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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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Article

9 pages, 1111 KiB  
Article
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 2421
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 KiB  
Article
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 3161
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)
10 pages, 2426 KiB  
Article
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 8 | Viewed by 4825
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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12 pages, 1902 KiB  
Article
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 3 | Viewed by 2601
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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12 pages, 1919 KiB  
Article
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 8 | Viewed by 5497
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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12 pages, 1912 KiB  
Article
Sex Differences in the Evaluation of Congestion Markers in Patients with Acute Heart Failure
by Pietro Scicchitano, Claudio Paolillo, Micaela De Palo, Angela Potenza, Silvia Abruzzese, Marco Basile, Antonia Cannito, Maria Tangorra, Piero Guida, Pasquale Caldarola, Marco Matteo Ciccone and Francesco Massari
J. Cardiovasc. Dev. Dis. 2022, 9(3), 67; https://doi.org/10.3390/jcdd9030067 - 24 Feb 2022
Cited by 5 | Viewed by 3497
Abstract
The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We [...] Read more.
The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We consecutively enrolled 494 AHF patients (252 female). Clinical congestion assessment, B-type natriuretic peptide levels analysis, blood urea nitrogen to creatinine ratio (BUN/Cr), plasma volume status estimate (by means of Duarte or Kaplam-Hakim PVS), and hydration status evaluation through bioimpedance analysis were performed. There was no difference in medications between men and women. Women were older (79 ± 9 yrs vs. 77 ± 10 yrs, p = 0.005), and had higher left ventricular ejection fraction (45 ± 11% vs. 38 ± 11%, p < 0.001), and lower creatinine clearance (42 ± 25 mL/min vs. 47 ± 26 mL/min, p = 0.04). The prevalence of peripheral oedema, orthopnoea, and jugular venous distention were not significantly different between women and men. BUN/Cr (27 ± 9 vs. 23 ± 13, p = 0.04) and plasma volume were higher in women than men (Duarte PVS: 6.0 ± 1.5 dL/g vs. 5.1 ± 1.5 dL/g, p < 0.001; Kaplam–Hakim PVS: 7.9 ± 13% vs. −7.3 ± 12%, p < 0.001). At multivariate logistic regression analysis, female sex was independently associated with BUN/Cr and PVS. Female sex was independently associated with subclinical biomarkers of congestion such as BUN/Cr and PVS in patients with AHF. A sex-guided approach to the correct evaluation of patients with AHF might become the cornerstone for the correct management of these patients. Full article
(This article belongs to the Section Epidemiology, Lifestyle, and Cardiovascular Health)
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21 pages, 7129 KiB  
Article
DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse
by Kelsey S. Moore, Reece Moore, Diana B. Fulmer, Lilong Guo, Cortney Gensemer, Rebecca Stairley, Janiece Glover, Tyler C. Beck, Jordan E. Morningstar, Rachel Biggs, Rupak Muhkerjee, Alexander Awgulewitsch and Russell A. Norris
J. Cardiovasc. Dev. Dis. 2022, 9(2), 62; https://doi.org/10.3390/jcdd9020062 - 17 Feb 2022
Cited by 8 | Viewed by 4043
Abstract
Mitral valve prolapse (MVP) is a common cardiac valve disease that often progresses to serious secondary complications requiring surgery. MVP manifests as extracellular matrix disorganization and biomechanically incompetent tissues in the adult setting. However, MVP has recently been shown to have a developmental [...] Read more.
Mitral valve prolapse (MVP) is a common cardiac valve disease that often progresses to serious secondary complications requiring surgery. MVP manifests as extracellular matrix disorganization and biomechanically incompetent tissues in the adult setting. However, MVP has recently been shown to have a developmental basis, as multiple causal genes expressed during embryonic development have been identified. Disease phenotypes have been observed in mouse models with human MVP mutations as early as birth. This study focuses on the developmental function of DCHS1, one of the first genes to be shown as causal in multiple families with non-syndromic MVP. By using various biochemical techniques as well as mouse and cell culture models, we demonstrate a unique link between DCHS1-based cell adhesions and the septin-actin cytoskeleton through interactions with cytoplasmic protein Lix1-Like (LIX1L). This DCHS1-LIX1L-SEPT9 axis interacts with and promotes filamentous actin organization to direct cell-ECM alignment and valve tissue shape. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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11 pages, 1242 KiB  
Article
The Incidence, Electrophysiological Characteristics and Ablation Outcome of Left Atrial Tachycardias after Pulmonary Vein Isolation Using Three Different Ablation Technologies
by Patrick Leitz, Kristina Wasmer, Christian Andresen, Fatih Güner, Julia Köbe, Benjamin Rath, Florian Reinke, Julian Wolfes, Philipp S. Lange, Christian Ellermann, Gerrit Frommeyer and Lars Eckardt
J. Cardiovasc. Dev. Dis. 2022, 9(2), 50; https://doi.org/10.3390/jcdd9020050 - 3 Feb 2022
Cited by 2 | Viewed by 2554
Abstract
Background: Left atrial tachycardias (LAT) are a well-known outcome of pulmonary vein isolation (PVI). Few data are available on whether the catheter used to perform PVI influences the incidence, as well as the characteristics of post PVI LAT. We present data on LAT [...] Read more.
Background: Left atrial tachycardias (LAT) are a well-known outcome of pulmonary vein isolation (PVI). Few data are available on whether the catheter used to perform PVI influences the incidence, as well as the characteristics of post PVI LAT. We present data on LAT following PVI by the following three ablation technologies: (1) phased multi-electrode radiofrequency catheter (PVAC), (2) irrigated single-tip catheter (iRF), and (3) cryoballoon ablation. Methods: Using a prospectively designed single-center database, we analyzed 650 patients (300 iRF, 150 PVAC, and 200 cryoballoon) with paroxysmal (n = 401) and persistent atrial fibrillation (AF), who underwent their first PVI at our center. Results: The three populations were comparable in their baseline characteristics; however, the cryoballoon group comprised a higher percentage of patients with persistent AF (p = 0.05). The LAT rates were 3.7% in the iRF group (mean follow-up 22 ± 14 months), 0.7% in the PVAC group (mean follow-up 21 ± 14 months), and 4% in the cryoballoon group (mean follow-up 15 ± 8 months). The predominant mechanism of LAT was macro-reentrant tachycardia. Reconnection of at least one pulmonary vein was observed in 87% of the patients who underwent 3D mapping. No predictors for LAT occurrence were identified. Conclusion: The occurrence of LAT post PVI is rare; the predominant mechanism was macro-reentrant tachycardia. Reconnection of at least one pulmonary vein was observed in nearly all the LAT patients. In our retrospective analysis, the lowest rate of LAT was observed with the PVAC. No predictors for LAT occurrence were identified. Full article
(This article belongs to the Special Issue Catheter Ablation of Cardiac Arrhythmias: Practices and Outcomes)
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9 pages, 415 KiB  
Article
A Propensity Score Analysis of Early and Long-Term Outcomes of Retrograde Arterial Perfusion for Endoscopic and Minimally Invasive Heart Valve Surgery in Both Young and Elderly Patients
by Hind Elhassan, Abdelrahman Abdelbar, Rebecca Taylor, Grzegorz Laskawski, Palanikumar Saravanan, Andrew Knowles and Joseph Zacharias
J. Cardiovasc. Dev. Dis. 2022, 9(2), 44; https://doi.org/10.3390/jcdd9020044 - 28 Jan 2022
Viewed by 2591
Abstract
(1) Background: Minimal invasive cardiac surgery via right anterolateral thoracotomy for heart valve surgery and other intracardiac procedures proven to have lower postoperative complications. We aim to compare the neurological complications and post-operative outcomes in two cohort groups as well as survival rates [...] Read more.
(1) Background: Minimal invasive cardiac surgery via right anterolateral thoracotomy for heart valve surgery and other intracardiac procedures proven to have lower postoperative complications. We aim to compare the neurological complications and post-operative outcomes in two cohort groups as well as survival rates up to 5 years postoperatively; (2) Methodology: Retrospective observational study for patients who had minimally invasive cardiac valve surgery with retrograde femoral arterial perfusion between 2007 and 2021 (n = 596) and the categorized patients into two groups based on their age (≥70 years old and below 70). Propensity match analysis was conducted. The primary endpoint consisted of major postoperative complications and the secondary endpoint was the long-term survival rate. (3) Results: There was no difference between the two groups in terms of postoperative outcomes. Patients ≥ 70 years old had no increased risk for neurological complications (p = 0.75) compared with those below 70 years old. The mortality rate was also not significant between the two groups (p = 0.37) as well as the crude survival rates. (4) Conclusions: The use of retrograde femoral arterial perfusion in elderly patients is not associated with increased risk compared to the younger patients’ group for a spectrum of primary cardiac valve procedures. Hence, minimally invasive approaches could be offered to elderly patients who might benefit from it. Full article
(This article belongs to the Special Issue Less Invasive and Video-Assisted Mitral Surgery at a Crossroads)
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11 pages, 471 KiB  
Article
It Is Not Carved in Stone—The Need for a Genetic Reevaluation of Variants in Pediatric Cardiomyopathies
by Dominik Sebastian Westphal, Kathrin Pollmann, Christoph Marschall, Annette Wacker-Gussmann, Renate Oberhoffer-Fritz, Karl-Ludwig Laugwitz, Peter Ewert and Cordula Maria Wolf
J. Cardiovasc. Dev. Dis. 2022, 9(2), 41; https://doi.org/10.3390/jcdd9020041 - 25 Jan 2022
Cited by 4 | Viewed by 3082
Abstract
(1) Background: In cardiomyopathies, identification of genetic variants is important for the correct diagnosis and impacts family cascade screening. A classification system was published by the American College of Medical Genetics and Genomics (ACMG) in 2015 to standardize variants’ classification. The aim of [...] Read more.
(1) Background: In cardiomyopathies, identification of genetic variants is important for the correct diagnosis and impacts family cascade screening. A classification system was published by the American College of Medical Genetics and Genomics (ACMG) in 2015 to standardize variants’ classification. The aim of the study was to determine the rate of reclassification of previously identified variants in patients with childhood-onset cardiomyopathies. (2) Methods: Medical records of patients and their relatives were screened for clinical and genetic information at the Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich. Patients without an identified genetic variant were excluded from further analyses. Previously reported variants were reevaluated by the ACMG criteria in November 2021. (3) Results: Data from 167 patients or relatives of patients with childhood-onset cardiomyopathy from 137 families were analyzed. In total, 45 different genetic variants were identified in 71 individuals. Classification changed in 29% (13/45) with the greatest shift in “variants of unknown significance” to “(likely) benign” (9/13). (4) Conclusions: In patients with childhood-onset cardiomyopathies, nearly a third of reported genetic variants change mostly to more benign classes upon reclassification. Given the impact on patient management and cascade screening, this finding underlines the importance of continuous genetic counseling and variant. Full article
(This article belongs to the Special Issue Pediatric Cardiomyopathies: From Genotype to Phenotype)
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11 pages, 1826 KiB  
Article
Combining Prognostic Nutritional Index and Brain Natriuretic Peptide as a Predicting Tool for Heart Transplantation
by Ziwen Cai, Jingrong Tu, Li Xu, Yao Lin, Bowen Deng, Fei Li, Si Chen and Nianguo Dong
J. Cardiovasc. Dev. Dis. 2022, 9(2), 40; https://doi.org/10.3390/jcdd9020040 - 24 Jan 2022
Cited by 4 | Viewed by 2914
Abstract
Our study aimed to evaluate the potential of prognostic nutritional index (PNI) and Brain natriuretic peptide (BNP) in predicting the prognosis of heart transplantation (HTx). We retrospectively investigated 489 patients undergoing HTx between 2015 and 2020 in our center. The relationship between preoperative [...] Read more.
Our study aimed to evaluate the potential of prognostic nutritional index (PNI) and Brain natriuretic peptide (BNP) in predicting the prognosis of heart transplantation (HTx). We retrospectively investigated 489 patients undergoing HTx between 2015 and 2020 in our center. The relationship between preoperative index and prognosis was analyzed respectively, the optimal cut-off values for preoperative PNI and BNP level were evaluated with receiver operating curve analysis. Uni-variate analysis and multivariate analysis were used to compare baseline data (sex, age, diagnosis, etc.) of groups divided by the level of PNI and BNP. Propensity score matching (PSM) was applied to eliminate bias. We calculated the C-index from the prediction efficiency of PNI and BNP. During the period, 489 recipients undergoing HTx in our center were included according to the inclusion criteria; 383 (78.3%) males and 106 (21.7%) females were included in this study, with a median age of 47.57 years old. The ROC curve showed that the optimal cut-off values of each indicator were verified as 49.345 for PNI, and 4397.500 for BNP. The multivariate analyses indicated that PNI (p = 0.047), BNP (p = 0.024), age (p = 0.0023), and waiting time (p = 0.012) were risk factors for all-cause death after HTx. Propensity score matching generated 116 pairs based on PNI level and 126 pairs based on BNP level, and the results showed that OS (overall survival) was significantly correlated with PNI (n = 232, p = 0.0113) and BNP (n = 252, p = 0.0146). Our study implied that higher PNI and lower BNP level had direct correlation with better survival after HTx. Combining PNI and BNP together would be a potential clinical preoperative instrument to predict the survival of patients after HTx, especially in short-term survival. Full article
(This article belongs to the Special Issue Outcomes of Heart Transplantation)
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11 pages, 725 KiB  
Article
The Effect of TAVR on Left Ventricular and Left Atrial Mechanics in Patients with Aortic Stenosis
by Malcolm Anastasius, Richard Ro, Michael Gavalas, Neil Patel, Francesca Romana Prandi, Gilbert H. L. Tang, Parasuram Krishnamoorthy, Samin K. Sharma, Annapoorna Kini and Stamatios Lerakis
J. Cardiovasc. Dev. Dis. 2022, 9(2), 35; https://doi.org/10.3390/jcdd9020035 - 21 Jan 2022
Cited by 7 | Viewed by 3439
Abstract
Background. Measures of adverse cardiac remodeling, left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic function, are predictive of cardiac events in patients with severe aortic stenosis (AS). How these parameters of cardiac function change following TAVR requires further investigation. Methods. [...] Read more.
Background. Measures of adverse cardiac remodeling, left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic function, are predictive of cardiac events in patients with severe aortic stenosis (AS). How these parameters of cardiac function change following TAVR requires further investigation. Methods. A number of 109 consecutive patients with symptomatic severe AS who were seen in the heart valve clinic between 2014 and 2019 for TAVR were included. All patients underwent echocardiographic assessment prior to and 30 days following TAVR, with LVGLS and LA phasic function evaluation using 2D speckle-tracking echocardiography. Heart failure hospitalization, and death were assessed at 12 months. Results. The mean age of the study cohort was 81 ± 7.3 years. Following TAVR, there was a significant reduction in NYHA class III/IV symptoms [89 (82%) vs. 12 (11%), p < 0.01], and median mean aortic valve gradient [44 mmHg (16) vs. 9 mmHg (7), p < 0.01]. There was no significant change in the median LVEF [62% (13) vs. 62% (6.0), p = 0.2]; however, the LVGLS significantly increased following TAVR [15 ± 3.5% vs. 18 ± 3.3%, p < 0.01]. The median LA reservoir, conduit and contractile function significantly improved following TAVR [22.0% (14.0) vs. 18.0% (14.0) p < 0.01, 8.9% (5.4) vs. 7.8% (4.8) p < 0.01, 12% (11.0) vs. 9.6% (11.0) p < 0.01, respectively]. The incidence of death or heart failure hospitalization at 12 months was low, and occurred in eight patients (7.3%). Conclusions. TAVR results in significant short-term reverse LV and LA remodeling, as shown by improvement in LV GLS and all three components of LA phasic function, despite no change in the LVEF. The findings indicate the possible utility of strain imaging for the assessment of global LV and LA function following TAVR. Full article
(This article belongs to the Special Issue Transcatheter Aortic Valve Implantation (TAVI))
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14 pages, 1656 KiB  
Article
Vitamin D Inhibits IL-6 Pro-Atherothrombotic Effects in Human Endothelial Cells: A Potential Mechanism for Protection against COVID-19 Infection?
by Giovanni Cimmino, Stefano Conte, Mariarosaria Morello, Grazia Pellegrino, Laura Marra, Andrea Morello, Giuseppe Nicoletti, Gennaro De Rosa, Paolo Golino and Plinio Cirillo
J. Cardiovasc. Dev. Dis. 2022, 9(1), 27; https://doi.org/10.3390/jcdd9010027 - 13 Jan 2022
Cited by 19 | Viewed by 4406
Abstract
Background: Thrombosis with cardiovascular involvement is a crucial complication in COVID-19 infection. COVID-19 infects the host by the angiotensin converting enzyme-2 receptor (ACE2r), which is expressed in endothelial cells too. Thus, COVID-related thrombotic events might be due to endothelial dysfunction. IL-6 is one [...] Read more.
Background: Thrombosis with cardiovascular involvement is a crucial complication in COVID-19 infection. COVID-19 infects the host by the angiotensin converting enzyme-2 receptor (ACE2r), which is expressed in endothelial cells too. Thus, COVID-related thrombotic events might be due to endothelial dysfunction. IL-6 is one of the main cytokines involved in the COVID-19 inflammatory storm. Some evidence indicates that Vitamin D (VitD) has a protective role in COVID-19 patients, but the molecular mechanisms involved are still debated. Thus, we investigated the effect of VitD on Tissue Factor and adhesion molecules (CAMs) in IL-6-stimulated endothelial cells (HUVEC). Moreover, we evaluated levels of the ACE2r gene and proteins. Finally, we studied the modulation of NF-kB and STAT3 pathways. Methods: HUVEC cultivated in VitD-enriched medium were stimulated with IL-6 (0.5 ng/mL). The TF gene (RT-PCR), protein (Western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. Similarly, CAMs soluble values (ELISA) and ACE2r (RT-PCR and Western blot) levels were assessed. NF-kB and STAT3 modulation (Western blot) were also investigated. Results: VitD significantly reduced TF expression at both gene and protein levels as well as TF-procoagulant activity in IL-6-treated HUVEC. Similar effects were observed for CAMs and ACE2r expression. IL-6 modulates these effects by regulating NF-κB and STAT3 pathways. Conclusions: IL-6 induces endothelial dysfunction with TF and CAMs expression via upregulation of ACE2r. VitD prevented these IL-6 deleterious effects. Thus, it might be speculated that this is one of the hypothetical mechanism(s) by which VitD exerts its beneficial effects in COVID-19 infection. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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14 pages, 1466 KiB  
Article
Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level
by Benedetta Leonardi, Federica Gentili, Marco Alfonso Perrone, Fabrizio Sollazzo, Lucia Cocomello, Stefani Silva Kikina, Rachel M. Wald, Vincenzo Palmieri, Aurelio Secinaro, Maria Giulia Gagliardi, Attilio Parisi, Attilio Turchetta, Lorenzo Galletti, Massimiliano Bianco and Fabrizio Drago
J. Cardiovasc. Dev. Dis. 2022, 9(1), 26; https://doi.org/10.3390/jcdd9010026 - 13 Jan 2022
Cited by 15 | Viewed by 4355
Abstract
Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical [...] Read more.
Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25–33); median percent predicted peak VO2 68% (range 61–78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95%CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O2 pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies. Full article
(This article belongs to the Special Issue Cardiovascular Effects and Benefits of Exercise)
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11 pages, 1588 KiB  
Article
Impact of the COVID-19 Pandemic on Non-COVID-19 Clinical Trials
by Katia Audisio, Hillary Lia, Newell Bryce Robinson, Mohamed Rahouma, Giovanni Soletti, Gianmarco Cancelli, Roberto Perezgrovas Olaria, David Chadow, Derrick Y. Tam, Dominique Vervoort, Michael E. Farkouh, Deepak L. Bhatt, Stephen E. Fremes and Mario Gaudino
J. Cardiovasc. Dev. Dis. 2022, 9(1), 19; https://doi.org/10.3390/jcdd9010019 - 10 Jan 2022
Cited by 38 | Viewed by 5763
Abstract
Randomized controlled trials (RCT) were impacted by the COVID-19 pandemic, but no systematic analysis has evaluated the overall impact of COVID-19 on non-COVID-19-related RCTs. The ClinicalTrials.gov database was queried in February 2020. Eligible studies included all randomized trials with a start date after [...] Read more.
Randomized controlled trials (RCT) were impacted by the COVID-19 pandemic, but no systematic analysis has evaluated the overall impact of COVID-19 on non-COVID-19-related RCTs. The ClinicalTrials.gov database was queried in February 2020. Eligible studies included all randomized trials with a start date after 1 January 2010 and were active during the period from 1 January 2015 to 31 December 2020. The effect of the pandemic period on non-COVID-19 trials was determined by piece-wise regression models using 11 March 2020 as the start of the pandemic and by time series analysis (models fitted using 2015–2018 data and forecasted for 2019–2020). The study endpoints were early trial stoppage, normal trial completion, and trial activation. There were 161,377 non-COVID-19 trials analyzed. The number of active trials increased annually through 2019 but decreased in 2020. According to the piece-wise regression models, trial completion was not affected by the pandemic (p = 0.56) whereas trial stoppage increased (p = 0.001). There was a pronounced decrease in trial activation early during the pandemic (p < 0.001) which then recovered. The findings from the time series models were consistent comparing forecasted and observed results (trial completion p = 0.22; trial stoppage p < 0.01; trial activation, p = 0.01). During the pandemic, there was an increase in non-COVID-19 RCTs stoppage without changes in RCT completion. There was a sharp decline in new RCTs at the beginning of the pandemic, which later recovered. Full article
(This article belongs to the Special Issue Cardiac Surgery: Outcomes, Management and Critical Care)
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15 pages, 2950 KiB  
Article
Not Only Diagnostic Yield: Whole-Exome Sequencing in Infantile Cardiomyopathies Impacts on Clinical and Family Management
by Laura Pezzoli, Lidia Pezzani, Ezio Bonanomi, Chiara Marrone, Agnese Scatigno, Anna Cereda, Maria Francesca Bedeschi, Angelo Selicorni, Serena Gasperini, Paolo Bini, Silvia Maitz, Carla Maccioni, Cristina Pedron, Lorenzo Colombo, Daniela Marchetti, Matteo Bellini, Anna Rita Lincesso, Loredana Perego, Monica Pingue, Nunzia Della Malva, Giovanna Mangili, Paolo Ferrazzi and Maria Iasconeadd Show full author list remove Hide full author list
J. Cardiovasc. Dev. Dis. 2022, 9(1), 2; https://doi.org/10.3390/jcdd9010002 - 21 Dec 2021
Cited by 17 | Viewed by 4292
Abstract
Whole-exome sequencing (WES) is a powerful and comprehensive tool for the genetic diagnosis of rare diseases, but few reports describe its timely application and clinical impact on infantile cardiomyopathies (CM). We conducted a retrospective analysis of patients with infantile CMs who had trio [...] Read more.
Whole-exome sequencing (WES) is a powerful and comprehensive tool for the genetic diagnosis of rare diseases, but few reports describe its timely application and clinical impact on infantile cardiomyopathies (CM). We conducted a retrospective analysis of patients with infantile CMs who had trio (proband and parents)-WES to determine whether results contributed to clinical management in urgent and non-urgent settings. Twenty-nine out of 42 enrolled patients (69.0%) received a definitive molecular diagnosis. The mean time-to-diagnosis was 9.7 days in urgent settings, and 17 out of 24 patients (70.8%) obtained an etiological classification. In non-urgent settings, the mean time-to-diagnosis was 225 days, and 12 out of 18 patients (66.7%) had a molecular diagnosis. In 37 out of 42 patients (88.1%), the genetic findings contributed to clinical management, including heart transplantation, palliative care, or medical treatment, independent of the patient’s critical condition. All 29 patients and families with a definitive diagnosis received specific counseling about recurrence risk, and in seven (24.1%) cases, the result facilitated diagnosis in parents or siblings. In conclusion, genetic diagnosis significantly contributes to patients’ clinical and family management, and trio-WES should be performed promptly to be an essential part of care in infantile cardiomyopathy, maximizing its clinical utility. Full article
(This article belongs to the Special Issue Pediatric Cardiomyopathies: From Genotype to Phenotype)
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15 pages, 1256 KiB  
Article
LPA Genotypes and Haplotypes Are Associated with Lipoprotein(a) Levels but Not Arterial Wall Properties in Stable Post-Coronary Event Patients with Very High Lipoprotein(a) Levels
by Andreja Rehberger Likozar, Aleš Blinc, Katarina Trebušak Podkrajšek and Miran Šebeštjen
J. Cardiovasc. Dev. Dis. 2021, 8(12), 181; https://doi.org/10.3390/jcdd8120181 - 13 Dec 2021
Cited by 7 | Viewed by 3130
Abstract
Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether [...] Read more.
Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether in patients with stable CAD and high Lp(a) levels these genetic variants are associated with increased Lp(a) and arterial wall properties. Blood samples underwent biochemical and genetic analyses. Ultrasound measurements for the functional and morphological properties of arterial wall were performed. Genotypes of rs10455872 and haplotypes AT and GT showed significant association with Lp(a) levels. Patients with GG showed significantly higher Lp(a) levels compared with those with AG genotype (2180 vs. 1391 mg/L, p = 0.045). Patients with no AT haplotype had significantly higher Lp(a) compared to carriers of one AT haplotype (2158 vs. 1478 mg/L, p = 0.023) or two AT haplotypes (2158 vs. 1487 mg/L, p = 0.044). There were no significant associations with the properties of the arterial wall. Lp(a) levels significantly correlated also with number of KIV-2 repeats (r = −0.601; p < 0.0001). In our patients, these two LPA polymorphisms and number of KIV-2 repeats are associated with Lp(a), but not arterial wall properties. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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8 pages, 1151 KiB  
Article
Optimal Heart Rate and Prognosis in Patients with Cardiac Amyloidosis
by Toshihide Izumida, Teruhiko Imamura, Makiko Nakamura and Koichiro Kinugawa
J. Cardiovasc. Dev. Dis. 2021, 8(12), 182; https://doi.org/10.3390/jcdd8120182 - 12 Dec 2021
Cited by 3 | Viewed by 3001
Abstract
Background: Optimal heart rate (HR) that associates with higher cardiac output and greater clinical outcomes in patients with cardiac amyloidosis remains unknown. Methods: Consecutive patients with sinus rhythm who were diagnosed with cardiac amyloidosis at our institute between February 2015 and February 2021 [...] Read more.
Background: Optimal heart rate (HR) that associates with higher cardiac output and greater clinical outcomes in patients with cardiac amyloidosis remains unknown. Methods: Consecutive patients with sinus rhythm who were diagnosed with cardiac amyloidosis at our institute between February 2015 and February 2021 were retrospectively included. Ideal HR, at which E-wave and A-wave stand adjacent without any overlaps in the trans-mitral flow echocardiography, was calculated by the formula: 86.8−0.08 × deceleration time (msec). The association between optimal HR and cardiac death or heart failure readmission was investigated. Results: Ten patients (median 74 years old, 8 men) were included. On median, actual HR was 64 bpm and ideal HR was 69 bpm. An incidence rate of the primary endpoint in the sub-optimal HR group tended to be higher than optimal HR group: one of the four patients in optimal HR group had events (25%); two of the two patients in higher HR group had events (100%); two of the four patients in lower HR group had events (50%). Conclusions: The optimal HR was associated with greater clinical outcomes in patients with cardiac amyloidosis. The clinical impact of aggressive HR optimization in this cohort remains the next concern. Full article
(This article belongs to the Special Issue Understanding Heart Failure Management and Treatment)
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10 pages, 518 KiB  
Article
Season of Birth and Cardiovascular Mortality in Atrial Fibrillation: A Population-Based Cohort Study
by Ying X. Gue, Arnaud Bisson, Alexandre Bodin, Julien Herbert, Gregory Y. H. Lip and Laurent Fauchier
J. Cardiovasc. Dev. Dis. 2021, 8(12), 177; https://doi.org/10.3390/jcdd8120177 - 10 Dec 2021
Cited by 1 | Viewed by 2591
Abstract
Background: The fetal origins hypothesis have associated early life exposures with the development of adverse health outcomes in adulthood. Season of birth has been shown to be associated with overall and cardiovascular mortality. Methods: We performed a retrospective database study to explore the [...] Read more.
Background: The fetal origins hypothesis have associated early life exposures with the development of adverse health outcomes in adulthood. Season of birth has been shown to be associated with overall and cardiovascular mortality. Methods: We performed a retrospective database study to explore the association between season of birth and mortality in patients with atrial fibrillation. Results: A total of 8962 patients with AF were identified in the database with 1253 deaths recorded. AF patients born in spring and summer had a higher mortality rate when compared to those born in autumn and winter (hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.01–1.26, p = 0.03). This effect was consistent in the male subgroup (HR 1.25, 95% CI 1.03–1.51, p = 0.02 for males born in spring; HR 1.24, 95% CI 1.03–1.51, p = 0.03 for males born in summer when compared to winter as the reference) but not in females (HR 1.02, 95% CI 0.79–1.31, p = 0.88 for females born in spring; HR 1.11, 95% CI 0.87–1.42, p = 0.39 for females born in summer when compared to winter as the reference). Results persisted after adjustment for baseline characteristics and clinical risk profile. A similar pattern was observed with cardiovascular mortality. Conclusion: Birth in spring or summer is associated with a higher risk of cardiovascular mortality in male AF patients, but not in females. This could be related to the underlying differences in rates of major adverse clinical events between genders. Further studies should aim at clarifying the mechanisms behind this association, which may help us understand the higher level of risk in female patients with AF. Full article
(This article belongs to the Section Epidemiology, Lifestyle, and Cardiovascular Health)
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10 pages, 825 KiB  
Article
Medium- and Long-Term Lead Stability and Echocardiographic Outcomes of Left Bundle Branch Area Pacing Compared to Right Ventricular Pacing
by Haojie Zhu, Zhao Wang, Xiaofei Li, Yan Yao, Zhimin Liu and Xiaohan Fan
J. Cardiovasc. Dev. Dis. 2021, 8(12), 168; https://doi.org/10.3390/jcdd8120168 - 30 Nov 2021
Cited by 12 | Viewed by 3481
Abstract
The long-term lead stability and echocardiographic outcomes of left bundle branch area pacing (LBBAP) are not fully understood. This study aimed to observe the mid-long-term clinical impact of LBBAP compared to right ventricular pacing (RVP). Consecutive bradycardia patients undergoing LBBAP or RVP were [...] Read more.
The long-term lead stability and echocardiographic outcomes of left bundle branch area pacing (LBBAP) are not fully understood. This study aimed to observe the mid-long-term clinical impact of LBBAP compared to right ventricular pacing (RVP). Consecutive bradycardia patients undergoing LBBAP or RVP were enrolled. Pacing and electrophysiological characteristics, echocardiographic measurements, and procedural complications were prospectively recorded at baseline and follow-up. LBBAP was successful in 376 of 406 patients (92.6%), while 313 patients received RVP. During a mean follow-up of 13.6 ± 7.8 months, LBBAP presented with similar pacing parameters and complications to RVP, except a significantly narrower paced QRS duration (115.7 ± 12.3 ms vs. 148.0 ± 18.0 ms, p < 0.001). In 228 patients with ventricular pacing burden >40%, LBBAP at last follow-up resulted in decreased left atrial diameter (LAD) (40.1 ± 8.5 mm vs. 38.5 ± 8.0 mm, p < 0.001) while RVP produced decreased left ventricular ejection fraction (62.7 ± 4.8% vs. 60.5 ± 6.9%, p < 0.001) when compared to baseline. After adjusting for age, the presence of atrial fibrillation, and other clinical factors, LBBAP was still associated with a decrease in LAD (−1.601, 95% CI −3.094–−0.109, p = 0.036). We conclude that LBBAP might result in more preserved echocardiographic outcomes than RVP. Full article
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9 pages, 275 KiB  
Article
Acute Cardiorespiratory Responses to Different Exercise Modalities in Chronic Heart Failure Patients—A Pilot Study
by Eleftherios Karatzanos, Panagiotis Ferentinos, Georgios Mitsiou, Stavros Dimopoulos, Argyrios Ntalianis and Serafeim Nanas
J. Cardiovasc. Dev. Dis. 2021, 8(12), 164; https://doi.org/10.3390/jcdd8120164 - 26 Nov 2021
Cited by 5 | Viewed by 3751
Abstract
The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO2peak intensities between three “iso-work” protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON70) and (c) [...] Read more.
The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO2peak intensities between three “iso-work” protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON70) and (c) a lower intensity continuous protocol (CON50) in patients with chronic heart failure (CHF). Ten male CHF patients (aged 55.1 ± 16.2 years) performed in separate days a single session of a HIIT protocol consisted of 4 sets × 4 min cycling at 80% VO2peak with 3 min of recovery at 50% VO2peak, a CON70 protocol corresponding to 70% VO2peak and a CON50 protocol corresponding to 50% VO2peak. Cardiopulmonary data were collected by an online gas analysis system. The HIIT and CON70 elicited higher cardiorespiratory responses compared to CON50 with no differences between them (p > 0.05). In HIIT and CON70, patients exercised longer at >80% and >90% VO2peak. The completion rate was 100% for the three protocols. Not any adverse events were observed in either protocol. Both HIIT and CON70 elicited a stronger physiological stimulus and required shorter time than CON50. Both HIIT and CON70 also induced comparable hemodynamic responses and ventilatory demand. Full article
(This article belongs to the Special Issue Cardiovascular Effects and Benefits of Exercise)
13 pages, 2567 KiB  
Article
The Atherosclerotic Profile of a Young Symptomatic Population between 19 and 49 Years: Coronary Computed Tomography Angiography or Coronary Artery Calcium Score?
by Gudrun Maria Feuchtner, Christoph Beyer, Christian Langer, Sven Bleckwenn, Thomas Senoner, Fabian Barbieri, Anna Luger, Philipp Spitaler, Gerlig Widmann, Agne Adukauskaite, Wolfgang Dichtl, Guy Friedrich and Fabian Plank
J. Cardiovasc. Dev. Dis. 2021, 8(11), 157; https://doi.org/10.3390/jcdd8110157 - 18 Nov 2021
Cited by 4 | Viewed by 3310
Abstract
(1) Background: Whether coronary computed tomography angiography (CTA) or the coronary artery calcium score (CACS) should be used for diagnosis of coronary heart disease, is an open debate. The aim of our study was to compare the atherosclerotic profile by coronary CTA in [...] Read more.
(1) Background: Whether coronary computed tomography angiography (CTA) or the coronary artery calcium score (CACS) should be used for diagnosis of coronary heart disease, is an open debate. The aim of our study was to compare the atherosclerotic profile by coronary CTA in a young symptomatic high-risk population (age, 19–49 years) in comparison with the coronary artery calcium score (CACS). (2) Methods: 1137 symptomatic high-risk patients between 19–49 years (mean age, 42.4 y) who underwent coronary CTA and CACS were stratified into six age groups. CTA-analysis included stenosis severity and high-risk-plaque criteria (3) Results: Atherosclerosis was more often detected based on CTA than based on CACS (45 vs. 27%; p < 0.001), 50% stenosis in 13.6% and high-risk plaque in 17.7%. Prevalence of atherosclerosis was low and not different between CACS and CTA in the youngest age groups (19–30 y: 5.2 and 6.4% and 30–35 y: 10.6 and 16%). In patients older than >35 years, the rate of atherosclerosis based on CTA increased (p = 0.004, OR: 2.8, 95%CI:1.45–5.89); and was higher by CTA as compared to CACS (34.9 vs. 16.7%; p < 0.001), with a superior performance of CTA. In patients older than 35 years, stenosis severity (p = 0.002) and >50% stenosis increased from 2.6 to 12.5% (p < 0.001). High-risk plaque prevalence increased from 6.4 to 26.5%. The distribution of high-risk plaque between CACS 0 and >0.1 AU was similar among all age groups, with an increasing proportion in CACS > 0.1 AU with age. A total of 24.9% of CACS 0 patients had coronary artery disease based on CTA, 4.4% > 50% stenosis and 11.5% had high-risk plaque. (4) Conclusions: In a symptomatic young high-risk population older than 35 years, CTA performed superior than CACS. In patients aged 19–35 years, the rate of atherosclerosis was similar and low based on both modalities. CACS 0 did not rule out coronary artery disease in a young high-risk population. Full article
(This article belongs to the Section Imaging)
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10 pages, 1447 KiB  
Article
Outcomes of the Valve-Sparing Root Replacement Procedure with Partial Upper Sternotomy
by Bin Hou, Rui Zhao, De Wang, Wei Wang, Zhenhua Zhao, Xiaogang Sun, Xiangyang Qian and Cuntao Yu
J. Cardiovasc. Dev. Dis. 2021, 8(11), 154; https://doi.org/10.3390/jcdd8110154 - 9 Nov 2021
Cited by 4 | Viewed by 2518
Abstract
Due to better postoperative convalescence and quality of life, experienced centers focus on minimally invasive surgical techniques and approaches, but this approach is not routinely performed for valve-sparing root replacement procedures. The purpose of this study was to assess the safety and feasibility [...] Read more.
Due to better postoperative convalescence and quality of life, experienced centers focus on minimally invasive surgical techniques and approaches, but this approach is not routinely performed for valve-sparing root replacement procedures. The purpose of this study was to assess the safety and feasibility of valve-sparing root replacement via partial upper sternotomy. Between January 2016 and April 2021, 269 patients underwent a valve-sparing root replacement procedure, and partial upper sternotomy was performed in 52 patients. The clinical outcomes of the partial upper sternotomy (PUS) and complete sternotomy (CS) groups, including mortality, degree of aortic insufficiency, blood loss and consumption of blood products, postoperative complications, and hospitalization expenses, were compared. The Kaplan–Meier method was used to assess the degree of aortic regurgitation. Propensity score matching was performed as a sensitivity analysis. There was only one in-hospital death (in the CS group, p = 1) and no postoperative moderate to severe aortic insufficiency in either group. The blood loss and consumption of blood products in the PUS group were also lower than in the CS group, especially for plasma use. Regarding the need for re-exploration because of bleeding, acute kidney injury, pericardial pleural effusion, drainage volume within the first 24 h, mechanical ventilation time, and arrhythmia, the two groups were comparable. Patients in the CS group showed a longer ICU time (74.20 ± 47.21 vs. 50.9 30.16 h, p = 0.001) and higher hospitalization expenses (135,649.52 ± 29,992.21 vs. 123,380.15 ± 27,062.82 yuan, p < 0.001). None of the patients died or reoperated during the follow-up. Freedom from moderate or severe aortic insufficiency remained comparable after matching (p = 0.97). Minimally invasive valve-sparing aortic replacement via partial upper sternotomy can be safely performed in selected patients. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
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13 pages, 874 KiB  
Article
The Value of Fetuin-A as a Predictor to Identify Takotsubo Patients at Risk of Cardiovascular Events
by Albert Topf, Moritz Mirna, Nina Bacher, Vera Paar, Christoph Edlinger, Lukas J. Motloch, Sarah Gharibeh, Marwin Bannehr, Uta C. Hoppe and Michael Lichtenauer
J. Cardiovasc. Dev. Dis. 2021, 8(10), 127; https://doi.org/10.3390/jcdd8100127 - 5 Oct 2021
Cited by 3 | Viewed by 2207
Abstract
Introduction: Takotsubo cardiomyopathy (TTC) remains a life-threatening disease with the risk of decompensated heart failure and arrhythmias. Valid markers for the prediction of outcome are unavailable. The novel biomarkers fetuin-A, matrix metalloproteinases-2 (MMP-2), myeloperoxidase (MPO), Syndecan-1 and CD40-L show promising results for risk [...] Read more.
Introduction: Takotsubo cardiomyopathy (TTC) remains a life-threatening disease with the risk of decompensated heart failure and arrhythmias. Valid markers for the prediction of outcome are unavailable. The novel biomarkers fetuin-A, matrix metalloproteinases-2 (MMP-2), myeloperoxidase (MPO), Syndecan-1 and CD40-L show promising results for risk stratification of cardiovascular patients. Nevertheless, clinical implementation has not been investigated in TTC patients. Methods: To investigate this issue, we evaluated clinical complications in 51 patients hospitalized for TTC and measured the serum levels of fetuin-A, MPO, MMP-2, Syndecan-1 and CD40-L within 24 h after admission. Results: Serum levels of Fetuin-A correlated inversely with the risk of cardiac decompensation and all cause complications within the acute phase of TTC. Fetuin-A levels over 190.1 µg/mL (AUC: 0.738, sensitivity 87.5%, specificity: 52.6%) indicate an acute phase of TTC without cardiac decompensation. Despite lower fetuin-A levels in patients with all cause complications, the combined endpoint remained slightly unmet (p = 0.058, AUC: 0.655). Patients with fetuin-A levels over 213.3 µg/mL are at risk of experiencing hemodynamic relevant rhythm disorders (AUC: 0.794; sensitivity: 75.0%, specificity: 79.1%). Other biomarkers failed to reveal a prognostic impact. Pro-BNP and hs troponin levels at admission did not predict adverse cardiac events. Conclusion: Fetuin-A is a promising marker in our study and could be of benefit for the prediction of short-term adverse cardiac events in TTC patients. Therefore, fetuin-A might be of value to evaluate an individual’s risk for complications within the acute phase of TTC and to individually choose the time of intensive care and hospitalization. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
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17 pages, 9226 KiB  
Article
Deficient Myocardial Organization and Pathological Fibrosis in Fetal Aortic Stenosis—Association of Prenatal Ultrasound with Postmortem Histology
by Fleur Zwanenburg, Marco C. DeRuiter, Lambertus J. Wisse, Conny J. van Munsteren, Margot M. Bartelings, Marie-Jose Goumans, Arend D. J. Ten Harkel, Monique R. M. Jongbloed and Monique C. Haak
J. Cardiovasc. Dev. Dis. 2021, 8(10), 121; https://doi.org/10.3390/jcdd8100121 - 28 Sep 2021
Cited by 3 | Viewed by 3198
Abstract
In fetal aortic stenosis (AS), it remains challenging to predict left ventricular development over the course of pregnancy. Myocardial organization, differentiation and fibrosis could be potential biomarkers relevant for biventricular outcome. We present four cases of fetal AS with varying degrees of severity [...] Read more.
In fetal aortic stenosis (AS), it remains challenging to predict left ventricular development over the course of pregnancy. Myocardial organization, differentiation and fibrosis could be potential biomarkers relevant for biventricular outcome. We present four cases of fetal AS with varying degrees of severity and associate myocardial deformation on fetal ultrasound with postmortem histopathological characteristics. During routine fetal echocardiography, speckle tracking recordings of the cardiac four-chamber view were performed to assess myocardial strain as parameter for myocardial deformation. After pregnancy termination, postmortem cardiac specimens were examined using immunohistochemical labeling (IHC) of key markers for myocardial organization, differentiation and fibrosis and compared to normal fetal hearts. Two cases with critical AS presented extremely decreased left ventricular (LV) strain on fetal ultrasound. IHC showed overt endocardial fibro-elastosis, which correlated with pathological fibrosis patterns in the myocardium and extremely disturbed cardiomyocyte organization. The LV in severe AS showed mildly reduced myocardial strain and less severe disorganization of the cardiomyocytes. In conclusion, the degree of reduction in myocardial deformation corresponded with high extent to the amount of pathological fibrosis patterns and cardiomyocyte disorganization. Myocardial deformation on fetal ultrasound seems to hold promise as a potential biomarker for left ventricular structural damage in AS. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)
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11 pages, 1500 KiB  
Article
Left Cardiac Remodelling Assessed by Echocardiography Is Associated with Rho-Kinase Activation in Long-Distance Runners
by Felipe Contreras-Briceño, Julián Vega, Jorge Mandiola, María Paz Ocaranza, Sebastián Herrera, Manuel Salinas, Rodrigo Fernández, Jorge E. Jalil, Sergio Lavandero, Mario Chiong, Paz Godoy, Pablo F. Castro, Marta Sitges and Luigi Gabrielli
J. Cardiovasc. Dev. Dis. 2021, 8(10), 118; https://doi.org/10.3390/jcdd8100118 - 24 Sep 2021
Viewed by 3214
Abstract
This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDRs) during the training period before a marathon race. Thirty-six healthy male LDRs (37.0 ± 5.3 years; [...] Read more.
This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDRs) during the training period before a marathon race. Thirty-six healthy male LDRs (37.0 ± 5.3 years; 174.0 ± 7.0 height; BMI: 23.8 ± 2.8; V˙ O2-peak: 56.5 ± 7.3 mL·kg−1·min−1) were separated into two groups according to previous training level: high-training (HT, n = 16) ≥ 100 km·week−1 and low-training (LT, n = 20) ≥ 70 and < 100 km·week−1. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48 h without exercising) the week before the race. The HT group showed a higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p < 0.05, for both); also, higher levels of ROCK activity were found in LDRs (HT = 6.17 ± 1.41 vs. CTR = 1.64 ± 0.66 (p < 0.01); vs. LT = 2.74 ± 0.84; (p < 0.05)). In LDRs a direct correlation between ROCK activity levels and LVMi (r = 0.83; p < 0.001), and LAVi (r = 0.70; p < 0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography. Full article
(This article belongs to the Special Issue Echocardiography in Cardiovascular Disease)
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12 pages, 718 KiB  
Article
Potential Role of eNOS Genetic Variants in Ischemic Heart Disease Susceptibility and Clinical Presentation
by Paolo Severino, Andrea D’Amato, Silvia Prosperi, Michele Magnocavallo, Marco Valerio Mariani, Lucrezia Netti, Lucia Ilaria Birtolo, Paolo De Orchi, Cristina Chimenti, Viviana Maestrini, Fabio Miraldi, Carlo Lavalle, Viviana Caputo, Raffaele Palmirotta, Massimo Mancone and Francesco Fedele
J. Cardiovasc. Dev. Dis. 2021, 8(9), 116; https://doi.org/10.3390/jcdd8090116 - 18 Sep 2021
Cited by 22 | Viewed by 5770
Abstract
Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often [...] Read more.
Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD. Full article
(This article belongs to the Section Genetics)
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12 pages, 608 KiB  
Article
Diagnostic Performance of Serial High-Sensitivity Cardiac Troponin Measurements in the Emergency Setting
by Peter A. Kavsak, Mark K. Hewitt, Shawn E. Mondoux, Joshua O. Cerasuolo, Jinhui Ma, Natasha Clayton, Matthew McQueen, Lauren E. Griffith, Richard Perez, Hsien Seow, Craig Ainsworth, Dennis T. Ko and Andrew Worster
J. Cardiovasc. Dev. Dis. 2021, 8(8), 97; https://doi.org/10.3390/jcdd8080097 - 13 Aug 2021
Cited by 9 | Viewed by 3841
Abstract
Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using [...] Read more.
Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using serial measurements while incorporating absolute concentration changes for MI or death following ED presentation. We sought to determine the diagnostic estimates of these three algorithms and if one was superior in two different Canadian ED patient cohorts with serial hsTnI measurements. An undifferentiated ED population (Cohort-1) and an ED population with symptoms suggestive of acute coronary syndrome (ACS; Cohort-2) were clinically managed with non-hsTn testing with the hsTnI testing performed in real-time with physicians blinded to these results (i.e., hsTnI not reported). The three algorithms evaluated were the European Society of Cardiology (ESC), the High-STEACS pathway, and the COMPASS-MI algorithm. The diagnostic estimates were derived for each algorithm for the 30-day MI/death outcome for the rule-out and rule-in arm in each cohort and compared to proposed diagnostic benchmarks (i.e., sensitivity ≥ 99.0% and specificity ≥ 90.0%) with 95% confidence intervals (CI). In Cohort-1 (n = 2966 patients, 15.3% had outcome) and Cohort-2 (n = 935 patients, 15.6% had outcome), the algorithm that obtained the highest sensitivity (97.8%; 95% CI: 96.0–98.9 and 98.6%; 95% CI: 95.1–99.8, respectively) in both cohorts was COMPASS-MI. Only Cohort-2 with both the ESC and COMPASS-MI algorithms exceeded the specificity benchmark (97.0%; 95% CI: 95.5–98.0 and 96.7%; 95% CI: 95.2–97.8, respectively). Patient selection for serial hsTnI testing will affect specificity estimates, with no algorithm achieving a sensitivity ≥ 99% for 30-day MI or death. Full article
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12 pages, 2435 KiB  
Article
Applicability of the Leiden Convention and the Lipton Classification in Patients with a Single Coronary Artery in the Setting of Congenital Heart Disease
by Diana Isabel Katekaru-Tokeshi, Moisés Jiménez-Santos, Claire J. Koppel, Hubert W. Vliegen, Mariana Díaz-Zamudio, Francisco Castillo-Castellón, Monique R. M. Jongbloed and Eric Kimura-Hayama
J. Cardiovasc. Dev. Dis. 2021, 8(8), 93; https://doi.org/10.3390/jcdd8080093 - 4 Aug 2021
Cited by 7 | Viewed by 5804
Abstract
In single coronary artery (SCA) anatomy, all coronary tributaries arise from a single ostium, providing perfusion to the entire myocardium. Coronary classification systems can facilitate the description of SCA anatomy. Aim: Evaluation of the applicability of Lipton classification and the Leiden Convention coronary [...] Read more.
In single coronary artery (SCA) anatomy, all coronary tributaries arise from a single ostium, providing perfusion to the entire myocardium. Coronary classification systems can facilitate the description of SCA anatomy. Aim: Evaluation of the applicability of Lipton classification and the Leiden Convention coronary coding system in SCA. Methods: All patients (n = 6209) who underwent computed tomography (CT) scanning between 2014 and 2018 were retrospectively examined for the presence of SCA and classified, according to Lipton classification and the Leiden Convention coronary coding system. Results: The prevalence of SCA was 0.51% (32/6209). Twenty-eight patients (87.5%) had coexisting congenital heart disease (CHD), most frequently pulmonary atresia (9/32, 28.1%). Ten patients (10/32, 31.25%) could not be classified with either the Leiden Convention or Lipton classification (pulmonary atresia n = 9, common arterial trunk (CAT) n = 1). In one case with CAT, Lipton classification, but not the Leiden Convention, could be applied. In two cases with the transposition of the great arteries and in two cases of double outlet right ventricle, the Leiden Convention, but not the Lipton classification, could be applied. Conclusions: Both classifications are useful to detail information about SCA. As Lipton classification was not developed for structural heart disease cases, in complex CHD with abnormal position of the great arteries, the Leiden Convention is better applicable. The use of both systems is limited in pulmonary atresia. In this scenario, it is better to provide a precise description of the coronary origin and associated characteristics that might affect treatment and prognosis. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)
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10 pages, 990 KiB  
Article
A History of Heart Failure Is an Independent Risk Factor for Death in Patients Admitted with Coronavirus 19 Disease
by Francesco Castagna, Rachna Kataria, Shivank Madan, Syed Zain Ali, Karim Diab, Christopher Leyton, Angelos Arfaras-Melainis, Paul Kim, Federico M. Giorgi, Sasa Vukelic, Omar Saeed, Snehal R. Patel, Daniel B. Sims and Ulrich P. Jorde
J. Cardiovasc. Dev. Dis. 2021, 8(7), 77; https://doi.org/10.3390/jcdd8070077 - 30 Jun 2021
Cited by 10 | Viewed by 3628
Abstract
Aims: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on [...] Read more.
Aims: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. Methods and Results: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. Conclusions: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19. Full article
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15 pages, 2971 KiB  
Article
Early Aberrant Angiogenesis Due to Elastic Fiber Fragmentation in Aortic Valve Disease
by Robert B. Hinton, Amy L. Juraszek, Amy M. Opoka, Benjamin J. Landis, J. Michael Smith, Robert P. Mecham and Kevin E. Bove
J. Cardiovasc. Dev. Dis. 2021, 8(7), 75; https://doi.org/10.3390/jcdd8070075 - 25 Jun 2021
Cited by 7 | Viewed by 3482
Abstract
Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and [...] Read more.
Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments. Full article
(This article belongs to the Section Pediatric Cardiology and Congenital Heart Disease)
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9 pages, 837 KiB  
Article
Ablation of Atrioventricular Nodal Re-Entrant Tachycardia Combining Irrigated Flexible-Tip Catheters and Three-Dimensional Electroanatomic Mapping: Long-Term Outcomes
by Michele Malagù, Francesco Vitali, Federico Marchini, Alessio Fiorio, Paolo Sirugo, Daniela Mele, Alessandro Brieda, Cristina Balla and Matteo Bertini
J. Cardiovasc. Dev. Dis. 2021, 8(6), 61; https://doi.org/10.3390/jcdd8060061 - 25 May 2021
Cited by 4 | Viewed by 6432
Abstract
Background: Transcatheter ablation is the standasrd treatment for atrioventricular nodal re-entrant tachycardia (AVNRT). However, different techniques are available. Data about the use of irrigated flexible-tip catheters and three-dimensional electroanatomical mapping (3D EAM) for AVNRT ablation are scant. The aim of this study was [...] Read more.
Background: Transcatheter ablation is the standasrd treatment for atrioventricular nodal re-entrant tachycardia (AVNRT). However, different techniques are available. Data about the use of irrigated flexible-tip catheters and three-dimensional electroanatomical mapping (3D EAM) for AVNRT ablation are scant. The aim of this study was to evaluate in long-term follow-up efficacy and safety of a novel approach for AVNRT treatment. Methods: This is a cohort single arm study with long-term follow-up. Patients with AVNRT were treated with catheter ablation by means of irrigated flexible-tip catheters combined with 3D EAM. Results: One-hundred-and-fifty patients were enrolled and followed-up for a median of 38 months (minimum 12, maximum 74). Acute procedural success rate was 96.7% (145/150 patients). During follow-up, 11 patients had arrhythmia recurrences (7.3%). No patient developed atrioventricular conduction block with need for pacemaker implantation (0%). Fourteen patients died during follow-up (9.3%). Conclusions: Acute procedural success and long-term follow-up show that AVNRT could be safely and effectively treated with irrigated flexible-tip catheters and 3D EAM. Full article
(This article belongs to the Section Electrophysiology and Cardiovascular Physiology)
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10 pages, 713 KiB  
Article
Asymptomatic Patients with Severe Aortic Stenosis and the Impact of Intervention
by Mevlüt Çelik, Milan Milojevic, Andras P. Durko, Frans B. S. Oei, Edris A. F. Mahtab and Ad J. J. C. Bogers
J. Cardiovasc. Dev. Dis. 2021, 8(4), 35; https://doi.org/10.3390/jcdd8040035 - 31 Mar 2021
Cited by 11 | Viewed by 2698
Abstract
Objectives the exact timing of aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS) remains a matter of debate. Therefore, we described the natural history of asymptomatic patients with severe AS, and the effect of AVR on long-term survival. Methods: [...] Read more.
Objectives the exact timing of aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS) remains a matter of debate. Therefore, we described the natural history of asymptomatic patients with severe AS, and the effect of AVR on long-term survival. Methods: Asymptomatic patients who were found to have severe AS between June 2006 and May 2009 were included. Severe aortic stenosis was defined as peak aortic jet velocity Vmax ≥ 4.0 m/s or aortic valve area (AVA) ≤ 1 cm2. Development of symptoms, the incidence of AVR, and all-cause mortality were assessed. Results: A total of 59 asymptomatic patients with severe AS were followed, with a mean follow-up of 8.9 ± 0.4 years. A total of 51 (86.4%) patients developed AS related symptoms, and subsequently 46 patients underwent AVR. The mean 1-year, 2-year, 5-year, and 10-year overall survival rates were higher in patients receiving AVR compared to those who did not undergo AVR during follow-up (100%, 93.5%, 89.1%, and 69.4%, versus 92.3%, 84.6%, 65.8%, and 28.2%, respectively; p < 0.001). Asymptomatic patients with severe AS receiving AVR during follow-up showed an incremental benefit in survival of up to 31.9 months compared to conservatively managed patients (p = 0.002). Conclusions: The majority of asymptomatic patients turn symptomatic during follow-up. AVR during follow-up is associated with better survival in asymptomatic severe AS patients. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)
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9 pages, 794 KiB  
Article
Disagreement between Cardiac Troponin Tests Yielding a Higher Incidence of Myocardial Injury in the Emergency Setting
by Peter A. Kavsak, Shawn E. Mondoux, Janet Martin, Mark K. Hewitt, Lorna Clark, Nadia Caruso, Ching-Tong Mark, V. Tony Chetty, Craig Ainsworth and Andrew Worster
J. Cardiovasc. Dev. Dis. 2021, 8(3), 31; https://doi.org/10.3390/jcdd8030031 - 23 Mar 2021
Cited by 12 | Viewed by 3076
Abstract
Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another [...] Read more.
Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another hs-cTnI assay (Abbott hs-cTnI) in samples obtained from different emergency departments (EDs). Two different sample types were evaluated (lithium heparin and ethylenediaminetetraacetic acid (EDTA) plasma) in a non-selected ED population (study 1, n = 469 samples) and in patients for which ED physicians ordered cardiac troponin testing (study 2, n = 1147 samples), from five different EDs. The incidence of injury in study 1 was higher with the OCD hs-cTnI assay (30.9%; 95% CI: 26.9 to 35.2) compared to that of the Abbott hs-cTnI (17.3%; 95% CI: 14.1 to 21.0) and the OCD cTnI ES (15.4%; 95% CI: 12.4 to 18.9) assays, with repeat testing identifying 4.8% (95% CI: 3.0 to 7.5) of the OCD hs-cTnI results with poor reproducibility. In study 2, 4.6% (95% CI: 3.5 to 6.0) of the results were not reported for the OCD hs-cTnI assay (i.e., poor reproducibility) with 12.7% (95%CI: 8.7 to 17.8) of the OCD hs-cTnI results positive for injury being negative for injury with the Abbott hs-cTnI assay. In summary, the OCD hs-cTnI assay yields higher rates of biochemical injury with a higher rate of poor reproducible results in different ED populations. Full article
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15 pages, 12281 KiB  
Article
Myocardium-Specific Deletion of Rac1 Causes Ventricular Noncompaction and Outflow Tract Defects
by Carmen Leung, Anish Engineer, Mella Y. Kim, Xiangru Lu and Qingping Feng
J. Cardiovasc. Dev. Dis. 2021, 8(3), 29; https://doi.org/10.3390/jcdd8030029 - 15 Mar 2021
Cited by 9 | Viewed by 3946
Abstract
Background: Left ventricular noncompaction (LVNC) is a cardiomyopathy that can lead to arrhythmias, embolic events and heart failure. Despite our current knowledge of cardiac development, the mechanisms underlying noncompaction of the ventricular myocardium are still poorly understood. The small GTPase Rac1 acts as [...] Read more.
Background: Left ventricular noncompaction (LVNC) is a cardiomyopathy that can lead to arrhythmias, embolic events and heart failure. Despite our current knowledge of cardiac development, the mechanisms underlying noncompaction of the ventricular myocardium are still poorly understood. The small GTPase Rac1 acts as a crucial regulator of numerous developmental events. The present study aimed to investigate the cardiomyocyte specific role of Rac1 in embryonic heart development. Methods and Results: The Nkx2.5-Cre transgenic mice were crossed with Rac1f/f mice to generate mice with a cardiomyocyte specific deletion of Rac1 (Rac1Nkx2.5) during heart development. Embryonic Rac1Nkx2.5 hearts at E12.5–E18.5 were collected for histological analysis. Overall, Rac1Nkx2.5 hearts displayed a bifid apex, along with hypertrabeculation and a thin compact myocardium. Rac1Nkx2.5 hearts also exhibited ventricular septal defects (VSDs) and double outlet right ventricle (DORV) or overriding aorta. Cardiomyocytes had a rounded morphology and were highly disorganized, and the myocardial expression of Scrib, a planar cell polarity protein, was reduced in Rac1Nkx2.5 hearts. In addition, cell proliferation rate was significantly decreased in the Rac1Nkx2.5 ventricular myocardium at E9.5. Conclusions: Rac1 deficiency in the myocardium impairs cardiomyocyte elongation and organization, and proliferative growth of the heart. A spectrum of CHDs arises in Rac1Nkx2.5 hearts, implicating Rac1 signaling in the ventricular myocardium as a crucial regulator of OFT alignment, along with compact myocardium growth and development. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)
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15 pages, 5668 KiB  
Article
Myocardial TGFβ2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development
by Aniket Bhattacharya, Nadia Al-Sammarraie, Mengistu G. Gebere, John Johnson, John F. Eberth and Mohamad Azhar
J. Cardiovasc. Dev. Dis. 2021, 8(3), 26; https://doi.org/10.3390/jcdd8030026 - 2 Mar 2021
Cited by 3 | Viewed by 3595
Abstract
Among the three transforming growth factor beta (TGFβ) ligands, TGFβ2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, [...] Read more.
Among the three transforming growth factor beta (TGFβ) ligands, TGFβ2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, including mitral valve prolapse (MVP) with or without regurgitation. Tgfb2 germline knockout fetuses exhibit multiple cardiac defects but the role of myocardial-TGFβ2 in heart development is yet to be elucidated. Here, myocardial Tgfb2 conditional knockout (CKO) embryos were generated by crossing Tgfb2flox mice with Tgfb2+/−; cTntCre mice. Tgfb2flox/− embryos were normal, viable. Cell fate mapping was done using dual-fluorescent mT/mG+/− mice. Cre-mediated Tgfb2 deletion was assessed by genomic PCR. RNAscope in situ hybridization was used to detect the loss of myocardial Tgfb2 expression. Histological, morphometric, immunohistochemical, and in situ hybridization analyses of CKOs and littermate controls at different stages of heart development (E12.5–E18.5) were used to determine the role of myocardium-derived TGFβ2 in atrioventricular (AV) cushion remodeling and myocardial development. CKOs exhibit a thin ventricular myocardium, AV cushion remodeling defects and developed incomplete AV septation defects. The loss of myocardial Tgfb2 resulted in impaired cushion maturation and dysregulated cell death. Phosphorylated SMAD2, a surrogate for TGFβ signaling, was “paradoxically” increased in both AV cushion mesenchyme and ventricular myocardium in the CKOs. Our results indicate that TGFβ2 produced by cardiomyocytes acting as cells autonomously on myocardium and via paracrine signaling on AV cushions are required for heart development. Full article
(This article belongs to the Special Issue Mitral Valve Development and Disease)
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11 pages, 906 KiB  
Article
Lipoprotein(a), Immunity, and Inflammation in Polyvascular Atherosclerotic Disease
by Narek A. Tmoyan, Olga I. Afanasieva, Marat V. Ezhov, Elena A. Klesareva, Tatiana V. Balakhonova and Sergei N. Pokrovsky
J. Cardiovasc. Dev. Dis. 2021, 8(2), 11; https://doi.org/10.3390/jcdd8020011 - 27 Jan 2021
Cited by 13 | Viewed by 3986
Abstract
Background and aims: lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and its complications, although data on the association with other vascular beds and the severity of atherosclerosis is limited. The aim of this study was to evaluate the [...] Read more.
Background and aims: lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and its complications, although data on the association with other vascular beds and the severity of atherosclerosis is limited. The aim of this study was to evaluate the association of atherosclerosis of various vascular beds with Lp(a), as well as its autoantibodies and generalized inflammatory markers. Material and methods: this study included 1288 adult patients with clinical and imaging examination of three vascular beds (coronary, carotid, and lower limb arteries). Patients were categorized according to the number of affected vascular beds (with at least one atherosclerotic stenosis ≥50%): 0 (n = 339), 1 (n = 470), 2 (n = 315), 3 (n = 164). We assessed blood cell count, lipid profile, C-reactive protein, circulating immune complexes, Lp(a), and its autoantibodies. Results: the number of affected vascular beds was associated with an increasing level of Lp(a) and a lower level of IgM autoantibodies to Lp(a). Hyperlipoproteinemia(a) (Lp(a) ≥ 30 mg/dL) was detected more frequently in patients with atherosclerosis. In logistic regression analysis adjusted for age, sex, hypertension, type 2 diabetes, and smoking, an elevated Lp(a) level was independently associated with stenotic atherosclerosis and lesion severity. There was a positive association of the number of affected vascular beds with C-reactive protein (r = 0.21, p < 0.01) and a negative association with circulating immune complexes (r = −0.29, p < 0.01). The neutrophil-to-lymphocyte ratio was significantly higher and the lymphocyte-to-monocyte ratio was significantly lower in patients with atherosclerosis compared to the controls (p < 0.01). Conclusion: Lp(a), C-reactive protein, circulating immune complexes, and neutrophil-to-lymphocyte ratio are associated with the stenotic atherosclerosis of different vascular beds. Lp(a) levels increase and IgM autoantibodies to Lp(a) decrease with the number of affected vascular beds. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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17 pages, 2925 KiB  
Article
The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot
by Marcel Grunert, Sandra Appelt, Paul Grossfeld and Silke R. Sperling
J. Cardiovasc. Dev. Dis. 2020, 7(4), 55; https://doi.org/10.3390/jcdd7040055 - 2 Dec 2020
Cited by 11 | Viewed by 3842
Abstract
Congenital heart defects (CHDs) are the most common birth defect in human with an incidence of almost 1% of all live births. Most cases have a multifactorial origin with both genetics and the environment playing a role in its development and progression. Adding [...] Read more.
Congenital heart defects (CHDs) are the most common birth defect in human with an incidence of almost 1% of all live births. Most cases have a multifactorial origin with both genetics and the environment playing a role in its development and progression. Adding an epigenetic component to this aspect is exemplified by monozygotic twins which share the same genetic background but have a different disease status. As a result, the interplay between the genetic, epigenetic and the environmental conditions might contribute to the etiology and phenotype. To date, the underlying causes of the majority of CHDs remain poorly understood. In this study, we performed genome-wide high-throughput sequencing to examine the genetic, structural genomic and epigenetic differences of two identical twin pairs discordant for Tetralogy of Fallot (TOF), representing the most common cyanotic form of CHDs. Our results show the almost identical genetic and structural genomic identity of the twins. In contrast, several epigenetic alterations could be observed given by DNA methylation changes in regulatory regions of known cardiac-relevant genes. Overall, this study provides first insights into the impact of genetic and especially epigenetic factors underlying monozygotic twins discordant for CHD like TOF. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)
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10 pages, 912 KiB  
Article
Predictive Value of Pre-Operative 2D and 3D Transthoracic Echocardiography in Patients Undergoing Mitral Valve Repair: Long Term Follow Up of Mitral Valve Regurgitation Recurrence and Heart Chamber Remodeling
by Gloria Tamborini, Valentina Mantegazza, Marco Penso, Manuela Muratori, Laura Fusini, Sarah Ghulam Ali, Claudia Cefalù, Gianpiero Italiano, Valentina Volpato, Paola Gripari, Enrico G. Caiani, Marco Zanobini and Mauro Pepi
J. Cardiovasc. Dev. Dis. 2020, 7(4), 46; https://doi.org/10.3390/jcdd7040046 - 20 Oct 2020
Cited by 8 | Viewed by 2925
Abstract
The “ideal” management of asymptomatic severe mitral regurgitation (MR) in valve prolapse (MVP) is still debated. The aims of this study were to identify pre-operatory parameters predictive of residual MR and of early and long-term favorable remodeling after MVP repair. We included 295 [...] Read more.
The “ideal” management of asymptomatic severe mitral regurgitation (MR) in valve prolapse (MVP) is still debated. The aims of this study were to identify pre-operatory parameters predictive of residual MR and of early and long-term favorable remodeling after MVP repair. We included 295 patients who underwent MV repair for MVP with pre-operatory two- and three-dimensional transthoracic echocardiography (2DTTE and 3DTTE) and 6-months (6M) and 3-years (3Y) follow-up 2DTTE. MVP was classified by 3DTTE as simple or complex and surgical procedures as simple or complex. Pre-operative echo parameters were compared to post-operative values at 6M and 3Y. Patients were divided into Group 1 (6M-MR < 2) and Group 2 (6M-MR ≥ 2), and predictors of MR ≥ 2 were investigated. MVP was simple in 178/295 pts, and 94% underwent simple procedures, while in only 42/117 (36%) of complex MVP a simple procedure was performed. A significant relation among prolapse anatomy, surgical procedures and residual MR was found. Post-operative MR ≥ 2 was present in 9.8%: complex MVP undergoing complex procedures had twice the percentage of MR ≥ 2 vs. simple MVP and simple procedures. MVP complexity resulted independent predictor of 6M-MR ≥ 2. Favorable cardiac remodeling, initially found in all cases, was maintained only in MR < 2 at 3Y. Pre-operative 3DTTE MVP morphology identifies pts undergoing simple or complex procedures predicting MR recurrence and favorable cardiac remodeling. Full article
(This article belongs to the Special Issue Mitral Valve Development and Disease)
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17 pages, 9955 KiB  
Article
Cauterization as a Simple Method for Regeneration Studies in the Zebrafish Heart
by Papa K. Van Dyck, Natasha Hockaden, Emma C. Nelson, Alyssa R. Koch, Kamil L. Hester, Neil Pillai, Gabrielle C. Coffing, Alan R. Burns and Pascal J. Lafontant
J. Cardiovasc. Dev. Dis. 2020, 7(4), 41; https://doi.org/10.3390/jcdd7040041 - 3 Oct 2020
Cited by 8 | Viewed by 6253
Abstract
In the last two decades, the zebrafish has emerged as an important model species for heart regeneration studies. Various approaches to model loss of cardiac myocytes and myocardial infarction in the zebrafish have been devised, and have included resection, genetic ablation, and cryoinjury. [...] Read more.
In the last two decades, the zebrafish has emerged as an important model species for heart regeneration studies. Various approaches to model loss of cardiac myocytes and myocardial infarction in the zebrafish have been devised, and have included resection, genetic ablation, and cryoinjury. However, to date, the response of the zebrafish ventricle to cautery injury has not been reported. Here, we describe a simple and reproducible method using cautery injury via a modified nichrome inoculating needle as a probe to model myocardial infarction in the zebrafish ventricle. Using light and electron microscopy, we show that cardiac cautery injury is attended by significant inflammatory cell infiltration, accumulation of collagen in the injured area, and the reconstitution of the ventricular myocardium. Additionally, we document the ablation of cardiac nerve fibers, and report that the re-innervation of the injured zebrafish ventricle is protracted, compared to other repair processes that accompany the regeneration of the cauterized ventricle. Taken together, our study demonstrates that cautery injury is a simple and effective means for generating necrotic tissue and eliciting a remodeling and regenerative response in the zebrafish heart. This approach may serve as an important tool in the methods toolbox for regeneration studies in the zebrafish. Full article
(This article belongs to the Special Issue Zebrafish Heart Development, Regeneration, and Disease Modelling)
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15 pages, 2084 KiB  
Article
Left Ventricular Noncompaction Is More Prevalent in Ventricular Septal Defect Than Other Congenital Heart Defects: A Morphological Study
by Laís Costa Marques, Gabriel Romero Liguori, Ana Carolina Amarante Souza and Vera Demarchi Aiello
J. Cardiovasc. Dev. Dis. 2020, 7(4), 39; https://doi.org/10.3390/jcdd7040039 - 25 Sep 2020
Cited by 7 | Viewed by 3688
Abstract
Left ventricular noncompaction (LVNC) is a condition characterized by prominent ventricular trabeculae and deep intertrabecular recesses and has been described as a possible substrate for arrhythmias, thromboembolism, and heart failure. Herein, we explored the prevalence of LVNC morphology among hearts with congenital heart [...] Read more.
Left ventricular noncompaction (LVNC) is a condition characterized by prominent ventricular trabeculae and deep intertrabecular recesses and has been described as a possible substrate for arrhythmias, thromboembolism, and heart failure. Herein, we explored the prevalence of LVNC morphology among hearts with congenital heart defects (CHD). We examined 259 postnatal hearts with one of the following CHD: isolated ventricular septal defect (VSD); isolated atrial septal defect (ASD); atrioventricular septal defect (AVSD); transposition of the great arteries (TGA); isomerism of the atrial appendages (ISOM); Ebstein’s malformation (EB); Tetralogy of Fallot (TF). Eleven hearts from children who died of non-cardiovascular causes were used as controls. The thickness of the compacted and non-compacted left ventricular myocardial wall was determined and the specimens classified as presenting or not LVNC morphology according to three criteria, as proposed by Chin, Jenni, and Petersen. Normal hearts did not present LVNC, but the CHD group presented different percentages of LVNC in at least one diagnostic criterium. The prevalence of LVNC was respectively, according to Chin’s, Jenni´s and Petersen´s methods: for VSD—54.2%, 35.4%, and 12.5%; ASD—8.3%, 8.3%, and 8.3%; AVSD—2.9%, 2.9%, and 0.0%; TGA—22.6%, 17%, and 5.7%; ISOM—7.1%, 7.1%, and 7.1%; EB—28.6%, 9.5%, and 0.0%; TF—5.9%. 2.9%, and 2.9%. VSD hearts showed a significantly greater risk of presenting LVNC when compared to controls (Chin and Jenni criteria). No other CHD presented similar risk. Current results show some agreement with previous studies, such as LVNC morphology being more prevalent in VSDs. Nonetheless, this is a morphological study and cannot be correlated with symptoms or severity of the CHD. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A special issue dedicated to Professor Robert Anderson)
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11 pages, 5106 KiB  
Article
Identification and Morphogenesis of Vestibular Atrial Septal Defects
by Rohit S. Loomba, Justin T. Tretter, Timothy J. Mohun, Robert H. Anderson, Scott Kramer and Diane E. Spicer
J. Cardiovasc. Dev. Dis. 2020, 7(3), 35; https://doi.org/10.3390/jcdd7030035 - 10 Sep 2020
Cited by 8 | Viewed by 4564
Abstract
Background: The vestibular atrial septal defect is an interatrial communication located in the antero-inferior portion of the atrial septum. Reflecting either inadequate muscularization of the vestibular spine and mesenchymal cap during development, or excessive apoptosis within the developing antero-inferior septal component, the [...] Read more.
Background: The vestibular atrial septal defect is an interatrial communication located in the antero-inferior portion of the atrial septum. Reflecting either inadequate muscularization of the vestibular spine and mesenchymal cap during development, or excessive apoptosis within the developing antero-inferior septal component, the vestibular defect represents an infrequently recognized true deficiency of the atrial septum. We reviewed necropsy specimens from three separate archives to establish the frequency of such vestibular defects and their associated cardiac findings, providing additional analysis from developing mouse hearts to illustrate their potential morphogenesis. Materials and methods: We analyzed the hearts in the Farouk S. Idriss Cardiac Registry at Ann and Robert H. Lurie Children’s Hospital in Chicago, IL, the Van Mierop Archive at the University of Florida in Gainesville, Florida, and the archive at Johns Hopkins All Children’s Heart Institute in St. Petersburg, Florida, identifying all those exhibiting a vestibular atrial septal defect, along with the associated intracardiac malformations. We then assessed potential mechanisms for the existence of such defects, based on the assessment of 450 datasets of developing mouse hearts prepared using the technique of episcopic microscopy. Results: We analyzed a total of 2100 specimens. Of these, 68 (3%) were found to have a vestibular atrial septal defect. Comparable defects were identified in 10 developing mouse embryos sacrificed at embryonic data 15.5, by which stage the antero-inferior component of the atrial septum is usually normally formed. Conclusion: The vestibular defect is a true septal defect located in the muscular antero-inferior rim of the oval fossa. Our retrospective review of autopsied hearts suggests that the defect may be more common than previously thought. Increased awareness of the location of the defect should optimize its future clinical identification. We suggest that the defect exists because of failure, during embryonic development, of union of the components that bind the leading edge of the primary atrial septum to the atrioventricular junctions, either because of inadequate muscularisation or excessive apoptosis. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A special issue dedicated to Professor Robert Anderson)
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22 pages, 12647 KiB  
Article
Early Embryonic Expression of AP-2α Is Critical for Cardiovascular Development
by Amy-Leigh Johnson, Jürgen E. Schneider, Timothy J. Mohun, Trevor Williams, Shoumo Bhattacharya, Deborah J. Henderson, Helen M. Phillips and Simon D. Bamforth
J. Cardiovasc. Dev. Dis. 2020, 7(3), 27; https://doi.org/10.3390/jcdd7030027 - 23 Jul 2020
Cited by 9 | Viewed by 4313
Abstract
Congenital cardiovascular malformation is a common birth defect incorporating abnormalities of the outflow tract and aortic arch arteries, and mice deficient in the transcription factor AP-2α (Tcfap2a) present with complex defects affecting these structures. AP-2α is expressed in the pharyngeal surface [...] Read more.
Congenital cardiovascular malformation is a common birth defect incorporating abnormalities of the outflow tract and aortic arch arteries, and mice deficient in the transcription factor AP-2α (Tcfap2a) present with complex defects affecting these structures. AP-2α is expressed in the pharyngeal surface ectoderm and neural crest at mid-embryogenesis in the mouse, but the precise tissue compartment in which AP-2α is required for cardiovascular development has not been identified. In this study we describe the fully penetrant AP-2α deficient cardiovascular phenotype on a C57Bl/6J genetic background and show that this is associated with increased apoptosis in the pharyngeal ectoderm. Neural crest cell migration into the pharyngeal arches was not affected. Cre-expressing transgenic mice were used in conjunction with an AP-2α conditional allele to examine the effect of deleting AP-2α from the pharyngeal surface ectoderm and the neural crest, either individually or in combination, as well as the second heart field. This, surprisingly, was unable to fully recapitulate the global AP-2α deficient cardiovascular phenotype. The outflow tract and arch artery phenotype was, however, recapitulated through early embryonic Cre-mediated recombination. These findings indicate that AP-2α has a complex influence on cardiovascular development either being required very early in embryogenesis and/or having a redundant function in many tissue layers. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)
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9 pages, 1209 KiB  
Article
Why Some Patients Undergoing Lipoprotein Apheresis Therapy Develop New Cardiovascular Events?
by Ulrich Julius, Solveig Kuss, Sergey Tselmin, Ulrike Schatz and Stefan R. Bornstein
J. Cardiovasc. Dev. Dis. 2020, 7(3), 25; https://doi.org/10.3390/jcdd7030025 - 16 Jul 2020
Cited by 7 | Viewed by 3145
Abstract
Lipoprotein apheresis (LA) is an effective tool to reduce cardiovascular events (CVEs) in high-risk patients with elevations of low density lipoprotein-cholesterol (LDL-C) and/or Lipoprotein(a) (Lp(a)). All patients included into this retrospective analysis had experienced CVEs before the start of the LA therapy. We [...] Read more.
Lipoprotein apheresis (LA) is an effective tool to reduce cardiovascular events (CVEs) in high-risk patients with elevations of low density lipoprotein-cholesterol (LDL-C) and/or Lipoprotein(a) (Lp(a)). All patients included into this retrospective analysis had experienced CVEs before the start of the LA therapy. We compared personal and lab data in two groups: CVEx/0 (n 60) with no new events during LA therapy, CVEx/1+ (n 48) with at least one new event. Patients of Group CVEx/1+ were about 5 years older when they had started the extracorporeal therapy, and they experienced more CVEs prior to that timepoint. There was a positive correlation between the number of CVEs before and during LA therapy. No differences were seen with respect to lipid concentrations, even after a correction of LDL-C concentrations for the LDL-C transported with Lp(a) particles. LA sessions effectively reduced both LDL-C and Lp(a). Lp(a) levels measured before LA sessions were lower than those measured initially. It appeared difficult to reach the target values for LDL-C published in the ESC/EAS Guideline in 2019, although all patients were maximally treated including drugs when tolerated. In conclusion, it will be important to initiate an LA therapy earlier, at least after a second CVE and at a younger age. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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24 pages, 22141 KiB  
Article
Pax9 and Gbx2 Interact in the Pharyngeal Endoderm to Control Cardiovascular Development
by Catherine A. Stothard, Silvia Mazzotta, Arjun Vyas, Jurgen E. Schneider, Timothy J. Mohun, Deborah J. Henderson, Helen M. Phillips and Simon D. Bamforth
J. Cardiovasc. Dev. Dis. 2020, 7(2), 20; https://doi.org/10.3390/jcdd7020020 - 25 May 2020
Cited by 12 | Viewed by 4987
Abstract
The correct formation of the aortic arch arteries depends on a coordinated and regulated gene expression profile within the tissues of the pharyngeal arches. Perturbation of the gene regulatory networks in these tissues results in congenital heart defects affecting the arch arteries and [...] Read more.
The correct formation of the aortic arch arteries depends on a coordinated and regulated gene expression profile within the tissues of the pharyngeal arches. Perturbation of the gene regulatory networks in these tissues results in congenital heart defects affecting the arch arteries and the outflow tract of the heart. Aberrant development of these structures leads to interruption of the aortic arch and double outlet right ventricle, abnormalities that are a leading cause of morbidity in 22q11 Deletion Syndrome (DS) patients. We have recently shown that Pax9 functionally interacts with the 22q11DS gene Tbx1 in the pharyngeal endoderm for 4th pharyngeal arch artery morphogenesis, with double heterozygous mice dying at birth with interrupted aortic arch. Mice lacking Pax9 die perinatally with complex cardiovascular defects and in this study we sought to validate further potential genetic interacting partners of Pax9, focussing on Gbx2 which is down-regulated in the pharyngeal endoderm of Pax9-null embryos. Here, we describe the Gbx2-null cardiovascular phenotype and demonstrate a genetic interaction between Gbx2 and Pax9 in the pharyngeal endoderm during cardiovascular development. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A special issue dedicated to Professor Robert Anderson)
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21 pages, 5143 KiB  
Article
Transforming Growth Factor Beta3 is Required for Cardiovascular Development
by Mrinmay Chakrabarti, Nadia Al-Sammarraie, Mengistu G. Gebere, Aniket Bhattacharya, Sunita Chopra, John Johnson, Edsel A. Peña, John F. Eberth, Robert E. Poelmann, Adriana C. Gittenberger-de Groot and Mohamad Azhar
J. Cardiovasc. Dev. Dis. 2020, 7(2), 19; https://doi.org/10.3390/jcdd7020019 - 24 May 2020
Cited by 25 | Viewed by 5504
Abstract
Transforming growth factor beta3 (TGFB3) gene mutations in patients of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD1) and Loeys-Dietz syndrome-5 (LDS5)/Rienhoff syndrome are associated with cardiomyopathy, cardiac arrhythmia, cardiac fibrosis, cleft palate, aortic aneurysms, and valvular heart disease. Although the developing heart of [...] Read more.
Transforming growth factor beta3 (TGFB3) gene mutations in patients of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD1) and Loeys-Dietz syndrome-5 (LDS5)/Rienhoff syndrome are associated with cardiomyopathy, cardiac arrhythmia, cardiac fibrosis, cleft palate, aortic aneurysms, and valvular heart disease. Although the developing heart of embryos express Tgfb3, its overarching role remains unclear in cardiovascular development and disease. We used histological, immunohistochemical, and molecular analyses of Tgfb3−/− fetuses and compared them to wildtype littermate controls. The cardiovascular phenotypes were diverse with approximately two thirds of the Tgfb3−/− fetuses having one or more cardiovascular malformations, including abnormal ventricular myocardium (particularly of the right ventricle), outflow tract septal and alignment defects, abnormal aortic and pulmonary trunk walls, and thickening of semilunar and/or atrioventricular valves. Ventricular septal defects (VSD) including the perimembranous VSDs were observed in Tgfb3−/− fetuses with myocardial defects often accompanied by the muscular type VSD. In vitro studies using TGFβ3-deficient fibroblasts in 3-D collagen lattice formation assays indicated that TGFβ3 was required for collagen matrix reorganization. Biochemical studies indicated the ‘paradoxically’ increased activation of canonical (SMAD-dependent) and noncanonical (MAP kinase-dependent) pathways. TGFβ3 is required for cardiovascular development to maintain a balance of canonical and noncanonical TGFβ signaling pathways. Full article
(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Adriana Gittenberger-De Groot)
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11 pages, 536 KiB  
Article
The Prognostic Importance of TAPSE in Early and in Stable Cardiovascular Diseases
by Paolo Giovanardi, Enrico Tincani, Marco Maioli and Stefano Tondi
J. Cardiovasc. Dev. Dis. 2020, 7(1), 4; https://doi.org/10.3390/jcdd7010004 - 15 Jan 2020
Cited by 6 | Viewed by 5592
Abstract
The identification of predictors of major cardiovascular events (MACES) represents a big challenge, especially in early and stable cardiovascular diseases. This prospective study comparatively evaluated the prognostic importance of left ventricular (LV) and right ventricular (RV) systolic and diastolic function, pulmonary artery pressure [...] Read more.
The identification of predictors of major cardiovascular events (MACES) represents a big challenge, especially in early and stable cardiovascular diseases. This prospective study comparatively evaluated the prognostic importance of left ventricular (LV) and right ventricular (RV) systolic and diastolic function, pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) in a stable patient’s cohort with cardiovascular risk factors. The LV ejection fraction, mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), functional mitral regurgitation (FMR), doppler tissue imaging of mitral and tricuspid annulus with systolic and diastolic peaks estimation, tricuspid regurgitation velocity (TRV), pulmonary velocity outflow time integral (PVTI), mean pulmonary artery pressure (MPAP) and PVR were estimated at enrollment. During the follow-up, MACES and all-cause mortality were recorded. 369 subjects with or without previous MACES were enrolled. Bivariate analysis revealed LVEF, TAPSE, MPAP, TRV, PVR, LV diastolic function, and FMR were associated with the endpoints. When computing the influence of covariates to the primary endpoint (all-cause mortality and MACES) through Cox analysis, only LV diastolic function and TAPSE entered the final model; for the secondary endpoint (MACES) only TAPSE entered. TAPSE was able to predict MACES and all-cause mortality in early and stable cardiovascular diseases. The use of TAPSE should be implemented. Full article
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Review

13 pages, 6590 KiB  
Review
Not All SAVR Are Created Equal: All the Approaches Available for Surgical Aortic Valve Replacement
by Francesco Cabrucci, Serge Sicouri, Massimo Baudo, Dimitrios E. Magouliotis, Yoshiyuki Yamashita, Beatrice Bacchi, Dario Petrone, Beman Wasef, Aleksander Dokollari, Massimo Bonacchi and Basel Ramlawi
J. Cardiovasc. Dev. Dis. 2025, 12(3), 84; https://doi.org/10.3390/jcdd12030084 - 24 Feb 2025
Viewed by 1210
Abstract
Surgical Aortic Valve Replacement (SAVR) is still one of the pillars of cardiac surgery practice, and its role is evolving into a more complex operation. The competition with structural valve therapies and the urgent demand for less invasive solutions have unleashed surgeons’ creativity [...] Read more.
Surgical Aortic Valve Replacement (SAVR) is still one of the pillars of cardiac surgery practice, and its role is evolving into a more complex operation. The competition with structural valve therapies and the urgent demand for less invasive solutions have unleashed surgeons’ creativity in adapting to these new challenges. All the possible ways to surgically replace the aortic valve are analyzed in this review. Surgical techniques, advantages and disadvantages, and key differences are listed, helping surgeons navigate the available options. Sternotomy SAVR is the benchmark, but that is becoming obsolete and, in some cases, no longer performed for teaching purposes. Mini sternotomy is the easiest way to achieve minimal invasiveness in all anatomic situations, while right anterior thoracotomy is an elegant solution mastered by fewer surgeons. Endoscopic and robotic-assisted techniques are shaping the future of SAVR, yet they still lack wide adoption. The choice of approach is mainly dictated by the anatomic features of the patient and the surgeon’s skills. A flow diagram to overcome the learning curve and advance toward more complex surgery is provided here. Mastering as many techniques as possible is paramount when offering a patient-tailored approach and performing a safe and less invasive operation. Full article
(This article belongs to the Special Issue Feature Review Papers in Cardiovascular Clinical Research)
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18 pages, 3350 KiB  
Review
Beyond the Lumen: Molecular Imaging to Unmask Vulnerable Coronary Plaques
by Geoffrey Currie and Hosen Kiat
J. Cardiovasc. Dev. Dis. 2025, 12(2), 51; https://doi.org/10.3390/jcdd12020051 - 30 Jan 2025
Viewed by 1306
Abstract
Vulnerable coronary atherosclerotic plaque involves a dynamic pathophysiologic process within and surrounding an atheromatous plaque in coronary artery intima. The process drastically increases the risk of plaque rupture and is clinically responsible for most cases of acute coronary syndromes, myocardial infarctions, and sudden [...] Read more.
Vulnerable coronary atherosclerotic plaque involves a dynamic pathophysiologic process within and surrounding an atheromatous plaque in coronary artery intima. The process drastically increases the risk of plaque rupture and is clinically responsible for most cases of acute coronary syndromes, myocardial infarctions, and sudden cardiac deaths. Early detection of vulnerable plaque is crucial for clinicians to implement appropriate risk-mitigation treatment strategies, offer timely interventions, and prevent potentially life-threatening events. There is an imperative clinical need to develop practical diagnostic pathways that utilize non-invasive means to risk-stratify symptomatic patients. Since the early 1990s, the identification of vulnerable plaque in clinical practice has primarily relied on invasive imaging techniques. In the last two decades, CT coronary angiogram (CTCA) has rapidly evolved into the prevalent non-invasive diagnostic modality for assessing coronary anatomy. There are now validated plaque appearances on CTCA correlating with plaque vulnerability. It is worth noting that in clinical practice, most CTCA reports omit mention of vulnerable plaque details because spatial resolution (0.3–0.5 mm) is often insufficient to reliably detect some crucial features of vulnerable plaques, such as thin fibrous caps. Additionally, accurately identifying vulnerable plaque features requires substantial expertise and time, which many cardiologists or radiologists may lack in routine reporting. Cardiac magnetic resonance imaging (cMRI) is also non-invasive and allows simultaneous anatomic and functional assessment of coronary plaques. Despite several decades of research and development, routine clinical application of cMRI in coronary plaque imaging remains hampered by complex imaging protocols, inconsistent image quality, and cost. Molecular imaging with radiotracers, specifically positron emission tomography (PET) with sodium fluoride (Na18F PET), have demonstrated significant potential as a sensitive and specific imaging procedure for diagnosing vulnerable coronary artery plaque. The study protocol is robust and brief, requiring minimal patient preparation. Compared to CTCA and cMRI, the diagnostic accuracy of this test is less dependent on the experience and expertise of the readers. Furthermore, validated automated quantitative algorithms complement the visual interpretation of the study, enhancing confidence in the diagnosis. This combination of factors makes Na18F PET a promising tool in cardiology for identifying high-risk coronary plaques. Full article
(This article belongs to the Special Issue Current Practice in Cardiac Imaging)
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14 pages, 1506 KiB  
Review
Mitochondrial Dysfunction in Congenital Heart Disease
by Julie Pires Da Silva, Mariana Casa de Vito, Carissa Miyano and Carmen C. Sucharov
J. Cardiovasc. Dev. Dis. 2025, 12(2), 42; https://doi.org/10.3390/jcdd12020042 - 25 Jan 2025
Cited by 1 | Viewed by 1146
Abstract
Mitochondria play a crucial role in multiple cellular processes such as energy metabolism, generation of reactive oxygen species, excitation–contraction coupling, cell survival and death. Dysfunction of mitochondria contributes to the development of cancer; neuromuscular, cardiovascular/congenital heart disease; and metabolic diseases, including diabetes. Mitochondrial [...] Read more.
Mitochondria play a crucial role in multiple cellular processes such as energy metabolism, generation of reactive oxygen species, excitation–contraction coupling, cell survival and death. Dysfunction of mitochondria contributes to the development of cancer; neuromuscular, cardiovascular/congenital heart disease; and metabolic diseases, including diabetes. Mitochondrial dysfunction can result in excessive reactive oxygen species, a decrease in energy production, mitophagy and apoptosis. All these processes are known to be dysregulated in cardiovascular diseases. The focus of this review is to summarize our current knowledge of mitochondrial dysfunction, including mitophagy and apoptosis, in pediatric congenital heart disease due to maternal diabetes or due to structural cardiac defects, with a focus on single-ventricle congenital heart disease. We also discuss recent mitochondria-targeted therapies for cardiovascular diseases. Full article
(This article belongs to the Section Pediatric Cardiology and Congenital Heart Disease)
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