Journal of Cardiovascular Development and Disease

8 pages, 655 KB

Open AccessEditor’s ChoiceArticle

Right Ventricular Septal Versus Apical Pacing: Long-Term Incidence of Heart Failure and Survival

by André Dias-Frias, Ricardo Costa, Andreia Campinas, André Alexandre, David Sá-Couto, Maria João Sousa, Carla Roque, Pinheiro Vieira, Vitor Lagarto, Hipólito Reis and Severo Torres

J. Cardiovasc. Dev. Dis. 2022, 9(12), 444; https://doi.org/10.3390/jcdd9120444 - 9 Dec 2022

Cited by 6 | Viewed by 2960

Abstract

The clinical benefits of right ventricular septal (RVS) pacing compared to those of right ventricular apical (RVA) pacing are still in debate. We aimed to compare the incidence of heart failure (HF) and all-cause mortality in patients submitted to RVS and RVA pacing [...] Read more.

The clinical benefits of right ventricular septal (RVS) pacing compared to those of right ventricular apical (RVA) pacing are still in debate. We aimed to compare the incidence of heart failure (HF) and all-cause mortality in patients submitted to RVS and RVA pacing during a longer follow-up. This a single-center, retrospective study analysis of consecutive patients submitted to pacemaker implantation. The primary outcome was defined as the occurrence of HF during follow-up. The secondary outcome was all-cause death. A total of 251 patients were included, 47 (18.7%) with RVS pacing. RVS pacing was associated to younger age, male gender, lower body mass index, ischemic heart disease, and atrial fibrillation. During a follow-up period of 5.2 years, the primary outcome occurred in 89 (37.1%) patients. RVS pacing was independently associated with a 3-fold lower risk of HF, after adjustment. The secondary outcome occurred in 83 (34.2%) patients, and pacemaker lead position was not a predictor. Fluoroscopy time and rate of complications (rarely life-threatening) were similar in both groups. Our study points to a potential clinical benefit of RVS positioning, with a 3.3-fold lower risk of HF, without accompanying increase in procedure complexity nor complication rate. Full article

(This article belongs to the Special Issue Heart Failure: Clinical Diagnostics and Treatment)

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12 pages, 1428 KB

Open AccessEditor’s ChoiceReview

The Role of Cardiovascular Magnetic Resonance in Patients with Mitral Regurgitation

by Anna Giulia Pavon, Marco Guglielmo, Pierpaolo Mattia Mennilli, Mariana B. L. Falcão, Luca Bergamaschi, David Filip Costantin, Michele Vivaldo, Laura Anna Leo, Susanne Schlossbauer, Christopher W. Roy, Matthias Stuber, Giovanni Pedrazzini and Francesco Faletra

J. Cardiovasc. Dev. Dis. 2022, 9(11), 399; https://doi.org/10.3390/jcdd9110399 - 18 Nov 2022

Cited by 5 | Viewed by 3699

Abstract

The 2019 Global Burden of Disease (GBD) study estimated that there were approximately 24.2 million people affected worldwide by degenerative mitral regurgitation (MR), resulting in 34,200 deaths. After aortic stenosis, MR is the most prevalent VHD in Europe and the second-most common VHD [...] Read more.

The 2019 Global Burden of Disease (GBD) study estimated that there were approximately 24.2 million people affected worldwide by degenerative mitral regurgitation (MR), resulting in 34,200 deaths. After aortic stenosis, MR is the most prevalent VHD in Europe and the second-most common VHD to pose indications for surgery in western countries. Current ESC and AHA/ACC guidelines for the management of VHD emphasize the importance of an integrative approach for the assessment of MR severity, which is of paramount importance in dictating the timing for surgery. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are the first-line imaging modalities; however, despite the technological advancement, sometimes, the final diagnosis on the degree of the disease may still be challenging. In the last 20 years, CMR has emerged as a robust technique in the assessment of patients with cardiac disease, and, recently, its role is gaining more and more importance in the field of VHD. In fact, CMR is the gold standard in the assessment of cardiac volumes, and it is possible to accurately evaluate the regurgitant volume. The purpose of this review is to outline the current state-of-the-art management of MR by using Cardiac Magnetic Resonance (CMR). Full article

(This article belongs to the Special Issue Cardiac Imaging in Valvular Heart Disease)

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8 pages, 579 KB

Open AccessEditor’s ChoiceArticle

Pre-Stroke Statin Use Is Associated with Mild Neurological Deficits at the Onset of Acute Ischemic Stroke

by Takahisa Mori, Kazuhiro Yoshioka and Yuichi Miyazaki

J. Cardiovasc. Dev. Dis. 2022, 9(11), 396; https://doi.org/10.3390/jcdd9110396 - 16 Nov 2022

Cited by 2 | Viewed by 2245

Abstract

Pre-stroke statin use reduces infarct size. Therefore, this retrospective study aimed to investigate whether pre-stroke statin use is associated with mild neurological deficits (mND) at the onset of acute ischemic stroke (AIS). We included patients with AIS admitted to our institution within 24 [...] Read more.

Pre-stroke statin use reduces infarct size. Therefore, this retrospective study aimed to investigate whether pre-stroke statin use is associated with mild neurological deficits (mND) at the onset of acute ischemic stroke (AIS). We included patients with AIS admitted to our institution within 24 h of stroke onset between 2011 and 2019. We collected data on age, sex, pre-stroke use of statins, the National Institutes of Health Stroke Scale (NIHSS) score, the serum biomarker levels, and stroke subtypes at admission. In addition, we defined mND as an NIHSS score ≤3 points. We conducted a logistic regression analysis using variables for pre-stroke statin initiation, calculated the propensity scores for pre-stroke statin use, and implemented propensity score matching (PSM). Finally, we used the McNemar test to evaluate whether pre-stroke statin administration significantly affected mND. Of 4370 patients, 2615 met our inclusion criteria. Among the 594 patients with pre-stroke statin use, 308 presented with mND. After PSM, 555 patients received pre-stroke statin treatment, while 286 patients with pre-stroke statin use presented with mND at admission (p = 0.0411). The binary matched pairs contingency table of mND was not symmetrical (p = 0.0385). Pre-stroke statin use is thus associated with mND at the onset of AIS. Full article

(This article belongs to the Special Issue Ischemic Stroke: New Insights from Risk Factors, Mechanisms and Outcomes)

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16 pages, 20381 KB

Open AccessEditor’s ChoiceArticle

OCT Meets micro-CT: A Subject-Specific Correlative Multimodal Imaging Workflow for Early Chick Heart Development Modeling

by Nina Kraus, Fabian Placzek and Brian Metscher

J. Cardiovasc. Dev. Dis. 2022, 9(11), 379; https://doi.org/10.3390/jcdd9110379 - 3 Nov 2022

Cited by 4 | Viewed by 2932

Abstract

Structural and Doppler velocity data collected from optical coherence tomography have already provided crucial insights into cardiac morphogenesis. X-ray microtomography and other ex vivo methods have elucidated structural details of developing hearts. However, by itself, no single imaging modality can provide comprehensive information [...] Read more.

Structural and Doppler velocity data collected from optical coherence tomography have already provided crucial insights into cardiac morphogenesis. X-ray microtomography and other ex vivo methods have elucidated structural details of developing hearts. However, by itself, no single imaging modality can provide comprehensive information allowing to fully decipher the inner workings of an entire developing organ. Hence, we introduce a specimen-specific correlative multimodal imaging workflow combining OCT and micro-CT imaging which is applicable for modeling of early chick heart development—a valuable model organism in cardiovascular development research. The image acquisition and processing employ common reagents, lab-based micro-CT imaging, and software that is free for academic use. Our goal is to provide a step-by-step guide on how to implement this workflow and to demonstrate why those two modalities together have the potential to provide new insight into normal cardiac development and heart malformations leading to congenital heart disease. Full article

(This article belongs to the Special Issue Models and Methods for Computational Cardiology)

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18 pages, 904 KB

Open AccessEditor’s ChoiceReview

New Biomarkers and Their Potential Role in Heart Failure Treatment Optimisation—An African Perspective

by Marheb Badianyama, Dineo Mpanya, Umar Adamu, Farai Sigauke, Samantha Nel and Nqoba Tsabedze

J. Cardiovasc. Dev. Dis. 2022, 9(10), 335; https://doi.org/10.3390/jcdd9100335 - 2 Oct 2022

Cited by 8 | Viewed by 3470

Abstract

Heart failure is a clinical syndrome resulting from various cardiovascular diseases of different aetiologies and pathophysiology. These varying pathologies involve several complex mechanisms that lead to the activation of the neurohumoral system, inflammation, angiogenesis, apoptosis, fibrosis, and eventually adverse cardiac remodelling associated with [...] Read more.

Heart failure is a clinical syndrome resulting from various cardiovascular diseases of different aetiologies and pathophysiology. These varying pathologies involve several complex mechanisms that lead to the activation of the neurohumoral system, inflammation, angiogenesis, apoptosis, fibrosis, and eventually adverse cardiac remodelling associated with a progressive decline in cardiac function. Once a diagnosis is made, the cardiac function has a gradual decline characterised by multiple hospital admissions. It is therefore imperative to identify patients at different stages of the heart failure continuum to better risk stratify and initiate optimal management strategies. Biomarkers may play a role in the diagnosis, prognostication, and monitoring response to treatment. This review discusses the epidemiology of heart failure and biomarkers commonly used in clinical practice such as natriuretic peptides and cardiac troponins. In addition, we provide a brief overview of novel biomarkers and genetic coding and non-coding biomarkers used in the management of patients with heart failure. We also discuss barriers that hinder the clinical application of novel biomarkers. Finally, we appraise the value of polygenic risk scoring, focusing on sub-Saharan Africa. Full article

(This article belongs to the Special Issue Therapeutic Strategies for Heart Failure)

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10 pages, 522 KB

Open AccessEditor’s ChoiceArticle

Short-Term Atrioventricular Dysfunction Recovery after Post-TAVI Pacemaker Implantation

by Gaetano Pinnacchio, Eleonora Ruscio, Erica Rocco, Carlo Trani, Francesco Burzotta, Cristina Aurigemma, Enrico Romagnoli, Roberto Scacciavillani, Maria Lucia Narducci, Gianluigi Bencardino, Francesco Perna, Francesco Raffaele Spera, Gianluca Comerci, Antonio Bisignani and Gemma Pelargonio

J. Cardiovasc. Dev. Dis. 2022, 9(10), 324; https://doi.org/10.3390/jcdd9100324 - 24 Sep 2022

Cited by 1 | Viewed by 3746

Abstract

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 ± 6 years, 58% males, EuroSCORE: 7.8 ± 3.3%, [...] Read more.

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 ± 6 years, 58% males, EuroSCORE: 7.8 ± 3.3%, STS mortality score: 5 ± 2.8%). Pacemaker interrogations within 4–6 weeks from PPI were performed to collect data on AV conduction. The most common indication of PPI was persistent third-degree (44%)/high-degree (20%) AV block/atrial fibrillation (AF) with slow ventricular conduction (16%) after TAVI. At follow-up, 13 patients (26%) recovered AV conduction (i.e., sinus rhythm with stable 1:1 AV conduction/AF with a mean ventricular response >50 bpm, associated with a long-term ventricular pacing percentage < 5%). At multivariate analysis, complete atrio-ventricular block independently predicted pacemaker dependency at follow-up (p = 0.019). Patients with persistent AV dysfunction showed a significant AV conduction time prolongation after TAVI (PR interval from 207 ± 50 to 230 ± 51, p = 0.02; QRS interval from 124 ± 23 to 147 ± 16, p < 0.01) compared to patients with recovery, in whom AV conduction parameters remained unchanged. Several patients receiving PPI after TAVI have recovery of AV conduction within a few weeks. Longer observation periods prior to PPI might be justified, and algorithms to minimize ventricular pacing should be utilized whenever possible. Full article

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

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11 pages, 693 KB

Open AccessEditor’s ChoiceReview

The Management of Myocardial Injury Related to SARS-CoV-2 Pneumonia

by Mohammed Ahmed Akkaif, Ahmad Naoras Bitar, Laith A. I. K. Al-Kaif, Nur Aizati Athirah Daud, Abubakar Sha’aban, Dzul Azri Mohamed Noor, Fatimatuzzahra’ Abd Aziz, Arturo Cesaro, Muhamad Ali SK Abdul Kader, Mohamed Jahangir Abdul Wahab, Chee Sin Khaw and Baharudin Ibrahim

J. Cardiovasc. Dev. Dis. 2022, 9(9), 307; https://doi.org/10.3390/jcdd9090307 - 16 Sep 2022

Cited by 11 | Viewed by 3399

Abstract

The global evolution of the SARS-CoV-2 virus is known to all. The diagnosis of SARS-CoV-2 pneumonia is expected to worsen, and mortality will be higher when combined with myocardial injury (MI). The combination of novel coronavirus infections in patients with MI can cause [...] Read more.

The global evolution of the SARS-CoV-2 virus is known to all. The diagnosis of SARS-CoV-2 pneumonia is expected to worsen, and mortality will be higher when combined with myocardial injury (MI). The combination of novel coronavirus infections in patients with MI can cause confusion in diagnosis and assessment, with each condition exacerbating the other, and increasing the complexity and difficulty of treatment. It would be a formidable challenge for clinical practice to deal with this situation. Therefore, this review aims to gather literature on the progress in managing MI related to SARS-CoV-2 pneumonia. This article reviews the definition, pathogenesis, clinical evaluation, management, and treatment plan for MI related to SARS-CoV-2 pneumonia based on the most recent literature, diagnosis, and treatment trial reports. Many studies have shown that early diagnosis and implementation of targeted treatment measures according to the different stages of disease can reduce the mortality rate among patients with MI related to SARS-CoV-2 pneumonia. The reviewed studies show that multiple strategies have been adopted for the management of MI related to COVID-19. Clinicians should closely monitor SARS-CoV-2 pneumonia patients with MI, as their condition can rapidly deteriorate and progress to heart failure, acute myocardial infarction, and/or cardiogenic shock. In addition, appropriate measures need to be implemented in the diagnosis and treatment to provide reasonable care to the patient. Full article

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22 pages, 1115 KB

Open AccessEditor’s ChoiceReview

Effects of COVID-19 on Arrhythmia

by Yujia Zhan, Honghua Yue, Weitao Liang and Zhong Wu

J. Cardiovasc. Dev. Dis. 2022, 9(9), 292; https://doi.org/10.3390/jcdd9090292 - 2 Sep 2022

Cited by 15 | Viewed by 6915

Abstract

The World Health Organization announced that COVID-19, with SARS-CoV-2 as its pathogen, had become a pandemic on 11 March 2020. Today, the global epidemic situation is still serious. With the development of research, cardiovascular injury in patients with COVID-19, such as arrhythmia, myocardial [...] Read more.

The World Health Organization announced that COVID-19, with SARS-CoV-2 as its pathogen, had become a pandemic on 11 March 2020. Today, the global epidemic situation is still serious. With the development of research, cardiovascular injury in patients with COVID-19, such as arrhythmia, myocardial injury, and heart failure, is the second major symptom in addition to respiratory symptoms, and cardiovascular injury is related to the prognosis and mortality of patients. The incidence of arrhythmia in COVID-19 patients ranges from 10% to 20%. The potential mechanisms include viral infection-induced angiotensin-converting enzyme 2 expression change, myocarditis, cytokine storm, cardiac injury, electrophysiological effects, hypoxemia, myocardial strain, electrolyte abnormalities, intravascular volume imbalance, drug toxicities and interactions, and stress response caused by virus infection. COVID-19 complicated with arrhythmia needs to be accounted for and integrated in management. This article reviews the incidence, potential mechanisms, and related management measures of arrhythmia in COVID-19 patients. Full article

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

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15 pages, 3062 KB

Open AccessEditor’s ChoiceReview

Ventricular Tachycardia Ablation Guided by Functional Substrate Mapping: Practices and Outcomes

by Sara Vázquez-Calvo, Ivo Roca-Luque and Andreu Porta-Sánchez

J. Cardiovasc. Dev. Dis. 2022, 9(9), 288; https://doi.org/10.3390/jcdd9090288 - 30 Aug 2022

Cited by 7 | Viewed by 4620

Abstract

Catheter ablation of ventricular tachycardia has demonstrated its important role in the treatment of ventricular tachycardia in patients with structural cardiomyopathy. Conventional mapping techniques used to define the critical isthmus, such as activation mapping and entrainment, are limited by the non-inducibility of the [...] Read more.

Catheter ablation of ventricular tachycardia has demonstrated its important role in the treatment of ventricular tachycardia in patients with structural cardiomyopathy. Conventional mapping techniques used to define the critical isthmus, such as activation mapping and entrainment, are limited by the non-inducibility of the clinical tachycardia or its poor hemodynamic tolerance. To overcome these limitations, a voltage mapping strategy based on bipolar electrograms peak to peak analysis was developed, but a low specificity (30%) for VT isthmus has been described with this approach. Functional mapping strategy relies on the analysis of the characteristics of the electrograms but also their propagation patterns and their response to extra-stimulus or alternative pacing wavefronts to define the targets for ablation. With this review, we aim to summarize the different functional mapping strategies described to date to identify ventricular arrhythmic substrate in patients with structural heart disease. Full article

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

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12 pages, 304 KB

Open AccessFeature PaperEditor’s ChoiceReview

Technical Aspects and Development of Transcatheter Aortic Valve Implantation

by Klemen Steblovnik and Matjaz Bunc

J. Cardiovasc. Dev. Dis. 2022, 9(8), 282; https://doi.org/10.3390/jcdd9080282 - 22 Aug 2022

Cited by 5 | Viewed by 3751

Abstract

Aortic stenosis is the most common valve disease requiring surgery or percutaneous treatment. Since the first-in-man implantation in 2002 we have witnessed incredible progress in transcatheter aortic valve implantation (TAVI). In this article, we review the technical aspects of TAVI development with a [...] Read more.

Aortic stenosis is the most common valve disease requiring surgery or percutaneous treatment. Since the first-in-man implantation in 2002 we have witnessed incredible progress in transcatheter aortic valve implantation (TAVI). In this article, we review the technical aspects of TAVI development with a look at the future. Durability, low thrombogenicity, good hydrodynamics, biocompatibility, low catheter profile, and deployment stability are the attributes of an ideal TAVI device. Two main design types exist—balloon-expandable and self-expanding prostheses. Balloon-expandable prostheses use a cobalt-chromium alloy frame providing high radial strength and radiopacity, while the self-expanding prostheses use a nickel-titanium (Nitinol) alloy frame, which expands to its original shape once unsheathed and heated to the body temperature. The valve is sewn onto the frame and consists of the porcine or bovine pericardium, which is specially treated to prevent calcinations and prolong durability. The lower part of the frame can be covered by polyethylene terephthalate fabric or a pericardial skirt, providing better sealing between the frame and aortic annulus. The main future challenges lie in achieving lower rates of paravalvular leaks and new pacemaker implantations following the procedure, lower delivery system profiles, more precise positioning, longer durability, and a good hemodynamic profile. Patient-specific design and the use of autologous tissue might solve these issues. Full article

(This article belongs to the Special Issue Atherosclerotic Cardiovascular Disease: Risk Assessment, Prevention and Treatment Strategies)

12 pages, 1742 KB

Open AccessEditor’s ChoiceReview

The Left Ventricular Myocardium in Hypoplastic Left Heart Syndrome

by Bill Chaudhry, Ahlam Alqahtani, Lorraine Eley, Louise Coats, Corina Moldovan, Srinivas R. Annavarapu and Deborah J. Henderson

J. Cardiovasc. Dev. Dis. 2022, 9(8), 279; https://doi.org/10.3390/jcdd9080279 - 19 Aug 2022

Cited by 7 | Viewed by 3816

Abstract

Hypoplastic left heart syndrome (HLHS) is a collective term applied to severe congenital cardiac malformations, characterised by a combination of abnormalities mainly affecting the left ventricle, associated valves, and ascending aorta. Although in clinical practice HLHS is usually sub-categorised based on the patency [...] Read more.

Hypoplastic left heart syndrome (HLHS) is a collective term applied to severe congenital cardiac malformations, characterised by a combination of abnormalities mainly affecting the left ventricle, associated valves, and ascending aorta. Although in clinical practice HLHS is usually sub-categorised based on the patency of the mitral and aortic (left-sided) valves, it is also possible to comprehensively categorise HLHS into defined sub-groups based on the left ventricular morphology. Here, we discuss the published human-based studies of the ventricular myocardium in HLHS, evaluating whether the available evidence is in keeping with this ventricular morphology concept. Specifically, we highlight results from histological studies, indicating that the appearance of cardiomyocytes can be different based on the sub-group of HLHS. In addition, we discuss the histological appearances of endocardial fibroelastosis (EFE), which is a common feature of one specific sub-group of HLHS. Lastly, we suggest investigations that should ideally be undertaken using HLHS myocardial tissues at early stages of HLHS development to identify biological pathways and aid the understanding of HLHS aetiology. Full article

(This article belongs to the Special Issue Hypoplastic Left Heart Syndrome: Etiology, Pathogenesis, Management and The Future)

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12 pages, 1760 KB

Open AccessEditor’s ChoiceReview

Following the Beat: Imaging the Valveless Pumping Function in the Early Embryonic Heart

by Shang Wang and Irina V. Larina

J. Cardiovasc. Dev. Dis. 2022, 9(8), 267; https://doi.org/10.3390/jcdd9080267 - 15 Aug 2022

Cited by 6 | Viewed by 2650

Abstract

In vertebrates, the coordinated beat of the early heart tube drives cardiogenesis and supports embryonic growth. How the heart pumps at this valveless stage marks a fascinating problem that is of vital significance for understanding cardiac development and defects. The developing heart achieves [...] Read more.

In vertebrates, the coordinated beat of the early heart tube drives cardiogenesis and supports embryonic growth. How the heart pumps at this valveless stage marks a fascinating problem that is of vital significance for understanding cardiac development and defects. The developing heart achieves its function at the same time as continuous and dramatic morphological changes, which in turn modify its pumping dynamics. The beauty of this muti-time-scale process also highlights its complexity that requires interdisciplinary approaches to study. High-resolution optical imaging, particularly fast, four-dimensional (4D) imaging, plays a critical role in revealing the process of pumping, instructing numerical modeling, and enabling biomechanical analyses. In this review, we aim to connect the investigation of valveless pumping mechanisms with the recent advancements in embryonic cardiodynamic imaging, facilitating interactions between these two areas of study, in hopes of encouraging and motivating innovative work to further understand the early heartbeat. Full article

(This article belongs to the Special Issue Models and Methods for Computational Cardiology)

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10 pages, 280 KB

Open AccessEditor’s ChoiceArticle

Contractile Reserve in Heart Failure with Preserved Ejection Fraction

by Daniela Di Lisi, Quirino Ciampi, Cristina Madaudo, Girolamo Manno, Francesca Macaione, Salvatore Novo and Giuseppina Novo

J. Cardiovasc. Dev. Dis. 2022, 9(8), 248; https://doi.org/10.3390/jcdd9080248 - 4 Aug 2022

Cited by 1 | Viewed by 2519

Abstract

Background: Diastolic stress echocardiography (SE) is useful for confirming the diagnosis of heart failure with preserved left ventricular ejection fraction (HFpEF) when it is uncertain. The aim of this study was to assess the value of new echocardiographic parameters during diastolic SE in [...] Read more.

Background: Diastolic stress echocardiography (SE) is useful for confirming the diagnosis of heart failure with preserved left ventricular ejection fraction (HFpEF) when it is uncertain. The aim of this study was to assess the value of new echocardiographic parameters during diastolic SE in patients with dyspnea and suspected HFpEF. Methods: Sixty-two patients with exertional dyspnea and inconclusive rest echocardiography for a diagnosis of HFpEF were enrolled. Exercise SE was performed in all patients. Contractile reserve (LVCR) was assessed by measuring: 1. changes in the left ventricular ejection fraction (LVEF) between rest and peak stress; 2. stress-to-rest ratio of force (force was defined as the ratio between systolic arterial pressure and left ventricular end-systolic volume); and 3. mechanical reserve, defined as the change in systolic strain (GLS) between rest and peak stress. Results: Diagnosis of HFpEF was performed by SE in 26 patients. Comparing patients with a diagnosis of HFpEF (group A) to patients with other causes of dyspnea (group B), we found a significant increase in the E/e’ ratio in group A at peak stress. LV GLS was significantly reduced in group A compared to group B at rest and stress (p value 0.01 at rest; p value 0.04 at stress). At peak stress, GLS did not significantly increase in group A, while it increased in group B (p value 0.04). LVEF increased significantly in both groups. Conclusion: Patients with HFpEF have impaired LVCR when assessed using GLS. Thus, the assessment of mechanical reserve could give additional diagnostic information during stress tests in patients with HFpEF. Full article

(This article belongs to the Section Imaging)

11 pages, 1052 KB

Open AccessEditor’s ChoiceReview

Congenital Heart Disease and the Risk of Cancer: An Update on the Genetic Etiology, Radiation Exposure Damage, and Future Research Strategies

by Jonica Campolo, Giuseppe Annoni, Marzia Giaccardi and Maria Grazia Andreassi

J. Cardiovasc. Dev. Dis. 2022, 9(8), 245; https://doi.org/10.3390/jcdd9080245 - 1 Aug 2022

Cited by 17 | Viewed by 3438

Abstract

Epidemiological studies have shown an increased prevalence of cancer in patients with congenital heart disease (CHD) as compared with the general population. The underlying risk factors for the acquired cancer risk remain poorly understood, and shared genetic anomalies and cumulative radiation exposure from [...] Read more.

Epidemiological studies have shown an increased prevalence of cancer in patients with congenital heart disease (CHD) as compared with the general population. The underlying risk factors for the acquired cancer risk remain poorly understood, and shared genetic anomalies and cumulative radiation exposure from repeated imaging and catheterization procedures may be contributing factors. In the present review, we provide an update on the most recent literature regarding the associations between CHD and cancer, with a particular focus on genetic etiology and radiation exposure from medical procedures. The current evidence indicates that children with CHD may be a high-risk population, already having the first genetic “hit”, and, consequently, may have increased sensitivity to ionizing radiation from birth or earlier. Future research strategies integrating biological and molecular measures are also discussed in this article. Full article

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

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13 pages, 3337 KB

Open AccessEditor’s ChoiceArticle

Characteristics and Prognostic Relevance of Ventricular Arrhythmia in Patients with Myocarditis

by Ann-Kathrin Kahle, Rebekka Güde, Jana M. Schwarzl, Paula Münkler, Ruken Ö. Akbulak, Charlotte Jahnke, Sebastian Bohnen, Tilman Würger, Michael Schwarzl, Stephan Willems, Ulf K. Radunski and Christian Meyer

J. Cardiovasc. Dev. Dis. 2022, 9(8), 243; https://doi.org/10.3390/jcdd9080243 - 29 Jul 2022

Viewed by 3832

Abstract

Myocarditis is characterized by various clinical manifestations, with ventricular arrhythmia (VA) as a frequent symptom at initial presentation. Here, we investigated characteristics and prognostic relevance of VA in patients with myocarditis. The study population consisted of 76 patients with myocarditis, verified by biopsy [...] Read more.

Myocarditis is characterized by various clinical manifestations, with ventricular arrhythmia (VA) as a frequent symptom at initial presentation. Here, we investigated characteristics and prognostic relevance of VA in patients with myocarditis. The study population consisted of 76 patients with myocarditis, verified by biopsy and/or cardiac magnetic resonance (CMR) imaging, including 38 consecutive patients with VA (45 ± 3 years, 68% male) vs. 38 patients without VA (NVA) (38 ± 2 years, 84% male) serving as a control group. VA was monomorphic ventricular tachycardia in 55% of patients, premature ventricular complexes in 50% and ventricular fibrillation in 29%. The left ventricular ejection fraction at baseline was 47 ± 2% vs. 40 ± 3% in VA vs. NVA patients (p = 0.069). CMR showed late gadolinium enhancement more often in VA patients (94% vs. 69%; p = 0.016), incorporating 17.6 ± 1.8% vs. 8.2 ± 1.3% of myocardial mass (p < 0.001). Radiofrequency catheter ablation for VA was initially performed in nine (24%) patients, of whom five remained free from any recurrence over 24 ± 3 months. Taken together, in patients with myocarditis, reduced left ventricular ejection fraction does not predict VA occurrence but CMR shows late gadolinium enhancement more frequently and to a larger extent in VA than in NVA patients, potentially guiding catheter ablation as a reasonable treatment of VA in this population. Full article

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

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12 pages, 5052 KB

Open AccessEditor’s ChoiceArticle

Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro

by Jara M. Baena-Montes, Tony O’Halloran, Cormac Clarke, Kevin Donaghey, Eoghan Dunne, Martin O’Halloran and Leo R. Quinlan

J. Cardiovasc. Dev. Dis. 2022, 9(8), 240; https://doi.org/10.3390/jcdd9080240 - 28 Jul 2022

Cited by 24 | Viewed by 4341

Abstract

Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy [...] Read more.

Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy sources. However, more tissue and cell-specific evidence is required to demonstrate the selective threshold parameters for human cells. The aim here is to determine the optimal ablation threshold parameters related to lesion size for human cardiomyocytes in 2D culture. Conventional biphasic pulses of different field strengths and on-times were delivered in a monolayer culture system of human AC16 cardiomyocytes. The dynamics of cell death and lesion dimensions were examined at different time points. Human cardiomyocytes are susceptible to significant electroporation and cell death at a field strength of 750 V/cm or higher with 100 μs pulses. Increasing the IRE on-time from 3 ms to 60 ms reduces the effective field threshold to 250 V/cm. Using very short pulses of 2 μs and 5 μs also causes significant cell death, but only at fields higher than 1000 V/cm. A longer on-time results in more cell death and induced greater lesion area in 2D models. In addition, different forms of cell death are predicted based on the evolution of cell death over time. This study presents important findings on the ability of different IRE parameters to induce human cardiomyocyte cell death. Lesion size can be tuned by appropriate choice of IRE parameters and cardiomyocytes display an upregulation of delayed cell death 24 h after electroporation, which is an important consideration for clinical practice. Full article

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

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19 pages, 1053 KB

Open AccessEditor’s ChoiceReview

Effects of Exercise on Heart Failure with Preserved Ejection Fraction: An Updated Review of Literature

by Giulia Crisci, Mariarosaria De Luca, Roberta D’Assante, Brigida Ranieri, Anna D’Agostino, Valeria Valente, Federica Giardino, Valentina Capone, Salvatore Chianese, Salvatore Rega, Rosangela Cocchia, Muhammad Zubair Israr, Radek Debiek, Liam M. Heaney and Andrea Salzano

J. Cardiovasc. Dev. Dis. 2022, 9(8), 241; https://doi.org/10.3390/jcdd9080241 - 28 Jul 2022

Cited by 28 | Viewed by 10779

Abstract

Heart failure with preserved ejection fraction (HFpEF) represents the most common HF phenotype of patients aged > 65 years, with an incidence and a prevalence that are constantly growing. The HFpEF cardinal symptom is exercise intolerance (EI), defined as the impaired ability to [...] Read more.

Heart failure with preserved ejection fraction (HFpEF) represents the most common HF phenotype of patients aged > 65 years, with an incidence and a prevalence that are constantly growing. The HFpEF cardinal symptom is exercise intolerance (EI), defined as the impaired ability to perform physical activity and to reach the predicted age-related level of exercise duration in the absence of symptoms—such as fatigue or dyspnea—and is associated with a poor quality of life, a higher number of hospitalizations, and poor outcomes. The evidence of the protective effect between exercise and adverse cardiovascular outcomes is numerous and long-established. Regular exercise is known to reduce cardiovascular events and overall mortality both in apparently healthy individuals and in patients with established cardiovascular disease, representing a cornerstone in the prevention and treatment of many cardio-metabolic conditions. Several studies have investigated the role of exercise in HFpEF patients. The present review aims to dwell upon the effects of exercise on HFpEF. For this purpose, the relevant data from a literature search (PubMed, EMBASE, and Medline) were reviewed. The analysis of these studies underlines the fact that exercise training programs improve the cardiorespiratory performance of HFpEF patients in terms of the increase in peak oxygen uptake, the 6 min walk test distance, and the ventilatory threshold; on the other hand, diastolic or systolic functions are generally unchanged or only partially modified by exercise, suggesting that multiple mechanisms contribute to the improvement of exercise tolerance in HFpEF patients. In conclusion, considering that exercise training programs are able to improve the cardiorespiratory performance of HFpEF patients, the prescription of exercise training programs should be encouraged in stable HFpEF patients, and further research is needed to better elucidate the pathophysiological mechanisms underpinning the beneficial effects described. Full article

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

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20 pages, 1471 KB

Open AccessEditor’s ChoiceReview

Sex Differences in Acute Coronary Syndromes: A Global Perspective

by F Aaysha Cader, Shrilla Banerjee and Martha Gulati

J. Cardiovasc. Dev. Dis. 2022, 9(8), 239; https://doi.org/10.3390/jcdd9080239 - 27 Jul 2022

Cited by 38 | Viewed by 8483

Abstract

Despite increasing evidence and improvements in the care of acute coronary syndromes (ACS), sex disparities in presentation, comorbidities, access to care and invasive therapies remain, even in the most developed countries. Much of the currently available data are derived from more developed regions [...] Read more.

Despite increasing evidence and improvements in the care of acute coronary syndromes (ACS), sex disparities in presentation, comorbidities, access to care and invasive therapies remain, even in the most developed countries. Much of the currently available data are derived from more developed regions of the world, particularly Europe and the Americas. In contrast, in more resource-constrained settings, especially in Sub-Saharan Africa and some parts of Asia, more data are needed to identify the prevalence of sex disparities in ACS, as well as factors responsible for these disparities, particularly cultural, socioeconomic, educational and psychosocial. This review summarizes the available evidence of sex differences in ACS, including risk factors, pathophysiology and biases in care from a global perspective, with a focus on each of the six different World Health Organization (WHO) regions of the world. Regional trends and disparities, gaps in evidence and solutions to mitigate these disparities are also discussed. Full article

(This article belongs to the Special Issue Heart Disease in Women)

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13 pages, 1548 KB

Open AccessEditor’s ChoiceArticle

Left Atrial Remodeling after Mitral Valve Repair for Primary Mitral Regurgitation: Evolution over Time and Prognostic Significance

by Jan Stassen, Aniek L. van Wijngaarden, Hoi W. Wu, Meindert Palmen, Anton Tomsic, Victoria Delgado, Jeroen J. Bax and Nina Ajmone Marsan

J. Cardiovasc. Dev. Dis. 2022, 9(7), 230; https://doi.org/10.3390/jcdd9070230 - 18 Jul 2022

Cited by 6 | Viewed by 3706

Abstract

Left atrial (LA) dilatation is associated with worse outcomes in primary mitral regurgitation (MR). However, the effects of mitral valve repair on LA size and its prognostic implications are not well known. In the current study, LA volume index (LAVi) and LA reservoir [...] Read more.

Left atrial (LA) dilatation is associated with worse outcomes in primary mitral regurgitation (MR). However, the effects of mitral valve repair on LA size and its prognostic implications are not well known. In the current study, LA volume index (LAVi) and LA reservoir strain (LASr) were evaluated immediately before and after surgery, and during long-term follow-up in 226 patients undergoing mitral valve repair for primary MR (age 62 ± 13 years, 66% male). Mean LAVi was reduced significantly after surgery and at long-term follow-up (from 56 ± 28 to 38 ± 21 to 32 ± 17 mL/m²; p < 0.001). LASr reduced significantly after surgery but increased again during the long-term (from 23.6 ± 9.4 to 11.5 ± 5.0 to 17.3 ± 7.5%; p < 0.001). Age, pre-operative LAVi, MR severity, and postoperative transmitral pressure gradient were associated with LA reverse remodeling by the long-term check-up. During a median follow-up of 72 (40–114) months, 43 (19%) patients died. Patients with LAVi ≥ 42 mL/m² at long-term follow-up showed significant higher mortality rates compared to patients with LAVI < 42 mL/m² (p < 0.001), even after adjusting for clinical covariates. In conclusion, significant LA reverse remodeling was observed both immediately and at long-term follow-up after mitral valve repair. LA dilatation at long term follow-up after surgery was still associated with all-cause mortality. Full article

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

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18 pages, 2122 KB

Open AccessEditor’s ChoiceReview

TAVR for All? The Surgical Perspective

by Xiling Zhang, Thomas Puehler, Derk Frank, Janarthanan Sathananthan, Stephanie Sellers, David Meier, Marcus Both, Philipp Blanke, Hatim Seoudy, Mohammed Saad, Oliver J. Müller, Lars Sondergaard and Georg Lutter

J. Cardiovasc. Dev. Dis. 2022, 9(7), 223; https://doi.org/10.3390/jcdd9070223 - 12 Jul 2022

Cited by 3 | Viewed by 4086

Abstract

In spite of the noninferiority of transcatheter aortic valve replacement (TAVR) in high- and intermediate-risk patients, there are still obstacles that need to be overcome before the procedure is further expanded and clinically integrated. The lack of evidence on the long-term durability of [...] Read more.

In spite of the noninferiority of transcatheter aortic valve replacement (TAVR) in high- and intermediate-risk patients, there are still obstacles that need to be overcome before the procedure is further expanded and clinically integrated. The lack of evidence on the long-term durability of the bioprostheses used for TAVR remains of particular concern. In addition, surgery may be preferred over TAVR in patients with bicuspid aortic valve (BAV) or with concomitant pathologies such as other valve diseases (mitral regurgitation/tricuspid regurgitation), aortopathy, and coronary artery disease. In this review, we discuss and summarize relevant data from clinical trials, current trends, and remaining obstacles, and provide our perspective on the indications for the expansion of TAVR. Full article

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

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11 pages, 899 KB

Open AccessEditor’s ChoiceArticle

Low Prevalence of Cardiomyopathy in Patients with Mitochondrial Disease and Neurological Manifestations

by Anish Nikhanj, Jesi Bautista, Zaeem A. Siddiqi, Cecile L. Phan and Gavin Y. Oudit

J. Cardiovasc. Dev. Dis. 2022, 9(7), 221; https://doi.org/10.3390/jcdd9070221 - 9 Jul 2022

Cited by 2 | Viewed by 3244

Abstract

Patients with mitochondrial diseases can develop cardiomyopathy but with variable expressivity and penetrance. Our prospective study enrolled and evaluated a cohort of 53 patients diagnosed with chronic progressive ophthalmoplegia (CPEO, n = 34), Kearns–Sayre syndrome (KSS, n = 3), neuropathy ataxia and retinitis [...] Read more.

Patients with mitochondrial diseases can develop cardiomyopathy but with variable expressivity and penetrance. Our prospective study enrolled and evaluated a cohort of 53 patients diagnosed with chronic progressive ophthalmoplegia (CPEO, n = 34), Kearns–Sayre syndrome (KSS, n = 3), neuropathy ataxia and retinitis pigmentosa (NARP, n = 1), myoclonic epilepsy with ragged red fibers (MERRF, n = 1), Harel–Yoon Syndrome (HYS, n = 1) and 13 patients with undefined mitochondrial diseases, presenting primarily with neurological symptoms. Over a 4-year period, six patients in our study cohort were diagnosed with heart disease (11.3%), with only three patients having defined cardiomyopathy (5.7%). Cardiomyopathy was present in a 21-year-old patient with HYS and two CPEO patients having mild cardiomyopathy at an older age. Two CPEO patients had congenital heart disease, and a third CPEO had LV hypertrophy secondary to hypertension. In three patients, traditional risk factors for heart disease, including dyslipidemia, hypertension, and respiratory disease, were present. The majority of our adult cohort of patients have normal cardiac investigations with a median left ventricular (LV) ejection fraction of 59.0%, indexed LV mass of 67.0 g/m², and normal diastolic and valvular function at baseline. A 12-lead electrocardiogram showed normal cardiac conduction across the study cohort. Importantly, follow-up assessments showed consistent cardiac structure and function. Our study shows a low prevalence of cardiomyopathy and highlights the breadth of phenotypic variability in patients with mitochondrial disorders. The presence of cardiovascular risk factors and aging are important comorbidities in our cohort. Full article

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9 pages, 1780 KB

Open AccessEditor’s ChoiceArticle

A Comparative Study on Surgical Treatment of Valvular Heart Disease between High-Volume Cardiac Centers in China and STS Data

by Hongyuan Lin, Jiamiao Gong, Yongjian Wu, Zhe Zheng and Jianfeng Hou

J. Cardiovasc. Dev. Dis. 2022, 9(7), 212; https://doi.org/10.3390/jcdd9070212 - 2 Jul 2022

Cited by 7 | Viewed by 2819

Abstract

The goal of this study is to summarize valvular surgery data from the Chinese Cardiac Surgery Registry (CCSR) and compare it to the most recent data from the Society of Thoracic Surgeons (STS). From 2016 to 2018, a total of 34,386 cases of [...] Read more.

The goal of this study is to summarize valvular surgery data from the Chinese Cardiac Surgery Registry (CCSR) and compare it to the most recent data from the Society of Thoracic Surgeons (STS). From 2016 to 2018, a total of 34,386 cases of the seven most common valvular surgical procedures was obtained from the CCSR. We calculated the proportions of different procedures in the CCSR cohort (n = 34,386) as well as the change in operation volume for each procedure. We also compiled rates of postoperative in-hospital mortality and five major complications across all procedures. All of the results were compared to the STS data. The CCSR and STS data showed divergent trends in valvular heart disease features and operation volume. Although the proportion of MV repair in the CCSR (13.7%) data was lower than in the STS data (23.2%), it demonstrated a substantial upward trend. In terms of operation volume, the CCSR data showed an upward trend, but the STS data showed a downward trend. CCSR procedures showed lower mortality (2% vs. 2.6%), reoperation (2.8% vs. 4.3%), and permanent stroke (0.5% vs. 1.6%) rates than STS procedures but higher rates of prolonged ventilation (22.4% vs. 10.4%) and renal failure (5.6% vs. 3.2%). Valvular surgery quality in China’s leading cardiac hospitals is roughly comparable to that in the United States. China, on the other hand, has some shortcomings that need improvement. Full article

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13 pages, 2385 KB

Open AccessEditor’s ChoiceArticle

Biventricular versus Conduction System Pacing after Atrioventricular Node Ablation in Heart Failure Patients with Atrial Fibrillation

by Maja Ivanovski, Miha Mrak, Anja Zupan Mežnar and David Žižek

J. Cardiovasc. Dev. Dis. 2022, 9(7), 209; https://doi.org/10.3390/jcdd9070209 - 1 Jul 2022

Cited by 29 | Viewed by 4596

Abstract

Conduction system pacing (CSP) modalities, including His-bundle pacing (HBP) and left bundle branch pacing (LBBP), are increasingly used as alternatives to biventricular (BiV) pacing in heart failure (HF) patients scheduled for pace and ablate strategy. The aim of the study was to compare [...] Read more.

Conduction system pacing (CSP) modalities, including His-bundle pacing (HBP) and left bundle branch pacing (LBBP), are increasingly used as alternatives to biventricular (BiV) pacing in heart failure (HF) patients scheduled for pace and ablate strategy. The aim of the study was to compare clinical outcomes of HF patients with refractory AF who received either BiV pacing or CSP in conjunction with atrio-ventricular node ablation (AVNA). Fifty consecutive patients (male 48%, age 70 years (IQR 9), left ventricular ejection fraction (LVEF) 39% (IQR 12)) were retrospectively analysed. Thirteen patients (26%) received BiV pacing, 27 patients (54%) HBP and 10 patients (20%) LBBP. All groups had similar baseline characteristics and acute success rate. While New York Heart. Association (NYHA) class improved in both HBP (p < 0.001) and LBBP (p = 0.008), it did not improve in BiV group (p = 0.096). At follow-up, LVEF increased in HBP (form 39% (IQR 15) to 49% (IQR 16), p < 0.001) and LBBP (from 28% (IQR 13) to 40% (IQR 13), p = 0.041), but did not change in BiV group (p = 0.916). Conduction system pacing modalities showed superior symptomatic and echocardiographic improvement compared to BiV pacing after AVNA. With more stable pacing parameters, LBBP could present a more feasible pacing option compared to HBP. Full article

(This article belongs to the Special Issue Atherosclerotic Cardiovascular Disease: Risk Assessment, Prevention and Treatment Strategies)

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14 pages, 896 KB

Open AccessEditor’s ChoiceReview

Left Ventricular Noncompaction in Children: The Role of Genetics, Morphology, and Function for Outcome

by Sabine Klaassen, Jirko Kühnisch, Alina Schultze-Berndt and Franziska Seidel

J. Cardiovasc. Dev. Dis. 2022, 9(7), 206; https://doi.org/10.3390/jcdd9070206 - 30 Jun 2022

Cited by 4 | Viewed by 3576

Abstract

Left ventricular noncompaction (LVNC) is a ventricular wall anomaly morphologically characterized by numerous, excessively prominent trabeculations and deep intertrabecular recesses. Accumulating data now suggest that LVNC is a distinct phenotype but must not constitute a pathological phenotype. Some individuals fulfill the morphologic criteria [...] Read more.

Left ventricular noncompaction (LVNC) is a ventricular wall anomaly morphologically characterized by numerous, excessively prominent trabeculations and deep intertrabecular recesses. Accumulating data now suggest that LVNC is a distinct phenotype but must not constitute a pathological phenotype. Some individuals fulfill the morphologic criteria of LVNC and are without clinical manifestations. Most importantly, morphologic criteria for LVNC are insufficient to diagnose patients with an associated cardiomyopathy (CMP). Genetic testing has become relevant to establish a diagnosis associated with CMP, congenital heart disease, neuromuscular disease, inborn error of metabolism, or syndromic disorder. Genetic factors play a more decisive role in children than in adults and severe courses of LVNC tend to occur in childhood. We reviewed the current literature and highlight the difficulties in establishing the correct diagnosis for children with LVNC. Novel insights show that the interplay of genetics, morphology, and function determine the outcome in pediatric LVNC. Full article

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

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22 pages, 1201 KB

Open AccessEditor’s ChoiceReview

Congenital Heart Disease: The State-of-the-Art on Its Pharmacological Therapeutics

by Carlos Daniel Varela-Chinchilla, Daniela Edith Sánchez-Mejía and Plinio A. Trinidad-Calderón

J. Cardiovasc. Dev. Dis. 2022, 9(7), 201; https://doi.org/10.3390/jcdd9070201 - 26 Jun 2022

Cited by 10 | Viewed by 8421

Abstract

Congenital heart disease is one of the most common causes of death derived from malformations. Historically, its treatment has depended on timely diagnosis and early pharmacological and surgical interventions. Survival rates for patients with this disease have increased, primarily due to advancements in [...] Read more.

Congenital heart disease is one of the most common causes of death derived from malformations. Historically, its treatment has depended on timely diagnosis and early pharmacological and surgical interventions. Survival rates for patients with this disease have increased, primarily due to advancements in therapeutic choices, but mortality remains high. Since this disease is a time-sensitive pathology, pharmacological interventions are needed to improve clinical outcomes. Therefore, we analyzed the applications, dosage, and side effects of drugs currently used for treating congenital heart disease. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and potassium-sparing diuretics have shown a mortality benefit in most patients. Other therapies, such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostaglandins, and soluble guanylyl cyclase stimulators, have benefited patients with pulmonary artery hypertension. Likewise, the adjunctive symptomatic treatment of these patients has further improved the outcomes, since antiarrhythmics, digoxin, and non-steroidal anti-inflammatory drugs have shown their benefits in these cases. Conclusively, these drugs also carry the risk of troublesome adverse effects, such as electrolyte imbalances and hemodynamic compromise. However, their benefits for survival, symptom improvement, and stabilization outweigh the possible complications from their use. Thus, cases must be assessed individually to accurately identify interventions that would be most beneficial for patients. Full article

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

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16 pages, 667 KB

Open AccessEditor’s ChoiceReview

Arrhythmias and Heart Failure in Pregnancy: A Dialogue on Multidisciplinary Collaboration

by Kamala P. Tamirisa, Cicely Dye, Rachel M. Bond, Lisa M. Hollier, Karolina Marinescu, Marmar Vaseghi, Andrea M. Russo, Martha Gulati and Annabelle Santos Volgman

J. Cardiovasc. Dev. Dis. 2022, 9(7), 199; https://doi.org/10.3390/jcdd9070199 - 24 Jun 2022

Cited by 10 | Viewed by 5668

Abstract

The prevalence of CVD in pregnant people is estimated to be around 1 to 4%, and it is imperative that clinicians that care for obstetric patients can promptly and accurately diagnose and manage common cardiovascular conditions as well as understand when to promptly [...] Read more.

The prevalence of CVD in pregnant people is estimated to be around 1 to 4%, and it is imperative that clinicians that care for obstetric patients can promptly and accurately diagnose and manage common cardiovascular conditions as well as understand when to promptly refer to a high-risk obstetrics team for a multidisciplinary approach for managing more complex patients. In pregnant patients with CVD, arrhythmias and heart failure (HF) are the most common complications that arise. The difficulty in the management of these patients arises from variable degrees of severity of both arrhythmia and heart failure presentation. For example, arrhythmia-based complications in pregnancy can range from isolated premature ventricular contractions to life-threatening arrhythmias such as sustained ventricular tachycardia. HF also has variable manifestations in pregnant patients ranging from mild left ventricular impairment to patients with advanced heart failure with acute decompensated HF. In high-risk patients, a collaboration between the general obstetrics, maternal-fetal medicine, and cardiovascular teams (which may include cardio-obstetrics, electrophysiology, adult congenital, or advanced HF)—physicians, nurses and allied professionals—can provide the multidisciplinary approach necessary to properly risk-stratify these women and provide appropriate management to improve outcomes. Full article

(This article belongs to the Special Issue Heart Disease in Women)

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17 pages, 670 KB

Open AccessEditor’s ChoiceReview

Infective Endocarditis in the Elderly: Challenges and Strategies

by Carlos Bea, Sara Vela, Sergio García-Blas, Jose-Angel Perez-Rivera, Pablo Díez-Villanueva, Ana Isabel de Gracia, Eladio Fuertes, Maria Rosa Oltra, Ana Ferrer, Andreu Belmonte, Enrique Santas, Mauricio Pellicer, Javier Colomina, Alberto Doménech, Vicente Bodi, Maria José Forner, Francisco Javier Chorro and Clara Bonanad

J. Cardiovasc. Dev. Dis. 2022, 9(6), 192; https://doi.org/10.3390/jcdd9060192 - 17 Jun 2022

Cited by 19 | Viewed by 5794

Abstract

The specific management of infective endocarditis (IE) in elderly patients is not specifically addressed in recent guidelines despite its increasing incidence and high mortality in this population. The term “elderly” corresponds to different ages in the literature, but it is defined by considerable [...] Read more.

The specific management of infective endocarditis (IE) in elderly patients is not specifically addressed in recent guidelines despite its increasing incidence and high mortality in this population. The term “elderly” corresponds to different ages in the literature, but it is defined by considerable comorbidity and heterogeneity. Cancer incidence, specifically colorectal cancer, is increased in older patients with IE and impacts its outcome. Diagnosis of IE in elderly patients is challenging due to the atypical presentation of the disease and the lower performance of imaging studies. Enterococcal etiology is more frequent than in younger patients. Antibiotic treatment should prioritize diminishing adverse effects and drug interactions while maintaining the best efficacy, as surgical treatment is less commonly performed in this population due to the high surgical risk. The global assessment of elderly patients with IE, with particular attention to frailty and geriatric profiles, should be performed by multidisciplinary teams to improve disease management in this population. Full article

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13 pages, 677 KB

Open AccessEditor’s ChoiceArticle

Serum and Vascular Stiffness Biomarkers Associated with the Severity of Degenerative Aortic Valve Stenosis and Cardiovascular Outcomes

by Jakub Baran, Łukasz Niewiara, Jakub Podolec, Mateusz Siedliński, Ewelina Józefczuk, Anna Bernacik, Rafał Badacz, Tadeusz Przewłocki, Piotr Pieniążek, Krzysztof Żmudka, Jacek Legutko and Anna Kabłak-Ziembicka

J. Cardiovasc. Dev. Dis. 2022, 9(6), 193; https://doi.org/10.3390/jcdd9060193 - 17 Jun 2022

Cited by 9 | Viewed by 3166

Abstract

Background: Although degenerative aortic valve stenosis (DAS) is the most prevalent growth-up congestive heart valve disease, still little known about relationships between DAS severity, vascular stiffness (VS), echocardiographic parameters, and serum biomarkers in patients undergoing transcatheter (TAVR) or surgical aortic valve replacement (SAVR). [...] Read more.

Background: Although degenerative aortic valve stenosis (DAS) is the most prevalent growth-up congestive heart valve disease, still little known about relationships between DAS severity, vascular stiffness (VS), echocardiographic parameters, and serum biomarkers in patients undergoing transcatheter (TAVR) or surgical aortic valve replacement (SAVR). The objective of this study was to identify biomarkers associated with DAS severity, and those that are associated with cardiovascular death (CVD) and episodes of chronic heart failure (CHF) exacerbation. Methods: A total of 137 patients with initially moderate-to-severe DAS were prospectively evaluated for the relationship between DAS severity, baseline VS, and serum biomarkers (uPAR, GDF-15, Gal-3, IL-6Rα, ET-1, PCSK9, RANTES/CCL5, NT-proBNP, and hs-TnT), and were followed-up for 48 months. The prognostic significance of each variable for CVD and CHF risk was measured by hazard ratio of risk (HR), which was calculated by Cox’s proportional hazard model. Results: DAS severity showed correlations with IL-6Rα (r = 0.306, p < 0.001), uPAR (r = 0.184, p = 0.032), and NT-proBNP (r = −0.389, p < 0.001). Levels of ET-1 and Gal-3 were strongly correlated with VS parameters (r = 0.674, p < 0.001; r = 0.724, p < 0.001). Out of 137 patients, 20 were referred to TAVR, 88 to SAVR, and 29 to OMT. In TAVR patients, the highest levels of ET-1, Gal-3, and VS were found as compared to other patients. The highest incidence of CVD was observed in patients who underwent TAVR (35%), compared to SAVR (8%) and OMT (10.3%) (p = 0.004). In a multivariate analysis, ET-1 occurred predictive of CVD risk (HR 25.1, p = 0.047), while Gal-3 > 11.5 ng/mL increased the risk of CHF exacerbation episodes requiring hospital admission by 12%. Conclusions: Our study indicated that ET-1 and Gal-3 levels may be associated with the outcomes in patients with DAS. Full article

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

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16 pages, 1239 KB

Open AccessEditor’s ChoiceReview

Epigenetics and Congenital Heart Diseases

by Léa Linglart and Damien Bonnet

J. Cardiovasc. Dev. Dis. 2022, 9(6), 185; https://doi.org/10.3390/jcdd9060185 - 9 Jun 2022

Cited by 19 | Viewed by 4814

Abstract

Congenital heart disease (CHD) is a frequent occurrence, with a prevalence rate of almost 1% in the general population. However, the pathophysiology of the anomalous heart development is still unclear in most patients screened. A definitive genetic origin, be it single-point mutation or [...] Read more.

Congenital heart disease (CHD) is a frequent occurrence, with a prevalence rate of almost 1% in the general population. However, the pathophysiology of the anomalous heart development is still unclear in most patients screened. A definitive genetic origin, be it single-point mutation or larger chromosomal disruptions, only explains about 35% of identified cases. The precisely choreographed embryology of the heart relies on timed activation of developmental molecular cascades, spatially and temporally regulated through epigenetic regulation: chromatin conformation, DNA priming through methylation patterns, and spatial accessibility to transcription factors. This multi-level regulatory network is eminently susceptible to outside disruption, resulting in faulty cardiac development. Similarly, the heart is unique in its dynamic development: growth is intrinsically related to mechanical stimulation, and disruption of the intrauterine environment will have a direct impact on fetal embryology. These two converging axes offer new areas of research to characterize the cardiac epigenetic regulation and identify points of fragility in order to counteract its teratogenic consequences. Full article

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

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25 pages, 2530 KB

Open AccessEditor’s ChoiceReview

When Does the Human Embryonic Heart Start Beating? A Review of Contemporary and Historical Sources of Knowledge about the Onset of Blood Circulation in Man

by Jörg Männer

J. Cardiovasc. Dev. Dis. 2022, 9(6), 187; https://doi.org/10.3390/jcdd9060187 - 9 Jun 2022

Cited by 13 | Viewed by 9247

Abstract

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the first human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary [...] Read more.

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the first human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the fourth post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19th century, but did not receive much recognition by embryologists. Full article

(This article belongs to the Special Issue Assessment of Normal and Abnormal Functions of the Human Embryonic and Fetal Cardiovascular System: In Vivo and In Vitro Studies)

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9 pages, 1111 KB

Open AccessEditor’s ChoiceArticle

Evaluation of the Appropriate Use of Coronary Computed Tomography Angiography: A Retrospective, Single-Center Analysis

by Katharina Birkl, Christoph Beyer, Fabian Plank, Gudrun Maria Feuchtner and Guy Friedrich

J. Cardiovasc. Dev. Dis. 2022, 9(6), 180; https://doi.org/10.3390/jcdd9060180 - 4 Jun 2022

Cited by 2 | Viewed by 2541

Abstract

Purpose: We assessed the application of appropriate use criteria of coronary computed tomography angiography (CCTA) in comparison to invasive coronary angiography results and revascularization rates in patients with coronary artery disease (CAD). Methods: 1305 patients referred to invasive coronary angiography (ICA) after CCTA [...] Read more.

Purpose: We assessed the application of appropriate use criteria of coronary computed tomography angiography (CCTA) in comparison to invasive coronary angiography results and revascularization rates in patients with coronary artery disease (CAD). Methods: 1305 patients referred to invasive coronary angiography (ICA) after CCTA were evaluated retrospectively. The primary indication for CCTA was assessed according to the consensus for intermediate-risk (15–85% pre-test probability) into appropriate (A), inappropriate (I), and uncertain while referring to published guidelines. Patients’ risk factors, angina, and heart failure symptoms (Canadian Cardiovascular Society classification (CCSC), New York Heart Association (NYHA); clinical data; and ICA results were gathered. Results: Of 1305 patients referred to CCTA prior to ICA, 496 (38.0%) were appropriate, 766 (56.9%) inappropriate, and 43 (3.3%) uncertain. Of 766 patients with inappropriate CCTA referrals, 370 (48.3%) were classified as “inappropriately low” (<15% pre-test probability) and 396 (51.7%) as “inappropriately high” (>85%) in regard to the recommended CCTA utilization. Sub-analysis of the adherence to the appropriate use criteria did not differ between the source of the referring physicians (intramural tertiary, private practice primary care, or external secondary care hospitals). Obstructive CAD with subsequent revascularization rates (total of 39.2%) did not differ significantly between the appropriate (38.3%), inappropriate (41.0%), or uncertain (23.3%) groups (p = 0.068). Conclusion: The total coronary revascularization rate after CCTA was 39.2% and not different among low, intermediate, and pre-test probability groups. These findings support the role of CCTA as an excellent gatekeeper in patients with suspected obstructive CAD even beyond pre-test probability calculation models. Full article

(This article belongs to the Special Issue Atherosclerotic Cardiovascular Disease: Risk Assessment, Prevention and Treatment Strategies)

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9 pages, 267 KB

Open AccessEditor’s ChoiceArticle

Effects of Concurrent Aerobic Plus Resistance Training on Blood Pressure Variability and Blood Pressure Values in Patients with Hypertension and Coronary Artery Disease: Gender-Related Differences

by Giuseppe Caminiti, Marco Alfonso Perrone, Maurizio Volterrani, Ferdinando Iellamo, Giuseppe Marazzi, Serena Selli, Alessio Franchini and Elvira Padua

J. Cardiovasc. Dev. Dis. 2022, 9(6), 172; https://doi.org/10.3390/jcdd9060172 - 27 May 2022

Cited by 5 | Viewed by 3366

Abstract

The purpose of this study was to compare changes in blood pressure variability (BPV) and blood pressure (BP) values occurring in response to concurrent training (CT) between the two genders. A total of 35 males and 20 women aged 55–80 years, with hypertension and [...] Read more.

The purpose of this study was to compare changes in blood pressure variability (BPV) and blood pressure (BP) values occurring in response to concurrent training (CT) between the two genders. A total of 35 males and 20 women aged 55–80 years, with hypertension and coronary artery disease, were included. They underwent a 12-week CT program. The aerobic component of CT was performed according to the rate of perceived exertion while the intensity of the resistance component was set at 60% of 1 repetition maximum for the first 4 weeks and then increased to 80%. BP and BPV were evaluated at baseline and at the end of the CT program through 24 h ambulatory blood pressure monitoring. After 12-weeks, 24 h and daytime systolic BPV decreased in both men and women without significant between-groups differences. Twenty-four-hour daytime and nighttime diastolic BPV decreased in both genders with a significantly greater decrease in women compared to men. Twenty-four-hour daytime systolic and 24 h diastolic BP decreased in men while they were unchanged in women. In conclusion, CT induced similar reductions of systolic BPV in men and women and a greater decrease in diastolic BPV in women. Conversely, CT decreased BP values in males but not in females. CT appears to be an effective intervention for reducing BPV in both genders. Full article

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

15 pages, 2310 KB

Open AccessEditor’s ChoiceReview

Contemporary Diagnosis and Management of Hypertrophic Cardiomyopathy: The Role of Echocardiography and Multimodality Imaging

by Takeshi Kitai, Andrew Xanthopoulos, Shoko Nakagawa, Natsuko Ishii, Masashi Amano, Filippos Triposkiadis and Chisato Izumi

J. Cardiovasc. Dev. Dis. 2022, 9(6), 169; https://doi.org/10.3390/jcdd9060169 - 25 May 2022

Cited by 10 | Viewed by 9528

Abstract

Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease with an estimated prevalence of 0.2–0.5%. Although the prognosis of HCM is relatively good, with an annual general mortality of ~0.7%, some patients have an increased risk of sudden death, or of developing severe [...] Read more.

Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease with an estimated prevalence of 0.2–0.5%. Although the prognosis of HCM is relatively good, with an annual general mortality of ~0.7%, some patients have an increased risk of sudden death, or of developing severe heart failure requiring heart transplantation or left ventricular (LV) assist device therapy. Therefore, earlier diagnosis and proper identification of high-risk patients may reduce disease-related morbidity/mortality by promoting timely treatment. Echocardiography is the primary imaging modality for patients with suspected HCM; it plays central roles in differential diagnosis from other causes of LV hypertrophy and in evaluating morphology, hemodynamic disturbances, LV function, and associated valvular disease. Echocardiography is also an essential tool for the continuous clinical management of patients with confirmed HCM. Other imaging modalities, such as cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI), can supplement echocardiography in identifying high-risk as well as milder HCM phenotypes. The role of such multimodality imaging has been steadily expanding along with recent advancements in surgical techniques and minimally invasive procedures, and the emergence of novel pharmacotherapies directly targeting pathogenic molecules such as myosin inhibitors. Here we review essential knowledge surrounding HCM with a specific focus on structural and functional abnormalities assessed by imaging modalities, leading to treatment strategies. Full article

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

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17 pages, 3775 KB

Open AccessEditor’s ChoiceReview

Heart Failure—Do We Need New Drugs or Have Them Already? A Case of Coenzyme Q10

by Krzysztof J. Filipiak, Stanisław Surma, Monika Romańczyk and Bogusław Okopień

J. Cardiovasc. Dev. Dis. 2022, 9(5), 161; https://doi.org/10.3390/jcdd9050161 - 16 May 2022

Cited by 6 | Viewed by 9158

Abstract

Heart failure (HF) is a global epidemic that contributes to the deterioration of quality of life and its shortening in 1–3% of adult people in the world. Pharmacotherapy of HF should rely on highly effective drugs that improve prognosis and prolong life. Currently, [...] Read more.

Heart failure (HF) is a global epidemic that contributes to the deterioration of quality of life and its shortening in 1–3% of adult people in the world. Pharmacotherapy of HF should rely on highly effective drugs that improve prognosis and prolong life. Currently, the ESC guidelines from 2021 indicate that ACEI, ARNI, BB, and SGLT2 inhibitors are the first-line drugs in HF. It is also worth remembering that the use of coenzyme Q10 brought many benefits in patients with HF. Coenzyme Q10 is a very important compound that performs many functions in the human body. The most important function of coenzyme Q10 is participation in the production of energy in the mitochondria, which determines the proper functioning of all cells, tissues, and organs. The highest concentration of coenzyme Q10 is found in the tissue of the heart muscle. As the body ages, the concentration of coenzyme Q10 in the tissue of the heart muscle decreases, which makes it more susceptible to damage by free radicals. It has been shown that in patients with HF, the aggravation of disease symptoms is inversely related to the concentration of coenzyme Q10. Importantly, the concentration of coenzyme Q10 in patients with HF was an important predictor of the risk of death. Long-term coenzyme Q10 supplementation at a dose of 300 mg/day (Q-SYMBIO study) has been shown to significantly improve heart function and prognosis in patients with HF. This article summarizes the latest and most important data on CoQ10 in pathogenesis. Full article

(This article belongs to the Special Issue Therapeutic Strategies for Heart Failure)

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10 pages, 1182 KB

Open AccessEditor’s ChoiceReview

Flow-Mediated Factors in the Pathogenesis of Hypoplastic Left Heart Syndrome

by Anum Rahman, Rajiv R. Chaturvedi and John G. Sled

J. Cardiovasc. Dev. Dis. 2022, 9(5), 154; https://doi.org/10.3390/jcdd9050154 - 12 May 2022

Cited by 12 | Viewed by 4215

Abstract

Hypoplastic left heart syndrome (HLHS) is a life-threatening congenital heart disease that is characterized by severe underdevelopment of left heart structures. Currently, there is no cure, and affected individuals require surgical palliation or cardiac transplantation to survive. Despite these resource-intensive measures, only about [...] Read more.

Hypoplastic left heart syndrome (HLHS) is a life-threatening congenital heart disease that is characterized by severe underdevelopment of left heart structures. Currently, there is no cure, and affected individuals require surgical palliation or cardiac transplantation to survive. Despite these resource-intensive measures, only about half of individuals reach adulthood, often with significant comorbidities such as liver disease and neurodevelopmental disorders. A major barrier in developing effective treatments is that the etiology of HLHS is largely unknown. Here, we discuss how intracardiac blood flow disturbances are an important causal factor in the pathogenesis of impaired left heart growth. Specifically, we highlight results from a recently developed mouse model in which surgically reducing blood flow through the mitral valve after cardiogenesis led to the development of HLHS. In addition, we discuss the role of interventional procedures that are based on improving blood flow through the left heart, such as fetal aortic valvuloplasty. Lastly, using the surgically-induced mouse model, we suggest investigations that can be undertaken to identify the currently unknown biological pathways in left heart growth failure and their associated therapeutic targets. Full article

(This article belongs to the Special Issue Hypoplastic Left Heart Syndrome: Etiology, Pathogenesis, Management and The Future)

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13 pages, 3394 KB

Open AccessEditor’s ChoiceReview

The Significance of Ventricular Topology in the Analysis of Congenitally Malformed Hearts

by Adrian C. Crucean, Diane E. Spicer and Robert H. Anderson

J. Cardiovasc. Dev. Dis. 2022, 9(5), 155; https://doi.org/10.3390/jcdd9050155 - 12 May 2022

Cited by 2 | Viewed by 3336

Abstract

There are still confusing descriptions of how congenitally malformed hearts should be categorised, even in their simplest forms. Despite repeated attempts toward a unified and simplified analysis, morphologists and clinicians continue to use different nomenclatures. This variability has a profound impact not only [...] Read more.

There are still confusing descriptions of how congenitally malformed hearts should be categorised, even in their simplest forms. Despite repeated attempts toward a unified and simplified analysis, morphologists and clinicians continue to use different nomenclatures. This variability has a profound impact not only on how we communicate with patients but also on how the healthcare professionals produce clinical reports, research papers and educational and training materials, not to mention the impact on other levels such as managerial, administrative, coding, financial and media communications. Moreover, there are influences on how we actually treat patients based on a different understanding of nomenclature. This paper aims to explain a method of analysing the cardiac segments and their connections based on the current understanding of structural development. Full article

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

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10 pages, 2426 KB

Open AccessEditor’s ChoiceArticle

Comparison of Different Laboratory Tests to Identify “Aspirin Resistance” and Risk of Vascular Events among Ischaemic Stroke Patients: A Double-Blind Study

by Narayanaswamy Venketasubramanian, Sherwin Joy Agustin, Jorge L. Padilla, Maricar P. Yumul, Christina Sum, Sze Haur Lee, Kuperan Ponnudurai and Robert N. Gan

J. Cardiovasc. Dev. Dis. 2022, 9(5), 156; https://doi.org/10.3390/jcdd9050156 - 12 May 2022

Cited by 9 | Viewed by 5067

Abstract

“Aspirin resistance” (AR) is associated with increased risk of vascular events. We aimed to compare different platelet function tests used in identifying AR and assess their implications on clinical outcome. We performed platelet aggregation studies on non-cardioembolic ischaemic stroke patients taking aspirin 100 [...] Read more.

“Aspirin resistance” (AR) is associated with increased risk of vascular events. We aimed to compare different platelet function tests used in identifying AR and assess their implications on clinical outcome. We performed platelet aggregation studies on non-cardioembolic ischaemic stroke patients taking aspirin 100 mg/day and 30 non-stroke controls. Data were collected on demographics, vascular risk factors, and concomitant medications. Cut-offs for AR were (1) light transmission aggregometry (LTA) of ≥20% using arachidonic acid (AA), ≥70% using ADP, or ≥60% using collagen; and (2) VerifyNow^® assay ≥ 550 ARU. Telephone follow-ups were conducted by study staff blinded to AR status to ascertain the occurrence of vascular outcomes (stroke, myocardial infarction, amputation, death). A total of 113 patients were recruited, mean age 65 ± 8 years, 47% women, 45 ± 15 days from index stroke. 50 (44.3%, 95% CI 34.9–53.9) had AR on at least 1 test. Frequency of AR varied from 0% to 39% depending on method used and first vs. recurrent stroke. There were strong correlations between LTA AA, VerifyNow^® and Multiplate^® ASPItest (r = 0.7457–0.8893), but fair to poor correlation between LTA collagen and Multiplate^® COLtest (r = 0.5887) and between LTA ADP and Multiplate^® ADPtest (r = 0.0899). Of 103 patients with a mean follow up of 801 ± 249 days, 10 (9.7%) had vascular outcomes, of which six had AR by LTA-ADP. AR by LTA-ADP is associated with increased risk of vascular outcome (p = 0.034). Identification of AR is not consistent across different platelet function tests. LTA of ≥70% using 10 µM ADP in post-stroke patients taking aspirin is associated with increased risk of vascular outcome. Full article

(This article belongs to the Section Stroke and Cerebrovascular Disease)

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9 pages, 863 KB

Open AccessEditor’s ChoiceSystematic Review

Blood Pressure Increase following COVID-19 Vaccination: A Systematic Overview and Meta-Analysis

by Fabio Angeli, Gianpaolo Reboldi, Monica Trapasso, Gabriella Santilli, Martina Zappa and Paolo Verdecchia

J. Cardiovasc. Dev. Dis. 2022, 9(5), 150; https://doi.org/10.3390/jcdd9050150 - 9 May 2022

Cited by 37 | Viewed by 16895

Abstract

Coronavirus disease 2019 (COVID-19) vaccines proved a strong clinical efficacy against symptomatic or moderate/severe COVID-19 and are considered the most promising approach for curbing the pandemic. However, some questions regarding the safety of COVID-19 vaccines have been recently raised. Among adverse events to [...] Read more.

Coronavirus disease 2019 (COVID-19) vaccines proved a strong clinical efficacy against symptomatic or moderate/severe COVID-19 and are considered the most promising approach for curbing the pandemic. However, some questions regarding the safety of COVID-19 vaccines have been recently raised. Among adverse events to vaccines and despite a lack of signal during phase III clinical trials, an increase in blood pressure (BP) after COVID-19 vaccination has been reported as a potential adverse reaction. We systematically analyze this topic and undertook a meta-analysis of available data to estimate the proportion of patients with abnormal BP or raise in BP after vaccination. Six studies entered the final analysis. Overall, studies accrued 357,387 subjects with 13,444 events of abnormal or increased BP. After exclusion of outlier studies, the pooled estimated proportion of abnormal/increased BP after vaccination was 3.20% (95% CI: 1.62–6.21). Proportions of cases of stage III hypertension or hypertensive urgencies and emergencies was 0.6% (95% CI: 0.1% to 5.1%). In conclusion, abnormal BP is not rare after COVID-19 vaccination, but the basic mechanisms of this phenomenon are still unclear and require further research. Full article

(This article belongs to the Special Issue Recent Advances in the Treatment of Hypertension)

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15 pages, 1423 KB

Open AccessEditor’s ChoiceReview

Pediatric Myocarditis: What Have We Learnt So Far?

by Elettra Pomiato, Marco Alfonso Perrone, Rosalinda Palmieri and Maria Giulia Gagliardi

J. Cardiovasc. Dev. Dis. 2022, 9(5), 143; https://doi.org/10.3390/jcdd9050143 - 3 May 2022

Cited by 14 | Viewed by 6917

Abstract

Myocarditis is an inflammatory disease of the myocardium that is troublesome to diagnose and manage, especially in children. Since the introduction of endomyocardial biopsy (EMB), new diagnostic tools have provided useful data. Especially when enhanced with immunohistochemistry and polymerase chain reaction (PCR) studies, [...] Read more.

Myocarditis is an inflammatory disease of the myocardium that is troublesome to diagnose and manage, especially in children. Since the introduction of endomyocardial biopsy (EMB), new diagnostic tools have provided useful data. Especially when enhanced with immunohistochemistry and polymerase chain reaction (PCR) studies, EMB remains the gold standard for the diagnosis. Notably, cardiac magnetic resonance (MRI) is a non-invasive tool that can confirm the diagnosis and has a particular usefulness during the follow-up. The causes of myocarditis are heterogeneous (mostly viral in children). The course and outcome of the illness in the pediatric population represent a complex interaction between etiologic agents and the immune system, which is still not fully understood. The clinical presentation and course of myocarditis vary widely from paucisymptomatic illness to acute heart failure refractory to therapy, arrhythmias, angina-like presentation and sudden cardiac death. In this setting, cardiac biomarkers (i.e., troponins and BNP), although unspecific, can be used to support the diagnosis. Finally, the efficacy of therapeutic strategies is controversial and not confirmed by clinical trials. In this review, we summarized the milestones in diagnosis and provided an overview of the therapeutic options for myocarditis in children. Full article

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

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18 pages, 1022 KB

Open AccessEditor’s ChoiceReview

Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension

by Pasquale Ambrosino, Tiziana Bachetti, Silvestro Ennio D’Anna, Brurya Galloway, Andrea Bianco, Vito D’Agnano, Antimo Papa, Andrea Motta, Fabio Perrotta and Mauro Maniscalco

J. Cardiovasc. Dev. Dis. 2022, 9(5), 136; https://doi.org/10.3390/jcdd9050136 - 27 Apr 2022

Cited by 65 | Viewed by 12711

Abstract

The endothelium is composed of a monolayer of endothelial cells, lining the interior surface of blood and lymphatic vessels. Endothelial cells display important homeostatic functions, since they are able to respond to humoral and hemodynamic stimuli. Thus, endothelial dysfunction has been proposed as [...] Read more.

The endothelium is composed of a monolayer of endothelial cells, lining the interior surface of blood and lymphatic vessels. Endothelial cells display important homeostatic functions, since they are able to respond to humoral and hemodynamic stimuli. Thus, endothelial dysfunction has been proposed as a key and early pathogenic mechanism in many clinical conditions. Given the relevant repercussions on cardiovascular risk, the complex interplay between endothelial dysfunction and systemic arterial hypertension has been a matter of study in recent years. Numerous articles have been published on this issue, all of which contribute to providing an interesting insight into the molecular mechanisms of endothelial dysfunction in arterial hypertension and its role as a biomarker of inflammation, oxidative stress, and vascular disease. The prognostic and therapeutic implications of endothelial dysfunction have also been analyzed in this clinical setting, with interesting new findings and potential applications in clinical practice and future research. The aim of this review is to summarize the pathophysiology of the relationship between endothelial dysfunction and systemic arterial hypertension, with a focus on the personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction while treating hypertension and cardiovascular comorbidities. Full article

(This article belongs to the Special Issue Recent Advances in the Treatment of Hypertension)

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12 pages, 1902 KB

Open AccessEditor’s ChoiceArticle

Combining Stress Speckle Tracking with High-Sensitivity C-Reactive Protein in Diagnosis of Coronary Artery Disease

by Ahmed M. Saleh, Konstantin Zintl and Johannes Brachmann

J. Cardiovasc. Dev. Dis. 2022, 9(5), 123; https://doi.org/10.3390/jcdd9050123 - 20 Apr 2022

Cited by 4 | Viewed by 2700

Abstract

Introduction: CAD (coronary artery disease) is a leading cause of death and disability in developed nations. Exercise testing is recommended as a first-line diagnostic test for patients with stable angina pectoris. In addition to myocardial strain, high-sensitivity CRP (hs-CRP) can predict the presence [...] Read more.

Introduction: CAD (coronary artery disease) is a leading cause of death and disability in developed nations. Exercise testing is recommended as a first-line diagnostic test for patients with stable angina pectoris. In addition to myocardial strain, high-sensitivity CRP (hs-CRP) can predict the presence of significant coronary artery disease. Aim of work: The purpose of this study was to demonstrate the utility of 2D-speckle tracking at rest and under stress along with hs-CRP for detection of CAD in patients who were referred to the chest pain unit with stable or low risk unstable angina pectoris. Methods: A total of 108 individuals met the inclusion criteria and gave their written consent to participate in this study. Coronary angiography was performed within 48 h after admission to the chest pain unit. Myocardial strain was recorded at rest and during dobutamine administration. Results: Global longitudinal strain at stress appeared to be moderately correlated with the presence of significant coronary artery disease (CAD); r = 0.41, p < 0.0001. A moderate correlation was also found between global longitudinal strain at stress and the severity of coronary occlusion; r = 0.62, p < 0.0001. With a cut-off value of −19.1, global longitudinal strain under stress had a sensitivity of 74.1% and a specificity of 76.7% for detecting significant CAD. Hs-CRP was significantly higher in patients with manifested CAD. Conclusion: Evaluation of longitudinal strain parameters at rest and under stress may predict coronary artery disease in patients with stable angina pectoris. A measurable Hs-CRP is a potential marker of coronary stenosis. Strain data could assist in diagnosing CAD severity. Full article

(This article belongs to the Topic Targeting Inflammation for the Prevention and Management of Cardiometabolic Disease)

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25 pages, 1563 KB

Open AccessEditor’s ChoiceReview

Endocardial Regulation of Cardiac Development

by Lara Feulner, Patrick Piet van Vliet, Michel Puceat and Gregor Andelfinger

J. Cardiovasc. Dev. Dis. 2022, 9(5), 122; https://doi.org/10.3390/jcdd9050122 - 19 Apr 2022

Cited by 9 | Viewed by 5975

Abstract

The endocardium is a specialized form of endothelium that lines the inner side of the heart chambers and plays a crucial role in cardiac development. While comparatively less studied than other cardiac cell types, much progress has been made in understanding the regulation [...] Read more.

The endocardium is a specialized form of endothelium that lines the inner side of the heart chambers and plays a crucial role in cardiac development. While comparatively less studied than other cardiac cell types, much progress has been made in understanding the regulation of and by the endocardium over the past two decades. In this review, we will summarize what is currently known regarding endocardial origin and development, the relationship between endocardium and other cardiac cell types, and the various lineages that endocardial cells derive from and contribute to. These processes are driven by key molecular mechanisms such as Notch and BMP signaling. These pathways in particular have been well studied, but other signaling pathways and mechanical cues also play important roles. Finally, we will touch on the contribution of stem cell modeling in combination with single cell sequencing and its potential translational impact for congenital heart defects such as bicuspid aortic valves and hypoplastic left heart syndrome. The detailed understanding of cellular and molecular processes in the endocardium will be vital to further develop representative stem cell-derived models for disease modeling and regenerative medicine in the future. Full article

(This article belongs to the Special Issue Endothelial Regulation of Cardiac Development, Homeostasis, and Pathology)

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7 pages, 1648 KB

Open AccessEditor’s ChoiceReview

HLHS: Power of the Chick Model

by David Sedmera

J. Cardiovasc. Dev. Dis. 2022, 9(4), 113; https://doi.org/10.3390/jcdd9040113 - 11 Apr 2022

Cited by 2 | Viewed by 3131

Abstract

Background: Hypoplastic left heart syndrome (HLHS) is a rare but deadly form of human congenital heart disease, most likely of diverse etiologies. Hemodynamic alterations such as those resulting from premature foramen ovale closure or aortic stenosis are among the possible pathways. Methods: The [...] Read more.

Background: Hypoplastic left heart syndrome (HLHS) is a rare but deadly form of human congenital heart disease, most likely of diverse etiologies. Hemodynamic alterations such as those resulting from premature foramen ovale closure or aortic stenosis are among the possible pathways. Methods: The information gained from studies performed in the chick model of HLHS is reviewed. Altered hemodynamics leads to a decrease in myocyte proliferation causing hypoplasia of the left heart structures and their functional changes. Conclusions: Although the chick phenocopy of HLHS caused by left atrial ligation is certainly not representative of all the possible etiologies, it provides many useful hints regarding the plasticity of the genetically normal developing myocardium under altered hemodynamic loading leading to the HLHS phenotype, and even suggestions on some potential strategies for prenatal repair. Full article

(This article belongs to the Special Issue Hypoplastic Left Heart Syndrome: Etiology, Pathogenesis, Management and The Future)

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17 pages, 1462 KB

Open AccessEditor’s ChoiceReview

Hypertension and Arrhythmias: A Clinical Overview of the Pathophysiology-Driven Management of Cardiac Arrhythmias in Hypertensive Patients

by Jacopo Marazzato, Federico Blasi, Michele Golino, Paolo Verdecchia, Fabio Angeli and Roberto De Ponti

J. Cardiovasc. Dev. Dis. 2022, 9(4), 110; https://doi.org/10.3390/jcdd9040110 - 6 Apr 2022

Cited by 15 | Viewed by 5852

Abstract

Because of demographic aging, the prevalence of arterial hypertension (HTN) and cardiac arrhythmias, namely atrial fibrillation (AF), is progressively increasing. Not only are these clinical entities strongly connected, but, acting with a synergistic effect, their association may cause a worse clinical outcome in [...] Read more.

Because of demographic aging, the prevalence of arterial hypertension (HTN) and cardiac arrhythmias, namely atrial fibrillation (AF), is progressively increasing. Not only are these clinical entities strongly connected, but, acting with a synergistic effect, their association may cause a worse clinical outcome in patients already at risk of ischemic and/or haemorrhagic stroke and, consequently, disability and death. Despite the well-known association between HTN and AF, several pathogenetic mechanisms underlying the higher risk of AF in hypertensive patients are still incompletely known. Although several trials reported the overall clinical benefit of renin–angiotensin–aldosterone inhibitors in reducing incident AF in HTN, the role of this class of drugs is greatly reduced when AF diagnosis is already established, thus hinting at the urgent need for primary prevention measures to reduce AF occurrence in these patients. Through a thorough review of the available literature in the field, we investigated the basic mechanisms through which HTN is believed to promote AF, summarising the evidence supporting a pathophysiology-driven approach to prevent this arrhythmia in hypertensive patients, including those suffering from primary aldosteronism, a non-negligible and under-recognised cause of secondary HTN. Finally, in the hazy scenario of AF screening in hypertensive patients, we reviewed which patients should be screened, by which modality, and who should be offered oral anticoagulation for stroke prevention. Full article

(This article belongs to the Special Issue Recent Advances in the Treatment of Hypertension)

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15 pages, 1277 KB

Open AccessEditor’s ChoiceReview

The Role of Cardiac Magnetic Resonance in Aortic Stenosis and Regurgitation

by Marco Guglielmo, Chiara Rovera, Mark G. Rabbat and Gianluca Pontone

J. Cardiovasc. Dev. Dis. 2022, 9(4), 108; https://doi.org/10.3390/jcdd9040108 - 4 Apr 2022

Cited by 14 | Viewed by 6242

Abstract

Cardiac magnetic resonance (CMR) imaging is a well-set diagnostic technique for assessment of valvular heart diseases and is gaining ground in current clinical practice. It provides high-quality images without the administration of ionizing radiation and occasionally without the need of contrast agents. It [...] Read more.

Cardiac magnetic resonance (CMR) imaging is a well-set diagnostic technique for assessment of valvular heart diseases and is gaining ground in current clinical practice. It provides high-quality images without the administration of ionizing radiation and occasionally without the need of contrast agents. It offers the unique possibility of a comprehensive stand-alone assessment of the heart including biventricular function, left ventricle remodeling, myocardial fibrosis, and associated valvulopathies. CMR is the recognized reference for the quantification of ventricular volumes, mass, and function. A particular strength is the ability to quantify flow, especially with new techniques which allow accurate measurement of stenosis and regurgitation. Furthermore, tissue mapping enables the visualization and quantification of structural changes in the myocardium. In this way, CMR has the potential to yield important prognostic information predicting those patients who will progress to surgery and impact outcomes. In this review, the fundamentals of CMR in assessment of aortic valve diseases (AVD) are described, together with its strengths and weaknesses. This state-of-the-art review provides an updated overview of CMR potentials in all AVD issues, including valve anatomy, flow quantification, ventricular volumes and function, and tissue characterization. Full article

(This article belongs to the Special Issue Cardiac Imaging in Valvular Heart Disease)

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11 pages, 1254 KB

Open AccessEditor’s ChoiceReview

Arrhythmogenic Cardiomyopathy: Diagnosis, Evolution, Risk Stratification and Pediatric Population—Where Are We?

by Marianna Cicenia and Fabrizio Drago

J. Cardiovasc. Dev. Dis. 2022, 9(4), 98; https://doi.org/10.3390/jcdd9040098 - 27 Mar 2022

Cited by 13 | Viewed by 3558

Abstract

Arrhythmogenic cardiomyopathy (ACM) is a cardiomyopathy characterized by the occurrence of a high risk of life-threatening ventricular arrhythmias and sudden cardiac death even at presentation. Diagnosis, evolution and outcomes in adults have been extensively reported, but little data in pediatric population are available. [...] Read more.

Arrhythmogenic cardiomyopathy (ACM) is a cardiomyopathy characterized by the occurrence of a high risk of life-threatening ventricular arrhythmias and sudden cardiac death even at presentation. Diagnosis, evolution and outcomes in adults have been extensively reported, but little data in pediatric population are available. Risk stratification in this particular setting is still a matter of debate and new risk factors are needed in a model of an ever more “individualized medicine”. Full article

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

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12 pages, 1919 KB

Open AccessEditor’s ChoiceArticle

Efficacy and Safety of Acute Phase Intensive Electrical Muscle Stimulation in Frail Older Patients with Acute Heart Failure: Results from the ACTIVE-EMS Trial

by Shinya Tanaka, Kentaro Kamiya, Yuya Matsue, Ryusuke Yonezawa, Hiroshi Saito, Nobuaki Hamazaki, Ryota Matsuzawa, Kohei Nozaki, Masashi Yamashita, Kazuki Wakaume, Yoshiko Endo, Emi Maekawa, Minako Yamaoka-Tojo, Takaaki Shiono, Takayuki Inomata and Junya Ako

J. Cardiovasc. Dev. Dis. 2022, 9(4), 99; https://doi.org/10.3390/jcdd9040099 - 27 Mar 2022

Cited by 10 | Viewed by 6073

Abstract

As frailty in older patients with acute heart failure (AHF) has an adverse effect on clinical outcomes, the addition of electrical muscle stimulation (EMS) to exercise-based early rehabilitation may improve the effects of treatment. Post hoc analysis was performed on a randomized controlled [...] Read more.

As frailty in older patients with acute heart failure (AHF) has an adverse effect on clinical outcomes, the addition of electrical muscle stimulation (EMS) to exercise-based early rehabilitation may improve the effects of treatment. Post hoc analysis was performed on a randomized controlled study for clinical outcomes and prespecified subgroups (ACTIVE-EMS: UMIN000019551). In this trial, 31 AHF patients aged ≥ 75 years with frailty (Short Physical Performance Battery [SPPB] score 4–9) were randomized 1:1 to receive treatment with an early rehabilitation program only (n = 16) or early rehabilitation with add-on EMS therapy (n = 15) for 2 weeks. Changes in physical function and cognitive function between baseline and after two weeks of treatment were assessed. There were no adverse events during the EMS period. The EMS group showed significantly greater changes in quadriceps’ isometric strength and SPPB compared to the control group, and EMS therapy showed uniform effects in the prespecified subgroups. There were no significant differences in the changes in other indexes of physical function and cognitive function between groups. There was no significant difference in the rate of heart failure hospitalization at 90 days between groups. In conclusion, older AHF patients with frailty showed greater improvement in lower extremity function with the addition of EMS therapy to early rehabilitation without adverse events. Full article

(This article belongs to the Special Issue Cardiac Rehabilitation: State of the Art and Perspectives)

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13 pages, 1999 KB

Open AccessEditor’s ChoiceReview

The Arrhythmogenic Face of COVID-19: Brugada ECG Pattern in SARS-CoV-2 Infection

by Paul Zimmermann, Felix Aberer, Martin Braun, Harald Sourij and Othmar Moser

J. Cardiovasc. Dev. Dis. 2022, 9(4), 96; https://doi.org/10.3390/jcdd9040096 - 25 Mar 2022

Cited by 8 | Viewed by 4506

Abstract

In 1992, Brugada syndrome (BS) was first described; an often unrecognized cardiac conduction disorder mainly associated with unexplained sudden cardiac arrest and consecutive syncope. Nevertheless, the pathomechanism of BS and sudden cardiac death remains mainly explained. Mutations in the cardiac sodium channels, which [...] Read more.

In 1992, Brugada syndrome (BS) was first described; an often unrecognized cardiac conduction disorder mainly associated with unexplained sudden cardiac arrest and consecutive syncope. Nevertheless, the pathomechanism of BS and sudden cardiac death remains mainly explained. Mutations in the cardiac sodium channels, which cause a reduction or functional loss of these channels, are associated with characteristic electrocardiographic (ECG) abnormalities and malignant arrhythmia. The majority of affected people are previously healthy and unaware of their genetic predisposition for BS and might experience ventricular tachyarrhythmias and cardiac arrest potentially triggered by several factors (e.g., alcohol, sodium channel blockers, psychotropic drugs, and fever). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was firstly identified in Wuhan in early December 2019 and rapidly spread worldwide as coronavirus disease (COVID-19). COVID-19 is typically characterized by a severe inflammatory response, activation of the immune system, and high febrile illness. Due to this condition, symptomatic COVID-19 infection or vaccination might serve as inciting factor for unmasking the Brugada pattern and represents a risk factor for developing proarrhythmic complications. The aim of this narrative review was to detail the association between virus-related issues such as fever, electrolyte disturbance, and inflammatory stress of COVID-19 infection with transient Brugada-like symptoms and ECG-pattern and its susceptibility to proarrhythmogenic episodes. Full article

(This article belongs to the Special Issue Takotsubo Syndrome, Short QT Syndrome and Brugada Syndrome)

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10 pages, 270 KB

Open AccessEditor’s ChoiceReview

Pulsed Field Ablation to Treat Atrial Fibrillation: A Review of the Literature

by Antonio Di Monaco, Nicola Vitulano, Federica Troisi, Federico Quadrini, Imma Romanazzi, Valeria Calvi and Massimo Grimaldi

J. Cardiovasc. Dev. Dis. 2022, 9(4), 94; https://doi.org/10.3390/jcdd9040094 - 24 Mar 2022

Cited by 37 | Viewed by 8757

Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and catheter ablation, which can be used in symptomatic patients refractory to antiarrhythmic therapy. Pulmonary vein isolation (PVI) remains the cornerstone of any ablation procedure. A major limitation of current catheter ablation procedures [...] Read more.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and catheter ablation, which can be used in symptomatic patients refractory to antiarrhythmic therapy. Pulmonary vein isolation (PVI) remains the cornerstone of any ablation procedure. A major limitation of current catheter ablation procedures is important to recognize because even when the PVI is performed in highly experienced centers, PVI reconnection was documented in about 20% of patients. Therefore, better technology is needed to improve ablation lesions. One of the novelties in recent years is pulsed filed ablation (PFA), a non-thermal energy that uses trains of high-voltage, very-short-duration pulses to kill the cells. The mechanism of action of this energy consists of creating pores in the myocardiocyte cell membrane in a highly selective and tissue-specific way; this leads to death of the target cells reducing the risk of damage to surrounding non-cardiac tissues. In particular during the animal studies, PVI and atrial lines were performed effectively without PV stenosis. Using PFA directly on coronary arteries, there was no luminal narrowing, there has been no evidence of incidental phrenic nerve injury, and finally, PFA has been shown not to injure esophageal tissue when directly applied to the esophagus or indirectly through ablation in the left atrium. The aim of this review is to report all published animal and clinical studies regarding this new technology to treat paroxysmal and persistent AF. Full article

11 pages, 1422 KB

Open AccessEditor’s ChoiceReview

Porcine Models of Heart Regeneration

by Nivedhitha Velayutham and Katherine E. Yutzey

J. Cardiovasc. Dev. Dis. 2022, 9(4), 93; https://doi.org/10.3390/jcdd9040093 - 23 Mar 2022

Cited by 6 | Viewed by 5592

Abstract

Swine are popular large mammals for cardiac preclinical testing due to their similarities with humans in terms of organ size and physiology. Recent studies indicate an early neonatal regenerative capacity for swine hearts similar to small mammal laboratory models such as rodents, inspiring [...] Read more.

Swine are popular large mammals for cardiac preclinical testing due to their similarities with humans in terms of organ size and physiology. Recent studies indicate an early neonatal regenerative capacity for swine hearts similar to small mammal laboratory models such as rodents, inspiring exciting possibilities for studying cardiac regeneration with the goal of improved clinical translation to humans. However, while swine hearts are anatomically similar to humans, fundamental differences exist in growth mechanisms, nucleation, and the maturation of pig cardiomyocytes, which could present difficulties for the translation of preclinical findings in swine to human therapeutics. In this review, we discuss the maturational dynamics of pig cardiomyocytes and their capacity for proliferative cardiac regeneration during early neonatal development to provide a perspective on swine as a preclinical model for developing cardiac gene- and cell-based regenerative therapeutics. Full article

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

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