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Pubblicazioni recenti - cardiac disease
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Effect of single nucleotide polymorphisms in SEPS1 and SEPP1 on expression in the protein level in metabolic syndrome in subjects with cardiovascular disease.
Mol Biol Rep2019 Sep;():. doi: 10.1007/s11033-019-05000-5.
Gharipour Mojgan, Ouguerram Khadija, Nazih El-Hassane, Salehi Mansoor, Behmanesh Mehrdad, Razavi Rouzbeh, Gharipour Amin, Diantkhah Minoo, Sadeghi Masoumeh,
Abstract
Metabolic syndrome (MetS) results from the interaction between environmental and genetic factors. Several previous studies considered the role of selenium in developing MetS. Two selenoproteins, selenoprotein S (SelS), and the Selenoprotein P (SePP) play an important role in antioxidative defense and therefore susceptibility to MetS. The involvement of SNPs in SEPP1 and SEPS1 have not been studied in MetS subjects. This study aims to investigate the association between the risk of MetS and four polymorphisms SEPS1 (rs28665122, rs4965373), SEPP1 (rs7579, rs3877899) in an Iranian population. The sample of this case-control study consisted of 132 Iranian patients with cardiovascular disease (71 MetS and 65 non-MetS subjects) from December 2015 to March 2016. Demographic data, medical history, and para-clinical were measured, and Taqman probes were used for allelic discrimination. The level of the SelS and the SePP were measured by the ELIZA method. No significant differences were found in the genotype frequencies of SEPS1 (rs4965373, rs28665122), SEPP1 (rs7579, rs3877899) in patients with MetS and the non-MetS group. The mean of SelS in MetS subjects with SEPS1 (rs4965373) GG genotype is significantly lower than the non-MetS group (4496.99?±?3688.5 vs. 6148.6?±?1127.0, P?=?0.009). The mean of SePP in MetS subjects with SEPP1 (rs3877899) GG genotype is significantly lower than the non-MetS group (40.73?±?8.44 vs.83.91?±?21.33, P?=?0.002). The mean of SePP in MetS subjects with SEPP1 (rs7579) GG genotype is lower than the non-MetS group (55.52?±?16.7 vs. 109.48?±?29.78, P?=?0.01). In summary, the results of this study does not indicate significant differences in the SEPP1 (rs7579, rs3877899) and SEPS1 (rs4965373, rs28665122) genotypes between MetS and non-MetS subjects. However, the results show that the mean of expression of SelS and SePP decreased in the subjects with SEPP1 (rs7579) GG and SEPP1 (rs3877899) GG.
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Elevated Cardiac Troponin in Clinical Scenarios Beyond Obstructive Coronary Artery Disease.
Med Sci Monit2019 Sep;25():7115-7125. doi: 10.12659/MSM.915830.
Sternberg Michael, Pasini Evasio, Chen-Scarabelli Carol, Corsetti Giovannii, Patel Hemang, Linardi Daniele, Onorati Francesco, Faggian Giuseppe, Scarabelli Tiziano, Saravolatz Louis,
Abstract
In this systematic review article, we aim to summarize the most up-to-date evidence regarding elevations of cardiac troponin, especially in clinical scenarios other than obstructive coronary artery disease. The accurate interpretation of raised cardiac troponin is challenging because it relies on unconfirmed postulations and dogmatic knowledge (e.g., the exclusive provenience of cardiac troponin from cardiac myocytes), based on which every troponin elevation is assumed to definitely indicate myocardial damage. Indeed, the investigation of the pathophysiologic mechanism leading to the release in the bloodstream of cardiac biomarkers should be the first step of the diagnostic process to fully understand the clinical significance of the elevated serum levels and identify the best management. A prominent effort should be put in place to identify the contribution of potential confounding factors, both cardiac and non-cardiac in etiology, with the ability to affect synthesis and clearance of cardiac biomarkers. Regardless of the underlying cause, it is well established that cardiovascular biomarkers are increasingly useful to further risk stratification and prognosticate patients. Accordingly, we sought to clarify the meaning and impact of elevated cardiac troponin in those frequently encountered real-world scenarios presenting clinicians with a diagnostic dilemma, with the final goal of facilitating the diagnosis and help optimize individually tailored treatment strategies.
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The Interstitium in the Hypertrophied Heart.
JACC Cardiovasc Imaging2019 Sep;():. doi: S1936-878X(19)30714-4.
Halliday Brian P, Prasad Sanjay K,
Abstract
Pathological left ventricular hypertrophy is a common feature of many cardiac diseases. It results from both myocyte hypertrophy and interstitial expansion. Interstitial expansion is most commonly secondary to the accumulation of mature cross-linked collagen fibers due to dysregulated metabolism, known as interstitial fibrosis. This occurs secondary to a variety of stimuli including ischemic, toxic, metabolic, infective, genetic, and hemodynamic factors. Less commonly, interstitial expansion may occur because of the accumulation of misfolded amyloid protein or interstitial edema. It is now well recognized that the presence and extent of interstitial disease are associated with adverse outcomes. There is therefore interest in the development of novel therapies that target the pathways that drive these disease processes. With the emergence of such therapies, it is becoming increasingly important to be able to characterize the type and extent of interstitial disease to enable the use of such targeted therapies in a personalized manner.
Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Cardiac Magnetic Resonance for Evaluating Nonculprit Lesions After Myocardial Infarction: Comparison With Fractional Flow Reserve.
JACC Cardiovasc Imaging2019 Sep;():. doi: S1936-878X(19)30731-4.
Everaars Henk, van der Hoeven Nina W, Janssens Gladys N, van Leeuwen Maarten A, van Loon Ramon B, Schumacher Stefan P, Demirkiran Ahmet, Hofman Mark B M, van der Geest Rob J, van de Ven Peter M, Götte Marco J, van Rossum Albert C, van Royen Niels, Nijveldt Robin,
Abstract
OBJECTIVES:
This study sought to determine the agreement between cardiac magnetic resonance (CMR) imaging and invasive measurements of fractional flow reserve (FFR) in the evaluation of nonculprit lesions after ST-segment elevation myocardial infarction (STEMI). In addition, we investigated whether fully quantitative analysis of myocardial perfusion is superior to semiquantitative and visual analysis.
BACKGROUND:
The agreement between CMR and FFR in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease is unknown.
METHODS:
Seventy-seven patients with STEMI with at least 1 intermediate (diameter stenosis 50% to 90%) nonculprit lesion underwent CMR and invasive coronary angiography in conjunction with FFR measurements at 1 month after primary intervention. The imaging protocol included stress and rest perfusion, cine imaging, and late gadolinium enhancement. Fully quantitative, semiquantitative, and visual analysis of myocardial perfusion were compared against a reference of FFR. Hemodynamically obstructive was defined as FFR ?0.80.
RESULTS:
Hemodynamically obstructive nonculprit lesions were present in 31 (40%) patients. Visual analysis displayed an area under the curve (AUC) of 0.74 (95% confidence interval [CI]: 0.62 to 0.83), with a sensitivity of 73% and a specificity of 70%. For semiquantitative analysis, the relative upslope of the stress signal intensity time curve and the relative upslope derived myocardial flow reserve had respective AUCs of 0.66 (95% CI: 0.54 to 0.77) and 0.71 (95% CI: 0.59 to 0.81). Fully quantitative analysis did not augment diagnostic performance (all p > 0.05). Stress myocardial blood flow displayed an AUC of 0.76 (95% CI: 0.64 to 0.85), with a sensitivity of 69% and a specificity of 77%. Similarly, MFR displayed an AUC of 0.82 (95% CI: 0.71 to 0.90), with a sensitivity of 82% and a specificity of 71%.
CONCLUSIONS:
CMR and FFR have moderate-good agreement in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease. Fully quantitative, semiquantitative, and visual analysis yield similar diagnostic performance.
Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Stress Myocardial Blood Flow Ratio by Dynamic CT Perfusion Identifies Hemodynamically Significant CAD.
JACC Cardiovasc Imaging2019 Sep;():. doi: S1936-878X(19)30601-1.
Yang Junjie, Dou Guanhua, He Bai, Jin Qinhua, Chen Zhiye, Jing Jing, Di Carli Marcelo F, Chen Yundai, Blankstein Ron,
Abstract
OBJECTIVES:
The aim of this study was to evaluate the diagnostic accuracy of stress myocardial blood flow ratio (SFR), a novel parameter derived from stress dynamic computed tomographic perfusion (CTP), for the detection of hemodynamically significant coronary stenosis.
BACKGROUND:
A comprehensive cardiac computed tomographic protocol combining coronary computed tomographic angiography (CTA) and CTP can provide a simultaneous assessment of both coronary artery anatomy and ischemia.
METHODS:
Patients with chest pain scheduled for invasive angiography were prospectively enrolled in this study. Stress dynamic CTP was performed followed by coronary CTA using a second-generation dual-source computed tomographic system. At subsequent invasive angiography, fractional flow reserve was performed to identify hemodynamically significant stenosis. For each coronary territory, SFR was defined as the ratio of hyperemic myocardial blood flow (MBF) in an artery with stenosis to hyperemic MBF in a nondiseased artery. The diagnostic accuracy of SFR to identify hemodynamically significant stenosis was determined against the reference standard of invasive fractional flow reserve ?0.80.
RESULTS:
A total of 82 patients (mean age 58.5 ± 10 years) with 101 vessels with either 1- or 2-vessel disease were included. By FFR, 48 (47.5%) vessels were deemed hemodynamically significant. Hyperemic MBF and SFR were lower for vessels with hemodynamically significant lesions (95.1 ± 32.4 min/100 ml/min vs. 142.5 ± 31.2 min/100 ml/min and 0.66 ± 0.14 vs. 0.90 ± 0.07, respectively; p < 0.01 for both). When compared with ?50% stenosis by CTA, the specificity for detecting ischemia by SFR increased from 43% to 91%, while the sensitivity decreased from 95% to 62%. Accordingly, the positive and negative predictive values were 85% and 73%, respectively. The combination of stenosis ?50% by CTA and SFR resulted in an area under the curve of 0.91, which was significantly higher compared with hyperemic MBF (area under the curve = 0.79; p = 0.013).
CONCLUSIONS:
Calculation of SFR by dynamic CTP provides a novel and accurate method to identify flow-limiting coronary stenosis.
Copyright © 2019. Published by Elsevier Inc.
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Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension.
J Heart Lung Transplant2019 Sep;():. doi: S1053-2498(19)31667-5.
Hiraide Takahiro, Kataoka Masaharu, Suzuki Hisato, Aimi Yuki, Chiba Tomohiro, Isobe Sarasa, Katsumata Yoshinori, Goto Shinichi, Kanekura Kohsuke, Yamada Yoshitake, Moriyama Hidenori, Kitakata Hiroki, Endo Jin, Yuasa Shinsuke, Arai Yasumichi, Hirose Nobuyoshi, Satoh Toru, Hakamata Yoji, Sano Motoaki, Gamou Shinobu, Kosaki Kenjiro, Fukuda Keiichi,
Abstract
BACKGROUND:
A variant of c.14429G>A (p.Arg4810Lys, rs112735431) in the ring finger protein 213 gene (RNF213; NM_001256071.2) has been recently identified as a risk allele for pulmonary arterial hypertension (PAH). PAH can be added as a new member of RNF213-associated vascular diseases, which include Moyamoya disease and peripheral pulmonary stenosis. Our aim was to identify the clinical features and outcomes of PAH patients with this variant.
METHODS:
Whole-exome sequencing was performed in 139 idiopathic (or possibly heritable) PAH patients.
RESULTS:
The RNF213 p.Arg4810Lys variant was identified in a heterozygous state in 11 patients (7.9%). Time-course changes in hemodynamics after combination therapy in the patients with the RNF213 p.Arg4810Lys variant were significantly poorer compared with those carrying the bone morphogenic protein receptor type 2 (BMPR2) mutation (n?=?36) (comparison of changes in mean pulmonary arterial pressure, p?=?0.007). The event-free rate of death or lung transplantation was significantly poorer in RNF213 p.Arg4810Lys variant carriers than in BMPR2 mutation carriers (5-year event-free rate since the introduction of prostaglandin I infusion, 0% vs 93%, respectively; p < 0.001).
CONCLUSIONS:
Idiopathic PAH patients with the RNF213 p.Arg4810Lys variant are associated with poor clinical outcomes even in recent times. Earlier consideration of lung transplantation might be required for RNF213 p.Arg4810Lys variant carriers who are developing PAH. Documentation of the RNF213 p.Arg4810Lys variant, as well as already known pathogenic genes, such as BMPR2, can provide clinically relevant information for therapeutic strategies, leading to a personalized approach for the treatment of PAH.
Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
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Arrhythmias in Patients on Maintenance Dialysis: A Cross-sectional Study.
Am J Kidney Dis2019 Sep;():. doi: S0272-6386(19)30888-1.
Rantanen Jesper Moesgaard, Riahi Sam, Schmidt Erik Berg, Johansen Martin Berg, Søgaard Peter, Christensen Jeppe Hagstrup,
Abstract
RATIONALE & OBJECTIVE:
Patients with kidney failure treated with maintenance dialysis experience a high rate of mortality, in part due to sudden cardiac death caused by arrhythmias. The prevalence of arrhythmias, including the subset that are clinically significant, is not well known. This study sought to estimate the prevalence of arrhythmias, characterize the pattern of arrhythmic events in relation to dialysis treatments, and identify associated clinical characteristics.
STUDY DESIGN:
Cross-sectional study.
SETTING & PARTICIPANTS:
152 patients with kidney failure treated with maintenance dialysis in Denmark.
EXPOSURES:
Dialysis treatment; clinical characteristics; cardiac output and preload defined using echocardiography.
OUTCOMES:
Prevalence and pattern of arrhythmias on 48-hour Holter monitoring; odds ratios for arrhythmias.
ANALYTICAL APPROACH:
Descriptive analysis of the prevalence of arrhythmias. Pattern of arrhythmias described using a repeated-measures negative binomial regression model. Associations between clinical characteristics and echocardiographic findings with arrhythmias were assessed using logistic regression.
RESULTS:
Among the 152 patients studied, 83.6% were treated with in-center dialysis; 10.5%, with home hemodialysis; and 5.9%, with peritoneal dialysis. Premature atrial and ventricular complexes were seen in nearly all patients and 41% had paroxysmal supraventricular tachycardia. Clinically significant arrhythmias included persistent atrial fibrillation observed among 8.6% of patients, paroxysmal atrial fibrillation among 3.9%, nonsustained ventricular tachycardia among 19.7%, bradycardia among 4.6%, advanced second-degree atrioventricular block among 1.3%, and third-degree atrioventricular block among 2.6%. Premature ventricular complexes were more common on dialysis days, while tachyarrhythmias were more often observed during dialysis and in the immediate postdialytic period. Older age (OR per 10 years older, 1.53; 95% CI, 1.15-2.03; P=0.003), elevated preload (OR, 4.02; 95% CI, 1.05-15.35; P=0.04), and lower cardiac output (OR per 1L/min greater, 0.66; 95% CI, 0.44-1.00; P=0.05) were independently associated with clinically significant arrhythmias.
LIMITATIONS:
Arrhythmia monitoring limited to 48 hours; small sample size; heterogeneous nature of the population, risk for residual confounding.
CONCLUSIONS:
Arrhythmias, including clinically significant abnormal rhythms, were common. Tachyarrhythmias were more frequent during dialysis and the immediate postdialytic period. The relevance of these findings to clinical outcomes requires additional study.
Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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[Hot issues in bifurcation lesions PCI in 2019].
Ann Cardiol Angeiol (Paris)2019 Sep;():. doi: S0003-3928(19)30064-2.
Landolff Q, Veugeois A, Godin M, Boussaada M M, Dibie A, Caussin C, Amabile N,
Abstract
Coronary bifurcations are involved in 15-20% of all percutaneous coronary interventions (PCI) and remain one of the most challenging lesions in interventional cardiology in terms of procedural success rate as well as long-term cardiac events. The optimal management of bifurcation lesions is still debated but involves careful assessment, planning and a sequential provisional approach. The preferential strategy for PCI of bifurcation lesions remains to use main vessel (MV) stenting with a proximal optimisation technique (POT) and provisional side branch (SB) stenting as a preferred approach. Final kissing balloon inflation is not recommended in all cases. In the minority of lesions where two stents are required, careful deployment and optimal expansion are essential to achieve a long-term result. Intracoronary imaging techniques (IVUS, OCT) and FFR are useful endovascular tools to achieve optimal results.
Copyright © 2019 Elsevier Masson SAS. All rights reserved.
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Assessment of 6 STR loci for prenatal diagnosis of Duchenne Muscular Dystrophy.
Taiwan J Obstet Gynecol2019 Sep;58(5):645-649. doi: S1028-4559(19)30166-4.
Dinh Linh Thuy, Tran Van Khanh, Luong Long Hoang, Le Phuong Thi, Nguyen Anh Duy, Thi Nguyen Bang Suong, Chi Dung Vu, Tran Thinh Huy, Bui The-Hung, Van Ta Thanh, Nguyen Duc Hinh,
Abstract
OBJECTIVE:
Duchenne Muscular Dystrophy is an X-linked recessive disorder characterized by progressive muscular degeneration, patients often develop cardiac failure in the later stage and death occurs before 20 years of age. For a disease with poor postnatal prognosis such as Duchenne Muscular Dystrophy (DMD), providing the carrier mother with the option of prenatal diagnosis in a subsequent pregnancy is accepted practice in many places where termination of pregnancy is allowed. Though methods of direct sequencing such as Sanger's sequencing has been widely used, Next-Generation Sequencing is been increasingly replacing most of its application. For the DMD gene, being the longest gene in the human genome, methods of direct sequencing is often unpractical and time-consuming, instead, STR analysis for linkage analysis would be a cost-effective option and have been used routinely for prenatal diagnosis of DMD. The diagnostic significance of the STRs is based on several criteria, the most important one being the heterozygosity of the locus, power of discrimination (PD) and power of exclusion (PE).
MATERIAL AND METHODS:
In this study, we investigated the feasibility of application and diagnostic value of 6 STR loci (DSTR49, DSTR50, DXS1036, DXS1067, DXS890, DXS9907) in the proximity of the DMD gene, 66 healthy individuals were recruited for STR analysis and 5 cases of prenatal diagnosis for carrier mother were performed.
RESULT:
Allele frequency, heterozygosity, polymorphic information content, the power of discrimination and exclusion and Hardy-Weinberg equilibrium were analyzed and calculated for the 6 STR loci. 5 of these loci (DSTR49, DSTR50, DXS1067, DXS890, DXS9907) were found practical and useful for preimplantation Genetic diagnosis (PGD) and prenatal diagnosis. All 5 cases of prenatal diagnosis using the method had informative STR results and correct diagnosis.
CONCLUSION:
We concluded that our protocol of STR analysis can be applied for prenatal diagnosis and pre-implantation genetic diagnosis of DMD with high confidence and accuracy, especially in clinical settings where diagnostic resources are more limited.
Copyright © 2019. Published by Elsevier B.V.
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Clethodim exposure induced development toxicity and behaviour alteration in early stages of zebrafish life.
Environ Pollut2019 Sep;255(Pt 1):113218. doi: S0269-7491(19)31820-2.
Wang Honglei, Zhou Liqun, Meng Zhen, Su Meile, Zhang Shouhua, Huang Pinzhen, Jiang Fen, Liao Xinjun, Cao Zigang, Lu Huiqiang,
Abstract
Clethodim is one of the most widely used herbicides in agriculture, however, its potential toxic effects on organisms and the underlying toxicity mechanism are still poorly understood. In this study, zebrafish embryos at 6?h post-fertilization (hpf) were exposed to 10?mg/L, 20?mg/L, and 30?mg/L clethodim for up to 24 hpf, and zebrafish larvae at 6 days post-fertilization (dpf) were exposed to the same density gradient for 24?h. Our results showed that clethodim could cause head and cardiovascular malformations in embryos: blurred brain ventricles, unapparent brain regions, condensation of nucleus and cytoplasm in brain cells, increased intercellular space, developmental malformations of eyes and ears, reduced neonatal neurons, disorder migration of neural ridge cells; morphological aberrations of the vascular ICM, slowing of heart beat and blood flow, reduction of circulating red blood cells, and delayed development of head and tail blood vessels. These defects could be a result of clethodim-induced oxidative stress and decreased acetylcholinesterase (AChE) activity, which in turn affected the expression of neurodevelopmental genes, decreased ATPase activity, and ultimately led to developmental malformations. The swimming behaviour of zebrafish larvae was observed to decrease with increasing concentration of clethodim exposure, but the angular velocity and mobility increased. These could be due to reduced AChE activity and disturbed gene expression of GABA, dopamine and glutamatergic neurotransmitter systems, which thus altered the locomotor behaviour. In summary, we found that clethodim induces developmental toxicity and neurotoxicity in zebrafish embryos and larvae.
Copyright © 2019 Elsevier Ltd. All rights reserved.
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MicroRNA-494 Inhibits the LRG1 Expression to Induce Proliferation and Migration of VECs in Rats following Myocardial Infarction.
Mol Ther Nucleic Acids2019 Aug;18():110-122. doi: S2162-2531(19)30219-7.
Su Qiang, Lv Xiang-Wei, Sun Yu-Han, Ye Zi-Liang, Kong Bing-Hui, Qin Zhen-Bai,
Abstract
Myocardial infarction (MI) is a life-threatening cardiac event that results in extreme damage to the heart muscle. The Wnt signaling pathway has been implicated in the development of heart diseases. Hence, the current study aimed to investigate the role of microRNA (miRNA) in association with the Wnt signaling pathway to identify potential candidates for MI therapy. Differentially expressed miRNAs associated with MI occurrence were screened, and miR-494 was selected for subsequent experiments. Sprague-Dawley rats were included to establish a MI model via intraperitoneal injection of 0.1 mg/kg atropine sulfate and 40 mg/kg pentobarbital sodium. Then, the interaction between miR-494 and LRG1 was identified. The effect of miR-494 on expression of the Wnt signaling pathway-related genes, proliferation, migration, and invasion ability of fibroblasts and vascular endothelial cells (VECs) was subsequently evaluated through a series of gain- and loss-of-function experiments. The results revealed that miR-494 was poorly expressed and LRG1 was highly expressed in MI rats. miR-494 targets and downregulates LRG1, which resulted in the inactivation of the Wnt signaling pathway and promoted proliferation, migration, and invasion ability of fibroblasts and VECs. In conclusion, this study provided evidence suggesting that overexpressed miR-494 could potentially promote the proliferation, migration, and invasion of fibroblasts and VECs in MI through the inactivation of the Wnt signaling pathway by binding to LRG1.
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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Key Regulators of Cardiovascular Differentiation and Regeneration: Harnessing the Potential of Direct Reprogramming to Treat Heart Failure.
J Card Fail2019 Sep;():. doi: S1071-9164(19)30366-5.
Ieda Masaki,
Abstract
Cardiovascular diseases remain a leading cause of death worldwide, with the number of patients with heart failure increasing rapidly in aging societies. As adult cardiomyocytes are terminally differentiated cells and opportunities for heart transplantation are very limited, regenerative medicine may become a game changer in heart failure treatment. To develop strategies for generating cardiomyocytes, vascular cells, and other supporting cells, it is necessary to understand the mechanism of cardiovascular differentiation during development and from pluripotent stem cells. Master regulators for cardiovascular differentiation can generate new cardiomyocytes and vascular cells directly from other differentiated cells such as fibroblasts. Fibroblasts can be directly reprogrammed into cardiomyocytes by overexpressing a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5) both in vitro and in vivo, which restores cardiac function after myocardial infarction in mice. Moreover, a direct reprogramming-based approach can be used to identify new key regulators of the cardiovascular mesoderm, which can differentiate into all three types of cardiovascular cells including cardiomyocytes, endothelial cells, and smooth muscle cells. This review provides a perspective on how key regulators for cardiovascular differentiation and regeneration can be identified and used to develop new treatments for heart failure.
Copyright © 2019. Published by Elsevier Inc.
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Do Drugs That Ameliorate Epicardial Adipose Tissue Inflammation Have Concordant Benefits on Atrial Fibrillation and on Heart Failure with a Preserved Ejection Fraction?
J Card Fail2019 Sep;():. doi: S1071-9164(19)30529-9.
Packer Milton,
Abstract
Heart failure with a preserved ejection fraction (HFpEF) and heart failure with a reduced ejection fraction (HFrEF) have distinctive pathophysiologies, and thus, therapeutic approaches to the two disorders should differ. Neurohormonal activation drives the progression of HFrEF, and neurohormonal antagonists are highly effective in HFrEF, but not in HFpEF. Conversely, a broad range of chronic systemic inflammatory or metabolic disorders cause an expansion and inflammation of epicardial adipose tissue; the secretion of adipocytokines may lead to microvascular dysfunction and fibrosis of the underlying myocardium, which (if the left atrium is affected) may lead to atrial fibrillation (AF) and (if the left ventricle is affected) may lead to HFpEF. Anti-inflammatory drugs (such as statins and anticytokine agents) can ameliorate epicardial adipose tissue dysfunction. Statins appear to ameliorate the development of atrial myopathy (both experimentally and clinically), and in randomized controlled trials, they reduce the incidence of new-onset and recurrent AF and decrease the risk of heart failure with the features of HFpEF; yet, they have no benefits in HFrEF. Similarly, anticytokine agents appear to prevent heart failure in patients with or prone to HFpEF, but adversely affect HFrEF. Several antihyperglycemic agents also reduce epicardial fat mass and inflammation, but this benefit may be offset by additional actions to cause sodium retention and neurohormonal activation. Thiazolidinediones have favorable effects on experimental AF and HFpEF, but their antinatriuretic actions negate these benefits, and they worsen the clinical course of HFrEF. Glucagon-like peptide-1 receptor agonists also ameliorate AF and HFpEF in laboratory models, but their positive inotropic and chronotropic effects may be deleterious in HFrEF. By contrast, metformin and sodium-glucose cotransporter 2 inhibitors alleviate epicardial adipose tissue dysfunction and may reduce the risk of AF and HFpEF; yet, they may have additional actions to promote cardiomyocyte survival that are useful in HFrEF. The concordance of the benefits of anti-inflammatory and antihyperglycemic drugs on AF and HFpEF (but not on HFrEF) supports the paradigm that epicardial adipose tissue is an central pathogenetic mechanism and therapeutic target for both AF and HFpEF in patients with chronic systemic inflammatory or metabolic diseases.
Copyright © 2019. Published by Elsevier Inc.
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Metabolic Profiling Associates with Disease Severity in Non-Ischemic Dilated Cardiomyopathy.
J Card Fail2019 Sep;():. doi: S1071-9164(19)30210-6.
Verdonschot Job A J, Wang Ping, van Bilsen Marc, Hazebroek Mark R, Merken Jort J, Vanhoutte Els K, Henkens Michiel T H M, van den Wijngaard Arthur, Glatz Jan F C, Krapels Ingrid P C, Brunner Han G, Heymans Stephane R B, Bierau Jörgen,
Abstract
AIMS:
Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in non-ischemic dilated cardiomyopathy (DCM) patients and compared its incremental value on top of NT-proBNP.
METHODS AND RESULTS:
A total of 149 metabolites were measured in plasma and urine samples of 273 DCM patients with different stages of disease (DCM patients with LVRR (normal LVEF), n=70; asymptomatic DCM, n=72 and symptomatic DCM, n=131). Acylcarnitines, sialic acid, and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by uni-biomarker linear regression, sPLSDA, Random Forest and conditional Random Forest analyses. However, the absolute difference of the metabolic profile among groups was marginal. A decision tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish DCM patients with LVRR from symptomatic DCM (AUC 0.813±0.138 versus 0.739±0.114; p=0.02).
CONCLUSION:
Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in non-ischemic DCM.
Copyright © 2019. Published by Elsevier Inc.
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Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: results from The Health Improvement Network (THIN) database.
J Steroid Biochem Mol Biol2019 Sep;():105480. doi: S0960-0760(19)30363-2.
Crowe Francesca L, Thayakaran Rasiah, Gittoes Neil, Hewison Martin, Thomas G Neil, Scragg Robert, Nirantharakumar Krishnarajah,
Abstract
BACKGROUND:
There is increasing evidence that vitamin D supplementation may only be beneficial in people with vitamin D deficiency, and the lack of sufficient people with very low vitamin D levels could explain the lack of protection against cardiovascular disease (CVD) reported in recent clinical trials of vitamin D supplementation. The aim of this study was to assess associations of low to moderate circulating concentrations of 25-hydroxyvitamin D (25(OH)D with risk of incident CVD and all-cause mortality, as well as the risk of ischaemic heart disease (IHD), cerebrovascular disease, and heart failure separately.
METHODS AND RESULTS:
Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a UK primary care database. The analysis included 180,263 patients age 18 years and older without a history of CVD and with circulating concentrations of 25(OH)D. After a mean follow-up of 2.2 (SD 1.7) years, there were 3,747 patients diagnosed with CVD and 3,912 patients died. Compared to patients in the highest quintile of 25(OHD) (? 67.5?nmol/L), those in the lowest 25(OH)D quintile (<23.1?nmol/L) had a hazard ratio (HR) of 1.24 (95% CI 1.12-1.38, P?
CONCLUSION:
Low 25(OH)D are associated with highest risk of CVD and mortality, and are consistent with accumulating evidence that increased risk of these diseases occurs primarily in people with vitamin D deficiency.
Copyright © 2019. Published by Elsevier Ltd.
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Role of 3D transesophageal echocardiography in transcatheter closure of atrial septal aneurysms.
Echocardiography2019 Sep;():. doi: 10.1111/echo.14482.
Taha Fatma, Elshedoudy Sahar,
Abstract
BACKGROUND:
Three dimensional transesophageal echocardiography (3DTEE) is superior to two dimensional transesophageal echocardiography (2DTEE) as it provides all atrial septal information from a single view.
AIM:
To evaluate 3DTEE role in analysis of atrial septal aneurysm (ASA) and in device closure guiding.
METHODS:
Three dimensional transesophageal echocardiography were recorded with Vivid*E9,GE system over 14 months. ASAs were classified into 4 types (A: with PFO, B: with one ASD, C: with 2 ASDs, and D: with multiple fenestrations). Each aneurysm was assessed according to its type, shape, dimensions, orientation, aneurysmal tissue, and the surrounding rims. All patients passed to transcatheter aneurysm closure.
RESULTS:
A total of 26 patients with ASAs were assessed (7 imperforated aneurysms excluded). The remaining 19 patients' age was 12.84 ± 5.82years. Four patients had type A aneurysms, 6 had type B, 4 had type C, and 5 had type D. 3DTEE demonstrated oval aneurysms in 17 patients. The orientation was oblique in 8 patients, vertical in 7, and horizontal in 4. The ASAs dimensions were 23.5 ± 5.1, 23.2 ± 5.1, and 22.0 ± 4.0 mm for oblique, vertical, and horizontal axes. Percutaneous closure succeeded in 18 patients. Balloon sizing was used in 4 patients. Devices used were: In type A:PFO devices, in type B:ASO devices, in type C:two patients required two ASO devices in each patient and two patients required one cribriform device, and in type D:Cribriform devices used for three patients, PFO for one and ASO for one. LA, LUPV, and RUPV approaches were used. Aspirin was received for 6 months.
CONCLUSION:
Three dimensional transesophageal echocardiography helps to select aneurysms suitable for transcatheter closure, select the suitable devices, and guide the transcatheter procedure.
© 2019 Wiley Periodicals, Inc.
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A "Cat"-astrophic Case of Bartonella henselae Infective Endocarditis Followed by Cardiac Transplantation Salvage Therapy.
Transpl Infect Dis2019 Sep;():. doi: 10.1111/tid.13179.
Kuan William, Dulnuan Kenneth, Guglin Maya E, El Haddad Hanine, Kolodziej Andrew R, Leventhal Andrew, Rajagopalan Navin,
Abstract
To our knowledge, no cases of Bartonella henselae endocarditis leading to subsequent heart transplantation salvage therapy have been published. We present a case of a 29-year old male with cat-inflicted Bartonella henselae endocarditis and concurrent worsening heart failure, who then underwent successful heart transplantation 50 days following diagnosis. Treatment and monitoring strategies used in this patient are discussed. Furthermore, we review literature related to heart transplantation salvage therapy for endocarditis due to other intracellular pathogens.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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YAP/TEAD3 signal mediates cardiac lineage commitment of human-induced pluripotent stem cells.
J Cell Physiol2019 Sep;():. doi: 10.1002/jcp.29179.
Han Zhenbo, Yu Ying, Cai Benzhi, Xu Zihang, Bao Zhengyi, Zhang Ying, Bamba Djibril, Ma Wenya, Gao Xinlu, Yuan Ye, Zhang Lai, Yu Meixi, Liu Shenzhen, Yan Gege, Jin Mengyu, Huang Qi, Wang Xiuxiu, Hua Bingjie, Yang Fan, Pan Zhenwei, Liang Haihai, Liu Yu,
Abstract
Cardiomyocytes differentiated from human-induced pluripotent stem cells (hiPSCs) hold great potential for therapy of heart diseases. However, the underlying mechanisms of its cardiac differentiation have not been fully elucidated. Hippo-YAP signal pathway plays important roles in cell differentiation, tissue homeostasis, and organ size. Here, we identify the role of Hippo-YAP signal pathway in determining cardiac differentiation fate of hiPSCs. We found that cardiac differentiation of hiPSCs were significantly inhibited after treatment with verteporfin (a selective and potent YAP inhibitor). During hiPSCs differentiation from mesoderm cells (MESs) into cardiomyocytes, verteporfin treatment caused the cells retained in the earlier cardiovascular progenitor cells (CVPCs) stage. Interestingly, during hiPSCs differentiation from CVPC into cardiomyocytes, verteporfin treatment induced cells dedifferentiation into the earlier CVPC stage. Mechanistically, we found that YAP interacted with transcriptional enhanced associate domain transcription factor 3 (TEAD3) to regulate cardiac differentiation of hiPSCs during the CVPC stage. Consistently, RNAi-based silencing of TEAD3 mimicked the phenotype as the cells treated with verteporfin. Collectively, our study suggests that YAP-TEAD3 signaling is important for cardiomyocyte differentiation of hiPSCs. Our findings provide new insight into the function of Hippo-YAP signal in cardiovascular lineage commitment.
© 2019 Wiley Periodicals, Inc.
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Comparison of Lacrosse Non-Slip Elements and Cutting Balloons in Treating Calcified Coronary Lesions: a Retrospective, Single-Blind Randomized Controlled Study.
Adv Ther2019 Sep;():. doi: 10.1007/s12325-019-01072-8.
Zhang Xin-Yong, Tang Zhe, Zeng Ya-Ping, Nie Shao-Ping,
Abstract
INTRODUCTION:
The present study aimed to compare Lacrosse non-slip elements (NSE) and cutting balloons in treating calcified coronary lesions.
METHODS:
A retrospective analysis was performed in 79 patients, who were diagnosed with moderate to severe calcified coronary lesions by coronary angiography, and underwent interventional therapy from January to December 2017. Lacrosse NSEs were used in 41 patients, while cutting balloons were used in 38 patients. The basic clinical characteristics, angiographic images, perioperative parameters, operation durations, interventional complications and incidence of major adverse cardiovascular events were compared.
RESULTS:
There was no significant difference in age, gender and risk factors between the two groups (P?>?0.05). Furthermore, there was no significant difference in operation duration, and perioperative and postoperative complications between the two groups (P?>?0.05).
CONCLUSION:
Compared with cutting balloons, the Lacrosse NSE has a similar effect in treating moderate to severe calcified coronary lesions.
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Prospects for PLD Inhibition in Cancer and Thrombotic Disease.
Handb Exp Pharmacol2019 Sep;():. doi: 10.1007/164_2019_244.
Salazar Christian, Frohman Michael A,
Abstract
Functions for phospholipase D1 and D2 (PLD1 and PLD2), the canonical isoforms of the PLD superfamily in mammals, have been explored using cell biological and animal disease models for two decades. PLD1 and PLD2, which are activated as a consequence of extracellular signaling events and generate the second messenger signaling lipid phosphatidic acid (PA), have been reported to play roles in settings ranging from platelet activation to the response to cardiac ischemia, viral infection, neurodegenerative disease, and cancer. Of these, the most tractable as therapeutic targets may be thrombotic disease and cancer, as will be discussed here in the context of ongoing efforts to develop small molecule PLD inhibitors.
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