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Pubblicazioni recenti - cardiac hypertrophy
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Autocrine Signaling in Cardiac Remodeling: A Rich Source of Therapeutic Targets.
J Am Heart Assoc2021 Jan;():e019169. doi: 10.1161/JAHA.120.019169.
Segers Vincent F M, De Keulenaer Gilles W,
Abstract
The myocardium consists of different cell types, of which endothelial cells, cardiomyocytes, and fibroblasts are the most abundant. Communication between these different cell types, also called paracrine signaling, is essential for normal cardiac function, but also important in cardiac remodeling and heart failure. Systematic studies on the expression of ligands and their corresponding receptors in different cell types showed that for 60% of the expressed ligands in a particular cell, the receptor is also expressed. The fact that many ligand-receptor pairs are present in most cells, including the major cell types in the heart, indicates that autocrine signaling is a widespread phenomenon. Autocrine signaling in cardiac remodeling and heart failure is involved in all pathophysiological mechanisms generally observed: hypertrophy, fibrosis, angiogenesis, cell survival, and inflammation. Herein, we review ligand-receptor pairs present in the major cardiac cell types based on RNA-sequencing expression databases, and we review current literature on extracellular signaling proteins with an autocrine function in the heart; these include C-type natriuretic peptide, fibroblast growth factors 2, F21, and 23, macrophage migration inhibitory factor, heparin binding-epidermal growth factor, angiopoietin-like protein 2, leptin, adiponectin, follistatin-like 1, apelin, neuregulin 1, vascular endothelial growth factor, transforming growth factor ?, wingless-type integration site family, member 1-induced secreted protein-1, interleukin 11, connective tissue growth factor/cellular communication network factor, and calcitonin gene?related peptide. The large number of autocrine signaling factors that have been studied in the literature supports the concept that autocrine signaling is an essential part of myocardial biology and disease.
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Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy.
Sci Rep2021 Jan;11(1):1755. doi: 10.1038/s41598-020-80868-z.
Sonnenschein Kristina, Fiedler Jan, de Gonzalo-Calvo David, Xiao Ke, Pfanne Angelika, Just Annette, Zwadlo Carolin, Soltani Samira, Bavendiek Udo, Kraft Theresia, Dos Remedios Cristobal, Cebotari Serghei, Bauersachs Johann, Thum Thomas,
Abstract
Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.
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CRD-733, a Novel PDE9 (Phosphodiesterase 9) Inhibitor, Reverses Pressure Overload-Induced Heart Failure.
Circ Heart Fail2021 Jan;14(1):e007300. doi: 10.1161/CIRCHEARTFAILURE.120.007300.
Richards Daniel A, Aronovitz Mark J, Liu Peiwen, Martin Gregory L, Tam Kelly, Pande Suchita, Karas Richard H, Bloomfield Daniel M, Mendelsohn Michael E, Blanton Robert M,
Abstract
BACKGROUND:
Augmentation of NP (natriuretic peptide) receptor and cyclic guanosine monophosphate (cGMP) signaling has emerged as a therapeutic strategy in heart failure (HF). cGMP-specific PDE9 (phosphodiesterase 9) inhibition increases cGMP signaling and attenuates stress-induced hypertrophic heart disease in preclinical studies. A novel cGMP-specific PDE9 inhibitor, CRD-733, is currently being advanced in human clinical studies. Here, we explore the effects of chronic PDE9 inhibition with CRD-733 in the mouse transverse aortic constriction pressure overload HF model.
METHODS:
Adult male C57BL/6J mice were subjected to transverse aortic constriction and developed significant left ventricular (LV) hypertrophy after 7 days (<0.001). Mice then received daily treatment with CRD-733 (600 mg/kg per day; n=10) or vehicle (n=17), alongside sham-operated controls (n=10).
RESULTS:
CRD-733 treatment reversed existing LV hypertrophy compared with vehicle (<0.001), significantly improved LV ejection fraction (=0.009), and attenuated left atrial dilation (<0.001), as assessed by serial echocardiography. CRD-733 prevented elevations in LV end diastolic pressures (=0.037) compared with vehicle, while lung weights, a surrogate for pulmonary edema, were reduced to sham levels. Chronic CRD-733 treatment increased plasma cGMP levels compared with vehicle (<0.001), alongside increased phosphorylation of Ser of cardiac myosin binding protein-C, a cGMP-dependent protein kinase I phosphorylation site.
CONCLUSIONS:
The PDE9 inhibitor, CRD-733, improves key hallmarks of HF including LV hypertrophy, LV dysfunction, left atrial dilation, and pulmonary edema after pressure overload in the mouse transverse aortic constriction HF model. Additionally, elevated plasma cGMP may be used as a biomarker of target engagement. These findings support future investigation into the therapeutic potential of CRD-733 in human HF.
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A rare cause of newborn central cyanosis.
Echocardiography2020 Sep;37(9):1524-1525. doi: 10.1111/echo.14809.
Wa?doch Anna, Sabiniewicz Robert, Kwiatkowska Joanna,
Abstract
Pulmonary arteriovenous malformations are rare congenital vascular anomalies. They are usually associated with congenital hemorrhagic hemangioma. The hemodynamic effect of fistulas depends on their size, as well as the location. The most common manifestations include central cyanosis, ischemic stroke, murmur over the lung fields, cardiomegaly and, less often, heart failure. We present the case of a child who was admitted to the Department of Pediatric Cardiology and Congenital Heart Defects due to central cyanosis and heart murmur.
© 2020 Wiley Periodicals LLC.
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Antibody-mediated neutralization of IL11 signalling reduces ERK activation and cardiac fibrosis in a mouse model of severe pressure overload.
Clin Exp Pharmacol Physiol2021 Jan;():. doi: 10.1111/1440-1681.13458.
Lim Wei-Wen, Corden Ben, Ye Lei, Viswanathan Sivakumar, Widjaja Anissa A, Xie Chen, Su Liping, Tee Nicole G Z, Schafer Sebastian, Cook Stuart A,
Abstract
Interleukin-11 (IL11) is important for fibroblast-to-myofibroblast transformations. Here, we examined the signalling and phenotypic effects of inhibiting IL11 signalling using neutralizing antibodies against IL11 or its cognate receptor (IL11RA) in a mouse model of acute and severe pressure overload. C57BL/6J mice underwent ascending aortic constriction (AAC) surgery and were randomized to anti-IL11, anti-IL11RA, or isotype control antibodies (20 mg/kg, bi-weekly for 2 weeks). AAC surgery induced the expression of IL11, IL11RA and extracellular matrix (ECM) genes that was associated with cardiac hypertrophy and aortic remodelling. Inhibition of IL11 signalling reduced AAC-induced cardiac fibrosis and ECM gene expression as well as ERK1/2 phosphorylation but had no effect on cardiac hypertrophy. STAT3 was phosphorylated in the hearts of AAC-treated mice but this was unrelated to IL11 activity, which we confirmed in mouse cardiac fibroblasts in vitro. These data highlight that blocking IL11 signalling reduces cardiac fibrosis due to severe pressure overload and suggests ERK, but not STAT3, activity as the relevant underlying signalling pathway.
© 2021 John Wiley & Sons Australia, Ltd.
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6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway.
Acta Pharmacol Sin2021 Jan;():. doi: 10.1038/s41401-020-00587-z.
Ma Shu-Qing, Guo Zhen, Liu Fang-Yuan, Hasan Shahzad-Gul, Yang Dan, Tang Nan, An Peng, Wang Ming-Yu, Wu Hai-Ming, Yang Zheng, Fan Di, Tang Qi-Zhu,
Abstract
6-Gingerol, a pungent ingredient of ginger, has been reported to possess anti-inflammatory and antioxidant activities, but the effect of 6-gingerol on pressure overload-induced cardiac remodeling remains inconclusive. In this study, we investigated the effect of 6-gingerol on cardiac remodeling in in vivo and in vitro models, and to clarify the underlying mechanisms. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 6-gingerol (20?mg/kg, ig) three times a week (1 week in advance and continued until the end of the experiment). Four weeks after TAC surgery, the mice were subjected to echocardiography, and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of 6-gingerol in response to phenylephrine (PE) and transforming growth factor-? (TGF-?) challenge. We showed that 6-gingerol administration protected against pressure overload-induced cardiac hypertrophy, fibrosis, inflammation, and dysfunction in TAC mice. In the in vitro study, we showed that treatment with 6-gingerol (20??M) blocked PE-induced-cardiomyocyte hypertrophy and TGF-?-induced cardiac fibroblast activation. Furthermore, 6-gingerol treatment significantly decreased mitogen-activated protein kinase p38 (p38) phosphorylation in response to pressure overload in vivo and extracellular stimuli in vitro, which was upregulated in the absence of 6-gingerol treatment. Moreover, transfection with mitogen-activated protein kinase kinase 6 expressing adenoviruses (Ad-MKK6), which specifically activated p38, abolished the protective effects of 6-gingerol in both in vitro and in vivo models. In conclusion, 6-gingerol improves cardiac function and alleviates cardiac remodeling induced by pressure overload in a p38-dependent manner. The present study demonstrates that 6-gingerol is a promising agent for the intervention of pathological cardiac remodeling.
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The adapted Heart Donor Score.
Transpl Int2021 Jan;():. doi: 10.1111/tri.13822.
Angleitner Philipp, Kaider Alexandra, Smits Jacqueline M, Aliabadi-Zuckermann Arezu Z, Osorio-Jaramillo Emilio, Laufer Günther, Zuckermann Andreas O,
Abstract
BACKGROUND:
The Heart Donor Score (HDS) predicts donor organ discard for medical reasons and survival after heart transplantation (HTX) in the Eurotransplant allocation system. Our aim was to adapt the HDS for application in the United Network for Organ Sharing (UNOS) registry.
METHODS:
To adjust for differences between the Eurotransplant and UNOS registries, the "adapted HDS" was created (aHDS) by exclusion of the covariates "valve function", "left-ventricular hypertrophy", and exclusion of "drug abuse" from the variable "compromised history". Two datasets were analyzed to evaluate associations of the aHDS with donor organ discard (n = 70948) and survival (n = 19279).
RESULTS:
The aHDS was significantly associated with donor organ discard (odds ratio 2.72, 95% confidence interval [CI] 2.68 - 2.76, p < 0.001; c-statistic: 0.937). The score performed comparably in donors < 60 years and ? 60 years of age. The aHDS was a significant predictor of survival as evaluated by univariate Cox proportional hazards analysis (hazard ratio 1.04, 95% CI 1.01 - 1.07, p = 0.023), although the association lost significance in a multivariable model.
CONCLUSIONS:
The aHDS predicts donor organ discard. Negative effects of most aHDS components on survival are likely eliminated by highly accurate donor selection processes.
This article is protected by copyright. All rights reserved.
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Fast Strain-Encoded Cardiac Magnetic Resonance for Diagnostic Classification and Risk Stratification of Heart Failure Patients.
JACC Cardiovasc Imaging2021 Jan;():. doi: S1936-878X(20)31004-4.
Korosoglou Grigorios, Giusca Sorin, Montenbruck Moritz, Patel Amit R, Lapinskas Tomas, Götze Collin, Zieschang Victoria, Al-Tabatabaee Sarah, Pieske Burkert, Florian Andre, Erley Jennifer, Katus Hugo A, Kelle Sebastian, Steen Henning,
Abstract
OBJECTIVES:
The purpose of this study was to compare the ability of fast-strain encoded magnetic resonance (fast-SENC) cardiac magnetic resonance (CMR) to classify and risk stratify all-comer patients with different stages of chronic heart failure (Stages of heart failure A to D) based on American College of Cardiology/American Heart Association guidelines with standard clinical and CMR imaging data.
BACKGROUND:
Heart failure is a major cause of morbidity and mortality, resulting in millions of deaths and hospitalizations annually.
METHODS:
The study population consisted of 1,169 consecutive patients between September 2017 and February 2019 who underwent CMR for clinical reasons, and 61 healthy volunteers. In addition, clinical follow-up was performed in Stages A and B patients after 1.9 ± 0.4 years. Wall motion score and late gadolinium enhancement score indexes, left ventricular (LV) ejection fraction, and global circumferential and longitudinal strain based on fast-SENC acquisitions, were calculated in all subjects. The percentage of myocardial segments with strain ?-17% (% normal myocardium) was determined in all subjects.
RESULTS:
LV ejection fraction, global circumferential and longitudinal strain, and % normal myocardium significantly decreased with increasing heart failure stages (p < 0.001 for all by analysis of variance). By multivariable analysis, % normal myocardium remained an independent predictor of heart failure stages, exhibiting closer association than LV ejection fraction (r = 0.76 vs. r = 0.30; p < 0.001). Importantly, 149 of 399 (37%) with Stage A were reclassified to Stage B, that is, as having subclinical LV dysfunction based on % normal myocardium <80%. Such patients exhibited significantly higher rates of all-cause mortality and hospital stay due to heart failure during follow-up, compared with patients with % normal myocardium ?80% (? = 6.9; p = 0.03).
CONCLUSIONS:
% normal myocardium, determined by fast-SENC, enables improved identification of asymptomatic patients with subclinical LV dysfunction compared with LV ejection fraction and risk stratification of patients with so far asymptomatic heart failure. The identification of such presumably healthy patients at high risk for heart failure-related outcomes may bear important medical implications.
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Efficacy of echocardiography for differential diagnosis of left ventricular hypertrophy: special focus on speckle-tracking longitudinal strain.
J Echocardiogr2021 Jan;():. doi: 10.1007/s12574-020-00508-3.
Tanaka Hidekazu,
Abstract
Left ventricular (LV) hypertrophy (LVH) is a frequent imaging finding in daily clinical practice, and its presence is associated with poor outcomes and ventricular arrhythmias. It is commonly detected in athletes, arterial hypertension, aortic stenosis, hypertrophic cardiomyopathy, cardiac amyloidosis, Fabry disease, or Friedreich's ataxia. Echocardiography plays an important role in detecting LVH and underlying causes in current clinical practice. While echocardiography is essential for the quantification and early detection of LV structural findings for various cardiovascular diseases, it has been reported that speckle-tracking echocardiographic parameters are also useful for the detection of early LV structural abnormalities. In particular, global longitudinal strain (GLS) assessed by two-dimensional speckle-tracking echocardiography is reportedly a sensitive marker for early subtle abnormalities of LV myocardial performance, helpful for the prediction of outcomes for various cardiac diseases, and superior to conventional echocardiographic indices. GLS is determined as the averaged peak longitudinal strain of 18 LV segments from standard apical views and can be assessed as a polar plot. This polar plot longitudinal strain mapping offers an intuitive visual overview of the global and regional LV longitudinal myocardial function status of various cardiomyopathies with LVH. This mapping is clinically practicable and the plot patterns obtainable as the result of further development of this technique for clinical practice provide clues to the etiology of cardiomyopathies. This article reviews the efficacy of echocardiography for differential diagnosis of LVH, with a special focus on the utility of speckle-tracking longitudinal strain.
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Electrocardiographic Strain Pattern Is a Major Determinant of Rehospitalization for Heart Failure After Transcatheter Aortic Valve Replacement.
J Am Heart Assoc2021 Jan;():e014481. doi: 10.1161/JAHA.119.014481.
Heger Joé, Trimaille Antonin, Kibler Marion, Marchandot Benjamin, Peillex Marilou, Carmona Adrien, Matsushita Kensuke, Trinh Annie, Reydel Antje, Zeyons Floriane, Petit-Eisenmann Hélène, Jesel Laurence, Ohlmann Patrick, Morel Olivier,
Abstract
Background Electrocardiographic strain pattern (ESP) has recently been associated with increased adverse outcome in aortic stenosis and after surgical aortic valve replacement. Our study sought to determine the impact and incremental value of ESP pattern in predicting adverse outcome after transcatheter aortic valve replacement. Methods and Results A total of 585 patients with severe aortic stenosis (mean age, 83±7 years; men, 39.8%) were enrolled for transcatheter aortic valve replacement from November 2012 to May 2018. ESP was defined as ?1-mm concave down-sloping ST-segment depression and asymmetrical T-wave inversion in the lateral leads. The primary end points of the study were all-cause mortality, rehospitalization for heart failure, myocardial infarction, and stroke. A total of 178 (30.4%) patients were excluded because of left bundle-branch block (n=103) or right bundle-branch block (n=75). Among the 407 remaining patients, 106 had ESP (26.04%). At a median follow-up of 20.00 months (11.70-29.42 months), no impact of electric strain on overall and cardiac death could be established. By contrast, incidence of rehospitalization for heart failure was significantly higher (33/106 [31.1%] versus 33/301 [11%]; <0.001) in patients with ESP. By multivariate analyses, ESP remained a strong predictor of rehospitalization for heart failure (hazard ratio, 2.75 [95% CI, 1.61-4.67]; <0.001). Conclusions In patients with aortic stenosis who were eligible for transcatheter aortic valve replacement, ESP is frequent and associated with an increased risk of postinterventional heart failure regardless of preoperative left ventricular hypertrophy. ESP represents an easy, objective, reliable, and low-cost tool to identify patients who may benefit from intensified postinterventional follow-up.
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Angiotensin II Increases HMGB1 Expression in the Myocardium Through AT1 and AT2 Receptors When Under Pressure Overload.
Int Heart J2021 Jan;():. doi: 10.1536/ihj.20-384.
Zhang Lei, Zhang Baoli, Yu Ying, Wang Jingfeng, Wu Jian, Su Yangang, Jiang Hong, Zou Yunzeng, Ge Junbo,
Abstract
High-mobility group box 1 (HMGB1) is increased in the myocardium under pressure overload (PO) and is involved in PO-induced cardiac remodeling. The mechanisms of the upregulation of cardiac HMGB1 expression have not been fully elucidated. In the present study, a mouse transverse aortic constriction (TAC) model was used, and an angiotensin II (Ang II) type 1 (AT1) receptor inhibitor (losartan) or Ang II type 2 (AT2) receptor inhibitor (PD123319) was administrated to mice for 14 days. Cardiac myocytes were cultured and treated with Ang II for 5 minutes to 48 hours conditionally with the blockage of the AT1 or AT2 receptor. TAC-induced cardiac hypertrophy was observed at 14 days after the operation, which was partially reversed by losartan, but not by PD123319. Similarly, the upregulated HMGB1 expression levels observed in both the serum and myocardium induced by TAC were reduced by losartan. Elevated cardiac HMGB1 protein levels, but not mRNA or serum levels, were significantly decreased by PD123319. Furthermore, HMGB1 expression levels in culture media and cardiac myocytes were increased following Ang II treatment in vitro, positively associated with the duration of treatment. Similarly, Ang II-induced upregulation of HMGB1 in vitro was inhibited by both losartan and PD123319. These results suggest that upregulation of HMGB1 in serum and myocardium under PO, which are partially derived from cardiac myocytes, may be induced by Ang II via the AT1 and AT2 receptors. Additionally, amelioration of PO-induced cardiac hypertrophy following losartan treatment may be associated with the reduction of HMGB1 expression through the AT1 receptor.
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Real-time exercise reduces impaired cardiac function in breast cancer patients undergoing chemotherapy: a randomized controlled trial.
Ann Phys Rehabil Med2021 Jan;():101485. doi: S1877-0657(21)00003-8.
Chung Wei-Pang, Yang Hsin-Lun, Hsu Ya-Ting, Hung Ching-Hsia, Liu Ping-Yen, Liu Yen-Wen, Chan Shih-Hung, Tsai Kun-Ling,
Abstract
BACKGROUND:
Previous studies have reported that chemotherapy results in substantial long-term risk of heart failure. Exercise ameliorates exercise responses and exercise tolerance in patients receiving chemotherapy. The cardioprotective effect of real-time exercise in breast cancer is still unclear.
OBJECTIVES:
The aim of the present study was to determine the effect of real-time moderate-to-high-intensity exercise training in women with breast cancer undergoing chemotherapy and to follow up on parameters of cardiac function and exercise capacity at different times. We hypothesized that early moderate-to-high-intensity exercise training has beneficial effects on cardiac function in women with breast cancer undergoing chemotherapy.
METHODS:
This was a randomized controlled study that included 32 women randomly allocated into the control or exercise group. Exercise began with the first cycle of chemotherapy, and the training program was maintained during chemotherapy with 2 to 3 sessions per week for 3 months. Patients were instructed to perform moderate-to-high-intensity training with aerobic and resistance training. Outcome measurements were echocardiography and cardiopulmonary exercise test. The primary outcome was the change in left ventricle ejection fraction (LVEF). The secondary outcome was peak oxygen consumption (peak VO).
RESULTS:
The control group showed lower cardiac systolic function than the exercise group [mean (SD) LVEF 62% (2) and 70% (5), p < 0.05], reduced cardiac diastolic function, and cardiac hypertrophy at 3, 6 and 12 months after chemotherapy. At 6 months after chemotherapy, the exercise group exhibited relatively higher exercise capacity than controls [mean (SD) VO 12.1 (2.2) and 13.6 (2.2) mL/kg/min, p < 0.05]. The main effect size of the study based on echocardiography outcomes was 0.25 (95% confidence interval 0.23 to 0.27), a medium effect size.
CONCLUSIONS:
Moderate-to-high-intensity exercise training in breast cancer patients undergoing chemotherapy may prevent impaired cardiac function.
Copyright © 2021 Elsevier Masson SAS. All rights reserved.
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Challenge in diagnosis of COVID-19 in hemodialysis patient: a case report and brief review of the literature.
CEN Case Rep2021 Jan;():. doi: 10.1007/s13730-020-00571-w.
Andhika Rizky, Makmun Afiatin, Hartantri Yovita, Wijaya Indra, Huang Ian,
Abstract
Diagnosis of COVID-19 in end-stage kidney disease (ESKD) patients on hemodialysis is challenging, as the symptoms are often atypical. Herein, we reported a confimed case of COVID-19 in a patient on maintenance hemodialysis. A 38-year-old man with ESKD on regular hemodialysis initially presented with progressive shortness of breath and dry cough, without fever. He had lymphopenia, and chest X-ray suggested pulmonary edema with cardiomegaly and suspected bilateral bronchopneumonia. The patient clinically improved after 7 days of hospitalization, and was subsequently discharged from hospital. Ten days after being discharged, the patient was re-admitted with progressive shortness of breath and dry cough, without fever. SARS-CoV-2 infection was later confirmed by a qualitative RT-PCR test and the diagnosis COVID-19 pneumonia was established. We presented a case of atypical presentation of COVID-19 in an ESKD patient on maintenance hemodialysis with a brief review of the current literature.
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Practical recommendations for the diagnosis and management of transthyretin cardiac amyloidosis.
Heart Fail Rev2021 Jan;():. doi: 10.1007/s10741-020-10062-w.
Bistola Vasiliki, Parissis John, Foukarakis Emmanouil, Valsamaki Pipitsa N, Anastasakis Aris, Koutsis Georgios, Efthimiadis Georgios, Kastritis Efstathios,
Abstract
Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by accumulation in the heart interstitium of amyloid fibrils formed by misfolded proteins. Most common CA types are light chain amyloidosis (AL) caused by monoclonal immunoglobulin light chains and transthyretin amyloidosis (ATTR) caused by either mutated or wild-type transthyretin aggregates. Previously considered a rare disease, CA is increasingly recognized among patients who may be misdiagnosed as undifferentiated heart failure with preserved ejection fraction (HFPEF), paradoxical low-flow/low-gradient aortic stenosis, or otherwise unexplained left ventricular hypertrophy. Progress in diagnosis has been due to the refinement of cardiac echocardiographic techniques (speckle tracking imaging) and magnetic resonance (T1 mapping) and mostly due to the advent of bone scintigraphy that has enabled noninvasive diagnosis of ATTR, limiting the need for endomyocardial biopsy. Importantly, proper management of CA starts from early recognition of suspected cases among high prevalence populations, followed by advanced diagnostic evaluation to confirm diagnosis and typing, preferentially in experienced amyloidosis centers. Differentiating ATTR from other types of amyloidosis, especially AL, is critical. Emerging targeted ATTR therapies offer the potential to improve outcomes of these patients previously treated only palliatively.
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Identification of a Multiplex Biomarker Panel for Hypertrophic Cardiomyopathy Using Quantitative Proteomics and Machine Learning.
Mol Cell Proteomics2020 Jan;19(1):114-127. doi: S1535-9476(20)30009-8.
Captur Gabriella, Heywood Wendy E, Coats Caroline, Rosmini Stefania, Patel Vimal, Lopes Luis R, Collis Richard, Patel Nina, Syrris Petros, Bassett Paul, O'Brien Ben, Moon James C, Elliott Perry M, Mills Kevin,
Abstract
Hypertrophic cardiomyopathy (HCM) is defined by pathological left ventricular hypertrophy (LVH). It is the commonest inherited cardiac condition and a significant number of high risk cases still go undetected until a sudden cardiac death (SCD) event. Plasma biomarkers do not currently feature in the assessment of HCM disease progression, which is tracked by serial imaging, or in SCD risk stratification, which is based on imaging parameters and patient/family history. There is a need for new HCM plasma biomarkers to refine disease monitoring and improve patient risk stratification. To identify new plasma biomarkers for patients with HCM, we performed exploratory myocardial and plasma proteomics screens and subsequently developed a multiplexed targeted liquid chromatography-tandem/mass spectrometry-based assay to validate the 26 peptide biomarkers that were identified. The association of discovered biomarkers with clinical phenotypes was prospectively tested in plasma from 110 HCM patients with LVH (LVH+ HCM), 97 controls, and 16 HCM sarcomere gene mutation carriers before the development of LVH (subclinical HCM). Six peptides (aldolase fructose-bisphosphate A, complement C3, glutathione S-transferase omega 1, Ras suppressor protein 1, talin 1, and thrombospondin 1) were increased significantly in the plasma of LVH+ HCM compared with controls and correlated with imaging markers of phenotype severity: LV wall thickness, mass, and percentage myocardial scar on cardiovascular magnetic resonance imaging. Using supervised machine learning (ML), this six-biomarker panel differentiated between LVH+ HCM and controls, with an area under the curve of ? 0.87. Five of these peptides were also significantly increased in subclinical HCM compared with controls. In LVH+ HCM, the six-marker panel correlated with the presence of nonsustained ventricular tachycardia and the estimated five-year risk of sudden cardiac death. Using quantitative proteomic approaches, we have discovered six potentially useful circulating plasma biomarkers related to myocardial substrate changes in HCM, which correlate with the estimated sudden cardiac death risk.
Copyright © 2020 © 2020 Captur et al. Published by Elsevier Inc. All rights reserved.
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Diosmetin attenuates metabolic syndrome and left ventricular alterations the suppression of angiotensin II/AT receptor/gp/p-NF-?B protein expression in high-fat diet fed rats.
Food Funct2021 Jan;():. doi: 10.1039/d0fo02744h.
Meephat Sariya, Prasatthong Patoomporn, Rattanakanokchai Siwayu, Bunbupha Sarawoot, Maneesai Putcharawipa, Pakdeechote Poungrat,
Abstract
Diosmetin, a monomethoxyflavone, is isolated from citrus fruits. The objective of this research was to test the biological role of diosmetin on parameters of metabolic syndrome (MS) and left ventricular (LV) alterations in rats fed with a high-fat (HF) diet. MS was induced by feeding male Sprague-Dawley rats with a HF diet plus 15% fructose in drinking water for 16 weeks. MS rats were given diosmetin (20 or 40 mg per kg per day) or metformin (100 mg per kg per day) for the final four weeks. Diosmetin attenuated signs of MS including, hypertension, hyperglycemia, insulin resistance, and dyslipidemia in rats that received the HF diet (p < 0.05). A decreased stroke volume, ejection fraction, fractional shortening, LV hypertrophy and fibrosis present in the MS group were alleviated by diosmetin treatment (p < 0.05). Diosmetin also suppressed angiotensin-converting enzyme activity, plasma angiotensin II (Ang II) levels and angiotensin II type 1 (AT1) receptor protein expression in MS rats. Increases in superoxide (O2?-) formation, plasma malondialdehyde, plasma nitrate and nitrite and gp91phox expression induced by a HF diet were ameliorated in the diosmetin treated group. Inflammation indicated by an increased phospho nuclear factor kappa B (p-NF-?B) protein expression and cardiac TNF-? concentration was reduced in MS rats receiving diosmetin (p < 0.05). Metformin also attenuated MS, cardiac abnormalities relevant to decreasing the renin-angiotensin system stimulation, reactive oxygen species and inflammation in MS rats (p < 0.05). Diosmetin alleviated MS and LV dysfunction and remodeling in HF diet-induced MS rats. These results could be associated with the suppression of the Ang II/AT1 receptor/gp91phox/p-NF-?B protein pathway.
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Cardioprotective potential of amygdalin against angiotensin II induced cardiac hypertrophy, oxidative stress and inflammatory responses through modulation of Nrf2 and NF-?B activation.
Environ Toxicol2021 Jan;():. doi: 10.1002/tox.23094.
Kung Yen-Lun, Lu Cheng-You, Badrealam Khan Fareen, Kuo Wei-Wen, Shibu Marthandam Asokan, Day Cecilia Hsuan, Chen Ray-Jade, Lu Shang-Yeh, Padma Viswanadha Vijaya, Huang Chih-Yang,
Abstract
Heart failure (HF) and cardiac hypertrophy is an unfavorable outcome of pathological cardiac remodeling and represents the most important contributing factor for HF and cardiac hypertrophy. Amygdalin (AMG) is a cyanogenic glycoside derived from bitter almonds. Accumulating evidences have highlighted their pharmacological potentials against various diseases. However, there is no report delineating the potential of AMG against angiotensin (Ang II) induced cardiac injuries. Thus, the present study was performed to explore whether AMG could ameliorate Ang II induced cardiomyopathies and thereby ascertain the underlying mechanisms thereof. To this end, H9c2 cells were treated with Ang II and thereafter treated with various concentration of AMG and finally the cardio-protective effects of AMG were analyzed through Western blotting, immunofluorescence, and insilico analysis. Our results showed that the cardiomyocyte cell size, inflammatory markers and cytokines(pNF-?B, TNF-?, iNOS and COX-2) were markedly increased following Ang II treatment; nevertheless, treatment with AMG led to considerable decrement in the Ang II induced enlargement of the cardiomyocytes, and attenuate the expression of hypertrophic markers(ANP, BNP and MHC-7), inflammatory markers and cytokines. Additionally, oxidative stress related proteins (Nrf2, catalase, SOD-2, and GPX-4) were markedly increased following AMG treatment. Molecular docking reveals the interaction of AMG with Nrf2 possessing good binding affinity. Cumulatively, our study highlights the cardio-protective role of AMG against Ang II induced cardiomyopathies, including oxidative stress and inflammation effects. The intriguing in vitro results warrants the need of further animal studies to truly ascertain their potentialities.
© 2021 Wiley Periodicals LLC.
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What Every Intensivist should Know about Impairment of Cardiac Function and Arrhythmias in Liver Disease Patients: A Review.
Indian J Crit Care Med2020 Dec;24(12):1251-1255. doi: 10.5005/jp-journals-10071-23695.
Arya Sanjeev, Kumar Prashant, Tiwari Bhuwan, Belwal Shantanu, Saxena Sanjay, Abbas Haider,
Abstract
Objectives:
Impairment of cardiac function and arrhythmias often coexist in patients with liver diseases. Many studies have proved this coexistence and put forward various theories toward its pathophysiology. This narrative review tries to find the answers with supporting evidence on five main questions:Do high serum bilirubin levels have a strong association with cardiac arrhythmias?Can corrected QT interval (QTc) be relied upon for predicting a risk factor toward imminent arrhythmias?Is there an association between QTc prolongation and mortality?Are high serum bilirubin and cardiac dysfunction closely associated?What is the probable pathophysiology behind this association?
Materials and methods:
Clinical evidence was obtained by using search engines, namely, Cochrane Library, PubMed, and Google Scholar. Studies published in journals in the English language, between January 1969 and December 2019, which mentioned the relationship between cardiac arrhythmia and liver disease, were included. We used the keywords: jaundice, bilirubin, arrhythmia, ECG, QTc interval, QT dispersion, liver, and cirrhosis. Relevant animal or human studies answering the five main questions were extracted and reviewed.
Conclusion:
The evidence included in our review sheds light on the fact that approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy (CC) and there has been an association between liver abnormalities and cardiac pathology. The present review also supports that there exists a strong association between high levels of serum bilirubin levels and cardiac arrhythmias, QTc value can be relied upon as a risk factor for predicting imminent arrhythmias, and that it is associated with mortality. Its basic pathophysiology can be explained by the potential action of bile acids in prolonging the QT interval. It also causes cardiac hypertrophy and apoptosis of cardiomyocytes leading to cardiac dysfunction.
How to cite this article:
Arya S, Kumar P, Tiwari B, Belwal S, Saxena S, Abbas H. What Every Intensivist should Know about Impairment of Cardiac Function and Arrhythmias in Liver Disease Patients: A Review. Indian J Crit Care Med 2020;24(12):1251-1255.
Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.
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Shear wave cardiovascular MR elastography using intrinsic cardiac motion for transducer-free non-invasive evaluation of myocardial shear wave velocity.
Sci Rep2021 Jan;11(1):1403. doi: 10.1038/s41598-020-79231-z.
Troelstra Marian Amber, Runge Jurgen Henk, Burnhope Emma, Polcaro Alessandro, Guenthner Christian, Schneider Torben, Razavi Reza, Ismail Tevfik F, Martorell Jordi, Sinkus Ralph,
Abstract
Changes in myocardial stiffness may represent a valuable biomarker for early tissue injury or adverse remodeling. In this study, we developed and validated a novel transducer-free magnetic resonance elastography (MRE) approach for quantifying myocardial biomechanics using aortic valve closure-induced shear waves. Using motion-sensitized two-dimensional pencil beams, septal shear waves were imaged at high temporal resolution. Shear wave speed was measured using time-of-flight of waves travelling between two pencil beams and corrected for geometrical biases. After validation in phantoms, results from twelve healthy volunteers and five cardiac patients (two left ventricular hypertrophy, two myocardial infarcts, and one without confirmed pathology) were obtained. Torsional shear wave speed in the phantom was 3.0?±?0.1 m/s, corresponding with reference speeds of 2.8?±?0.1 m/s. Geometrically-biased flexural shear wave speed was 1.9?±?0.1 m/s, corresponding with simulation values of 2.0 m/s. Corrected septal shear wave speeds were significantly higher in patients than healthy volunteers [14.1 (11.0-15.8) m/s versus 3.6 (2.7-4.3) m/s, p?=?0.001]. The interobserver 95%-limits-of-agreement in healthy volunteers were?±?1.3 m/s and interstudy 95%-limits-of-agreement - 0.7 to 1.2 m/s. In conclusion, myocardial shear wave speed can be measured using aortic valve closure-induced shear waves, with cardiac patients showing significantly higher shear wave speeds than healthy volunteers. This non-invasive measure may provide valuable insights into the pathophysiology of heart failure.
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Two-dimensional echocardiographic measures of left ventricular dimensions agree with M-mode measurements in dogs.
J Vet Cardiol2020 Dec;33():69-75. doi: S1760-2734(20)30112-0.
Rishniw M, Corda A, Spina F, Caivano D,
Abstract
INTRODUCTION:
Clinicians measure left ventricular dimensions in dogs from both M-mode and two-dimensional images. Little information currently exists as to whether these two methods provide measurements similar enough to be interchangeable.
ANIMALS:
The animals included in this study are 206 client-owned dogs: 68 healthy, 105 with myxomatous mitral valve disease, 33 with other cardiac or extracardiac disease.
MATERIALS AND METHODS:
Investigators measured left ventricular diastolic and systolic dimensions from archived M-mode and two-dimensional images obtained from the right parasternal short-axis view. Agreement between the pairs of measurements was examined using limits of agreement (Bland-Altman) plots.
RESULTS:
Left ventricular diastolic dimensions showed no fixed or proportional bias but did show heteroscedasticity. Ninety-five percent limits of agreement for normalized differences approximated ±10%; 95% of the absolute differences for any pair of measurements were <3.9 mm regardless of bodyweight and <2.7 mm for dogs <15 kg. Left ventricular systolic dimensions showed slight proportional bias, with two-dimensional measurements being progressively larger than M-mode measurements as ventricular size increased. Ninety-five percent limits of agreement for normalized differences approximated ±20%; 95% of the absolute differences for any pair of measurements were <4.6 mm regardless of bodyweight and <3.5 mm for dogs <15 kg. Mitral valve disease did not appreciably affect these findings.
CONCLUSIONS:
Left ventricular internal dimensions in dogs with and without cardiac disease measured from two-dimensional right parasternal short-axis images are interchangeable with those measured from M-mode images using the same view.
Copyright © 2020. Published by Elsevier B.V.
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