Journal of Cardiovascular Development and Disease

15 pages, 4617 KiB

Open AccessEditor’s ChoiceReview

Echocardiographic Assessment of Atrial Function: From Basic Mechanics to Specific Cardiac Diseases

by Katsuji Inoue, Hiroshi Kawakami, Yusuke Akazawa, Haruhiko Higashi, Takashi Higaki and Osamu Yamaguchi

J. Cardiovasc. Dev. Dis. 2022, 9(3), 68; https://doi.org/10.3390/jcdd9030068 - 27 Feb 2022

Cited by 7 | Viewed by 4574

Abstract

The left and right atria serve as buffer chambers to control the flow of venous blood for ventricular filling. If an atrium is absent, blood does not flow effectively into the ventricle, leading to venous blood retention and low cardiac output. The importance [...] Read more.

The left and right atria serve as buffer chambers to control the flow of venous blood for ventricular filling. If an atrium is absent, blood does not flow effectively into the ventricle, leading to venous blood retention and low cardiac output. The importance of atrial function has become increasingly recognized, because left atrial (LA) function contributes to cardiac performance, and loss of LA function is associated with heart failure. LA volume change has been used for LA function assessment in experimental and clinical studies. In conjunction with LA pressure, the LA pressure–volume relationship provides a better understanding of LA mechanics. LA strain measurement by speckle tracking echocardiography was introduced to evaluate three components of LA function as a (booster) pump, reservoir and conduit. Furthermore, increasing evidence supports the theory that LA reservoir strain has prognostic utility in various cardiac diseases. In this review, we summarize LA contribution to maintain cardiac performance by evaluating LA function with echocardiography according to our experiences and previous reports. Furthermore, we discuss LA dysfunction in challenging cardiac diseases of cardiac amyloidosis and adult congenital heart disease. Full article

(This article belongs to the Special Issue Echocardiography in Cardiovascular Disease)

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12 pages, 1912 KiB

Open AccessEditor’s ChoiceArticle

Sex Differences in the Evaluation of Congestion Markers in Patients with Acute Heart Failure

by Pietro Scicchitano, Claudio Paolillo, Micaela De Palo, Angela Potenza, Silvia Abruzzese, Marco Basile, Antonia Cannito, Maria Tangorra, Piero Guida, Pasquale Caldarola, Marco Matteo Ciccone and Francesco Massari

J. Cardiovasc. Dev. Dis. 2022, 9(3), 67; https://doi.org/10.3390/jcdd9030067 - 24 Feb 2022

Cited by 5 | Viewed by 3077

Abstract

The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We [...] Read more.

The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We consecutively enrolled 494 AHF patients (252 female). Clinical congestion assessment, B-type natriuretic peptide levels analysis, blood urea nitrogen to creatinine ratio (BUN/Cr), plasma volume status estimate (by means of Duarte or Kaplam-Hakim PVS), and hydration status evaluation through bioimpedance analysis were performed. There was no difference in medications between men and women. Women were older (79 ± 9 yrs vs. 77 ± 10 yrs, p = 0.005), and had higher left ventricular ejection fraction (45 ± 11% vs. 38 ± 11%, p < 0.001), and lower creatinine clearance (42 ± 25 mL/min vs. 47 ± 26 mL/min, p = 0.04). The prevalence of peripheral oedema, orthopnoea, and jugular venous distention were not significantly different between women and men. BUN/Cr (27 ± 9 vs. 23 ± 13, p = 0.04) and plasma volume were higher in women than men (Duarte PVS: 6.0 ± 1.5 dL/g vs. 5.1 ± 1.5 dL/g, p < 0.001; Kaplam–Hakim PVS: 7.9 ± 13% vs. −7.3 ± 12%, p < 0.001). At multivariate logistic regression analysis, female sex was independently associated with BUN/Cr and PVS. Female sex was independently associated with subclinical biomarkers of congestion such as BUN/Cr and PVS in patients with AHF. A sex-guided approach to the correct evaluation of patients with AHF might become the cornerstone for the correct management of these patients. Full article

(This article belongs to the Section Epidemiology, Lifestyle, and Cardiovascular Health)

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31 pages, 1092 KiB

Open AccessEditor’s ChoiceReview

Leukocyte-Mediated Cardiac Repair after Myocardial Infarction in Non-Regenerative vs. Regenerative Systems

by Elizabeth Anne Peterson, Jisheng Sun and Jinhu Wang

J. Cardiovasc. Dev. Dis. 2022, 9(2), 63; https://doi.org/10.3390/jcdd9020063 - 21 Feb 2022

Cited by 7 | Viewed by 4640

Abstract

Innate and adaptive leukocytes rapidly mobilize to ischemic tissues after myocardial infarction in response to damage signals released from necrotic cells. Leukocytes play important roles in cardiac repair and regeneration such as inflammation initiation and resolution; the removal of dead cells and debris; [...] Read more.

Innate and adaptive leukocytes rapidly mobilize to ischemic tissues after myocardial infarction in response to damage signals released from necrotic cells. Leukocytes play important roles in cardiac repair and regeneration such as inflammation initiation and resolution; the removal of dead cells and debris; the deposition of the extracellular matrix and granulation tissue; supporting angiogenesis and cardiomyocyte proliferation; and fibrotic scar generation and resolution. By organizing and comparing the present knowledge of leukocyte recruitment and function after cardiac injury in non-regenerative to regenerative systems, we propose that the leukocyte response to cardiac injury differs in non-regenerative adult mammals such as humans and mice in comparison to cardiac regenerative models such as neonatal mice and adult zebrafish. Specifically, extensive neutrophil, macrophage, and T-cell persistence contributes to a lengthy inflammatory period in non-regenerative systems for adverse cardiac remodeling and heart failure development, whereas their quick removal supports inflammation resolution in regenerative systems for new contractile tissue formation and coronary revascularization. Surprisingly, other leukocytes have not been examined in regenerative model systems. With this review, we aim to encourage the development of improved immune cell markers and tools in cardiac regenerative models for the identification of new immune targets in non-regenerative systems to develop new therapies. Full article

(This article belongs to the Special Issue Model Systems for Heart Regeneration)

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21 pages, 7129 KiB

Open AccessEditor’s ChoiceArticle

DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse

by Kelsey S. Moore, Reece Moore, Diana B. Fulmer, Lilong Guo, Cortney Gensemer, Rebecca Stairley, Janiece Glover, Tyler C. Beck, Jordan E. Morningstar, Rachel Biggs, Rupak Muhkerjee, Alexander Awgulewitsch and Russell A. Norris

J. Cardiovasc. Dev. Dis. 2022, 9(2), 62; https://doi.org/10.3390/jcdd9020062 - 17 Feb 2022

Cited by 6 | Viewed by 3431

Abstract

Mitral valve prolapse (MVP) is a common cardiac valve disease that often progresses to serious secondary complications requiring surgery. MVP manifests as extracellular matrix disorganization and biomechanically incompetent tissues in the adult setting. However, MVP has recently been shown to have a developmental [...] Read more.

Mitral valve prolapse (MVP) is a common cardiac valve disease that often progresses to serious secondary complications requiring surgery. MVP manifests as extracellular matrix disorganization and biomechanically incompetent tissues in the adult setting. However, MVP has recently been shown to have a developmental basis, as multiple causal genes expressed during embryonic development have been identified. Disease phenotypes have been observed in mouse models with human MVP mutations as early as birth. This study focuses on the developmental function of DCHS1, one of the first genes to be shown as causal in multiple families with non-syndromic MVP. By using various biochemical techniques as well as mouse and cell culture models, we demonstrate a unique link between DCHS1-based cell adhesions and the septin-actin cytoskeleton through interactions with cytoplasmic protein Lix1-Like (LIX1L). This DCHS1-LIX1L-SEPT9 axis interacts with and promotes filamentous actin organization to direct cell-ECM alignment and valve tissue shape. Full article

(This article belongs to the Section Basic and Translational Cardiovascular Research)

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15 pages, 3835 KiB

Open AccessEditor’s ChoiceReview

Arrhythmic Mitral Valve Prolapse and Mitral Annular Disjunction: Clinical Features, Pathophysiology, Risk Stratification, and Management

by Apurba K. Chakrabarti, Frank Bogun and Jackson J. Liang

J. Cardiovasc. Dev. Dis. 2022, 9(2), 61; https://doi.org/10.3390/jcdd9020061 - 16 Feb 2022

Cited by 14 | Viewed by 6790

Abstract

Mitral valve prolapse (MVP) is a common cause of valvular heart disease. Although many patients with MVP have a benign course, there is increasing recognition of an arrhythmic phenotype associated with ventricular arrhythmias and sudden cardiac death (SCD). Pathophysiologic mechanisms associated with arrhythmias [...] Read more.

Mitral valve prolapse (MVP) is a common cause of valvular heart disease. Although many patients with MVP have a benign course, there is increasing recognition of an arrhythmic phenotype associated with ventricular arrhythmias and sudden cardiac death (SCD). Pathophysiologic mechanisms associated with arrhythmias include cardiac fibrosis, mechanical stress induced changes in ventricular refractory periods, as well as electrophysiologic changes in Purkinje fibers. Clinically, a variety of risk factors including demographic, electrocardiographic, and imaging characteristics help to identify patients with MVP at the highest at risk of SCD and arrhythmias. Once identified, recent advances in treatment including device therapy, catheter ablation, and surgical interventions show promising outcomes. In this review, we will summarize the incidence of ventricular arrhythmias and SCD in patients with MVP, the association with mitral annular disjunction, mechanisms of arrhythmogenesis, methods for arrhythmic and SCD risk stratification including findings with multimodality imaging, and treatments for the primary and secondary prevention of SCD. Full article

(This article belongs to the Special Issue Mitral Valve Prolapse and Mitral Regurgitation)

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11 pages, 911 KiB

Open AccessEditor’s ChoiceReview

What the near Future Holds for Sacubitril/Valsartan: A Summary of Major Ongoing Studies

by Hisham A. Badreldin, Nasser Aldosari, Lama Alnashwan, Taif Almutairi, Nada Yousif, Khalid Alsulaiman, Ohoud Aljuhani, Awatif Hafiz and Omar Alshaya

J. Cardiovasc. Dev. Dis. 2022, 9(2), 54; https://doi.org/10.3390/jcdd9020054 - 10 Feb 2022

Cited by 3 | Viewed by 5214

Abstract

Early research on neprilysin inhibition showed that sacubitril/valsartan, a combination of the valsartan and the neprilysin inhibitor sacubitril, was superior to enalapril in patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF study in 2014. Therefore, for patients with HFrEF, [...] Read more.

Early research on neprilysin inhibition showed that sacubitril/valsartan, a combination of the valsartan and the neprilysin inhibitor sacubitril, was superior to enalapril in patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF study in 2014. Therefore, for patients with HFrEF, worldwide recommendations have been reformed to include sacubitril/valsartan. In addition, sacubitril/valsartan has been investigated in other cardiovascular disease states, such as patients with heart failure and preserved ejection fraction (HFpEF) and following myocardial infarction (MI) events. In February 2021, the FDA expanded the indication use of sacubitril/valsartan to include the HFpEF patient population based on the results of the PARAGON-HF trial. However, randomized clinical trials post-MI did not show promising results. Sacubitril/valsartan is currently being investigated in many other cardiovascular and non-cardiovascular conditions. This review aims to shed light and summarize the ongoing sacubitril/valsartan registered studies on the United States National Library of Medicine clinical trials registry. Full article

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11 pages, 1242 KiB

Open AccessEditor’s ChoiceArticle

The Incidence, Electrophysiological Characteristics and Ablation Outcome of Left Atrial Tachycardias after Pulmonary Vein Isolation Using Three Different Ablation Technologies

by Patrick Leitz, Kristina Wasmer, Christian Andresen, Fatih Güner, Julia Köbe, Benjamin Rath, Florian Reinke, Julian Wolfes, Philipp S. Lange, Christian Ellermann, Gerrit Frommeyer and Lars Eckardt

J. Cardiovasc. Dev. Dis. 2022, 9(2), 50; https://doi.org/10.3390/jcdd9020050 - 3 Feb 2022

Cited by 2 | Viewed by 2151

Abstract

Background: Left atrial tachycardias (LAT) are a well-known outcome of pulmonary vein isolation (PVI). Few data are available on whether the catheter used to perform PVI influences the incidence, as well as the characteristics of post PVI LAT. We present data on LAT [...] Read more.

Background: Left atrial tachycardias (LAT) are a well-known outcome of pulmonary vein isolation (PVI). Few data are available on whether the catheter used to perform PVI influences the incidence, as well as the characteristics of post PVI LAT. We present data on LAT following PVI by the following three ablation technologies: (1) phased multi-electrode radiofrequency catheter (PVAC), (2) irrigated single-tip catheter (iRF), and (3) cryoballoon ablation. Methods: Using a prospectively designed single-center database, we analyzed 650 patients (300 iRF, 150 PVAC, and 200 cryoballoon) with paroxysmal (n = 401) and persistent atrial fibrillation (AF), who underwent their first PVI at our center. Results: The three populations were comparable in their baseline characteristics; however, the cryoballoon group comprised a higher percentage of patients with persistent AF (p = 0.05). The LAT rates were 3.7% in the iRF group (mean follow-up 22 ± 14 months), 0.7% in the PVAC group (mean follow-up 21 ± 14 months), and 4% in the cryoballoon group (mean follow-up 15 ± 8 months). The predominant mechanism of LAT was macro-reentrant tachycardia. Reconnection of at least one pulmonary vein was observed in 87% of the patients who underwent 3D mapping. No predictors for LAT occurrence were identified. Conclusion: The occurrence of LAT post PVI is rare; the predominant mechanism was macro-reentrant tachycardia. Reconnection of at least one pulmonary vein was observed in nearly all the LAT patients. In our retrospective analysis, the lowest rate of LAT was observed with the PVAC. No predictors for LAT occurrence were identified. Full article

(This article belongs to the Special Issue Catheter Ablation of Cardiac Arrhythmias: Practices and Outcomes)

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33 pages, 7245 KiB

Open AccessEditor’s ChoiceReview

Cardiomyopathies in Children and Systemic Disorders When Is It Useful to Look beyond the Heart?

by Valentina Lodato, Giovanni Parlapiano, Federica Calì, Massimo Stefano Silvetti, Rachele Adorisio, Michela Armando, May El Hachem, Antonino Romanzo, Carlo Dionisi-Vici, Maria Cristina Digilio, Antonio Novelli, Fabrizio Drago, Massimiliano Raponi and Anwar Baban

J. Cardiovasc. Dev. Dis. 2022, 9(2), 47; https://doi.org/10.3390/jcdd9020047 - 31 Jan 2022

Cited by 9 | Viewed by 4506

Abstract

Cardiomyopathy (CMP) is a rare disease in the pediatric population, with a high risk of morbidity and mortality. The genetic etiology of CMPs in children is extremely heterogenous. These two factors play a major role in the difficulties of establishing standard diagnostic and [...] Read more.

Cardiomyopathy (CMP) is a rare disease in the pediatric population, with a high risk of morbidity and mortality. The genetic etiology of CMPs in children is extremely heterogenous. These two factors play a major role in the difficulties of establishing standard diagnostic and therapeutic protocols. Isolated CMP in children is a frequent finding, mainly caused by sarcomeric gene variants with a detection rate that can reach up to 50% of analyzed cohorts. Complex multisystemic forms of pediatric CMP are even more heterogenous. Few studies in literature take into consideration this topic as the main core since it represents a rarity (systemic CMP) within a rarity (pediatric population CMP). Identifying etiology in this cohort is essential for understanding prognosis, risk stratification, eligibility to heart transplantation and/or mechanical-assisted procedures, preventing multiorgan complications, and relatives’ recurrence risk calculation. The previous points represent a cornerstone in patients’ empowerment and personalized medical care approach. The aim of this work is to propose a new approach for an algorithm in the setting of the diagnostic framework of systemic pediatric CMP. On the other hand, during the literature review, we noticed a relatively common etiologic pattern in some forms of complex/multisystem CMP. In other words, certain syndromes such as Danon, Vici, Alström, Barth, and Myhre syndrome share a common pathway of directly or indirectly defective “autophagy” process, which appears to be a possible initiating/triggering factor for CMPs. This conjoint aspect could be important for possible prognostic/therapeutic implications in this category of patients. However, multicentric studies detailed functional and experimental models are needed prior to deriving conclusions. Full article

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9 pages, 415 KiB

Open AccessEditor’s ChoiceArticle

A Propensity Score Analysis of Early and Long-Term Outcomes of Retrograde Arterial Perfusion for Endoscopic and Minimally Invasive Heart Valve Surgery in Both Young and Elderly Patients

by Hind Elhassan, Abdelrahman Abdelbar, Rebecca Taylor, Grzegorz Laskawski, Palanikumar Saravanan, Andrew Knowles and Joseph Zacharias

J. Cardiovasc. Dev. Dis. 2022, 9(2), 44; https://doi.org/10.3390/jcdd9020044 - 28 Jan 2022

Viewed by 2323

Abstract

(1) Background: Minimal invasive cardiac surgery via right anterolateral thoracotomy for heart valve surgery and other intracardiac procedures proven to have lower postoperative complications. We aim to compare the neurological complications and post-operative outcomes in two cohort groups as well as survival rates [...] Read more.

(1) Background: Minimal invasive cardiac surgery via right anterolateral thoracotomy for heart valve surgery and other intracardiac procedures proven to have lower postoperative complications. We aim to compare the neurological complications and post-operative outcomes in two cohort groups as well as survival rates up to 5 years postoperatively; (2) Methodology: Retrospective observational study for patients who had minimally invasive cardiac valve surgery with retrograde femoral arterial perfusion between 2007 and 2021 (n = 596) and the categorized patients into two groups based on their age (≥70 years old and below 70). Propensity match analysis was conducted. The primary endpoint consisted of major postoperative complications and the secondary endpoint was the long-term survival rate. (3) Results: There was no difference between the two groups in terms of postoperative outcomes. Patients ≥ 70 years old had no increased risk for neurological complications (p = 0.75) compared with those below 70 years old. The mortality rate was also not significant between the two groups (p = 0.37) as well as the crude survival rates. (4) Conclusions: The use of retrograde femoral arterial perfusion in elderly patients is not associated with increased risk compared to the younger patients’ group for a spectrum of primary cardiac valve procedures. Hence, minimally invasive approaches could be offered to elderly patients who might benefit from it. Full article

(This article belongs to the Special Issue Less Invasive and Video-Assisted Mitral Surgery at a Crossroads)

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11 pages, 471 KiB

Open AccessEditor’s ChoiceArticle

It Is Not Carved in Stone—The Need for a Genetic Reevaluation of Variants in Pediatric Cardiomyopathies

by Dominik Sebastian Westphal, Kathrin Pollmann, Christoph Marschall, Annette Wacker-Gussmann, Renate Oberhoffer-Fritz, Karl-Ludwig Laugwitz, Peter Ewert and Cordula Maria Wolf

J. Cardiovasc. Dev. Dis. 2022, 9(2), 41; https://doi.org/10.3390/jcdd9020041 - 25 Jan 2022

Cited by 2 | Viewed by 2776

Abstract

(1) Background: In cardiomyopathies, identification of genetic variants is important for the correct diagnosis and impacts family cascade screening. A classification system was published by the American College of Medical Genetics and Genomics (ACMG) in 2015 to standardize variants’ classification. The aim of [...] Read more.

(1) Background: In cardiomyopathies, identification of genetic variants is important for the correct diagnosis and impacts family cascade screening. A classification system was published by the American College of Medical Genetics and Genomics (ACMG) in 2015 to standardize variants’ classification. The aim of the study was to determine the rate of reclassification of previously identified variants in patients with childhood-onset cardiomyopathies. (2) Methods: Medical records of patients and their relatives were screened for clinical and genetic information at the Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich. Patients without an identified genetic variant were excluded from further analyses. Previously reported variants were reevaluated by the ACMG criteria in November 2021. (3) Results: Data from 167 patients or relatives of patients with childhood-onset cardiomyopathy from 137 families were analyzed. In total, 45 different genetic variants were identified in 71 individuals. Classification changed in 29% (13/45) with the greatest shift in “variants of unknown significance” to “(likely) benign” (9/13). (4) Conclusions: In patients with childhood-onset cardiomyopathies, nearly a third of reported genetic variants change mostly to more benign classes upon reclassification. Given the impact on patient management and cascade screening, this finding underlines the importance of continuous genetic counseling and variant. Full article

(This article belongs to the Special Issue Pediatric Cardiomyopathies: From Genotype to Phenotype)

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17 pages, 4942 KiB

Open AccessEditor’s ChoiceReview

Tachyarrhythmias in Congenital Heart Diseases: From Ion Channels to Catheter Ablation

by Victor Waldmann, Jean-Baptiste Guichard, Eloi Marijon and Paul Khairy

J. Cardiovasc. Dev. Dis. 2022, 9(2), 39; https://doi.org/10.3390/jcdd9020039 - 24 Jan 2022

Cited by 3 | Viewed by 3037

Abstract

Major advances in pediatric cardiology in recent decades, especially surgical techniques, have resulted in an increasing number of patients with congenital heart disease (CHD) surviving to adulthood. This has generated new challenges, particularly with regards to the late onset of complex arrhythmias. Abnormal [...] Read more.

Major advances in pediatric cardiology in recent decades, especially surgical techniques, have resulted in an increasing number of patients with congenital heart disease (CHD) surviving to adulthood. This has generated new challenges, particularly with regards to the late onset of complex arrhythmias. Abnormal anatomy, surgical scarring, chronic hypoxemia, hemodynamic compromise, neuro-hormonal abnormalities, and genetic factors can all contribute to creating a unique substrate for arrhythmia development. This review attempts to synthesize the current state of knowledge spanning the spectrum from underlying mechanisms of arrhythmias in patients with congenital heart disease to current ablative strategies. We discuss existing knowledge gaps and highlight important areas for future research. Full article

(This article belongs to the Special Issue Congenital Heart Defects: Diagnosis, Management, and Treatment)

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11 pages, 1826 KiB

Open AccessEditor’s ChoiceArticle

Combining Prognostic Nutritional Index and Brain Natriuretic Peptide as a Predicting Tool for Heart Transplantation

by Ziwen Cai, Jingrong Tu, Li Xu, Yao Lin, Bowen Deng, Fei Li, Si Chen and Nianguo Dong

J. Cardiovasc. Dev. Dis. 2022, 9(2), 40; https://doi.org/10.3390/jcdd9020040 - 24 Jan 2022

Cited by 2 | Viewed by 2607

Abstract

Our study aimed to evaluate the potential of prognostic nutritional index (PNI) and Brain natriuretic peptide (BNP) in predicting the prognosis of heart transplantation (HTx). We retrospectively investigated 489 patients undergoing HTx between 2015 and 2020 in our center. The relationship between preoperative [...] Read more.

Our study aimed to evaluate the potential of prognostic nutritional index (PNI) and Brain natriuretic peptide (BNP) in predicting the prognosis of heart transplantation (HTx). We retrospectively investigated 489 patients undergoing HTx between 2015 and 2020 in our center. The relationship between preoperative index and prognosis was analyzed respectively, the optimal cut-off values for preoperative PNI and BNP level were evaluated with receiver operating curve analysis. Uni-variate analysis and multivariate analysis were used to compare baseline data (sex, age, diagnosis, etc.) of groups divided by the level of PNI and BNP. Propensity score matching (PSM) was applied to eliminate bias. We calculated the C-index from the prediction efficiency of PNI and BNP. During the period, 489 recipients undergoing HTx in our center were included according to the inclusion criteria; 383 (78.3%) males and 106 (21.7%) females were included in this study, with a median age of 47.57 years old. The ROC curve showed that the optimal cut-off values of each indicator were verified as 49.345 for PNI, and 4397.500 for BNP. The multivariate analyses indicated that PNI (p = 0.047), BNP (p = 0.024), age (p = 0.0023), and waiting time (p = 0.012) were risk factors for all-cause death after HTx. Propensity score matching generated 116 pairs based on PNI level and 126 pairs based on BNP level, and the results showed that OS (overall survival) was significantly correlated with PNI (n = 232, p = 0.0113) and BNP (n = 252, p = 0.0146). Our study implied that higher PNI and lower BNP level had direct correlation with better survival after HTx. Combining PNI and BNP together would be a potential clinical preoperative instrument to predict the survival of patients after HTx, especially in short-term survival. Full article

(This article belongs to the Special Issue Outcomes of Heart Transplantation)

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11 pages, 725 KiB

Open AccessEditor’s ChoiceArticle

The Effect of TAVR on Left Ventricular and Left Atrial Mechanics in Patients with Aortic Stenosis

by Malcolm Anastasius, Richard Ro, Michael Gavalas, Neil Patel, Francesca Romana Prandi, Gilbert H. L. Tang, Parasuram Krishnamoorthy, Samin K. Sharma, Annapoorna Kini and Stamatios Lerakis

J. Cardiovasc. Dev. Dis. 2022, 9(2), 35; https://doi.org/10.3390/jcdd9020035 - 21 Jan 2022

Cited by 5 | Viewed by 3012

Abstract

Background. Measures of adverse cardiac remodeling, left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic function, are predictive of cardiac events in patients with severe aortic stenosis (AS). How these parameters of cardiac function change following TAVR requires further investigation. Methods. [...] Read more.

Background. Measures of adverse cardiac remodeling, left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic function, are predictive of cardiac events in patients with severe aortic stenosis (AS). How these parameters of cardiac function change following TAVR requires further investigation. Methods. A number of 109 consecutive patients with symptomatic severe AS who were seen in the heart valve clinic between 2014 and 2019 for TAVR were included. All patients underwent echocardiographic assessment prior to and 30 days following TAVR, with LVGLS and LA phasic function evaluation using 2D speckle-tracking echocardiography. Heart failure hospitalization, and death were assessed at 12 months. Results. The mean age of the study cohort was 81 ± 7.3 years. Following TAVR, there was a significant reduction in NYHA class III/IV symptoms [89 (82%) vs. 12 (11%), p < 0.01], and median mean aortic valve gradient [44 mmHg (16) vs. 9 mmHg (7), p < 0.01]. There was no significant change in the median LVEF [62% (13) vs. 62% (6.0), p = 0.2]; however, the LVGLS significantly increased following TAVR [15 ± 3.5% vs. 18 ± 3.3%, p < 0.01]. The median LA reservoir, conduit and contractile function significantly improved following TAVR [22.0% (14.0) vs. 18.0% (14.0) p < 0.01, 8.9% (5.4) vs. 7.8% (4.8) p < 0.01, 12% (11.0) vs. 9.6% (11.0) p < 0.01, respectively]. The incidence of death or heart failure hospitalization at 12 months was low, and occurred in eight patients (7.3%). Conclusions. TAVR results in significant short-term reverse LV and LA remodeling, as shown by improvement in LV GLS and all three components of LA phasic function, despite no change in the LVEF. The findings indicate the possible utility of strain imaging for the assessment of global LV and LA function following TAVR. Full article

(This article belongs to the Special Issue Transcatheter Aortic Valve Implantation (TAVI))

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29 pages, 710 KiB

Open AccessEditor’s ChoiceReview

Modalities of Exercise Training in Patients with Extracorporeal Membrane Oxygenation Support

by Christos Kourek, Serafim Nanas, Anastasia Kotanidou, Vasiliki Raidou, Maria Dimopoulou, Stamatis Adamopoulos, Andreas Karabinis and Stavros Dimopoulos

J. Cardiovasc. Dev. Dis. 2022, 9(2), 34; https://doi.org/10.3390/jcdd9020034 - 20 Jan 2022

Cited by 11 | Viewed by 6736

Abstract

The aim of this qualitative systematic review is to summarize and analyze the different modalities of exercise training and its potential effects in patients on extracorporeal membrane oxygenation (ECMO) support. ECMO is an outbreaking, life-saving technology of the last decades which is being [...] Read more.

The aim of this qualitative systematic review is to summarize and analyze the different modalities of exercise training and its potential effects in patients on extracorporeal membrane oxygenation (ECMO) support. ECMO is an outbreaking, life-saving technology of the last decades which is being used as a gold standard treatment in patients with severe cardiac, respiratory or combined cardiorespiratory failure. Critically ill patients on ECMO very often present intensive care unit-acquired weakness (ICU-AW); thus, leading to decreased exercise capacity and increased mortality rates. Early mobilization and physical therapy have been proven to be safe and feasible in critically ill patients on ECMO, either as a bridge to lung/heart transplantation or as a bridge to recovery. Rehabilitation has beneficial effects from the early stages in the ICU, resulting in the prevention of ICU-AW, and a decrease in episodes of delirium, the duration of mechanical ventilation, ICU and hospital length of stay, and mortality rates. It also improves functional ability, exercise capacity, and quality of life. Rehabilitation requires a very careful, multi-disciplinary approach from a highly specialized team from different specialties. Initial risk assessment and screening, with appropriate physical therapy planning and exercise monitoring in patients receiving ECMO therapy are crucial factors for achieving treatment goals. However, more randomized controlled trials are required in order to establish more appropriate individualized exercise training protocols. Full article

(This article belongs to the Special Issue Sports Cardiology: From Diagnosis to Clinical Management)

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14 pages, 1656 KiB

Open AccessEditor’s ChoiceArticle

Vitamin D Inhibits IL-6 Pro-Atherothrombotic Effects in Human Endothelial Cells: A Potential Mechanism for Protection against COVID-19 Infection?

by Giovanni Cimmino, Stefano Conte, Mariarosaria Morello, Grazia Pellegrino, Laura Marra, Andrea Morello, Giuseppe Nicoletti, Gennaro De Rosa, Paolo Golino and Plinio Cirillo

J. Cardiovasc. Dev. Dis. 2022, 9(1), 27; https://doi.org/10.3390/jcdd9010027 - 13 Jan 2022

Cited by 18 | Viewed by 3947

Abstract

Background: Thrombosis with cardiovascular involvement is a crucial complication in COVID-19 infection. COVID-19 infects the host by the angiotensin converting enzyme-2 receptor (ACE2r), which is expressed in endothelial cells too. Thus, COVID-related thrombotic events might be due to endothelial dysfunction. IL-6 is one [...] Read more.

Background: Thrombosis with cardiovascular involvement is a crucial complication in COVID-19 infection. COVID-19 infects the host by the angiotensin converting enzyme-2 receptor (ACE2r), which is expressed in endothelial cells too. Thus, COVID-related thrombotic events might be due to endothelial dysfunction. IL-6 is one of the main cytokines involved in the COVID-19 inflammatory storm. Some evidence indicates that Vitamin D (VitD) has a protective role in COVID-19 patients, but the molecular mechanisms involved are still debated. Thus, we investigated the effect of VitD on Tissue Factor and adhesion molecules (CAMs) in IL-6-stimulated endothelial cells (HUVEC). Moreover, we evaluated levels of the ACE2r gene and proteins. Finally, we studied the modulation of NF-kB and STAT3 pathways. Methods: HUVEC cultivated in VitD-enriched medium were stimulated with IL-6 (0.5 ng/mL). The TF gene (RT-PCR), protein (Western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. Similarly, CAMs soluble values (ELISA) and ACE2r (RT-PCR and Western blot) levels were assessed. NF-kB and STAT3 modulation (Western blot) were also investigated. Results: VitD significantly reduced TF expression at both gene and protein levels as well as TF-procoagulant activity in IL-6-treated HUVEC. Similar effects were observed for CAMs and ACE2r expression. IL-6 modulates these effects by regulating NF-κB and STAT3 pathways. Conclusions: IL-6 induces endothelial dysfunction with TF and CAMs expression via upregulation of ACE2r. VitD prevented these IL-6 deleterious effects. Thus, it might be speculated that this is one of the hypothetical mechanism(s) by which VitD exerts its beneficial effects in COVID-19 infection. Full article

(This article belongs to the Section Basic and Translational Cardiovascular Research)

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14 pages, 1466 KiB

Open AccessEditor’s ChoiceArticle

Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level

by Benedetta Leonardi, Federica Gentili, Marco Alfonso Perrone, Fabrizio Sollazzo, Lucia Cocomello, Stefani Silva Kikina, Rachel M. Wald, Vincenzo Palmieri, Aurelio Secinaro, Maria Giulia Gagliardi, Attilio Parisi, Attilio Turchetta, Lorenzo Galletti, Massimiliano Bianco and Fabrizio Drago

J. Cardiovasc. Dev. Dis. 2022, 9(1), 26; https://doi.org/10.3390/jcdd9010026 - 13 Jan 2022

Cited by 12 | Viewed by 3758

Abstract

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical [...] Read more.

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO₂ 30 mL/kg/min (range 25–33); median percent predicted peak VO₂ 68% (range 61–78)). Peak VO₂, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95%CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O₂ pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO₂/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO₂ irrespective of RV size. OUES and peak O₂ pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO₂, the incremental value of this parameter should be the focus of future studies. Full article

(This article belongs to the Special Issue Cardiovascular Effects and Benefits of Exercise)

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11 pages, 270 KiB

Open AccessEditor’s ChoiceReview

Endomyocardial Biopsy in Pediatric Myocarditis and Dilated Cardiomyopathy: A Tool in Search for a Role

by Mara Pilati, Micol Rebonato, Roberto Formigari and Gianfranco Butera

J. Cardiovasc. Dev. Dis. 2022, 9(1), 24; https://doi.org/10.3390/jcdd9010024 - 12 Jan 2022

Cited by 12 | Viewed by 3311

Abstract

Endomyocardial biopsy (EMB) is a well-known diagnostic tool for the investigation and treatment of myocardial diseases and remains the gold standard for the diagnosis of myocarditis. Due to its invasiveness, with a complication rate ranging from 1 to 15%, its role in the [...] Read more.

Endomyocardial biopsy (EMB) is a well-known diagnostic tool for the investigation and treatment of myocardial diseases and remains the gold standard for the diagnosis of myocarditis. Due to its invasiveness, with a complication rate ranging from 1 to 15%, its role in the diagnostic work-up of pediatric heart failure is not well established. The aim of this review is to define the role of EMB as diagnostic technique in the work up of children presenting with severe left ventricular dysfunction with the support of our center experience. Full article

(This article belongs to the Special Issue Pediatric Cardiomyopathies: From Genotype to Phenotype)

11 pages, 1588 KiB

Open AccessEditor’s ChoiceArticle

Impact of the COVID-19 Pandemic on Non-COVID-19 Clinical Trials

by Katia Audisio, Hillary Lia, Newell Bryce Robinson, Mohamed Rahouma, Giovanni Soletti, Gianmarco Cancelli, Roberto Perezgrovas Olaria, David Chadow, Derrick Y. Tam, Dominique Vervoort, Michael E. Farkouh, Deepak L. Bhatt, Stephen E. Fremes and Mario Gaudino

J. Cardiovasc. Dev. Dis. 2022, 9(1), 19; https://doi.org/10.3390/jcdd9010019 - 10 Jan 2022

Cited by 29 | Viewed by 4720

Abstract

Randomized controlled trials (RCT) were impacted by the COVID-19 pandemic, but no systematic analysis has evaluated the overall impact of COVID-19 on non-COVID-19-related RCTs. The ClinicalTrials.gov database was queried in February 2020. Eligible studies included all randomized trials with a start date after [...] Read more.

Randomized controlled trials (RCT) were impacted by the COVID-19 pandemic, but no systematic analysis has evaluated the overall impact of COVID-19 on non-COVID-19-related RCTs. The ClinicalTrials.gov database was queried in February 2020. Eligible studies included all randomized trials with a start date after 1 January 2010 and were active during the period from 1 January 2015 to 31 December 2020. The effect of the pandemic period on non-COVID-19 trials was determined by piece-wise regression models using 11 March 2020 as the start of the pandemic and by time series analysis (models fitted using 2015–2018 data and forecasted for 2019–2020). The study endpoints were early trial stoppage, normal trial completion, and trial activation. There were 161,377 non-COVID-19 trials analyzed. The number of active trials increased annually through 2019 but decreased in 2020. According to the piece-wise regression models, trial completion was not affected by the pandemic (p = 0.56) whereas trial stoppage increased (p = 0.001). There was a pronounced decrease in trial activation early during the pandemic (p < 0.001) which then recovered. The findings from the time series models were consistent comparing forecasted and observed results (trial completion p = 0.22; trial stoppage p < 0.01; trial activation, p = 0.01). During the pandemic, there was an increase in non-COVID-19 RCTs stoppage without changes in RCT completion. There was a sharp decline in new RCTs at the beginning of the pandemic, which later recovered. Full article

(This article belongs to the Special Issue Cardiac Surgery: Outcomes, Management and Critical Care)

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22 pages, 1250 KiB

Open AccessEditor’s ChoiceReview

Modeling Human Cardiac Arrhythmias: Insights from Zebrafish

by Sébastien Gauvrit, Jaclyn Bossaer, Joyce Lee and Michelle M. Collins

J. Cardiovasc. Dev. Dis. 2022, 9(1), 13; https://doi.org/10.3390/jcdd9010013 - 5 Jan 2022

Cited by 13 | Viewed by 6102

Abstract

Cardiac arrhythmia, or irregular heart rhythm, is associated with morbidity and mortality and is described as one of the most important future public health challenges. Therefore, developing new models of cardiac arrhythmia is critical for understanding disease mechanisms, determining genetic underpinnings, and developing [...] Read more.

Cardiac arrhythmia, or irregular heart rhythm, is associated with morbidity and mortality and is described as one of the most important future public health challenges. Therefore, developing new models of cardiac arrhythmia is critical for understanding disease mechanisms, determining genetic underpinnings, and developing new therapeutic strategies. In the last few decades, the zebrafish has emerged as an attractive model to reproduce in vivo human cardiac pathologies, including arrhythmias. Here, we highlight the contribution of zebrafish to the field and discuss the available cardiac arrhythmia models. Further, we outline techniques to assess potential heart rhythm defects in larval and adult zebrafish. As genetic tools in zebrafish continue to bloom, this model will be crucial for functional genomics studies and to develop personalized anti-arrhythmic therapies. Full article

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15 pages, 2950 KiB

Open AccessEditor’s ChoiceArticle

Not Only Diagnostic Yield: Whole-Exome Sequencing in Infantile Cardiomyopathies Impacts on Clinical and Family Management

by Laura Pezzoli, Lidia Pezzani, Ezio Bonanomi, Chiara Marrone, Agnese Scatigno, Anna Cereda, Maria Francesca Bedeschi, Angelo Selicorni, Serena Gasperini, Paolo Bini, Silvia Maitz, Carla Maccioni, Cristina Pedron, Lorenzo Colombo, Daniela Marchetti, Matteo Bellini, Anna Rita Lincesso, Loredana Perego, Monica Pingue, Nunzia Della Malva, Giovanna Mangili, Paolo Ferrazzi and Maria Iascone Show full author list Hide full author list

J. Cardiovasc. Dev. Dis. 2022, 9(1), 2; https://doi.org/10.3390/jcdd9010002 - 21 Dec 2021

Cited by 14 | Viewed by 3832

Abstract

Whole-exome sequencing (WES) is a powerful and comprehensive tool for the genetic diagnosis of rare diseases, but few reports describe its timely application and clinical impact on infantile cardiomyopathies (CM). We conducted a retrospective analysis of patients with infantile CMs who had trio [...] Read more.

Whole-exome sequencing (WES) is a powerful and comprehensive tool for the genetic diagnosis of rare diseases, but few reports describe its timely application and clinical impact on infantile cardiomyopathies (CM). We conducted a retrospective analysis of patients with infantile CMs who had trio (proband and parents)-WES to determine whether results contributed to clinical management in urgent and non-urgent settings. Twenty-nine out of 42 enrolled patients (69.0%) received a definitive molecular diagnosis. The mean time-to-diagnosis was 9.7 days in urgent settings, and 17 out of 24 patients (70.8%) obtained an etiological classification. In non-urgent settings, the mean time-to-diagnosis was 225 days, and 12 out of 18 patients (66.7%) had a molecular diagnosis. In 37 out of 42 patients (88.1%), the genetic findings contributed to clinical management, including heart transplantation, palliative care, or medical treatment, independent of the patient’s critical condition. All 29 patients and families with a definitive diagnosis received specific counseling about recurrence risk, and in seven (24.1%) cases, the result facilitated diagnosis in parents or siblings. In conclusion, genetic diagnosis significantly contributes to patients’ clinical and family management, and trio-WES should be performed promptly to be an essential part of care in infantile cardiomyopathy, maximizing its clinical utility. Full article

(This article belongs to the Special Issue Pediatric Cardiomyopathies: From Genotype to Phenotype)

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15 pages, 1256 KiB

Open AccessEditor’s ChoiceArticle

LPA Genotypes and Haplotypes Are Associated with Lipoprotein(a) Levels but Not Arterial Wall Properties in Stable Post-Coronary Event Patients with Very High Lipoprotein(a) Levels

by Andreja Rehberger Likozar, Aleš Blinc, Katarina Trebušak Podkrajšek and Miran Šebeštjen

J. Cardiovasc. Dev. Dis. 2021, 8(12), 181; https://doi.org/10.3390/jcdd8120181 - 13 Dec 2021

Cited by 7 | Viewed by 2697

Abstract

Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether [...] Read more.

Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether in patients with stable CAD and high Lp(a) levels these genetic variants are associated with increased Lp(a) and arterial wall properties. Blood samples underwent biochemical and genetic analyses. Ultrasound measurements for the functional and morphological properties of arterial wall were performed. Genotypes of rs10455872 and haplotypes AT and GT showed significant association with Lp(a) levels. Patients with GG showed significantly higher Lp(a) levels compared with those with AG genotype (2180 vs. 1391 mg/L, p = 0.045). Patients with no AT haplotype had significantly higher Lp(a) compared to carriers of one AT haplotype (2158 vs. 1478 mg/L, p = 0.023) or two AT haplotypes (2158 vs. 1487 mg/L, p = 0.044). There were no significant associations with the properties of the arterial wall. Lp(a) levels significantly correlated also with number of KIV-2 repeats (r = −0.601; p < 0.0001). In our patients, these two LPA polymorphisms and number of KIV-2 repeats are associated with Lp(a), but not arterial wall properties. Full article

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

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8 pages, 1151 KiB

Open AccessEditor’s ChoiceArticle

Optimal Heart Rate and Prognosis in Patients with Cardiac Amyloidosis

by Toshihide Izumida, Teruhiko Imamura, Makiko Nakamura and Koichiro Kinugawa

J. Cardiovasc. Dev. Dis. 2021, 8(12), 182; https://doi.org/10.3390/jcdd8120182 - 12 Dec 2021

Cited by 2 | Viewed by 2677

Abstract

Background: Optimal heart rate (HR) that associates with higher cardiac output and greater clinical outcomes in patients with cardiac amyloidosis remains unknown. Methods: Consecutive patients with sinus rhythm who were diagnosed with cardiac amyloidosis at our institute between February 2015 and February 2021 [...] Read more.

Background: Optimal heart rate (HR) that associates with higher cardiac output and greater clinical outcomes in patients with cardiac amyloidosis remains unknown. Methods: Consecutive patients with sinus rhythm who were diagnosed with cardiac amyloidosis at our institute between February 2015 and February 2021 were retrospectively included. Ideal HR, at which E-wave and A-wave stand adjacent without any overlaps in the trans-mitral flow echocardiography, was calculated by the formula: 86.8−0.08 × deceleration time (msec). The association between optimal HR and cardiac death or heart failure readmission was investigated. Results: Ten patients (median 74 years old, 8 men) were included. On median, actual HR was 64 bpm and ideal HR was 69 bpm. An incidence rate of the primary endpoint in the sub-optimal HR group tended to be higher than optimal HR group: one of the four patients in optimal HR group had events (25%); two of the two patients in higher HR group had events (100%); two of the four patients in lower HR group had events (50%). Conclusions: The optimal HR was associated with greater clinical outcomes in patients with cardiac amyloidosis. The clinical impact of aggressive HR optimization in this cohort remains the next concern. Full article

(This article belongs to the Special Issue Understanding Heart Failure Management and Treatment)

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7 pages, 1092 KiB

Open AccessEditor’s ChoiceReview

When Should Premature Ventricular Contractions Be Considered as a Red Flag in Children with Cardiomyopathy?

by Marianna Cicenia, Massimo S. Silvetti and Fabrizio Drago

J. Cardiovasc. Dev. Dis. 2021, 8(12), 176; https://doi.org/10.3390/jcdd8120176 - 10 Dec 2021

Cited by 3 | Viewed by 4208

Abstract

Premature ventricular contractions (PVCs) are common and generally benign in childhood and tend to resolve spontaneously in most cases. When PVCs occur frequently, an arrhythmia-induced cardiomyopathy may be present requiring medical or catheter ablation. PVCs are only rarely the manifestation of a cardiomyopathy. [...] Read more.

Premature ventricular contractions (PVCs) are common and generally benign in childhood and tend to resolve spontaneously in most cases. When PVCs occur frequently, an arrhythmia-induced cardiomyopathy may be present requiring medical or catheter ablation. PVCs are only rarely the manifestation of a cardiomyopathy. The purpose of this review is to provide some tips and tricks to raise the suspicion of a cardiac disease based on the presence and characteristics of PVCs in children. Full article

(This article belongs to the Special Issue Pediatric Cardiomyopathies: From Genotype to Phenotype)

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10 pages, 518 KiB

Open AccessEditor’s ChoiceArticle

Season of Birth and Cardiovascular Mortality in Atrial Fibrillation: A Population-Based Cohort Study

by Ying X. Gue, Arnaud Bisson, Alexandre Bodin, Julien Herbert, Gregory Y. H. Lip and Laurent Fauchier

J. Cardiovasc. Dev. Dis. 2021, 8(12), 177; https://doi.org/10.3390/jcdd8120177 - 10 Dec 2021

Cited by 1 | Viewed by 2266

Abstract

Background: The fetal origins hypothesis have associated early life exposures with the development of adverse health outcomes in adulthood. Season of birth has been shown to be associated with overall and cardiovascular mortality. Methods: We performed a retrospective database study to explore the [...] Read more.

Background: The fetal origins hypothesis have associated early life exposures with the development of adverse health outcomes in adulthood. Season of birth has been shown to be associated with overall and cardiovascular mortality. Methods: We performed a retrospective database study to explore the association between season of birth and mortality in patients with atrial fibrillation. Results: A total of 8962 patients with AF were identified in the database with 1253 deaths recorded. AF patients born in spring and summer had a higher mortality rate when compared to those born in autumn and winter (hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.01–1.26, p = 0.03). This effect was consistent in the male subgroup (HR 1.25, 95% CI 1.03–1.51, p = 0.02 for males born in spring; HR 1.24, 95% CI 1.03–1.51, p = 0.03 for males born in summer when compared to winter as the reference) but not in females (HR 1.02, 95% CI 0.79–1.31, p = 0.88 for females born in spring; HR 1.11, 95% CI 0.87–1.42, p = 0.39 for females born in summer when compared to winter as the reference). Results persisted after adjustment for baseline characteristics and clinical risk profile. A similar pattern was observed with cardiovascular mortality. Conclusion: Birth in spring or summer is associated with a higher risk of cardiovascular mortality in male AF patients, but not in females. This could be related to the underlying differences in rates of major adverse clinical events between genders. Further studies should aim at clarifying the mechanisms behind this association, which may help us understand the higher level of risk in female patients with AF. Full article

(This article belongs to the Section Epidemiology, Lifestyle, and Cardiovascular Health)

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10 pages, 825 KiB

Open AccessEditor’s ChoiceArticle

Medium- and Long-Term Lead Stability and Echocardiographic Outcomes of Left Bundle Branch Area Pacing Compared to Right Ventricular Pacing

by Haojie Zhu, Zhao Wang, Xiaofei Li, Yan Yao, Zhimin Liu and Xiaohan Fan

J. Cardiovasc. Dev. Dis. 2021, 8(12), 168; https://doi.org/10.3390/jcdd8120168 - 30 Nov 2021

Cited by 9 | Viewed by 3055

Abstract

The long-term lead stability and echocardiographic outcomes of left bundle branch area pacing (LBBAP) are not fully understood. This study aimed to observe the mid-long-term clinical impact of LBBAP compared to right ventricular pacing (RVP). Consecutive bradycardia patients undergoing LBBAP or RVP were [...] Read more.

The long-term lead stability and echocardiographic outcomes of left bundle branch area pacing (LBBAP) are not fully understood. This study aimed to observe the mid-long-term clinical impact of LBBAP compared to right ventricular pacing (RVP). Consecutive bradycardia patients undergoing LBBAP or RVP were enrolled. Pacing and electrophysiological characteristics, echocardiographic measurements, and procedural complications were prospectively recorded at baseline and follow-up. LBBAP was successful in 376 of 406 patients (92.6%), while 313 patients received RVP. During a mean follow-up of 13.6 ± 7.8 months, LBBAP presented with similar pacing parameters and complications to RVP, except a significantly narrower paced QRS duration (115.7 ± 12.3 ms vs. 148.0 ± 18.0 ms, p < 0.001). In 228 patients with ventricular pacing burden >40%, LBBAP at last follow-up resulted in decreased left atrial diameter (LAD) (40.1 ± 8.5 mm vs. 38.5 ± 8.0 mm, p < 0.001) while RVP produced decreased left ventricular ejection fraction (62.7 ± 4.8% vs. 60.5 ± 6.9%, p < 0.001) when compared to baseline. After adjusting for age, the presence of atrial fibrillation, and other clinical factors, LBBAP was still associated with a decrease in LAD (−1.601, 95% CI −3.094–−0.109, p = 0.036). We conclude that LBBAP might result in more preserved echocardiographic outcomes than RVP. Full article

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9 pages, 275 KiB

Open AccessEditor’s ChoiceArticle

Acute Cardiorespiratory Responses to Different Exercise Modalities in Chronic Heart Failure Patients—A Pilot Study

by Eleftherios Karatzanos, Panagiotis Ferentinos, Georgios Mitsiou, Stavros Dimopoulos, Argyrios Ntalianis and Serafeim Nanas

J. Cardiovasc. Dev. Dis. 2021, 8(12), 164; https://doi.org/10.3390/jcdd8120164 - 26 Nov 2021

Cited by 4 | Viewed by 3213

Abstract

The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO_2peak intensities between three “iso-work” protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON₇₀) and (c) [...] Read more.

The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO_2peak intensities between three “iso-work” protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON₇₀) and (c) a lower intensity continuous protocol (CON₅₀) in patients with chronic heart failure (CHF). Ten male CHF patients (aged 55.1 ± 16.2 years) performed in separate days a single session of a HIIT protocol consisted of 4 sets × 4 min cycling at 80% VO_2peak with 3 min of recovery at 50% VO_2peak, a CON₇₀ protocol corresponding to 70% VO_2peak and a CON₅₀ protocol corresponding to 50% VO_2peak. Cardiopulmonary data were collected by an online gas analysis system. The HIIT and CON₇₀ elicited higher cardiorespiratory responses compared to CON₅₀ with no differences between them (p > 0.05). In HIIT and CON₇₀, patients exercised longer at >80% and >90% VO_2peak. The completion rate was 100% for the three protocols. Not any adverse events were observed in either protocol. Both HIIT and CON₇₀ elicited a stronger physiological stimulus and required shorter time than CON₅₀. Both HIIT and CON₇₀ also induced comparable hemodynamic responses and ventilatory demand. Full article

(This article belongs to the Special Issue Cardiovascular Effects and Benefits of Exercise)

22 pages, 1646 KiB

Open AccessEditor’s ChoiceReview

The Role of POPDC Proteins in Cardiac Pacemaking and Conduction

by Lena Gruscheski and Thomas Brand

J. Cardiovasc. Dev. Dis. 2021, 8(12), 160; https://doi.org/10.3390/jcdd8120160 - 23 Nov 2021

Cited by 7 | Viewed by 3768

Abstract

The Popeye domain-containing (POPDC) gene family, consisting of Popdc1 (also known as Bves), Popdc2, and Popdc3, encodes transmembrane proteins abundantly expressed in striated muscle. POPDC proteins have recently been identified as cAMP effector proteins and have been proposed to [...] Read more.

The Popeye domain-containing (POPDC) gene family, consisting of Popdc1 (also known as Bves), Popdc2, and Popdc3, encodes transmembrane proteins abundantly expressed in striated muscle. POPDC proteins have recently been identified as cAMP effector proteins and have been proposed to be part of the protein network involved in cAMP signaling. However, their exact biochemical activity is presently poorly understood. Loss-of-function mutations in animal models causes abnormalities in skeletal muscle regeneration, conduction, and heart rate adaptation after stress. Likewise, patients carrying missense or nonsense mutations in POPDC genes have been associated with cardiac arrhythmias and limb-girdle muscular dystrophy. In this review, we introduce the POPDC protein family, and describe their structure function, and role in cAMP signaling. Furthermore, the pathological phenotypes observed in zebrafish and mouse models and the clinical and molecular pathologies in patients carrying POPDC mutations are described. Full article

(This article belongs to the Special Issue Molecular Control of Development and Function of the Cardiac Conduction System)

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13 pages, 2567 KiB

Open AccessEditor’s ChoiceArticle

The Atherosclerotic Profile of a Young Symptomatic Population between 19 and 49 Years: Coronary Computed Tomography Angiography or Coronary Artery Calcium Score?

by Gudrun Maria Feuchtner, Christoph Beyer, Christian Langer, Sven Bleckwenn, Thomas Senoner, Fabian Barbieri, Anna Luger, Philipp Spitaler, Gerlig Widmann, Agne Adukauskaite, Wolfgang Dichtl, Guy Friedrich and Fabian Plank

J. Cardiovasc. Dev. Dis. 2021, 8(11), 157; https://doi.org/10.3390/jcdd8110157 - 18 Nov 2021

Cited by 3 | Viewed by 2956

Abstract

(1) Background: Whether coronary computed tomography angiography (CTA) or the coronary artery calcium score (CACS) should be used for diagnosis of coronary heart disease, is an open debate. The aim of our study was to compare the atherosclerotic profile by coronary CTA in [...] Read more.

(1) Background: Whether coronary computed tomography angiography (CTA) or the coronary artery calcium score (CACS) should be used for diagnosis of coronary heart disease, is an open debate. The aim of our study was to compare the atherosclerotic profile by coronary CTA in a young symptomatic high-risk population (age, 19–49 years) in comparison with the coronary artery calcium score (CACS). (2) Methods: 1137 symptomatic high-risk patients between 19–49 years (mean age, 42.4 y) who underwent coronary CTA and CACS were stratified into six age groups. CTA-analysis included stenosis severity and high-risk-plaque criteria (3) Results: Atherosclerosis was more often detected based on CTA than based on CACS (45 vs. 27%; p < 0.001), 50% stenosis in 13.6% and high-risk plaque in 17.7%. Prevalence of atherosclerosis was low and not different between CACS and CTA in the youngest age groups (19–30 y: 5.2 and 6.4% and 30–35 y: 10.6 and 16%). In patients older than >35 years, the rate of atherosclerosis based on CTA increased (p = 0.004, OR: 2.8, 95%CI:1.45–5.89); and was higher by CTA as compared to CACS (34.9 vs. 16.7%; p < 0.001), with a superior performance of CTA. In patients older than 35 years, stenosis severity (p = 0.002) and >50% stenosis increased from 2.6 to 12.5% (p < 0.001). High-risk plaque prevalence increased from 6.4 to 26.5%. The distribution of high-risk plaque between CACS 0 and >0.1 AU was similar among all age groups, with an increasing proportion in CACS > 0.1 AU with age. A total of 24.9% of CACS 0 patients had coronary artery disease based on CTA, 4.4% > 50% stenosis and 11.5% had high-risk plaque. (4) Conclusions: In a symptomatic young high-risk population older than 35 years, CTA performed superior than CACS. In patients aged 19–35 years, the rate of atherosclerosis was similar and low based on both modalities. CACS 0 did not rule out coronary artery disease in a young high-risk population. Full article

(This article belongs to the Section Imaging)

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15 pages, 7998 KiB

Open AccessEditor’s ChoiceReview

Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?

by Giandomenico Bisaccia, Fabrizio Ricci, Vittoria Recce, Antonio Serio, Giovanni Iannetti, Anwar A. Chahal, Marcus Ståhlberg, Mohammed Yunus Khanji, Artur Fedorowski and Sabina Gallina

J. Cardiovasc. Dev. Dis. 2021, 8(11), 156; https://doi.org/10.3390/jcdd8110156 - 15 Nov 2021

Cited by 77 | Viewed by 19357

Abstract

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and “brain fog”. Additionally, symptoms of orthostatic [...] Read more.

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and “brain fog”. Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

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10 pages, 1447 KiB

Open AccessEditor’s ChoiceArticle

Outcomes of the Valve-Sparing Root Replacement Procedure with Partial Upper Sternotomy

by Bin Hou, Rui Zhao, De Wang, Wei Wang, Zhenhua Zhao, Xiaogang Sun, Xiangyang Qian and Cuntao Yu

J. Cardiovasc. Dev. Dis. 2021, 8(11), 154; https://doi.org/10.3390/jcdd8110154 - 9 Nov 2021

Cited by 4 | Viewed by 2216

Abstract

Due to better postoperative convalescence and quality of life, experienced centers focus on minimally invasive surgical techniques and approaches, but this approach is not routinely performed for valve-sparing root replacement procedures. The purpose of this study was to assess the safety and feasibility [...] Read more.

Due to better postoperative convalescence and quality of life, experienced centers focus on minimally invasive surgical techniques and approaches, but this approach is not routinely performed for valve-sparing root replacement procedures. The purpose of this study was to assess the safety and feasibility of valve-sparing root replacement via partial upper sternotomy. Between January 2016 and April 2021, 269 patients underwent a valve-sparing root replacement procedure, and partial upper sternotomy was performed in 52 patients. The clinical outcomes of the partial upper sternotomy (PUS) and complete sternotomy (CS) groups, including mortality, degree of aortic insufficiency, blood loss and consumption of blood products, postoperative complications, and hospitalization expenses, were compared. The Kaplan–Meier method was used to assess the degree of aortic regurgitation. Propensity score matching was performed as a sensitivity analysis. There was only one in-hospital death (in the CS group, p = 1) and no postoperative moderate to severe aortic insufficiency in either group. The blood loss and consumption of blood products in the PUS group were also lower than in the CS group, especially for plasma use. Regarding the need for re-exploration because of bleeding, acute kidney injury, pericardial pleural effusion, drainage volume within the first 24 h, mechanical ventilation time, and arrhythmia, the two groups were comparable. Patients in the CS group showed a longer ICU time (74.20 ± 47.21 vs. 50.9 30.16 h, p = 0.001) and higher hospitalization expenses (135,649.52 ± 29,992.21 vs. 123,380.15 ± 27,062.82 yuan, p < 0.001). None of the patients died or reoperated during the follow-up. Freedom from moderate or severe aortic insufficiency remained comparable after matching (p = 0.97). Minimally invasive valve-sparing aortic replacement via partial upper sternotomy can be safely performed in selected patients. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

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14 pages, 316 KiB

Open AccessEditor’s ChoiceReview

Cardiac Tissue Engineering for the Treatment of Myocardial Infarction

by Dongmin Yu, Xiaowei Wang and Lei Ye

J. Cardiovasc. Dev. Dis. 2021, 8(11), 153; https://doi.org/10.3390/jcdd8110153 - 8 Nov 2021

Cited by 7 | Viewed by 3236

Abstract

Poor cell engraftment rate is one of the primary factors limiting the effectiveness of cell transfer therapy for cardiac repair. Recent studies have shown that the combination of cell-based therapy and tissue engineering technology can improve stem cell engraftment and promote the therapeutic [...] Read more.

Poor cell engraftment rate is one of the primary factors limiting the effectiveness of cell transfer therapy for cardiac repair. Recent studies have shown that the combination of cell-based therapy and tissue engineering technology can improve stem cell engraftment and promote the therapeutic effects of the treatment for myocardial infarction. This mini-review summarizes the recent progress in cardiac tissue engineering of cardiovascular cells from differentiated human pluripotent stem cells (PSCs), highlights their therapeutic applications for the treatment of myocardial infarction, and discusses the present challenges of cardiac tissue engineering and possible future directions from a clinical perspective. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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25 pages, 2280 KiB

Open AccessEditor’s ChoiceReview

Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering

by Astha Khanna, Maedeh Zamani and Ngan F. Huang

J. Cardiovasc. Dev. Dis. 2021, 8(11), 137; https://doi.org/10.3390/jcdd8110137 - 22 Oct 2021

Cited by 34 | Viewed by 8433

Abstract

Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic [...] Read more.

Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic scaffolding structure characterized by tissue-specific biochemical, biophysical, and mechanical properties that modulates cellular behavior and activates highly regulated signaling pathways. In light of technological advancements, biomaterial-based scaffolds have been developed that better mimic physiological ECM properties, provide signaling cues that modulate cellular behavior, and form functional tissues and organs. In this review, we summarize the in vitro, pre-clinical, and clinical research models that have been employed in the design of ECM-based biomaterials for cardiovascular regenerative medicine. We highlight the research advancements in the incorporation of ECM components into biomaterial-based scaffolds, the engineering of increasingly complex structures using biofabrication and spatial patterning techniques, the regulation of ECMs on vascular differentiation and function, and the translation of ECM-based scaffolds for vascular graft applications. Finally, we discuss the challenges, future perspectives, and directions in the design of next-generation ECM-based biomaterials for cardiovascular tissue engineering and clinical translation. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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13 pages, 874 KiB

Open AccessEditor’s ChoiceArticle

The Value of Fetuin-A as a Predictor to Identify Takotsubo Patients at Risk of Cardiovascular Events

by Albert Topf, Moritz Mirna, Nina Bacher, Vera Paar, Christoph Edlinger, Lukas J. Motloch, Sarah Gharibeh, Marwin Bannehr, Uta C. Hoppe and Michael Lichtenauer

J. Cardiovasc. Dev. Dis. 2021, 8(10), 127; https://doi.org/10.3390/jcdd8100127 - 5 Oct 2021

Cited by 3 | Viewed by 1905

Abstract

Introduction: Takotsubo cardiomyopathy (TTC) remains a life-threatening disease with the risk of decompensated heart failure and arrhythmias. Valid markers for the prediction of outcome are unavailable. The novel biomarkers fetuin-A, matrix metalloproteinases-2 (MMP-2), myeloperoxidase (MPO), Syndecan-1 and CD40-L show promising results for risk [...] Read more.

Introduction: Takotsubo cardiomyopathy (TTC) remains a life-threatening disease with the risk of decompensated heart failure and arrhythmias. Valid markers for the prediction of outcome are unavailable. The novel biomarkers fetuin-A, matrix metalloproteinases-2 (MMP-2), myeloperoxidase (MPO), Syndecan-1 and CD40-L show promising results for risk stratification of cardiovascular patients. Nevertheless, clinical implementation has not been investigated in TTC patients. Methods: To investigate this issue, we evaluated clinical complications in 51 patients hospitalized for TTC and measured the serum levels of fetuin-A, MPO, MMP-2, Syndecan-1 and CD40-L within 24 h after admission. Results: Serum levels of Fetuin-A correlated inversely with the risk of cardiac decompensation and all cause complications within the acute phase of TTC. Fetuin-A levels over 190.1 µg/mL (AUC: 0.738, sensitivity 87.5%, specificity: 52.6%) indicate an acute phase of TTC without cardiac decompensation. Despite lower fetuin-A levels in patients with all cause complications, the combined endpoint remained slightly unmet (p = 0.058, AUC: 0.655). Patients with fetuin-A levels over 213.3 µg/mL are at risk of experiencing hemodynamic relevant rhythm disorders (AUC: 0.794; sensitivity: 75.0%, specificity: 79.1%). Other biomarkers failed to reveal a prognostic impact. Pro-BNP and hs troponin levels at admission did not predict adverse cardiac events. Conclusion: Fetuin-A is a promising marker in our study and could be of benefit for the prediction of short-term adverse cardiac events in TTC patients. Therefore, fetuin-A might be of value to evaluate an individual’s risk for complications within the acute phase of TTC and to individually choose the time of intensive care and hospitalization. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

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19 pages, 1385 KiB

Open AccessEditor’s ChoiceReview

Acute and Chronic Effects of COVID-19 on the Cardiovascular System

by Victor Arévalos, Luis Ortega-Paz, Juan José Rodríguez-Arias, Margarita Calvo López, Leticia Castrillo-Golvano, Anthony Salazar-Rodríguez, Marta Sabaté-Tormos, Francesco Spione, Manel Sabaté and Salvatore Brugaletta

J. Cardiovasc. Dev. Dis. 2021, 8(10), 128; https://doi.org/10.3390/jcdd8100128 - 5 Oct 2021

Cited by 20 | Viewed by 5410

Abstract

COVID-19 has shown significant morbidity with the involvement of multiple systems, including the cardiovascular system. Cardiovascular manifestations in the acute phase can include myocardial injury itself, myocardial infarction, venous thromboembolic events, myocarditis, Takotsubo syndrome, and different arrhythmic events. Myocardial injury defined by the [...] Read more.

COVID-19 has shown significant morbidity with the involvement of multiple systems, including the cardiovascular system. Cardiovascular manifestations in the acute phase can include myocardial injury itself, myocardial infarction, venous thromboembolic events, myocarditis, Takotsubo syndrome, and different arrhythmic events. Myocardial injury defined by the rise of cardiac biomarkers in blood has been found in multiple studies with a prevalence of about 20%. Its presence is related to worse clinical outcomes and in-hospital mortality. The mechanisms of myocardial injury have been the subject of intense research but still need to be clarified. The characterization of the cardiac affectation with echocardiography and cardiac magnetic resonance has found mixed results in different studies, with a striking incidence of imaging criteria for myocarditis. Regarding post-acute and chronic follow-up results, the persistence of symptoms and imaging changes in recovered COVID-19 patients has raised concerns about the duration and the possible significance of these findings. Even though the knowledge about this disease has increased incredibly in the last year, many aspects are still unclear and warrant further research. Full article

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16 pages, 25841 KiB

Open AccessEditor’s ChoiceReview

Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration

by Angello Huerta Gomez, Sanika Joshi, Yong Yang, Johnathan D. Tune, Ming-Tao Zhao and Huaxiao Yang

J. Cardiovasc. Dev. Dis. 2021, 8(10), 125; https://doi.org/10.3390/jcdd8100125 - 30 Sep 2021

Cited by 7 | Viewed by 3583

Abstract

The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling [...] Read more.

The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling rely on animal models and a few clinical studies, which significantly bottleneck the understanding of Notch signaling-associated human cardiovascular development and disease. Recent advances in the bioengineering systems and human pluripotent stem cell-derived cardiovascular cells pave the way to decipher the role of Notch signaling in cardiovascular-related cells (endothelial cells, cardiomyocytes, smooth muscle cells, fibroblasts, and immune cells), and intercellular crosstalk in the physiological, pathological, and regenerative context of the complex human cardiovascular system. In this review, we first summarize the significant roles of Notch signaling in individual cardiac cell types. We then cover the bioengineering systems of microfluidics, hydrogel, spheroid, and 3D bioprinting, which are currently being used for modeling and studying Notch signaling in the cardiovascular system. At last, we provide insights into ancillary supports of bioengineering systems, varied types of cardiovascular cells, and advanced characterization approaches in further refining Notch signaling in cardiovascular development, disease, and regeneration. Full article

(This article belongs to the Special Issue Cardiovascular Tissue Engineering)

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17 pages, 9226 KiB

Open AccessEditor’s ChoiceArticle

Deficient Myocardial Organization and Pathological Fibrosis in Fetal Aortic Stenosis—Association of Prenatal Ultrasound with Postmortem Histology

by Fleur Zwanenburg, Marco C. DeRuiter, Lambertus J. Wisse, Conny J. van Munsteren, Margot M. Bartelings, Marie-Jose Goumans, Arend D. J. Ten Harkel, Monique R. M. Jongbloed and Monique C. Haak

J. Cardiovasc. Dev. Dis. 2021, 8(10), 121; https://doi.org/10.3390/jcdd8100121 - 28 Sep 2021

Cited by 3 | Viewed by 2743

Abstract

In fetal aortic stenosis (AS), it remains challenging to predict left ventricular development over the course of pregnancy. Myocardial organization, differentiation and fibrosis could be potential biomarkers relevant for biventricular outcome. We present four cases of fetal AS with varying degrees of severity [...] Read more.

In fetal aortic stenosis (AS), it remains challenging to predict left ventricular development over the course of pregnancy. Myocardial organization, differentiation and fibrosis could be potential biomarkers relevant for biventricular outcome. We present four cases of fetal AS with varying degrees of severity and associate myocardial deformation on fetal ultrasound with postmortem histopathological characteristics. During routine fetal echocardiography, speckle tracking recordings of the cardiac four-chamber view were performed to assess myocardial strain as parameter for myocardial deformation. After pregnancy termination, postmortem cardiac specimens were examined using immunohistochemical labeling (IHC) of key markers for myocardial organization, differentiation and fibrosis and compared to normal fetal hearts. Two cases with critical AS presented extremely decreased left ventricular (LV) strain on fetal ultrasound. IHC showed overt endocardial fibro-elastosis, which correlated with pathological fibrosis patterns in the myocardium and extremely disturbed cardiomyocyte organization. The LV in severe AS showed mildly reduced myocardial strain and less severe disorganization of the cardiomyocytes. In conclusion, the degree of reduction in myocardial deformation corresponded with high extent to the amount of pathological fibrosis patterns and cardiomyocyte disorganization. Myocardial deformation on fetal ultrasound seems to hold promise as a potential biomarker for left ventricular structural damage in AS. 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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11 pages, 1500 KiB

Open AccessEditor’s ChoiceArticle

Left Cardiac Remodelling Assessed by Echocardiography Is Associated with Rho-Kinase Activation in Long-Distance Runners

by Felipe Contreras-Briceño, Julián Vega, Jorge Mandiola, María Paz Ocaranza, Sebastián Herrera, Manuel Salinas, Rodrigo Fernández, Jorge E. Jalil, Sergio Lavandero, Mario Chiong, Paz Godoy, Pablo F. Castro, Marta Sitges and Luigi Gabrielli

J. Cardiovasc. Dev. Dis. 2021, 8(10), 118; https://doi.org/10.3390/jcdd8100118 - 24 Sep 2021

Viewed by 2846

Abstract

This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDRs) during the training period before a marathon race. Thirty-six healthy male LDRs (37.0 ± 5.3 years; [...] Read more.

This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDRs) during the training period before a marathon race. Thirty-six healthy male LDRs (37.0 ± 5.3 years; 174.0 ± 7.0 height; BMI: 23.8 ± 2.8;

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O₂-peak: 56.5 ± 7.3 mL·kg⁻¹·min⁻¹) were separated into two groups according to previous training level: high-training (HT, n = 16) ≥ 100 km·week⁻¹ and low-training (LT, n = 20) ≥ 70 and < 100 km·week⁻¹. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48 h without exercising) the week before the race. The HT group showed a higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p < 0.05, for both); also, higher levels of ROCK activity were found in LDRs (HT = 6.17 ± 1.41 vs. CTR = 1.64 ± 0.66 (p < 0.01); vs. LT = 2.74 ± 0.84; (p < 0.05)). In LDRs a direct correlation between ROCK activity levels and LVMi (r = 0.83; p < 0.001), and LAVi (r = 0.70; p < 0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography. Full article

(This article belongs to the Special Issue Echocardiography in Cardiovascular Disease)

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12 pages, 718 KiB

Open AccessEditor’s ChoiceArticle

Potential Role of eNOS Genetic Variants in Ischemic Heart Disease Susceptibility and Clinical Presentation

by Paolo Severino, Andrea D’Amato, Silvia Prosperi, Michele Magnocavallo, Marco Valerio Mariani, Lucrezia Netti, Lucia Ilaria Birtolo, Paolo De Orchi, Cristina Chimenti, Viviana Maestrini, Fabio Miraldi, Carlo Lavalle, Viviana Caputo, Raffaele Palmirotta, Massimo Mancone and Francesco Fedele

J. Cardiovasc. Dev. Dis. 2021, 8(9), 116; https://doi.org/10.3390/jcdd8090116 - 18 Sep 2021

Cited by 17 | Viewed by 5178

Abstract

Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often [...] Read more.

Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD. Full article

(This article belongs to the Section Genetics)

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11 pages, 1815 KiB

Open AccessEditor’s ChoiceReview

The Use of β-Blockers in Heart Failure with Reduced Ejection Fraction

by Daniele Masarone, Maria Luigia Martucci, Vittoria Errigo and Giuseppe Pacileo

J. Cardiovasc. Dev. Dis. 2021, 8(9), 101; https://doi.org/10.3390/jcdd8090101 - 24 Aug 2021

Cited by 29 | Viewed by 14927

Abstract

Treatment with β-blockers is the main strategy for managing patients with heart failure and reduced ejection fraction because of their ability to reverse the neurohumoral effects of the sympathetic nervous system, with consequent prognostic and symptomatic benefits. However, to date, they are underused, [...] Read more.

Treatment with β-blockers is the main strategy for managing patients with heart failure and reduced ejection fraction because of their ability to reverse the neurohumoral effects of the sympathetic nervous system, with consequent prognostic and symptomatic benefits. However, to date, they are underused, mainly because of the misconception that hypotension and bradycardia may worsen the haemodynamic status of patients with HFrEF and because of the presence of comorbidities falsely believed to be absolute contraindications to their use. To promote proper use of β-blockers in this article, we review the clinical pharmacology of β-blockers, the evidence of the beneficial effects of these drugs in heart failure with reduced ejection fraction, and the current guidelines for their use in clinical practice and in the presence of comorbidities (e.g., pulmonary disease, diabetes, atrial fibrillation, peripheral arterial disease, etc.). It is hoped that the practical approach discussed in this review will allow for a proper diffusion of knowledge about the correct use of β-blockers and the drug-disease interactions to achieve their increased use and titration, as well as for the selection of a specific agent with a view to a properly tailored approach for HFrEF patients. Full article

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16 pages, 2409 KiB

Open AccessEditor’s ChoiceReview

New Interventional Therapies beyond Stenting to Treat ST-Segment Elevation Acute Myocardial Infarction

by Pablo Vidal-Calés, Pedro L. Cepas-Guillén, Salvatore Brugaletta and Manel Sabaté

J. Cardiovasc. Dev. Dis. 2021, 8(9), 100; https://doi.org/10.3390/jcdd8090100 - 24 Aug 2021

Cited by 9 | Viewed by 6008

Abstract

Myocardial infarction remains the principal cause of death in Europe. In patients with ST-segment-elevation myocardial infarction (STEMI), a promptly revascularization with primary percutaneous intervention (PCI) has transformed prognosis in the last decades. However, despite increasing successful PCI procedures, mortality has remained unchanged in [...] Read more.

Myocardial infarction remains the principal cause of death in Europe. In patients with ST-segment-elevation myocardial infarction (STEMI), a promptly revascularization with primary percutaneous intervention (PCI) has transformed prognosis in the last decades. However, despite increasing successful PCI procedures, mortality has remained unchanged in recent years. Also, due to an unsatisfactory reperfusion, some patients have significant myocardial damage and suffer left ventricular adverse remodeling with reduced function—all that resulting in the onset of heart failure with all its inherent clinical and socioeconomic burden. As a consequence of longer ischemic times, distal thrombotic embolization, ischemia-reperfusion injury and microvascular dysfunction, the resultant myocardial infarct size is the major prognostic determinant in STEMI patients. The improved understanding of all the pathophysiology underlying these events has derived to the development of several novel therapies aiming to reduce infarct size and to improve clinical outcomes in these patients. In this article, based on the mechanisms involved in myocardial infarction prognosis, we review the new interventional strategies beyond stenting that may solve the suboptimal results that STEMI patients still experience. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

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12 pages, 608 KiB

Open AccessEditor’s ChoiceArticle

Diagnostic Performance of Serial High-Sensitivity Cardiac Troponin Measurements in the Emergency Setting

by Peter A. Kavsak, Mark K. Hewitt, Shawn E. Mondoux, Joshua O. Cerasuolo, Jinhui Ma, Natasha Clayton, Matthew McQueen, Lauren E. Griffith, Richard Perez, Hsien Seow, Craig Ainsworth, Dennis T. Ko and Andrew Worster

J. Cardiovasc. Dev. Dis. 2021, 8(8), 97; https://doi.org/10.3390/jcdd8080097 - 13 Aug 2021

Cited by 9 | Viewed by 3399

Abstract

Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using [...] Read more.

Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using serial measurements while incorporating absolute concentration changes for MI or death following ED presentation. We sought to determine the diagnostic estimates of these three algorithms and if one was superior in two different Canadian ED patient cohorts with serial hsTnI measurements. An undifferentiated ED population (Cohort-1) and an ED population with symptoms suggestive of acute coronary syndrome (ACS; Cohort-2) were clinically managed with non-hsTn testing with the hsTnI testing performed in real-time with physicians blinded to these results (i.e., hsTnI not reported). The three algorithms evaluated were the European Society of Cardiology (ESC), the High-STEACS pathway, and the COMPASS-MI algorithm. The diagnostic estimates were derived for each algorithm for the 30-day MI/death outcome for the rule-out and rule-in arm in each cohort and compared to proposed diagnostic benchmarks (i.e., sensitivity ≥ 99.0% and specificity ≥ 90.0%) with 95% confidence intervals (CI). In Cohort-1 (n = 2966 patients, 15.3% had outcome) and Cohort-2 (n = 935 patients, 15.6% had outcome), the algorithm that obtained the highest sensitivity (97.8%; 95% CI: 96.0–98.9 and 98.6%; 95% CI: 95.1–99.8, respectively) in both cohorts was COMPASS-MI. Only Cohort-2 with both the ESC and COMPASS-MI algorithms exceeded the specificity benchmark (97.0%; 95% CI: 95.5–98.0 and 96.7%; 95% CI: 95.2–97.8, respectively). Patient selection for serial hsTnI testing will affect specificity estimates, with no algorithm achieving a sensitivity ≥ 99% for 30-day MI or death. Full article

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17 pages, 2794 KiB

Open AccessEditor’s ChoiceReview

New Insights into the Development and Morphogenesis of the Cardiac Purkinje Fiber Network: Linking Architecture and Function

by Caroline Choquet, Lucie Boulgakoff, Robert G. Kelly and Lucile Miquerol

J. Cardiovasc. Dev. Dis. 2021, 8(8), 95; https://doi.org/10.3390/jcdd8080095 - 7 Aug 2021

Cited by 13 | Viewed by 4549

Abstract

The rapid propagation of electrical activity through the ventricular conduction system (VCS) controls spatiotemporal contraction of the ventricles. Cardiac conduction defects or arrhythmias in humans are often associated with mutations in key cardiac transcription factors that have been shown to play important roles [...] Read more.

The rapid propagation of electrical activity through the ventricular conduction system (VCS) controls spatiotemporal contraction of the ventricles. Cardiac conduction defects or arrhythmias in humans are often associated with mutations in key cardiac transcription factors that have been shown to play important roles in VCS morphogenesis in mice. Understanding of the mechanisms of VCS development is thus crucial to decipher the etiology of conduction disturbances in adults. During embryogenesis, the VCS, consisting of the His bundle, bundle branches, and the distal Purkinje network, originates from two independent progenitor populations in the primary ring and the ventricular trabeculae. Differentiation into fast-conducting cardiomyocytes occurs progressively as ventricles develop to form a unique electrical pathway at late fetal stages. The objectives of this review are to highlight the structure–function relationship between VCS morphogenesis and conduction defects and to discuss recent data on the origin and development of the VCS with a focus on the distal Purkinje fiber network. Full article

(This article belongs to the Special Issue Molecular Control of Development and Function of the Cardiac Conduction System)

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12 pages, 2435 KiB

Open AccessEditor’s ChoiceArticle

Applicability of the Leiden Convention and the Lipton Classification in Patients with a Single Coronary Artery in the Setting of Congenital Heart Disease

by Diana Isabel Katekaru-Tokeshi, Moisés Jiménez-Santos, Claire J. Koppel, Hubert W. Vliegen, Mariana Díaz-Zamudio, Francisco Castillo-Castellón, Monique R. M. Jongbloed and Eric Kimura-Hayama

J. Cardiovasc. Dev. Dis. 2021, 8(8), 93; https://doi.org/10.3390/jcdd8080093 - 4 Aug 2021

Cited by 7 | Viewed by 5082

Abstract

In single coronary artery (SCA) anatomy, all coronary tributaries arise from a single ostium, providing perfusion to the entire myocardium. Coronary classification systems can facilitate the description of SCA anatomy. Aim: Evaluation of the applicability of Lipton classification and the Leiden Convention coronary [...] Read more.

In single coronary artery (SCA) anatomy, all coronary tributaries arise from a single ostium, providing perfusion to the entire myocardium. Coronary classification systems can facilitate the description of SCA anatomy. Aim: Evaluation of the applicability of Lipton classification and the Leiden Convention coronary coding system in SCA. Methods: All patients (n = 6209) who underwent computed tomography (CT) scanning between 2014 and 2018 were retrospectively examined for the presence of SCA and classified, according to Lipton classification and the Leiden Convention coronary coding system. Results: The prevalence of SCA was 0.51% (32/6209). Twenty-eight patients (87.5%) had coexisting congenital heart disease (CHD), most frequently pulmonary atresia (9/32, 28.1%). Ten patients (10/32, 31.25%) could not be classified with either the Leiden Convention or Lipton classification (pulmonary atresia n = 9, common arterial trunk (CAT) n = 1). In one case with CAT, Lipton classification, but not the Leiden Convention, could be applied. In two cases with the transposition of the great arteries and in two cases of double outlet right ventricle, the Leiden Convention, but not the Lipton classification, could be applied. Conclusions: Both classifications are useful to detail information about SCA. As Lipton classification was not developed for structural heart disease cases, in complex CHD with abnormal position of the great arteries, the Leiden Convention is better applicable. The use of both systems is limited in pulmonary atresia. In this scenario, it is better to provide a precise description of the coronary origin and associated characteristics that might affect treatment and prognosis. 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, 745 KiB

Open AccessEditor’s ChoiceReview

The Cardiac Neural Crest Cells in Heart Development and Congenital Heart Defects

by Shannon Erhardt, Mingjie Zheng, Xiaolei Zhao, Tram P. Le, Tina O. Findley and Jun Wang

J. Cardiovasc. Dev. Dis. 2021, 8(8), 89; https://doi.org/10.3390/jcdd8080089 - 30 Jul 2021

Cited by 17 | Viewed by 6361

Abstract

The neural crest (NC) is a multipotent and temporarily migratory cell population stemming from the dorsal neural tube during vertebrate embryogenesis. Cardiac neural crest cells (NCCs), a specified subpopulation of the NC, are vital for normal cardiovascular development, as they significantly contribute to [...] Read more.

The neural crest (NC) is a multipotent and temporarily migratory cell population stemming from the dorsal neural tube during vertebrate embryogenesis. Cardiac neural crest cells (NCCs), a specified subpopulation of the NC, are vital for normal cardiovascular development, as they significantly contribute to the pharyngeal arch arteries, the developing cardiac outflow tract (OFT), cardiac valves, and interventricular septum. Various signaling pathways are shown to orchestrate the proper migration, compaction, and differentiation of cardiac NCCs during cardiovascular development. Any loss or dysregulation of signaling pathways in cardiac NCCs can lead to abnormal cardiovascular development during embryogenesis, resulting in abnormalities categorized as congenital heart defects (CHDs). This review focuses on the contributions of cardiac NCCs to cardiovascular formation, discusses cardiac defects caused by a disruption of various regulatory factors, and summarizes the role of multiple signaling pathways during embryonic development. A better understanding of the cardiac NC and its vast regulatory network will provide a deeper insight into the mechanisms of the associated abnormalities, leading to potential therapeutic advancements. Full article

(This article belongs to the Section Cardiac Development and Regeneration)

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14 pages, 1270 KiB

Open AccessEditor’s ChoiceReview

Acute Kidney Injury in Cardiogenic Shock: An Updated Narrative Review

by Sohrab Singh, Ardaas Kanwar, Pranathi R. Sundaragiri, Wisit Cheungpasitporn, Alexander G. Truesdell, Syed Tanveer Rab, Mandeep Singh and Saraschandra Vallabhajosyula

J. Cardiovasc. Dev. Dis. 2021, 8(8), 88; https://doi.org/10.3390/jcdd8080088 - 28 Jul 2021

Cited by 12 | Viewed by 8908

Abstract

Acute myocardial infarction with cardiogenic shock (AMI-CS) is associated with high mortality and morbidity despite advancements in cardiovascular care. AMI-CS is associated with multiorgan failure of non-cardiac organ systems. Acute kidney injury (AKI) is frequently seen in patients with AMI-CS and is associated [...] Read more.

Acute myocardial infarction with cardiogenic shock (AMI-CS) is associated with high mortality and morbidity despite advancements in cardiovascular care. AMI-CS is associated with multiorgan failure of non-cardiac organ systems. Acute kidney injury (AKI) is frequently seen in patients with AMI-CS and is associated with worse mortality and outcomes compared to those without. The pathogenesis of AMI-CS associated with AKI may involve more factors than previously understood. Early use of renal replacement therapies, management of comorbid conditions and judicious fluid administration may help improve outcomes. In this review, we seek to address the etiology, pathophysiology, management, and outcomes of AKI complicating AMI-CS. Full article

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10 pages, 990 KiB

Open AccessEditor’s ChoiceArticle

A History of Heart Failure Is an Independent Risk Factor for Death in Patients Admitted with Coronavirus 19 Disease

by Francesco Castagna, Rachna Kataria, Shivank Madan, Syed Zain Ali, Karim Diab, Christopher Leyton, Angelos Arfaras-Melainis, Paul Kim, Federico M. Giorgi, Sasa Vukelic, Omar Saeed, Snehal R. Patel, Daniel B. Sims and Ulrich P. Jorde

J. Cardiovasc. Dev. Dis. 2021, 8(7), 77; https://doi.org/10.3390/jcdd8070077 - 30 Jun 2021

Cited by 10 | Viewed by 3271

Abstract

Aims: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on [...] Read more.

Aims: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. Methods and Results: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. Conclusions: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19. Full article

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15 pages, 2971 KiB

Open AccessEditor’s ChoiceArticle

Early Aberrant Angiogenesis Due to Elastic Fiber Fragmentation in Aortic Valve Disease

by Robert B. Hinton, Amy L. Juraszek, Amy M. Opoka, Benjamin J. Landis, J. Michael Smith, Robert P. Mecham and Kevin E. Bove

J. Cardiovasc. Dev. Dis. 2021, 8(7), 75; https://doi.org/10.3390/jcdd8070075 - 25 Jun 2021

Cited by 5 | Viewed by 3064

Abstract

Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and [...] Read more.

Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments. Full article

(This article belongs to the Section Pediatric Cardiology and Congenital Heart Disease)

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21 pages, 795 KiB

Open AccessEditor’s ChoiceReview

Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart

by Emma Adams, Rachel McCloy, Ashley Jordan, Kaitlin Falconer and Iain M. Dykes

J. Cardiovasc. Dev. Dis. 2021, 8(7), 72; https://doi.org/10.3390/jcdd8070072 - 22 Jun 2021

Cited by 8 | Viewed by 3959

Abstract

Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, [...] Read more.

Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, modern medicine offers hope for treatment of this condition through regeneration of the myocardium by direct reprogramming of fibrotic scar tissue. Here, we will review mechanisms of cell fate specification leading to the generation of cardiovascular cell types in the embryo and use this as a framework in which to understand direct reprogramming. Driving expression of a network of transcription factors, micro RNA or small molecule epigenetic modifiers can reverse epigenetic silencing, reverting differentiated cells to a state of induced pluripotency. The pluripotent state can be bypassed by direct reprogramming in which one differentiated cell type can be transdifferentiated into another. Transdifferentiating cardiac fibroblasts to cardiomyocytes requires a network of transcription factors similar to that observed in embryonic multipotent cardiac progenitors. There is some flexibility in the composition of this network. These studies raise the possibility that the failing heart could one day be regenerated by directly reprogramming cardiac fibroblasts within post-infarct scar tissue. Full article

(This article belongs to the Section Cardiac Development and Regeneration)

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9 pages, 837 KiB

Open AccessEditor’s ChoiceArticle

Ablation of Atrioventricular Nodal Re-Entrant Tachycardia Combining Irrigated Flexible-Tip Catheters and Three-Dimensional Electroanatomic Mapping: Long-Term Outcomes

by Michele Malagù, Francesco Vitali, Federico Marchini, Alessio Fiorio, Paolo Sirugo, Daniela Mele, Alessandro Brieda, Cristina Balla and Matteo Bertini

J. Cardiovasc. Dev. Dis. 2021, 8(6), 61; https://doi.org/10.3390/jcdd8060061 - 25 May 2021

Cited by 4 | Viewed by 5792

Abstract

Background: Transcatheter ablation is the standasrd treatment for atrioventricular nodal re-entrant tachycardia (AVNRT). However, different techniques are available. Data about the use of irrigated flexible-tip catheters and three-dimensional electroanatomical mapping (3D EAM) for AVNRT ablation are scant. The aim of this study was [...] Read more.

Background: Transcatheter ablation is the standasrd treatment for atrioventricular nodal re-entrant tachycardia (AVNRT). However, different techniques are available. Data about the use of irrigated flexible-tip catheters and three-dimensional electroanatomical mapping (3D EAM) for AVNRT ablation are scant. The aim of this study was to evaluate in long-term follow-up efficacy and safety of a novel approach for AVNRT treatment. Methods: This is a cohort single arm study with long-term follow-up. Patients with AVNRT were treated with catheter ablation by means of irrigated flexible-tip catheters combined with 3D EAM. Results: One-hundred-and-fifty patients were enrolled and followed-up for a median of 38 months (minimum 12, maximum 74). Acute procedural success rate was 96.7% (145/150 patients). During follow-up, 11 patients had arrhythmia recurrences (7.3%). No patient developed atrioventricular conduction block with need for pacemaker implantation (0%). Fourteen patients died during follow-up (9.3%). Conclusions: Acute procedural success and long-term follow-up show that AVNRT could be safely and effectively treated with irrigated flexible-tip catheters and 3D EAM. Full article

(This article belongs to the Section Electrophysiology and Cardiovascular Physiology)

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24 pages, 2297 KiB

Open AccessFeature PaperEditor’s ChoiceReview

The Zebrafish Cardiac Endothelial Cell—Roles in Development and Regeneration

by Vanessa Lowe, Laura Wisniewski and Caroline Pellet-Many

J. Cardiovasc. Dev. Dis. 2021, 8(5), 49; https://doi.org/10.3390/jcdd8050049 - 1 May 2021

Cited by 12 | Viewed by 7357

Abstract

In zebrafish, the spatiotemporal development of the vascular system is well described due to its stereotypical nature. However, the cellular and molecular mechanisms orchestrating post-embryonic vascular development, the maintenance of vascular homeostasis, or how coronary vessels integrate into the growing heart are less [...] Read more.

In zebrafish, the spatiotemporal development of the vascular system is well described due to its stereotypical nature. However, the cellular and molecular mechanisms orchestrating post-embryonic vascular development, the maintenance of vascular homeostasis, or how coronary vessels integrate into the growing heart are less well studied. In the context of cardiac regeneration, the central cellular mechanism by which the heart regenerates a fully functional myocardium relies on the proliferation of pre-existing cardiomyocytes; the epicardium and the endocardium are also known to play key roles in the regenerative process. Remarkably, revascularisation of the injured tissue occurs within a few hours after cardiac damage, thus generating a vascular network acting as a scaffold for the regenerating myocardium. The activation of the endocardium leads to the secretion of cytokines, further supporting the proliferation of the cardiomyocytes. Although epicardium, endocardium, and myocardium interact with each other to orchestrate heart development and regeneration, in this review, we focus on recent advances in the understanding of the development of the endocardium and the coronary vasculature in zebrafish as well as their pivotal roles in the heart regeneration process. Full article

(This article belongs to the Special Issue Zebrafish Heart Development, Regeneration, and Disease Modelling)

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