Journal of Cardiovascular Development and Disease

9 pages, 794 KiB

Open AccessEditor’s ChoiceArticle

Disagreement between Cardiac Troponin Tests Yielding a Higher Incidence of Myocardial Injury in the Emergency Setting

by Peter A. Kavsak, Shawn E. Mondoux, Janet Martin, Mark K. Hewitt, Lorna Clark, Nadia Caruso, Ching-Tong Mark, V. Tony Chetty, Craig Ainsworth and Andrew Worster

J. Cardiovasc. Dev. Dis. 2021, 8(3), 31; https://doi.org/10.3390/jcdd8030031 - 23 Mar 2021

Cited by 11 | Viewed by 2827

Abstract

Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another [...] Read more.

Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another hs-cTnI assay (Abbott hs-cTnI) in samples obtained from different emergency departments (EDs). Two different sample types were evaluated (lithium heparin and ethylenediaminetetraacetic acid (EDTA) plasma) in a non-selected ED population (study 1, n = 469 samples) and in patients for which ED physicians ordered cardiac troponin testing (study 2, n = 1147 samples), from five different EDs. The incidence of injury in study 1 was higher with the OCD hs-cTnI assay (30.9%; 95% CI: 26.9 to 35.2) compared to that of the Abbott hs-cTnI (17.3%; 95% CI: 14.1 to 21.0) and the OCD cTnI ES (15.4%; 95% CI: 12.4 to 18.9) assays, with repeat testing identifying 4.8% (95% CI: 3.0 to 7.5) of the OCD hs-cTnI results with poor reproducibility. In study 2, 4.6% (95% CI: 3.5 to 6.0) of the results were not reported for the OCD hs-cTnI assay (i.e., poor reproducibility) with 12.7% (95%CI: 8.7 to 17.8) of the OCD hs-cTnI results positive for injury being negative for injury with the Abbott hs-cTnI assay. In summary, the OCD hs-cTnI assay yields higher rates of biochemical injury with a higher rate of poor reproducible results in different ED populations. Full article

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9 pages, 1403 KiB

Open AccessCase Report

Prognostic Value of Liver and Spleen Stiffness in Patients with Fontan Associated Liver Disease (FALD): A Case Series with Histopathologic Comparison

by Massimo A. Padalino, Liliana Chemello, Luisa Cavalletto, Annalisa Angelini and Marny Fedrigo

J. Cardiovasc. Dev. Dis. 2021, 8(3), 30; https://doi.org/10.3390/jcdd8030030 - 16 Mar 2021

Cited by 7 | Viewed by 3032

Abstract

The Fontan operation is the current surgical procedure to treat single-ventricle congenital heart disease, by splitting the systemic and pulmonary circulations and thus permitting lifespan to adulthood for the majority of newborns. However, emerging data are showing that Fontan-associated liver disease (FALD) is [...] Read more.

The Fontan operation is the current surgical procedure to treat single-ventricle congenital heart disease, by splitting the systemic and pulmonary circulations and thus permitting lifespan to adulthood for the majority of newborns. However, emerging data are showing that Fontan-associated liver disease (FALD) is an increasing related cause of morbidity and mortality in patients with the Fontan circuit. We described the clinical, laboratory, and transient elastography (TE) findings in a case series of adults with the Fontan circuit, and also correlated data with post-mortem histological features, aimed to define the prognostic value of TE in the staging of FALD. All patients presented signs of a long-standing Fontan failure, characterized by reoperation need, systemic ventricle dysfunction, and FALD stigmata (liver and spleen enlargement, portal vein and inferior vena cava dilation, and abnormal liver function tests). Liver and spleen stiffness (LS and SS) values were indicative of significant liver fibrosis/cirrhosis and the presence of suggestive portal hypertension (LS mean 35.9; range 27.3–44.7 kPa; SS mean 42.1, range 32.2–54.5 kPa). Post-mortem evaluations confirmed a gross hepatic architecture distortion in all cases. All patients died from severe complications related to liver dysfunction and bleeding. TE correlated well with pathological findings and FALD severity. We propose this validated and harmless technique to monitor liver fibrosis extension and portal hypertension over time in Fontan patients, and to identify the optimal timing for surgical reoperations or orthotopic-heart transplantation (OHT), avoiding a higher risk of morbidity and mortality in cases with severe FALD. Full article

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15 pages, 12281 KiB

Open AccessEditor’s ChoiceArticle

Myocardium-Specific Deletion of Rac1 Causes Ventricular Noncompaction and Outflow Tract Defects

by Carmen Leung, Anish Engineer, Mella Y. Kim, Xiangru Lu and Qingping Feng

J. Cardiovasc. Dev. Dis. 2021, 8(3), 29; https://doi.org/10.3390/jcdd8030029 - 15 Mar 2021

Cited by 9 | Viewed by 3640

Abstract

Background: Left ventricular noncompaction (LVNC) is a cardiomyopathy that can lead to arrhythmias, embolic events and heart failure. Despite our current knowledge of cardiac development, the mechanisms underlying noncompaction of the ventricular myocardium are still poorly understood. The small GTPase Rac1 acts as [...] Read more.

Background: Left ventricular noncompaction (LVNC) is a cardiomyopathy that can lead to arrhythmias, embolic events and heart failure. Despite our current knowledge of cardiac development, the mechanisms underlying noncompaction of the ventricular myocardium are still poorly understood. The small GTPase Rac1 acts as a crucial regulator of numerous developmental events. The present study aimed to investigate the cardiomyocyte specific role of Rac1 in embryonic heart development. Methods and Results: The Nkx2.5-Cre transgenic mice were crossed with Rac1^f/f mice to generate mice with a cardiomyocyte specific deletion of Rac1 (Rac1^Nkx2.5) during heart development. Embryonic Rac1^Nkx2.5 hearts at E12.5–E18.5 were collected for histological analysis. Overall, Rac1^Nkx2.5 hearts displayed a bifid apex, along with hypertrabeculation and a thin compact myocardium. Rac1^Nkx2.5 hearts also exhibited ventricular septal defects (VSDs) and double outlet right ventricle (DORV) or overriding aorta. Cardiomyocytes had a rounded morphology and were highly disorganized, and the myocardial expression of Scrib, a planar cell polarity protein, was reduced in Rac1^Nkx2.5 hearts. In addition, cell proliferation rate was significantly decreased in the Rac1^Nkx2.5 ventricular myocardium at E9.5. Conclusions: Rac1 deficiency in the myocardium impairs cardiomyocyte elongation and organization, and proliferative growth of the heart. A spectrum of CHDs arises in Rac1^Nkx2.5 hearts, implicating Rac1 signaling in the ventricular myocardium as a crucial regulator of OFT alignment, along with compact myocardium growth and development. Full article

(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)

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14 pages, 13472 KiB

Open AccessArticle

PDGFRα: Expression and Function during Mitral Valve Morphogenesis

by Kelsey Moore, Diana Fulmer, Lilong Guo, Natalie Koren, Janiece Glover, Reece Moore, Cortney Gensemer, Tyler Beck, Jordan Morningstar, Rebecca Stairley and Russell A. Norris

J. Cardiovasc. Dev. Dis. 2021, 8(3), 28; https://doi.org/10.3390/jcdd8030028 - 13 Mar 2021

Cited by 6 | Viewed by 3856

Abstract

Mitral valve prolapse (MVP) is a common form of valve disease and can lead to serious secondary complications. The recent identification of MVP causal mutations in primary cilia-related genes has prompted the investigation of cilia-mediated mechanisms of disease inception. Here, we investigate the [...] Read more.

Mitral valve prolapse (MVP) is a common form of valve disease and can lead to serious secondary complications. The recent identification of MVP causal mutations in primary cilia-related genes has prompted the investigation of cilia-mediated mechanisms of disease inception. Here, we investigate the role of platelet-derived growth factor receptor-alpha (PDGFRα), a receptor known to be present on the primary cilium, during valve development using genetically modified mice, biochemical assays, and high-resolution microscopy. While PDGFRα is expressed throughout the ciliated valve interstitium early in development, its expression becomes restricted on the valve endocardium by birth and through adulthood. Conditional ablation of Pdgfra with Nfatc1-enhancer Cre led to significantly enlarged and hypercellular anterior leaflets with disrupted endothelial adhesions, activated ERK1/2, and a dysregulated extracellular matrix. In vitro culture experiments confirmed a role in suppressing ERK1/2 activation while promoting AKT phosphorylation. These data suggest that PDGFRα functions to suppress mesenchymal transformation and disease phenotypes by stabilizing the valve endocardium through an AKT/ERK pathway. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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3 pages, 413 KiB

Open AccessPerspective

Coronary Anatomy in Congenital Heart Disease: The Important Contributions of Professor Dr. Adriana Gittenberger-de Groot

by Mark Hazekamp

J. Cardiovasc. Dev. Dis. 2021, 8(3), 27; https://doi.org/10.3390/jcdd8030027 - 9 Mar 2021

Cited by 2 | Viewed by 3962

Abstract

The contributions of Professor Dr. Adriana Gittenberger-de Groot in relation to coronary artery development and classification are described from the viewpoint of a pediatric cardiac surgeon. Full article

(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)

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15 pages, 5668 KiB

Open AccessEditor’s ChoiceArticle

Myocardial TGFβ2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development

by Aniket Bhattacharya, Nadia Al-Sammarraie, Mengistu G. Gebere, John Johnson, John F. Eberth and Mohamad Azhar

J. Cardiovasc. Dev. Dis. 2021, 8(3), 26; https://doi.org/10.3390/jcdd8030026 - 2 Mar 2021

Cited by 3 | Viewed by 3318

Abstract

Among the three transforming growth factor beta (TGFβ) ligands, TGFβ2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, [...] Read more.

Among the three transforming growth factor beta (TGFβ) ligands, TGFβ2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, including mitral valve prolapse (MVP) with or without regurgitation. Tgfb2 germline knockout fetuses exhibit multiple cardiac defects but the role of myocardial-TGFβ2 in heart development is yet to be elucidated. Here, myocardial Tgfb2 conditional knockout (CKO) embryos were generated by crossing Tgfb2^flox mice with Tgfb2^+/−; cTntCre mice. Tgfb2^flox/− embryos were normal, viable. Cell fate mapping was done using dual-fluorescent mT/mG^+/− mice. Cre-mediated Tgfb2 deletion was assessed by genomic PCR. RNAscope in situ hybridization was used to detect the loss of myocardial Tgfb2 expression. Histological, morphometric, immunohistochemical, and in situ hybridization analyses of CKOs and littermate controls at different stages of heart development (E12.5–E18.5) were used to determine the role of myocardium-derived TGFβ2 in atrioventricular (AV) cushion remodeling and myocardial development. CKOs exhibit a thin ventricular myocardium, AV cushion remodeling defects and developed incomplete AV septation defects. The loss of myocardial Tgfb2 resulted in impaired cushion maturation and dysregulated cell death. Phosphorylated SMAD2, a surrogate for TGFβ signaling, was “paradoxically” increased in both AV cushion mesenchyme and ventricular myocardium in the CKOs. Our results indicate that TGFβ2 produced by cardiomyocytes acting as cells autonomously on myocardium and via paracrine signaling on AV cushions are required for heart development. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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16 pages, 9961 KiB

Open AccessCase Report

The Clinical Spectrum of Kommerell’s Diverticulum in Adults with a Right-Sided Aortic Arch: A Case Series and Literature Overview

by Philippe J. van Rosendael, J. Lauran Stöger, Philippine Kiès, Hubert W. Vliegen, Mark G. Hazekamp, David R. Koolbergen, Hildo J. Lamb, Monique R. M. Jongbloed and Anastasia D. Egorova

J. Cardiovasc. Dev. Dis. 2021, 8(3), 25; https://doi.org/10.3390/jcdd8030025 - 26 Feb 2021

Cited by 15 | Viewed by 10938

Abstract

Background: Kommerell’s diverticulum is a rare vascular anomaly characterized as an outpouch at the onset of an aberrant subclavian artery. In the variant of a right-sided aortic arch, the trachea and esophagus are enclosed dorsally by the arch. In the configuration of an [...] Read more.

Background: Kommerell’s diverticulum is a rare vascular anomaly characterized as an outpouch at the onset of an aberrant subclavian artery. In the variant of a right-sided aortic arch, the trachea and esophagus are enclosed dorsally by the arch. In the configuration of an aberrant left subclavian artery, a Kommerell’s diverticulum and persisting ductus arteriosus or ductal ligament enclose the lateral side, forming a vascular ring which may result in (symptomatic) esophageal or tracheal compression. Spontaneous rupture of an aneurysmatic Kommerell’s diverticulum has also been reported. Due to the rarity of this condition and underreporting in the literature, the clinical implications of a Kommerell’s diverticulum are not well defined. Case summary: We describe seven consecutive adult patients with a right-sided aortic arch and an aberrant course of the left subclavian artery (arteria lusoria), and a Kommerell’s diverticulum, diagnosed in our tertiary hospital. One patient had severe symptoms related to the Kommerell’s diverticulum and underwent surgical repair. In total, two of the patients experienced mild non-limiting dyspnea complaints and in four patients the Kommerell’s diverticulum was incidentally documented on a computed tomography (CT) scan acquired for a different indication. The size of the Kommerell’s diverticulum ranged from 19 × 21 mm to 30 × 29 mm. In the six patients that did not undergo surgery, a strategy of periodic follow-up with structural imaging was pursued. No significant growth of the Kommerell’s diverticulum was observed and none of the patients experienced an acute aortic syndrome to date. Discussion: Kommerell’s diverticulum in the setting of a right-sided aortic arch with an aberrant left subclavian artery is frequently associated with tracheal and esophageal compression and this may result in a varying range of symptoms. Guidelines on management of Kommerell’s diverticulum are currently lacking. This case series and literature overview suggests that serial follow-up is warranted in adult patients with a Kommerell’s diverticulum with small dimensions and no symptoms, however, that surgical intervention should be considered when patients become symptomatic or when the diameter exceeds 30 mm in the absence of symptoms. Full article

(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)

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13 pages, 284 KiB

Open AccessFeature PaperReview

Statin Therapy in Post-Operative Atrial Fibrillation: Focus on the Anti-Inflammatory Effects

by Homa Nomani, Amir Hooshang Mohammadpour, Željko Reiner, Tannaz Jamialahmadi and Amirhossein Sahebkar

J. Cardiovasc. Dev. Dis. 2021, 8(3), 24; https://doi.org/10.3390/jcdd8030024 - 26 Feb 2021

Cited by 16 | Viewed by 3222

Abstract

Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in [...] Read more.

Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in long-term use. Therefore, more appropriate treatment strategies are needed. Methods: In this paper, the efficacy, safety, and other aspects of using statins in the prevention of POAF focusing on their anti-inflammatory effects are reviewed. Results: Recent studies have suggested that inflammation has a significant role in POAF, from the first AF episode to its serious complications including stroke and peripheral embolism. On the other hand, statins, the most widely used medications in cardiovascular patients, have pleiotropic effects, including anti-inflammatory properties. Therefore, they may potentially be effective in POAF prevention. Statins, especially atorvastatin, appear to be an effective option for primary prevention of POAF, especially in patients who had coronary artery bypass grafting (CABG), a cardiac surgery treatment associated with inflammation in the heart muscle. However, several large studies, particularly with rosuvastatin, did not confirm the beneficial effect of statins on POAF. One large clinical trial reported higher risk of acute kidney injury (AKI) following high-dose rosuvastatin in Chinese population. In this study, rosuvastatin reduced the level of C-reactive protein (CRP) but did not reduce the rate of POAF. Conclusion: Further studies are required to find the most effective statin regimen for POAF prevention with the least safety concern and the highest health benefits. Full article

(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)

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J. Cardiovasc. Dev. Dis., Volume 8, Issue 3 (March 2021) – 8 articles

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