fibroblast MMP production, both of which occur in heart failure. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the outcomes of patients with an Impella CP percutaneous mechanical circulatory support (MCS) device deployed during a cardiac arrest.Background: The Impella CP device is indicated for left ventricular support in patients with cardiogenic shock. The utility of percutaneous MCS in the setting of cardiac arrest during cardiopulmonary resuscitation (CPR) remains unclear.Methods: We retrospectively examined data from patients supported with an Impella CP device for cardiogenic shock complicated by cardiac arrest between April 2015 and April 2017 at a single academic medical center. Patients with cardiac arrest who underwent Impella CP placement during CPR were compared to those who had return of spontaneous circulation (ROSC) prior to Impella CP placement.Results: We identified 22 patients with cardiogenic shock complicated by cardiac arrest (average age 64 years, 23% female) who underwent placement of an Impella CP device. The majority of patients (68%) underwent support for cardiogenic shock secondary to an acute myocardial infarction. Seven of the 22 patients (32%) underwent Impella CP placement during CPR and 15 (68%) underwent Impella CP insertion following ROSC. The in-hospital mortality was 86% in the group of patients who had the Impella CP placed during CPR and 56% in the group with ROSC prior to Impella CP insertion, (p = 0.19).Conclusions: Based on our single center retrospective analysis, the mortality rate of patients undergoing placement of an Impella CP during CPR is 86%. Further study is necessary to better understand the utility of the Impella CP mechanical circulatory support device during a cardiac arrest. [ABSTRACT FROM AUTHOR]