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13 pages, 1675 KiB  
Article
In Vivo Imaging of Cardiac Attachment of TcI and TcII Variants of Trypanosoma cruzi in a Zebrafish Model
by Victoria E. Rodriguez-Castellanos, Cristhian David Perdomo-Gómez, Juan Carlos Santos-Barbosa, Manu Forero-Shelton, Verónica Akle and John M. González
Pathogens 2025, 14(1), 25; https://doi.org/10.3390/pathogens14010025 - 1 Jan 2025
Viewed by 800
Abstract
Trypanosoma cruzi, the etiological agent of Chagas disease, is a parasite known for its diverse genotypic variants, or Discrete Typing Units (DTUs), which have been associated with varying degrees of tissue involvement. However, aspects such as parasite attachment remain unclear. It has [...] Read more.
Trypanosoma cruzi, the etiological agent of Chagas disease, is a parasite known for its diverse genotypic variants, or Discrete Typing Units (DTUs), which have been associated with varying degrees of tissue involvement. However, aspects such as parasite attachment remain unclear. It has been suggested that the TcI genotype is associated with cardiac infection, the most common involved site in chronic human infection, while TcII is associated with digestive tract involvement. Traditional models for T. cruzi infection provide limited in vivo observation, making it challenging to observe the dynamics of parasite-host interactions. This study evaluates the cardiac attachment of trypomastigotes from TcI and TcII DTUs in zebrafish larvae. Labeled trypomastigotes were injected in the duct of Cuvier of zebrafish larvae and tracked by stereomicroscopy and light-sheet fluorescence microscopy (LSFM). Remarkably, it was possible to observe TcI parasites adhered to the atrium, atrioventricular valve, and circulatory system, while TcII trypomastigotes demonstrated adhesion to the atrium, atrioventricular valve, and yolk sac extension. When TcI and TcII were simultaneously injected, they both attached to the heart; however, more of the TcII trypomastigotes were observed attached to this organ. Although TcII DTU has previously been associated with digestive tissue infection, both parasite variants showed cardiac tissue attachment in this in vivo model. Full article
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Graphical abstract

Graphical abstract
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<p>Detection of fluorescently labeled <span class="html-italic">T. cruzi</span> trypomastigotes. (<b>a</b>) Flow cytometry dot plot of forward scatter (FSC) versus side scatter (SSC) of TcI trypomastigotes. (<b>b</b>) Upper panel histogram of unlabeled TcI trypomastigotes as the control group, At 670 nm detection. Lower panel histogram of TcI trypomastigotes labeled with CTFR at 670 nm detections. (<b>c</b>) Standardized droplet of 160 μm diameter for microinjection under stereomicroscopy to estimate live parasites by their movement.</p>
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<p>(<b>a</b>) Zebrafish larvae were injected with <span class="html-italic">T. cruzi</span> TcII trypomastigotes found attached to the heart valves of the larva under stereomicroscopy in the upper panel. Two trypomastigotes can be observed under LSFM 4 h after microinjection in the lower panel. (<b>b</b>) The upper panel shows the migration of the parasite towards the yolk sac extension under stereomicroscopy. The lower panel shows the same larva 4 h after microinjection under LSFM with a subtle movement towards the end of the yolk sac extension. (<b>c</b>) Zebrafish larvae injected with TcI trypomastigotes, one of which was attached to the cardinal vein (dotted blue line), observed under stereomicroscopy. (<b>d</b>) TcI trypomastigote attached to the dorsal aorta (dotted red line), observed under stereomicroscopy. The images shown came from different larvae.</p>
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<p>Dot plot of flow Cytometry assay with <span class="html-italic">T. cruzi</span> trypomastigotes. (<b>a</b>) The unlabeled population (P1) served as the control. (<b>b</b>) Region P2 represents TcII trypomastigotes labeled with CTCFSE, while region P3 represents TcI trypomastigotes labeled with CTFR.</p>
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<p>Schematic representation of zebrafish larvae heart showing the locations where trypomastigotes were detected using LSFM. Parasites (purple figures) were observed to be attached mainly to the heart valves and atrium, independent of DTU. V: Ventricle, A: Atrium, BA: Bulbus arteriosus. Figure was made using <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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9 pages, 841 KiB  
Article
Heart Disease and Pectus Excavatum: An Underestimated Issue—Single Center Experience and Literature Review
by Alice Ravasin, Domenico Viggiano, Simone Tombelli, Luca Checchi, Pierluigi Stefàno, Luca Voltolini and Alessandro Gonfiotti
Life 2024, 14(12), 1643; https://doi.org/10.3390/life14121643 - 11 Dec 2024
Viewed by 568
Abstract
Pectus excavatum (PE) can be associated with either congenital or acquired heart disease. This study highlights the importance of PE surgical repair in cases of severe chest depression on the heart in underlying cardiac diseases exacerbating cardiopulmonary impairment. From January 2023 to March [...] Read more.
Pectus excavatum (PE) can be associated with either congenital or acquired heart disease. This study highlights the importance of PE surgical repair in cases of severe chest depression on the heart in underlying cardiac diseases exacerbating cardiopulmonary impairment. From January 2023 to March 2024, four male patients underwent PE repair, having heart disease including pericarditis, mitral valve prolapse, ventricular fibrillation arrest and type 1 second-degree atrioventricular block. PE severity was determined by the Haller index (HI). Preoperative assessment included a pulmonary function test, chest computed tomography and cardiac evaluation. The Nuss procedure was performed in three patients, whereas, in one patient, it was performed in combination with a modified Ravitch procedure. The median HI was five. The median time of chest tube removal was 6.5 days. Postoperative complications were prolonged air leak, atrial fibrillation and atelectasis. The median length of hospital stay was 19.5 days, and no 30-day postoperative mortality was recorded. In all patients, surgical repair helped to resolve the underlying cardiological issues, and surgical follow-ups were deemed regular. PE is generally an isolated congenital chest wall abnormality, and, when associated with a heart disease, it can have severe life-threatening hemodynamic consequences due to mechanical compression on the heart for which surgical corrections should be considered. Full article
(This article belongs to the Special Issue Recent Advances in Modern Thoracic Surgery)
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<p>(<b>A</b>,<b>B</b>) Chest computed tomography and 3D reconstruction showing severe pectus excavatum (PE) in patient with Micra leadless pacemaker (MLP). (<b>C</b>,<b>D</b>) Cardiac magnetic resonance in a Marfan patient with severe PE and heart displaced to the left.</p>
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<p>(<b>A</b>) Chest radiograph showing pectus repair with the insertion of two retrosternal metal bars and (<b>B</b>) after subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation. (<b>C</b>) Chest radiograph showing pectus repair with the insertion of one retrosternal metal bar and MLP. (<b>D</b>) Chest radiograph showing pectus repair with the insertion of three retrosternal metal bars in a Marfan patient with a residual right-sided postoperative pneumothorax.</p>
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19 pages, 3447 KiB  
Systematic Review
Pregnancy Outcomes in Women with Biventricular Circulation and a Systemic Right Ventricle: A Systematic Review
by Triantafyllia Grantza, Alexandra Arvanitaki, Amalia Baroutidou, Ioannis Tsakiridis, Apostolos Mamopoulos, Andreas Giannopoulos, Antonios Ziakas and George Giannakoulas
J. Clin. Med. 2024, 13(23), 7281; https://doi.org/10.3390/jcm13237281 - 29 Nov 2024
Viewed by 445
Abstract
Background: Pregnancy in women with biventricular circulation and a systemic right ventricle (sRV) is considered high risk, with limited data available on pregnancy outcomes. This study aimed to investigate pregnancy outcomes in this population. Materials and Methods: A systematic review was conducted using [...] Read more.
Background: Pregnancy in women with biventricular circulation and a systemic right ventricle (sRV) is considered high risk, with limited data available on pregnancy outcomes. This study aimed to investigate pregnancy outcomes in this population. Materials and Methods: A systematic review was conducted using four major electronic databases. Pregnant women with a complete transposition of great arteries (d-TGA) after an atrial switch operation or a congenitally corrected transposition of the great arteries (ccTGA) were included. Results: In total, 15 studies including 632 pregnancies in 415 women with an sRV and biventricular circulation were identified, of whom 299 (72%) had d-TGA and 116 (28%) ccTGA. Maternal mortality or cardiac transplantation occurred in 0.8% of pregnancies. The most frequent maternal complications were the worsening of systemic atrioventricular valve regurgitation [pooled estimate (PE): 16%, 95% CI: 5;26], the deterioration of sRV function (PE: 15%, 95% CI: 2;27), the worsening of the NYHA class (PE: 13%, 95% CI: 6;20), all-cause hospitalization (PE): 10%, 95% CI: 7;12), arrhythmias (PE: 8%, 95% CI: 5;11), and symptomatic heart failure (PE: 6%, 95% CI: 3;10). Stillbirth occurred in 0.7% of pregnancies and neonatal death in 0.4%. Small-for-gestational-age neonates were encountered in 36% (95% CI: 21;52) of pregnancies and preterm delivery in 22% (95% CI: 14;30). A subgroup analysis showed no significant difference in outcomes between women with d-TGA and those with ccTGA, except for the worsening of the NYHA class, which occurred more often in d-TGA (18%, 95% CI: 12;27 vs. 6%, 95% CI: 3;15, respectively, p = 0.03). Conclusions: Maternal and fetal/neonatal mortality are low among pregnant women with biventricular circulation and an sRV. However, significant maternal morbidity and poor neonatal outcomes are frequently encountered, rendering management in specialized centers imperative. Full article
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<p>Pooled estimates of maternal outcomes during pregnancy. (<b>a</b>) Forest plot of worsening of systemic AV valve regurgitation during pregnancy. (<b>b</b>) Forest plot of worsening of systemic RV function during pregnancy. (<b>c</b>) Forest plot of worsening of NYHA class during pregnancy. (<b>d</b>) Forest plot of maternal all-cause hospitalization during pregnancy. (<b>e</b>) Forest plot of maternal arrythmia during pregnancy. (<b>f</b>) Forest plot of maternal symptomatic heart failure during pregnancy; NYHA: New York Heart Association [<a href="#B15-jcm-13-07281" class="html-bibr">15</a>,<a href="#B16-jcm-13-07281" class="html-bibr">16</a>,<a href="#B17-jcm-13-07281" class="html-bibr">17</a>,<a href="#B19-jcm-13-07281" class="html-bibr">19</a>,<a href="#B20-jcm-13-07281" class="html-bibr">20</a>,<a href="#B21-jcm-13-07281" class="html-bibr">21</a>,<a href="#B23-jcm-13-07281" class="html-bibr">23</a>,<a href="#B24-jcm-13-07281" class="html-bibr">24</a>,<a href="#B25-jcm-13-07281" class="html-bibr">25</a>,<a href="#B27-jcm-13-07281" class="html-bibr">27</a>,<a href="#B28-jcm-13-07281" class="html-bibr">28</a>,<a href="#B29-jcm-13-07281" class="html-bibr">29</a>,<a href="#B30-jcm-13-07281" class="html-bibr">30</a>].</p>
Full article ">Figure 2
<p>Pooled estimates of fetal/neonatal and pregnancy outcomes of women with biventricular circulation and an sRV. (<b>a</b>) Forest plot of SGA neonates. (<b>b</b>) Forest plot of preterm deliveries. (<b>c</b>) Forest plot of vaginal deliveries. (<b>d</b>) Forest plot of cesarean sections. (<b>e</b>) Forest plot of spontaneous abortions of women with biventricular circulation and an sRV. (<b>f</b>) Forest plot of induced abortions of women with biventricular circulation and an sRV reported. SGA: small for gestational age [<a href="#B15-jcm-13-07281" class="html-bibr">15</a>,<a href="#B16-jcm-13-07281" class="html-bibr">16</a>,<a href="#B17-jcm-13-07281" class="html-bibr">17</a>,<a href="#B18-jcm-13-07281" class="html-bibr">18</a>,<a href="#B19-jcm-13-07281" class="html-bibr">19</a>,<a href="#B20-jcm-13-07281" class="html-bibr">20</a>,<a href="#B21-jcm-13-07281" class="html-bibr">21</a>,<a href="#B22-jcm-13-07281" class="html-bibr">22</a>,<a href="#B23-jcm-13-07281" class="html-bibr">23</a>,<a href="#B24-jcm-13-07281" class="html-bibr">24</a>,<a href="#B25-jcm-13-07281" class="html-bibr">25</a>,<a href="#B26-jcm-13-07281" class="html-bibr">26</a>,<a href="#B27-jcm-13-07281" class="html-bibr">27</a>,<a href="#B28-jcm-13-07281" class="html-bibr">28</a>,<a href="#B29-jcm-13-07281" class="html-bibr">29</a>].</p>
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<p>Subgroup analysis for NYHA class between d-TGA and ccTGA group. NYHA: New York Heart Association; d-TGA: dextro-looped transposition of the great arteries; ccTGA: congenitally corrected transposition of the great arteries [<a href="#B16-jcm-13-07281" class="html-bibr">16</a>,<a href="#B17-jcm-13-07281" class="html-bibr">17</a>,<a href="#B19-jcm-13-07281" class="html-bibr">19</a>,<a href="#B22-jcm-13-07281" class="html-bibr">22</a>,<a href="#B24-jcm-13-07281" class="html-bibr">24</a>,<a href="#B25-jcm-13-07281" class="html-bibr">25</a>,<a href="#B27-jcm-13-07281" class="html-bibr">27</a>,<a href="#B29-jcm-13-07281" class="html-bibr">29</a>].</p>
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<p>Multidisciplinary cardio-obstetrics model of care for pregnant women with biventricular circulation and an sRV.</p>
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<p>Bar chart of maternal and fetal outcomes of pregnant women with biventricular circulation and an sRV.</p>
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27 pages, 2404 KiB  
Review
Pathogenesis and Surgical Treatment of Congenitally Corrected Transposition of the Great Arteries (ccTGA): Part III
by Marek Zubrzycki, Rene Schramm, Angelika Costard-Jäckle, Michiel Morshuis, Jochen Grohmann, Jan F. Gummert and Maria Zubrzycka
J. Clin. Med. 2024, 13(18), 5461; https://doi.org/10.3390/jcm13185461 - 14 Sep 2024
Viewed by 1693
Abstract
Congenitally corrected transposition of the great arteries (ccTGA) is an infrequent and complex congenital malformation, which accounts for approximately 0.5% of all congenital heart defects. This defect is characterized by both atrioventricular and ventriculoarterial discordance, with the right atrium connected to the morphological [...] Read more.
Congenitally corrected transposition of the great arteries (ccTGA) is an infrequent and complex congenital malformation, which accounts for approximately 0.5% of all congenital heart defects. This defect is characterized by both atrioventricular and ventriculoarterial discordance, with the right atrium connected to the morphological left ventricle (LV), ejecting blood into the pulmonary artery, while the left atrium is connected to the morphological right ventricle (RV), ejecting blood into the aorta. Due to this double discordance, the blood flow is physiologically normal. Most patients have coexisting cardiac abnormalities that require further treatment. Untreated natural course is often associated with progressive failure of the systemic right ventricle (RV), tricuspid valve (TV) regurgitation, arrhythmia, and sudden cardiac death, which occurs in approximately 50% of patients below the age of 40. Some patients do not require surgical intervention, but most undergo physiological repair leaving the right ventricle in the systemic position, anatomical surgery which restores the left ventricle as the systemic ventricle, or univentricular palliation. Various types of anatomic repair have been proposed for the correction of double discordance. They combine an atrial switch (Senning or Mustard procedure) with either an arterial switch operation (ASO) as a double-switch operation or, in the cases of relevant left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD), intra-ventricular rerouting by a Rastelli procedure. More recently implemented procedures, variations of aortic root translocations such as the Nikaidoh or the half-turned truncal switch/en bloc rotation, improve left ventricular outflow tract (LVOT) geometry and supposedly prevent the recurrence of LVOTO. Anatomic repair for congenitally corrected ccTGA has been shown to enable patients to survive into adulthood. Full article
(This article belongs to the Section Cardiology)
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<p>Diagrams of the normal heart (<b>A</b>) and ccTGA (<b>B</b>). In the normal heart, the pulmonary artery arises from the right ventricle, and the aorta arises from the left ventricle (RA with LV, LA with RV). In ccTGA, the right atrium is connected to the morphological LV, which ejects blood into the pulmonary artery, whereas the left atrium is connected to the morphological RV, which ejects blood into the aorta. The ventricles are inverted. RA: right atrium; RV: right ventricle; PA: pulmonary artery; LA: left atrium; LV: left ventricle. This figure was modified and reproduced with permission from Goldmuntz et al. [<a href="#B9-jcm-13-05461" class="html-bibr">9</a>].</p>
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<p>Disposition of cardiac conduction system in ccTGA. Ao indicates the aorta; AV, atrioventricular; cs, coronary sinus; LBB: left bundle branch; LV: left ventricle; PT: pulmonary trunk; RA: right atrium; RBB: right bundle branch; RV: right ventricle; VSD: ventricular septal defect. This figure was taken from the article of Baruteau et al. [<a href="#B19-jcm-13-05461" class="html-bibr">19</a>] distributed under the terms of the Creative Commons Attribution License (CC BY).</p>
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<p>Indications for surgical intervention in ccTGA. CcTGA: congenitally corrected transposition of the great arteries; RV: right ventricle; PA: pulmonary artery. This figure was reproduced with permission from Kumar [<a href="#B29-jcm-13-05461" class="html-bibr">29</a>], under the terms of the Creative Commons Attribution License (CC BY).</p>
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<p>Schematic representation of anatomic repair in the form of a double-switch operation by restoring flow in the normal arrangement. The figure shows the steps involved in the so-called double-switch procedure. Ao: aorta; IVC: inferior vena cava; SVC: superior vena cava; PV: pulmonary veins; PT: pulmonary trunk, mRV: morphologically right ventricle; mLV: morphologically left ventricle.</p>
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<p>Algorithm for anatomical correction of ccTGA. ccTGA: congenitally corrected transposition of the great arteries; LVOTO: left ventricular outflow tract obstruction; VSD: ventricular septal defect. This figure was reproduced with permission from Kumar [<a href="#B29-jcm-13-05461" class="html-bibr">29</a>], under the terms of the Creative Commons Attribution License (CC BY).</p>
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<p>Schematic representation of the Rastelli–Senning operation. The figure shows the final result after an atrial redirection procedure combined with intra-ventricular rerouting of the ventricular septal defect to the aorta, and the placement of a conduit from the morphologically right ventricle to the pulmonary arteries. Ao: aorta; IVC: inferior vena cava; SVC: superior vena cava; PV: pulmonary veins; 1: conduit from morphologically right ventricle to pulmonary arteries; 2: interventricular tunnel from morphologically left ventricle to aorta.</p>
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<p>Schematic representation of the hemi-Mustard–Rastelli–Glenn operation. (<b>A</b>) Diagram of hemi-Mustard/bidirectional Glenn (BDG) operation with the Rastelli–atrial switch procedure in a dextrorotated heart. BDG: bidirectional Glenn shunt; IVC: inferior vena cava; LV: left ventricle; RV: right ventricle. (<b>B</b>) The “Hemi-Mustard” technique. A bidirectional Glenn shunt has been performed and the atrial septum has been excised. A circular patch of Goretex<sup>®</sup> is used to baffle the IVC through to the tricuspid valve. The coronary sinus has been laid open to give extra volume to the pathway. Figure (<b>A</b>) was modified and adapted from Malhorta et al. [<a href="#B88-jcm-13-05461" class="html-bibr">88</a>].</p>
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17 pages, 554 KiB  
Review
Outcomes of Valve-in-Valve (VIV) Transcatheter Aortic Valve Replacement (TAVR) after Surgical Aortic Valve Replacement with Sutureless Surgical Aortic Valve Prostheses Perceval™: A Systematic Review of Published Cases
by Tamer Owais, Osama Bisht, Mostafa Hossam El Din Moawad, Mohammad El-Garhy, Sina Stock, Evaldas Girdauskas, Thomas Kuntze, Mohamed Amer and Philipp Lauten
J. Clin. Med. 2024, 13(17), 5164; https://doi.org/10.3390/jcm13175164 - 30 Aug 2024
Viewed by 1138
Abstract
Background: Valve-in-Valve (VIV) transcatheter aortic valve replacement (TAVR) is a potential solution for malfunctioning surgical aortic valve prostheses, though limited data exist for its use in Perceval valves. Methods: searches were performed on PubMed and Scopus up to 31 July 2023, [...] Read more.
Background: Valve-in-Valve (VIV) transcatheter aortic valve replacement (TAVR) is a potential solution for malfunctioning surgical aortic valve prostheses, though limited data exist for its use in Perceval valves. Methods: searches were performed on PubMed and Scopus up to 31 July 2023, focusing on case reports and series addressing VIV replacement for degenerated Perceval bioprostheses. Results: Our analysis included 57 patients from 27 case reports and 6 case series. Most patients (68.4%) were women, with a mean age of 76 ± 4.4 years and a mean STS score of 6.1 ± 4.3%. Follow-up averaged 9.8 ± 8.9 months, the mean gradient reduction was 15 ± 5.9 mmHg at discharge and 13 ± 4.2 mmHg at follow-up. Complications occurred in 15.7% of patients, including atrioventricular block III in four patients (7%), major bleeding or vascular complications in two patients (3.5%), an annular rupture in two patients (3.5%), and mortality in two patients (3.5%). No coronary obstruction was reported. Balloon-expanding valves were used in 61.4% of patients, predominantly the Sapien model. In the self-expanding group (38.6%), no valve migration occurred, with a permanent pacemaker implantation rate of 9%, compared to 5.7% for balloon-expanding valves. Conclusions: VIV-TAVR using both balloon-expanding and self-expanding technologies is feasible after the implantation of Perceval valves; however, it should be performed by experienced operators with experience both in TAVR and VIV procedures. Full article
(This article belongs to the Section Cardiovascular Medicine)
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<p>flow chart of the study.</p>
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12 pages, 819 KiB  
Article
Temporal Trends in Patient Characteristics and Clinical Outcomes of TAVR: Over a Decade of Practice
by Nour Karra, Amir Sharon, Eias Massalha, Paul Fefer, Elad Maor, Victor Guetta, Sagit Ben-Zekry, Rafael Kuperstein, Shlomi Matetzky, Roy Beigel, Amit Segev and Israel M. Barbash
J. Clin. Med. 2024, 13(17), 5027; https://doi.org/10.3390/jcm13175027 - 25 Aug 2024
Viewed by 1477
Abstract
Background/Objective: Transcatheter aortic valve replacement (TAVR) is indicated for severe aortic stenosis patients with a prohibitive surgical risk. However, its use has been expanding in recent years to include intermediate- and low-risk patients. Thus, registry data describing changes in patient characteristics and outcomes [...] Read more.
Background/Objective: Transcatheter aortic valve replacement (TAVR) is indicated for severe aortic stenosis patients with a prohibitive surgical risk. However, its use has been expanding in recent years to include intermediate- and low-risk patients. Thus, registry data describing changes in patient characteristics and outcomes are needed. The aim of this study was to analyse the temporal changes in patient profiles and clinical outcomes of all-comer TAVR. Methods: Baseline characteristics and VARC-3 outcomes of 1632 consecutive patients undergoing TAVR between 2008 and 2021 were analysed. Results: The annual rate of TAVR increased from 30 procedures in 2008–2009 to 398 in 2020–2021. Over the follow-up period, patient age decreased from 85 ± 4 to 80 ± 6.8 (p < 0.001) and the STS score decreased from 5.9% to 2.8% (p < 0.001). Procedural characteristics significantly changed, representing a shift into a minimally invasive approach: adoption of local anaesthesia (none to 48%, p < 0.001) and preference of transfemoral access (74% in 2011–2012 vs. 94.5% in 2020–2021, p < 0.001). The rates of almost all procedural complications decreased, including major vascular and bleeding complications, acute kidney injury (AKI) and in-hospital heart failure. There was a striking decline in rates of complete atrioventricular block (CAVB) and the need for a permanent pacemaker (PPM). PPM rates, however, remain high (17.8%). Thirty-day and one-year mortality significantly declined to 1.8% and 8.3%, respectively. Multivariable analysis shows that AKI, bleeding and stroke are strong predictors of one-year mortality (p < 0.001). Conclusions: The TAVR procedure has changed dramatically during the last 14 years in terms of patient characteristics, procedural aspects and device maturity. These shifts have led to improved procedural safety, contributing to improved short- and long-term patient outcomes. Full article
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<p>TAVR complication rates per year. Results are expressed as frequencies (N) and percentages (%) of yearly procedures. The χ<sup>2</sup> test was used to compare percentages of categorical variables. <span class="html-italic">p</span> &lt; 0.05 was considered significant.</p>
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<p>(<b>A</b>) Unadjusted cumulative probability of death over a one-year follow-up (<span class="html-italic">p</span> &lt; 0.05) (<b>B</b>) Cumulative probability of death over one year adjusted for STS score, stage 2–3 AKI, major bleeding and stroke.</p>
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39 pages, 4539 KiB  
Review
Pathogenesis and Surgical Treatment of Dextro-Transposition of the Great Arteries (D-TGA): Part II
by Marek Zubrzycki, Rene Schramm, Angelika Costard-Jäckle, Michiel Morshuis, Jan F. Gummert and Maria Zubrzycka
J. Clin. Med. 2024, 13(16), 4823; https://doi.org/10.3390/jcm13164823 - 15 Aug 2024
Cited by 1 | Viewed by 3130
Abstract
Dextro-transposition of the great arteries (D-TGA) is the second most common cyanotic heart disease, accounting for 5–7% of all congenital heart defects (CHDs). It is characterized by ventriculoarterial (VA) connection discordance, atrioventricular (AV) concordance, and a parallel relationship with D-TGA. As a result, [...] Read more.
Dextro-transposition of the great arteries (D-TGA) is the second most common cyanotic heart disease, accounting for 5–7% of all congenital heart defects (CHDs). It is characterized by ventriculoarterial (VA) connection discordance, atrioventricular (AV) concordance, and a parallel relationship with D-TGA. As a result, the pulmonary and systemic circulations are separated [the morphological right ventricle (RV) is connected to the aorta and the morphological left ventricle (LV) is connected to the pulmonary artery]. This anomaly is included in the group of developmental disorders of embryonic heart conotruncal irregularities, and their pathogenesis is multifactorial. The anomaly’s development is influenced by genetic, epigenetic, and environmental factors. It can occur either as an isolated anomaly, or in association with other cardiac defects. The typical concomitant cardiac anomalies that may occur in patients with D-TGA include ventriculoseptal defects, patent ductus arteriosus, left ventricular outflow tract obstruction (LVOTO), mitral and tricuspid valve abnormalities, and coronary artery variations. Correction of the defect during infancy is the preferred treatment for D-TGA. Balloon atrial septostomy (BAS) is necessary prior to the operation. The recommended surgical correction methods include arterial switch operation (ASO) and atrial switch operation (AtrSR), as well as the Rastelli and Nikaidoh procedures. The most common postoperative complications include coronary artery stenosis, neoaortic root dilation, neoaortic insufficiency and neopulmonic stenosis, right ventricular (RV) outflow tract obstruction (RVOTO), left ventricular (LV) dysfunction, arrhythmias, and heart failure. Early diagnosis and treatment of D-TGA is paramount to the prognosis of the patient. Improved surgical techniques have made it possible for patients with D-TGA to survive into adulthood. Full article
(This article belongs to the Section Cardiovascular Medicine)
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<p>Diagrams of the normal heart (<b>A</b>) and D-TGA (<b>B</b>). In the normal heart, the pulmonary artery arises from the right ventricle, and the aorta arises from the left ventricle. In D-TGA, due to a complete inversion of the great vessels, the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the left ventricle, whereas the ventricles are normally connected. RA: right atrium; RV: right ventricle; PA: pulmonary artery; LA: left atrium; LV: left ventricle; AO: aorta. This figure was modified and reproduced with permission from Goldmuntz et al. [<a href="#B13-jcm-13-04823" class="html-bibr">13</a>].</p>
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<p>Diagram summarizing the anatomy of the developing heart according to de la Cruz’s theory. (<b>A</b>). View of the straight early heart tube. (<b>B</b>). View of the looped heart tube. (<b>C</b>). View of a chamber-forming heart. (<b>D</b>). View of a four-chambered heart, showing the inflow of the left ventricle and the outflow of the right ventricle. LA: left atrium; LV: left ventricle; PT: pulmonary trunk; RA: right atrium; RV: right ventricle. OFT: cardiac outflow tract. This figure was reproduced with permission from van den Berg and Moorman [<a href="#B63-jcm-13-04823" class="html-bibr">63</a>].</p>
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<p>(<b>A</b>). Surgical/interventional Leiden convention. (<b>B</b>). Imaging Leiden convention. Description in the text. A: anterior; Ao: aorta; L: left; LAD: left anterior descending artery; LCA: left coronary artery; LCx: circumflex artery; NF: non-facing sinus; P: posterior; Pu: pulmonary artery; R: right; RCA: right coronary artery. This figure was reproduced with permission from Koppel et al. [<a href="#B150-jcm-13-04823" class="html-bibr">150</a>], under the terms of the Creative Commons Attribution License (CC BY).</p>
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<p>Leiden TGA coronary artery classification. LAD: left anterior descending artery; Cx: circumflex artery; RCA: right coronary artery. The figures are modifications based on the publications by Gittenberger-de Groot et al. [<a href="#B151-jcm-13-04823" class="html-bibr">151</a>] and Quaegebeur [<a href="#B152-jcm-13-04823" class="html-bibr">152</a>].</p>
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<p>Algorithm for physiological and anatomical correction of D-TGA. D-TGA: dextro-transposition of the great arteries; LVOTO: left ventricular outflow tract obstruction; VSD: ventricular septal defect; ASO: arterial switch operation; REV: réparation à l’étage ventriculaire.</p>
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<p>Scheme of arterial switch operation (Jatene procedure). (<b>A</b>). The great arteries are transected at the supra-valvar level and reversed in order to create a “normal” anatomical arrangement. 1. Original aortic root—neopulmonary artery root. 2. Original pulmonary artery root—neoaortic root. (<b>B</b>). Resection of the coronary arteries with the aortic wall margin surrounding the arterial ostium (marked in black). LV: left ventricle; RV: right ventricle; PA: pulmonary artery; Ao: aorta. The figure was modified based on the publication by Hornung et al. [<a href="#B179-jcm-13-04823" class="html-bibr">179</a>].</p>
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<p>The figures illustrate the surgical technique for arterial switch procedures. (<b>A</b>). Replacement of the great arteries with the Lecompte maneuver. (<b>B</b>). The harvesting and reimplantation of coronary buttons with normal coronary artery course. Source: The images are based on the publication by Lacour-Gayet [<a href="#B187-jcm-13-04823" class="html-bibr">187</a>].</p>
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<p>Scheme of the Rastelli operation. 1. The ventricular septal defect is closed with the creation of a left ventricular outflow tract. 2. A right ventricle to pulmonary artery conduit is inserted to bypass the pulmonary stenosis. LV: left ventricle; RV: right ventricle; PA: pulmonary artery; Ao: aorta. This figure was modified based on the publication by Hornung et al. [<a href="#B179-jcm-13-04823" class="html-bibr">179</a>].</p>
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<p>The figures illustrate the Rastelli operation technique. (<b>A</b>). The incisions in the pulmonary artery and right ventriclotomy. (<b>B</b>). Complete resection of the conal septum. (<b>C</b>). Enlargement VSD and the construction of a baffle from the LV to the aorta (ascending). (<b>D</b>). RV-to-pulmonary artery continuity is established with the use of a conduit. LV: left ventricle; RV: right ventricle; VSD: ventricular septal defect. Source: The images are based on the publication by Kreutzer [<a href="#B199-jcm-13-04823" class="html-bibr">199</a>].</p>
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<p>The figures illustrate the réparation à l’étage ventriculaire (REV) operation. (<b>A</b>). Construction of the intracardiac tunnel connecting the VSD with the aorta. (<b>B</b>). Reconstruction of the ascending aorta and closure of the pulmonary orifice. (<b>C</b>). Reconstruction of the pulmonary trunk. RV: right ventricle; VSD: ventricular septal defect. Source: The images are based on the publication by Vouhé and Raisky [<a href="#B202-jcm-13-04823" class="html-bibr">202</a>].</p>
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<p>The figures illustrate the Nikaidoh procedure. (<b>A</b>). Aortic root harvesting from the RV. (<b>B</b>). Closure of the VSD. (<b>C</b>). RVOT reconstruction with direct connection of the RV to the PA. RV: right ventricle; PA: pulmonary artery; VSD: ventricular septal defect; RVOT: right ventricle outflow tract. Source: The images are based on the publication by Morell [<a href="#B211-jcm-13-04823" class="html-bibr">211</a>].</p>
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<p>Scheme of the atrial switch operation (Mustard or Senning). (<b>A</b>). Neo-atrial baffle diverts blood from vena cava to LV and from pulmonary vein to RV. (<b>B</b>). Precise inflow into LV through MV. (<b>C</b>). Precise inflow to RV through TV. IVC: inferior vena cava; SVC: superior vena cava; LV: left ventricle; RV: right ventricle; PA: pulmonary artery; Ao: aorta; LL: left lower pulmonary vein; LU: left upper pulmonary vein; MV: mitral valve; RL: right lower pulmonary vein; RU: right upper pulmonary vein; TV: tricuspid valve. This figure was modified based on the publication by Hornung et al. [<a href="#B179-jcm-13-04823" class="html-bibr">179</a>].</p>
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22 pages, 4406 KiB  
Review
Advances in Diagnostic and Interventional Catheterization in Adults with Fontan Circulation
by Yassin Belahnech, Gerard Martí Aguasca and Laura Dos Subirà
J. Clin. Med. 2024, 13(16), 4633; https://doi.org/10.3390/jcm13164633 - 7 Aug 2024
Viewed by 1298
Abstract
Over the past five decades, the Fontan procedure has been developed to improve the life expectancy of patients with congenital heart defects characterized by a functionally single ventricle. The Fontan circulation aims at redirecting systemic venous return to the pulmonary circulation in the [...] Read more.
Over the past five decades, the Fontan procedure has been developed to improve the life expectancy of patients with congenital heart defects characterized by a functionally single ventricle. The Fontan circulation aims at redirecting systemic venous return to the pulmonary circulation in the absence of an impelling subpulmonary ventricle, which makes this physiology quite fragile and leads to several long-term complications. Despite the importance of hemodynamic assessment through cardiac catheterization in the management and follow-up of these patients, a thorough understanding of the ultimate functioning of this type of circulation is lacking, and the interpretation of the hemodynamic data is often complex. In recent years, new tools such as combined catheterization with cardiopulmonary exercise testing have been incorporated to improve the understanding of the hemodynamic profile of these patients. Furthermore, extensive percutaneous treatment options have been developed, addressing issues ranging from obstructive problems in Fontan pathway and acquired shunts through compensatory collaterals to the percutaneous treatment of lymphatic circulation disorders and transcatheter edge-to-edge repair of atrioventricular valves. The aim of this review is to detail the various tools used in cardiac catheterization for patients with Fontan circulation, analyze different percutaneous treatment strategies, and discuss the latest advancements in this field. Full article
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<p>Long-term Fontan complications. AV: Atrioventricular, FALD: Fontan-associated liver disease, HF: Heart failure. BioRender.com has been used for the creation of this figure (Agreement number: RI275JMOWR).</p>
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<p>Fontan gradient between the superior and inferior vena cava unmasking an obstructive gradient in the Fontan conduit during exercise. (<b>A</b>) SVC-IVC gradient at rest of 1 mmHg. (<b>B</b>) SVC-IVC gradient during exercise of 9 mmHg. LV: single ventricle, SVC: superior vena cava, IVC: inferior vena cava.</p>
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<p>Contrast angiographic studies: (<b>A</b>) Systemic to pulmonary venous collaterals (SPVCs); (<b>B</b>) Major aortopulmonary collateral arteries (MAPCAs); (<b>C</b>) Macrovascular pulmonary arteriovenous malformation (PAVM).</p>
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<p>Percutaneous treatment of Fontan pathway obstructions with stent angioplasty on (<b>A</b>,<b>B</b>) an obstructed extracardiac Fontan conduit, on (<b>C</b>,<b>D</b>) an atriopulmonary anastomosis in classic Fontan, and on (<b>E</b>,<b>F</b>) a complete occlusion of the left pulmonary branch artery. The arrows in each figure indicate the point of obstruction or occlusion.</p>
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<p>Percutaneous intervention in cyanotic patients due to right-to-left shunt: (<b>A</b>,<b>B</b>) Fenestration closure; (<b>C</b>,<b>D</b>) Veno-venous shunt closure from a persistent left superior vena cava (LSVC) to the coronary sinus (CS). The arrows in each figure indicate the shunt and its closure with an occlusion device.</p>
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<p>Acute pulmonary thromboembolism: (<b>A</b>) angiographic image of a thrombotic occlusion in the main branch of the left lower lobar artery (see arrow); (<b>B</b>) thrombus extracted after percutaneous aspiration thrombectomy.</p>
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<p>Double inlet left ventricle, initially palliated with a Damus-Kaye-Stansel (DKS) procedure and subsequently with a Fontan procedure, presenting an invasive gradient of 18 mmHg in the thoracic aorta. (<b>A</b>) Angiographic image of the neoaorta in a patient with DKS with an associated aortic coarctation (AC) marked by an arrow; (<b>B</b>) Placement of a stent at the level of the coarctation (arrow); (<b>C</b>) Percutaneous repair of the AC after stent deployment (arrow).</p>
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12 pages, 497 KiB  
Article
Chronic Right Ventricular Pacing Post-Transcatheter Aortic Valve Replacement Attenuates the Benefit on Left Ventricular Function
by Chieh-Ju Chao, Deepa Mandale, Juan M. Farina, Merna Abdou, Pattara Rattanawong, Marlene Girardo, Pradyumma Agasthi, Chadi Ayoub, Mohammad Alkhouli, Mackram Eleid, F. David Fortuin, John P. Sweeney, Peter Pollak, Abdallah El Sabbagh, David R. Holmes, Reza Arsanjani and Tasneem Z. Naqvi
J. Clin. Med. 2024, 13(15), 4553; https://doi.org/10.3390/jcm13154553 - 4 Aug 2024
Viewed by 904
Abstract
Background: Conduction abnormality post-transcatheter aortic valve implantation (TAVI) remains clinically significant and usually requires chronic pacing. The effect of right ventricular (RV) pacing post-TAVI on clinical outcomes warrants further studies. Methods: We identified 147 consecutive patients who required chronic RV pacing after a [...] Read more.
Background: Conduction abnormality post-transcatheter aortic valve implantation (TAVI) remains clinically significant and usually requires chronic pacing. The effect of right ventricular (RV) pacing post-TAVI on clinical outcomes warrants further studies. Methods: We identified 147 consecutive patients who required chronic RV pacing after a successful TAVI procedure and propensity-matched these patients according to the Society of Thoracic Surgeons (STS) risk score to a control group of patients that did not require RV pacing post-TAVI. We evaluated routine echocardiographic measurements and performed offline speckle-tracking strain analysis for the purpose of this study on transthoracic echocardiographic (TTE) images performed at 9 to 18 months post-TAVI. Results: The final study population comprised 294 patients (pacing group n = 147 and non-pacing group n = 147), with a mean age of 81 ± 7 years, 59% male; median follow-up was 354 days. There were more baseline conduction abnormalities in the pacing group compared to the non-pacing group (56.5% vs. 41.5%. p = 0.01). Eighty-eight patients (61.6%) in the pacing group required RV pacing due to atrioventricular (AV) conduction block post-TAVI. The mean RV pacing burden was 44% in the pacing group. Left ventricular ejection fraction (LVEF) was similar at follow-up in the pacing vs. non-pacing groups (57 ± 13.0%, 59 ± 11% p = 0.31); however, LV global longitudinal strain (−12.7 ± 3.5% vs. −18.8 ± 2.7%, p < 0.0001), LV apical strain (−12.9 ± 5.5% vs. 23.2 ± 9.2%, p < 0.0001), and mid-LV strain (−12.7 ± 4.6% vs. −18.7 ± 3.4%, p < 0.0001) were significantly worse in the pacing vs. non-pacing groups. Conclusions: Chronic RV pacing after the TAVI procedure is associated with subclinical LV systolic dysfunction within 1.5 years of follow-up. Full article
(This article belongs to the Special Issue Heart Valve Disease and Imaging Techniques)
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<p>Kaplan–Meier survival curves of the two groups (pacing versus non-pacing). There was no significant prognostic difference for all-cause mortality ((<b>A</b>), <span class="html-italic">p</span> = 0.50) and heart failure hospitalization ((<b>B</b>), <span class="html-italic">p</span> = 0.72).</p>
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9 pages, 239 KiB  
Article
Impact of Net Atrioventricular Compliance on Mitral Valve Area Assessment—A Perspective Considering Three-Dimensional Mitral Valve Area by Transesophageal Echocardiography
by Tony Li, Ryan Leow, Meei Wah Chan, William K. F. Kong, Ivandito Kuntjoro, Kian Keong Poh, Ching Hui Sia and Tiong Cheng Yeo
Diagnostics 2024, 14(15), 1595; https://doi.org/10.3390/diagnostics14151595 - 24 Jul 2024
Viewed by 658
Abstract
Background: Net atrioventricular compliance (Cn) can affect the accuracy of mitral valve area (MVA) assessment. We assessed how different methods of MVA assessment are affected by Cn, and if patients with abnormal Cn may be identified by clinical [...] Read more.
Background: Net atrioventricular compliance (Cn) can affect the accuracy of mitral valve area (MVA) assessment. We assessed how different methods of MVA assessment are affected by Cn, and if patients with abnormal Cn may be identified by clinical and/or echocardiographic parameters. Methods: We studied 244 patients with rheumatic MS. The concordance between mitral valve area (MVA) by 2D planimetry, pressure half-time (PHT), continuity equation (CE), Yeo’s index, and 3-dimensional mitral valve area assessed by transesophageal echocardiography (TEE 3DMVA) in patients with normal and abnormal Cn (Cn ≤ 4 mL/mmHg) were evaluated in the 110 patients with both transesophageal echocardiogram (TEE) and transthoracic echocardiogram (TTE). Variables that were associated with abnormal Cn were validated in the remaining 134 patients with only TTE. Results: Except for MVA by CE, concordance with TEE 3DMVA was poorer for all other methods of MVA assessment in patients with abnormal Cn. But, the difference in concordance was only statistically significant for MVA by PHT. Patients with MVA ≤ 1.5 cm2 by 2D planimetry and PHT ≤ 130 ms were likely to have an abnormal Cn. (specificity 98.5%). This finding was validated in the remaining 134 patients (specificity 93%). Conclusions: MVA assessment by PHT is significantly affected by Cn. Abnormal Cn should be suspected when 2D planimetry MVA is ≤1.5 cm2 together with an inappropriately short PHT that is ≤130 ms. In this scenario, MVA by PHT is inaccurate. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Heart Disease)
23 pages, 2807 KiB  
Review
Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology
by Aman Singh, Kriti S. Bhatt, Hien C. Nguyen, Jefferson C. Frisbee and Krishna K. Singh
Int. J. Mol. Sci. 2024, 25(11), 6180; https://doi.org/10.3390/ijms25116180 - 4 Jun 2024
Cited by 3 | Viewed by 2365
Abstract
Under different pathophysiological conditions, endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand [...] Read more.
Under different pathophysiological conditions, endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development; however, EndMT is also implicated in the pathogenesis of several genetically determined and acquired diseases, including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases, aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, and cardiac fibrosis. Accordingly, understanding the mechanisms behind the cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy for treating aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and a lack of robust animal models and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Cardiovascular Diseases)
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<p>Endothelium and CVDs. Different mechanisms leading to leaky vasculature, increased inflammation, plaque development, or apoptosis in CVDs. The figure provides a detailed depiction of the interconnected mechanisms within endothelial dysfunction and their relevance to CVDs. It illustrates how the endothelium plays a crucial role in the pathogenesis of CVDs through various processes. The sequence begins with endothelial dysfunction leading to a leaky vasculature and increased vascular permeability, facilitated by TLR4 activation of the NF-κB pathway, upregulation of ICAM-1, VCAM-1, Selectins and subsequent cytokine release—all contributing to heightened inflammation. This cascade of events culminates in inflammation, affecting claudin-1 and ZO-1. The progression of inflammation exacerbates plaque development through the transformation of macrophages into foam cells, releasing pro-inflammatory cytokines, including IL-6, TNF-α, and MMP-7. Reduced phagocytosis and decreased CD163 expression highlight the impact of these processes on plaque instability within the vasculature. Additionally, upregulated vWF mediates endothelial activation and platelet adhesion, crucial for the inflammatory response. Moreover, vWF facilitates immune cell recruitment and acts as a signaling molecule, amplifying the inflammatory cascade. Plaque formation and rupture are highlighted as critical events triggered by endothelial dysfunction and oxLDL accumulation, contributing to the progression of CVDs. Finally, the figure illustrates apoptosis induced by various factors such as oxidative stress, hypoxia, reduced NO, ER stress, and chemotherapeutic agents and shear stress (as shown by red arrows pointing in the same direction, while others veer left or right, and some proceeding straight, capturing the dynamic nature of biomechanical forces acting on the endothelium). These factors contribute to apoptotic cell death within the vascular environment, emphasizing the diverse mechanisms through which endothelial dysfunction can lead to adverse outcomes in cardiovascular health, ultimately impacting the development and progression of various CVDs. TLR4: Toll-like Receptor 4, ICAM-1: Intercellular Adhesion Molecule-1, VCAM-1: Vascular Cell Adhesion Molecule-1, NF-κB: Nuclear Factor Kappa B, IL-6: Interleukin-6, TNF-α: Tumor Necrosis Factor- α, MMP-7: Matrix Metalloproteinase-7, CD163: Cluster of Differentiation 163, vWF: von Willebrand Factor, NO—Nitric Oxide, ER—Endoplasmic Reticulum, oxLDL: Oxidized Low-Density Lipoprotein, ZO-1: Zonula Occludens-1, EndMT: Endothelial-to-Mesenchymal Transition.</p>
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<p>Figure depicting healthy endothelium and EndMT leading to different CVDs. Figure showing EndMT within endocardial endothelial cells, elucidating the contrast between the impermeable vascular structure of healthy endothelium and the disruptive impact of EndMT. Conversely, the EndMT, ignited by factors like shear stress, TGF-β, IL-1β, TNF-α, high glucose levels, and oxLDL, drives the transformation of active endothelial cells into myofibroblasts, promoting cardiac fibrosis. Beyond these factors, inflammation, aging, mitochondrial dysfunction, and autophagic dysfunction also contribute to the EndMT process. The appearance of a leaky endothelium signals the initiation of endothelial dysfunction within the endocardium, indicating a critical juncture in the path toward CVDs. This transformative journey not only disrupts endothelial integrity but heightens the risks of severe cardiovascular ailments such as heart failure, hypertension, peripheral coronary artery disease, cardiac fibrosis, and valvular abnormalities. These outcomes emphasize the intricate interplay between endothelial dysfunction, EndMT, and the spectrum of cardiovascular disorders, underscoring the necessity for a profound comprehension of these processes to drive targeted interventions and preserve cardiovascular well-being. EndMT: Endothelial-to-Mesenchymal Transition, TGF-β: Transforming Growth Factor-β, IL-1β: Interleukin-1β, TNF-α: Tumor Necrosis Factor-α, oxLDL: Oxidized Low-Density Lipoprotein.</p>
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<p>Canonical and noncanonical TGF- β signaling in EndMT. TGF-β homodimers interact with the TGF-β I/II receptor complex on the cell surface to initiate the canonical TGF-β pathway. This triggers the phosphorylation and activation of Smad2 and Smad3 proteins. Subsequently, the activated Smad2/3 complex with Smad4 translocate to the nucleus and activate transcription of genes involved in creating profibrotic extracellular matrix components such as Col4, Col1, Col3 and transcription factors like Snai1, Snai2, and Twist1. Noncanonical pathways involving kinases PI3K, Tak1, Ras, and c-Abl also influence EndMT. These pathways can lead to different cellular responses, independent of Smad2/3 activation, either by decreasing endothelial-specific gene transcription or increasing mesenchymal-specific gene expression. These pathways impact the expression of genes associated with EndMT, leading to variations in the transcription of markers like CD31, Col4, Col1, Col3, FSP1, and Acta2. Notably, these effects are also influenced by transcription factors such as Snai1, Snai2, and Twist1. TGF-β: Transforming Growth Factor-β, ECM: Extracellular Matrix, TGF-βRI/II: Transforming Growth Factor-β Receptor I/II, EndMT: Endothelial-to-Mesenchymal Transition, Col4: Collagen Type IV, Col1: Collagen Type I, Col3: Collagen Type III, PI3K: Phosphatidylinositol 3-Kinase, Tak1: TGF-β-activated kinase 1, c-Abl: Abelson Tyrosine-Protein Kinase 1, CD31: Cluster of Differentiation 31, FSP1: Fibroblast-Specific Protein 1, Acta2: Alpha Smooth Muscle Actin, Snail1: Zinc Finger Protein SNAI1, Snail2: Zinc Finger Protein SNAI2, Twist: Twist Family BHLH Transcription Factor 1.</p>
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<p>Unraveling the intricate interactions: TGF-β signaling, DNA damage repair, BRCA1/BRCA2, and EndMT. TGF-β signaling influences BRCA1/2 expression, pivotal in DNA damage repair, while DNA damage reciprocally enhances TGF-β signaling. Furthermore, TGF-β also induces EndMT. An established relationship exists between TGF-β and EndMT, TGF-β and DNA damage, and TGF-β and BRCA1/2. However, the direct effect of DNA damage and DNA damage repair molecules BRCA1/2 on EndMT remains unknown. TGF-β: Transforming Growth Factor-β, BRCA1/2: Breast Cancer Susceptibility Gene 1/2, EndMT: Endothelial-to-Mesenchymal Transition, DNA: Deoxyribonucleic Acid.</p>
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<p>EndMT in development and disease. During embryonic development, specific endothelial cells within the AV canal engage in EndMT, facilitating the creation of endocardial cushions essential for the proper development of the AV valve. As the embryo matures, these endocardial cushions undergo remodeling to form durable valve leaflets and the supporting chordae tendineae. In adult life, EndMT plays a crucial role in the initiation and progression of various CVDs and cancer. EndMT: Endothelial-to-Mesenchymal Transition, CVDs: Cardiovascular Diseases.</p>
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13 pages, 1213 KiB  
Article
Clinical Factors Affecting Survival in Patients with Congenitally Corrected Transposition of the Great Arteries: A Systematic Review and Meta-Analysis
by Sonia Alicja Nartowicz, Ewelina Jakielska, Piotr Ratajczak, Maciej Lesiak and Olga Trojnarska
J. Clin. Med. 2024, 13(11), 3127; https://doi.org/10.3390/jcm13113127 - 27 May 2024
Cited by 1 | Viewed by 1420
Abstract
Background: Congenitally corrected transposition of the great arteries (cc-TGA) is a defect characterized by arterio-ventricular and atrioventricular disconcordance. Most patients have co-existing cardiac abnormalities that warrant further treatment. Some patients do not require surgical intervention, but most undergo physiological repair or anatomical surgery, [...] Read more.
Background: Congenitally corrected transposition of the great arteries (cc-TGA) is a defect characterized by arterio-ventricular and atrioventricular disconcordance. Most patients have co-existing cardiac abnormalities that warrant further treatment. Some patients do not require surgical intervention, but most undergo physiological repair or anatomical surgery, which enables them to reach adulthood. Aims: We aimed to evaluate mortality risk factors in patients with cc-TGA. Results: We searched the PubMed database and included 10 retrospective cohort studies with at least a 5-year follow-up time with an end-point of cardiovascular death a minimum of 30 days after surgery. We enrolled 532 patients, and 83 met the end-point of cardiovascular death or equivalent event. As a risk factor for long-term mortality, we identified New York Heart Association (NYHA) class ≥III/heart failure hospitalization (OR = 10.53; 95% CI, 3.17–34.98) and systemic ventricle dysfunction (SVD; OR = 4.95; 95% CI, 2.55–9.64). We did not show history of supraventricular arrhythmia (OR = 2.78; 95% CI, 0.94–8.24), systemic valve regurgitation ≥moderate (SVR; OR = 4.02; 95% Cl, 0.84–19.18), and pacemaker implantation (OR = 1.48; 95% Cl, 0.12–18.82) to affect the long-term survival. In operated patients only, SVD (OR = 4.69; 95% CI, 2.06–10.71) and SVR (OR = 3.85; 95% CI, 1.5–9.85) showed a statistically significant impact on survival. Conclusions: The risk factors for long-term mortality for the entire cc-TGA population are NYHA class ≥III/heart failure hospitalization and systemic ventricle dysfunction. In operated patients, systemic ventricle dysfunction and at least moderate systemic valve regurgitation were found to affect survival. Full article
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<p>PRISMA summarizing selection process for inclusion of studies. Abbreviations: cc-TGA—congenitally corrected transposition of the great arteries.</p>
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<p>Forest plots showing pooled odds ratios of NYHA &gt;II/heart hospitalization (<b>A</b>), at least moderate SVR (<b>B</b>), SVD (<b>C</b>), history of SVT (<b>D</b>), and pacemaker implantation (<b>E</b>) for long-term mortality using a random effects meta-analysis approach. Abbreviations: cc-TGA—congenitally corrected transposition of the great arteries; NYHA—New York Heart Association; SVR—systemic valve regurgitation; SVD—systemic ventricular dysfunction; SVT—supraventricular tachyarrhythmia [<a href="#B9-jcm-13-03127" class="html-bibr">9</a>,<a href="#B10-jcm-13-03127" class="html-bibr">10</a>,<a href="#B12-jcm-13-03127" class="html-bibr">12</a>,<a href="#B13-jcm-13-03127" class="html-bibr">13</a>,<a href="#B14-jcm-13-03127" class="html-bibr">14</a>,<a href="#B15-jcm-13-03127" class="html-bibr">15</a>,<a href="#B16-jcm-13-03127" class="html-bibr">16</a>,<a href="#B17-jcm-13-03127" class="html-bibr">17</a>,<a href="#B18-jcm-13-03127" class="html-bibr">18</a>].</p>
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<p>Forest plots showing pooled odds ratios of SVD (<b>A</b>) and history of SVR (<b>B</b>) for long-term mortality after surgical repair using a random effects meta-analysis approach. Abbreviations—see <a href="#jcm-13-03127-f002" class="html-fig">Figure 2</a>A [<a href="#B9-jcm-13-03127" class="html-bibr">9</a>,<a href="#B10-jcm-13-03127" class="html-bibr">10</a>,<a href="#B13-jcm-13-03127" class="html-bibr">13</a>,<a href="#B14-jcm-13-03127" class="html-bibr">14</a>,<a href="#B18-jcm-13-03127" class="html-bibr">18</a>].</p>
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13 pages, 910 KiB  
Article
Prognosis and Predictor Factors of Permanent Pacemaker Implantation after Transcatheter Aortic Valve Replacement: A Retrospective Analysis of the Post-Transcatheter Aortic Replacement Clairval Hospital Registry
by Vassili Panagides, Emna Sakka, Edouard Cheneau, Ahmed Bouharaoua, Jacques Vicat, Elisabeth Leude-Vaillant, Philippe Rochas, Frédéric Collet and Marie-Paule Giacomoni
J. Clin. Med. 2024, 13(11), 3050; https://doi.org/10.3390/jcm13113050 - 22 May 2024
Viewed by 1072
Abstract
Background/Objectives: Despite procedural improvements, post-transcatheter aortic valve replacement (TAVR) conduction disorders remain high. Analyzing the data from a monocentric TAVR registry, this study aims to determine predictive factors for PPI (primary outcome), the indication for PPI, and long-term outcomes among these patients [...] Read more.
Background/Objectives: Despite procedural improvements, post-transcatheter aortic valve replacement (TAVR) conduction disorders remain high. Analyzing the data from a monocentric TAVR registry, this study aims to determine predictive factors for PPI (primary outcome), the indication for PPI, and long-term outcomes among these patients (secondary outcomes). Methods: Conducted at Clairval Hospital in Marseille, France, this retrospective study included all consecutive patients from June 2012 to June 2019. Clinical, electrocardiographic, echocardiographic, and procedural data were collected, with outcomes assessed annually. Logistic regression identified PPI predictors and survival analyses were performed. Results: Of the 1458 patients initially considered, 1157 patients were included. PPI was needed in 21.5% of patients, primarily for third-degree atrioventricular block (46.4%). Predictor factors for PPI included baseline right bundle branch block (ORadj 2.49, 95% CI 1.44 to 4.30; p = 0.001), longer baseline QRS duration (ORadj 1.01, 95% CI 1.00 to1.02, p = 0.002), and self-expandable valves (ORadj 1.82, 95% CI, 1.09 to 3.03; p = 0.021). Seven-year estimated mortality was higher in PPI (43.3%) vs. non-PPI patients (30.9%) (log rank p = 0.048). PPI was an independent predictive factor of death (ORadj 2.49, 95% CI 1.4 to 4.3; p = 0.002). Conclusions: This study reveals elevated rates of PPI post-TAVR associated with increased mortality. These results underscore the pressing necessity to refine our practices, delineate precise indications, and enhance the long-term prognosis for implanted patients. Full article
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<p>Flowchart of the study population. PM: pacemaker; PPI: permanent pacemaker implantation; and TAVR: transcatheter aortic valve replacement.</p>
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<p>Kaplan-Meier curves comparing survival stratified by PPI and the non-PPI group. The test comparing the two groups was based on the log-rank test.</p>
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17 pages, 3911 KiB  
Review
Contemporary Management of the Failing Fontan
by Prashanth Venkatesh, Hans Gao, Islam Abudayyeh, Ramdas G. Pai and Padmini Varadarajan
J. Clin. Med. 2024, 13(11), 3049; https://doi.org/10.3390/jcm13113049 - 22 May 2024
Viewed by 1342
Abstract
Adult patients with congenital heart disease have now surpassed the pediatric population due to advances in surgery and improved survival. One such complex congenital heart disease seen in adult patients is the Fontan circulation. These patients have complex physiology and are at risk [...] Read more.
Adult patients with congenital heart disease have now surpassed the pediatric population due to advances in surgery and improved survival. One such complex congenital heart disease seen in adult patients is the Fontan circulation. These patients have complex physiology and are at risk for several complications, including thrombosis of the Fontan pathway, pulmonary vascular disease, heart failure, atrial arrhythmias, atrioventricular valve regurgitation, and protein-losing enteropathy. This review discusses the commonly encountered phenotypes of Fontan circulatory failure and their contemporary management. Full article
(This article belongs to the Section Cardiology)
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<p>Hypoplastic left ventricle with extracardiac Fontan.</p>
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<p>Chest X-ray of a patient with hypoplastic left heart and extracardiac Fontan with temporary mechanical circulatory support as bridge to heart transplant.</p>
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<p>Selective angiography of extracardiac Fontan and left pulmonary artery status post multiple stents.</p>
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<p>Selective angiography of bidirectional right-sided Glenn shunt (<b>A</b>) and extracardiac Fontan (<b>B</b>).</p>
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<p>Transesophageal echocardiogram demonstrating an enlarged common atrium with a deformed atrioventricular valve (AV) (<b>A</b>) and severe AV valve regurgitation (<b>B</b>).</p>
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<p>Transesophageal echocardiogram demonstrating two MitraClips XTW (<b>A</b>), and an improvement in atrioventricular (AV) regurgitation severity (<b>B</b>).</p>
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<p>Fluoroscopic image showing the MitraClips in Position.</p>
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20 pages, 4543 KiB  
Review
Role and Applications of Experimental Animal Models of Fontan Circulation
by Zakaria Jalal, Elise Langouet, Nabil Dib, Soazig Le-Quellenec, Mansour Mostefa-Kara, Amandine Martin, François Roubertie and Jean-Benoît Thambo
J. Clin. Med. 2024, 13(9), 2601; https://doi.org/10.3390/jcm13092601 - 29 Apr 2024
Viewed by 1441
Abstract
Over the last four decades, the Fontan operation has been the treatment of choice for children born with complex congenital heart diseases and a single-ventricle physiology. However, therapeutic options remain limited and despite ongoing improvements in initial surgical repair, patients still experience a [...] Read more.
Over the last four decades, the Fontan operation has been the treatment of choice for children born with complex congenital heart diseases and a single-ventricle physiology. However, therapeutic options remain limited and despite ongoing improvements in initial surgical repair, patients still experience a multiplicity of cardiovascular complications. The causes for cardiovascular failure are multifactorial and include systemic ventricular dysfunction, pulmonary vascular resistance, atrioventricular valve regurgitation, arrhythmia, development of collaterals, protein-losing enteropathy, hepatic dysfunction, and plastic bronchitis, among others. The mechanisms leading to these late complications remain to be fully elucidated. Experimental animal models have been developed as preclinical steps that enable a better understanding of the underlying pathophysiology. They furthermore play a key role in the evaluation of the efficacy and safety of new medical devices prior to their use in human clinical studies. However, these experimental models have several limitations. In this review, we aim to provide an overview of the evolution and progress of the various types of experimental animal models used in the Fontan procedure published to date in the literature. A special focus is placed on experimental studies performed on animal models of the Fontan procedure with or without mechanical circulatory support as well as a description of their impact in the evolution of the Fontan design. We also highlight the contribution of animal models to our understanding of the pathophysiology and assess forthcoming developments that may improve the contribution of animal models for the testing of new therapeutic solutions. Full article
(This article belongs to the Special Issue Management of Pediatric Congenital Heart Disease)
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<p>First-in-human surgical atriopulmonary connection by Fontan et al. SVC derivated to the RPA, and RA to the LPA, using the RA as a pump [<a href="#B1-jcm-13-02601" class="html-bibr">1</a>]. SVC: superior vena cava; RA; right atrium; RV: right ventricle; IVC: inferior vena cava.</p>
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<p>Current total cavopulmonary connection with extracardiac tunnel. SVC: superior vena cava; SV: single ventricle; IVC: inferior vena cava.</p>
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<p>Kanakis et al.’s surgical model of the Fontan circulation without cardiopulmonary bypass, showing Y-shaped conduct between both the vena cava and MPA [<a href="#B16-jcm-13-02601" class="html-bibr">16</a>]. SVC: superior vena cava; MPA: main pulmonary artery; RV: right ventricle; IVC: inferior vena cava.</p>
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<p>Klima et al.’s hybrid model of the Fontan circulation without cardiopulmonary bypass. First step: surgical reimplantation of the SVC in the RPA, and ligature of the MPA; second step: transcatheter implantation of a covered stent between the IVC and RPA [<a href="#B17-jcm-13-02601" class="html-bibr">17</a>]. SVC: superior vena cava; RPA: right pulmonary artery; MPA: main pulmonary artery; RV: right ventricle; IVC: inferior vena cava.</p>
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<p>Main Fontan circulation hemodynamic features displayed as a pressure/time diagram over a cardiac cycle. SV: single ventricle, Ao: aorta, CV: caval veins, PA: pulmonary artery, LA: left atria, ∆P: transpulmonary gradient.</p>
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<p>Van Puyvelde’s model of the Fontan circulation, a unique chronic model. Derivation of the SVC to the MPA, and the IVC to the MPA with prosthetic conduct; both vena cava ostias are ligatured [<a href="#B47-jcm-13-02601" class="html-bibr">47</a>]. SVC: superior vena cava; RA: right atrium; MPA: main pulmonary artery; IVC: inferior vena cava.</p>
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<p>Rodefeld’s model of the Fontan circulation mechanical circulatory support, with two axial pumps draining venous blood from caval veins to pulmonary arteries and a derivation of residual venous blood of the ventricle to the vena cava [<a href="#B49-jcm-13-02601" class="html-bibr">49</a>]. SVC: superior vena cava; RPA; right pulmonary artery; RV: right ventricle; MPA: main pulmonary artery; IVC: inferior vena cava.</p>
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