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J. Cardiovasc. Dev. Dis., Volume 8, Issue 10 (October 2021) – 17 articles

Cover Story (view full-size image): Notch signaling pathways play crucial roles in cardiovascular development, disease, and regeneration. Most discoveries of Notch signaling rely on animal models, which constrict the understanding of Notch signaling-associated human cardiovascular development and disease. In this review, we first summarize the significant role of Notch signaling in individual cardiac cell types. Second, we discuss current bioengineering systems used for modeling and studying Notch signaling in the cardiovascular system, including microfluidics, exosomes, hydrogels, spheroids, and 3D bioprinting. Finally, we provide insights into supporting advanced characterizations with bioengineering systems in further refining Notch signaling in cardiovascular development, disease, and regeneration. View this paper.
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Article
Combined Use of Electrocardiography and Ultrasound to Detect Cardiac and Pulmonary Involvement after Recovery from COVID-19 Pneumonia: A Case Series
J. Cardiovasc. Dev. Dis. 2021, 8(10), 133; https://doi.org/10.3390/jcdd8100133 - 17 Oct 2021
Viewed by 432
Abstract
Background: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause an acute multiorgan syndrome (coronavirus disease 2019 (COVID-19)), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound [...] Read more.
Background: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause an acute multiorgan syndrome (coronavirus disease 2019 (COVID-19)), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement after COVID-19 pneumonia. Methods: Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia, as assessed on thoracic computed tomography (CT). Results: Out of 29 patients (mean age 70 ± 10 years; males 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. Persistence of ECG abnormalities from the acute phase was common, and nonspecific repolarisation abnormalities (93%) reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients, and values of systolic pulmonary artery pressure were abnormal in 16 (55%, despite the absence of prior comorbidities in 44% of them). Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%), which correlated well with the high prevalence (76%) of pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients. Conclusions: Data on cardiopulmonary involvement after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for the detection of cardiopulmonary complications after COVID-19 pneumonia. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
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Article
Ventricular Septation and Outflow Tract Development in Crocodilians Result in Two Aortas with Bicuspid Semilunar Valves
J. Cardiovasc. Dev. Dis. 2021, 8(10), 132; https://doi.org/10.3390/jcdd8100132 - 15 Oct 2021
Viewed by 216
Abstract
Background: The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy, however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortas originating from either the right or left [...] Read more.
Background: The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy, however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortas originating from either the right or left ventricular cavity. Mixing of blood in crocodilians cannot occur at the ventricular level as in other reptiles but instead takes place at the aortic root level by a shunt, the foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods: Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris were studied histologically. Results and Conclusions: The outflow tract septation complex can be divided into two components. The aorto-pulmonary septum divides the pulmonary trunk from both aortas, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion. Full article
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Article
Copeptin Levels Are Independent from Mild Therapeutic Hypothermia but Do Not Predict Infarct Size in Patients Presenting with ST-Segment Elevation Myocardial Infarction
J. Cardiovasc. Dev. Dis. 2021, 8(10), 131; https://doi.org/10.3390/jcdd8100131 - 14 Oct 2021
Viewed by 436
Abstract
Background: Mild therapeutic hypothermia (MTH) is a treatment adjunct in ST-segment elevation myocardial infarction (STEMI) that deserves investigation. Copeptin―a surrogate marker for vasopressin―is an early biomarker in STEMI. Data from cardiac arrest patients suggest a reduction of copeptin levels through MTH; however, copeptin [...] Read more.
Background: Mild therapeutic hypothermia (MTH) is a treatment adjunct in ST-segment elevation myocardial infarction (STEMI) that deserves investigation. Copeptin―a surrogate marker for vasopressin―is an early biomarker in STEMI. Data from cardiac arrest patients suggest a reduction of copeptin levels through MTH; however, copeptin levels have not been investigated in MTH during STEMI. Methods: We analyzed patients treated with MTH during STEMI in a sub-study of the STATIM trial (Testori, Heart 2019). Patients were randomized to normothermia or MTH with out-of-hospital initiation. Seven copeptin samples were collected from each patient. Primary endpoint was the difference in copeptin levels between the groups. As secondary endpoints, we defined differences in the kinetics between the sampling timepoints and the correlation between copeptin and the infarct size in relation to left ventricular myocardium. Results: We included 99 patients (MTH n = 47, control n = 52) in our intention to treat analysis. No differences in copeptin values at first medical contact between the MTH and normothermia groups were found. MTH showed no effect on copeptin levels, neither during cooling phase nor through the course. Copeptin peaked at first medical contact and hospital admission in both groups. No differences in kinetics between the timepoints were found. Copeptin showed no correlation with infarct size, neither at first medical contact nor hospital admission. Conclusions: Copeptin levels were not influenced by MTH in STEMI, suggesting the use of this biomarker also during temperature management. Furthermore, copeptin levels were not usable as a surrogate marker for infarct size at any timepoint. Full article
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Commentary
SARS-CoV-2 and Atherosclerosis: Should COVID-19 Be Recognized as a New Predisposing Cardiovascular Risk Factor?
J. Cardiovasc. Dev. Dis. 2021, 8(10), 130; https://doi.org/10.3390/jcdd8100130 - 10 Oct 2021
Viewed by 442
Abstract
At the beginning of the COVID-19 pandemic, the lung was recognized as the main target organ; now, new evidence suggests that SARS-CoV-2 infection leads to vascular disease. In a previous review, we supposed a bidirectional link between endothelial dysfunction and COVID-19, identifying atherosclerosis [...] Read more.
At the beginning of the COVID-19 pandemic, the lung was recognized as the main target organ; now, new evidence suggests that SARS-CoV-2 infection leads to vascular disease. In a previous review, we supposed a bidirectional link between endothelial dysfunction and COVID-19, identifying atherosclerosis as having a crucial role in its pathogenesis. Atherosclerosis with an existing endothelial dysfunction may worsen COVID-19 manifestations, leading to adverse outcomes, as largely reported. However, COVID-19 may be the trigger factor in the progression of the atherosclerotic process up to making it clinically manifest. The thrombotic complications can involve not only the atherosclerotic plaque, but also the durability of the surgical device implanted to treat a pre-existing coronary artery disease as recently reported. The burden of the disease makes necessary a long-term stratification of patients, revising drastically targeted therapy among others. Full article
Systematic Review
Meta-Analysis of Placebo-Controlled Trials of Levosimendan in Acute Myocardial Infarction
J. Cardiovasc. Dev. Dis. 2021, 8(10), 129; https://doi.org/10.3390/jcdd8100129 - 07 Oct 2021
Viewed by 812
Abstract
The treatment of acute myocardial infarction is early revascularization. Heart failure and cardiogenic shock may complicate acute myocardial infarction despite applying the best available strategy. Levosimendan is a relatively new drug to treat heart failure with a peculiar mechanism of action: calcium sensitization [...] Read more.
The treatment of acute myocardial infarction is early revascularization. Heart failure and cardiogenic shock may complicate acute myocardial infarction despite applying the best available strategy. Levosimendan is a relatively new drug to treat heart failure with a peculiar mechanism of action: calcium sensitization of myocardial fibres. Levosimendan has a direct inotropic effect but also pleiotropic effects; through the K+ATP channel’s opening, it also has a vasodilator effect which may participate concretely in the global effects of the drug. The focus of the literature is on the anti-heart failure and anti-cardiogenic shock properties of Levosimendan, but it may have effects also preventing the development of myocardial insufficiency in acute myocardial infarction. The aim of the meta-analysis is to evaluate the effect of Levosimendan on acute myocardial infarction in placebo-controlled trials. Based on the eight studies selected, we found a beneficial effect of Levosimendan on acute and long-term mortality of patients affected by acute myocardial infarction. With caution in interpreting the results of this meta-analysis, our data support the idea that Levosimendan may already have a role in the treatment of acute ischemic heart disease. Further studies specifically designed to investigate the early role in the treatment of ischemic heart failure are needed. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
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Review
Acute and Chronic Effects of COVID-19 on the Cardiovascular System
J. Cardiovasc. Dev. Dis. 2021, 8(10), 128; https://doi.org/10.3390/jcdd8100128 - 05 Oct 2021
Viewed by 751
Abstract
COVID-19 has shown significant morbidity with the involvement of multiple systems, including the cardiovascular system. Cardiovascular manifestations in the acute phase can include myocardial injury itself, myocardial infarction, venous thromboembolic events, myocarditis, Takotsubo syndrome, and different arrhythmic events. Myocardial injury defined by the [...] Read more.
COVID-19 has shown significant morbidity with the involvement of multiple systems, including the cardiovascular system. Cardiovascular manifestations in the acute phase can include myocardial injury itself, myocardial infarction, venous thromboembolic events, myocarditis, Takotsubo syndrome, and different arrhythmic events. Myocardial injury defined by the rise of cardiac biomarkers in blood has been found in multiple studies with a prevalence of about 20%. Its presence is related to worse clinical outcomes and in-hospital mortality. The mechanisms of myocardial injury have been the subject of intense research but still need to be clarified. The characterization of the cardiac affectation with echocardiography and cardiac magnetic resonance has found mixed results in different studies, with a striking incidence of imaging criteria for myocarditis. Regarding post-acute and chronic follow-up results, the persistence of symptoms and imaging changes in recovered COVID-19 patients has raised concerns about the duration and the possible significance of these findings. Even though the knowledge about this disease has increased incredibly in the last year, many aspects are still unclear and warrant further research. Full article
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Article
The Value of Fetuin-A as a Predictor to Identify Takotsubo Patients at Risk of Cardiovascular Events
J. Cardiovasc. Dev. Dis. 2021, 8(10), 127; https://doi.org/10.3390/jcdd8100127 - 05 Oct 2021
Viewed by 409
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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Review
Preoperative Assessment and Management of Cardiovascular Risk in Patients Undergoing Non-Cardiac Surgery: Implementing a Systematic Stepwise Approach during the COVID-19 Pandemic Era
J. Cardiovasc. Dev. Dis. 2021, 8(10), 126; https://doi.org/10.3390/jcdd8100126 - 03 Oct 2021
Viewed by 673
Abstract
Major adverse cardiac events, defined as death or myocardial infarction, are common causes of perioperative mortality and major morbidity in patients undergoing non-cardiac surgery. Reduction of perioperative cardiovascular risk in relation to non-cardiac surgery requires a stepwise patient evaluation that integrates clinical risk [...] Read more.
Major adverse cardiac events, defined as death or myocardial infarction, are common causes of perioperative mortality and major morbidity in patients undergoing non-cardiac surgery. Reduction of perioperative cardiovascular risk in relation to non-cardiac surgery requires a stepwise patient evaluation that integrates clinical risk factors, functional status and the estimated stress of the planned surgical procedure. Major guidelines on preoperative cardiovascular risk assessment recommend to establish, firstly, the risk of surgery per se (low, moderate, high) and the related timing (elective vs. urgent/emergent), evaluate the presence of unstable cardiac conditions or a recent coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), assess the functional capacity of the patient (usually expressed in metabolic equivalents), determine the value of non-invasive and/or invasive cardiovascular testing and then combine these data in estimating perioperative risk for major cardiac adverse events using validated scores (Revised Cardiac Risk Index (RCRI) or National Surgical Quality Improvement Program (NSQIP)). This stepwise approach has the potential to guide clinicians in determining which patients could benefit from cardiovascular therapy and/or coronary artery revascularization before non-cardiac surgery towards decreasing the incidence of perioperative morbidity and mortality. Finally, it should be highlighted that there is a need to implement specific strategies in the 2019 Coronavirus disease (COVID-19) pandemic to minimize the risk of transmission of COVID-19 infection during the preoperative risk assessment process. Full article
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Review
Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration
J. Cardiovasc. Dev. Dis. 2021, 8(10), 125; https://doi.org/10.3390/jcdd8100125 - 30 Sep 2021
Viewed by 542
Abstract
The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling [...] Read more.
The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling rely on animal models and a few clinical studies, which significantly bottleneck the understanding of Notch signaling-associated human cardiovascular development and disease. Recent advances in the bioengineering systems and human pluripotent stem cell-derived cardiovascular cells pave the way to decipher the role of Notch signaling in cardiovascular-related cells (endothelial cells, cardiomyocytes, smooth muscle cells, fibroblasts, and immune cells), and intercellular crosstalk in the physiological, pathological, and regenerative context of the complex human cardiovascular system. In this review, we first summarize the significant roles of Notch signaling in individual cardiac cell types. We then cover the bioengineering systems of microfluidics, hydrogel, spheroid, and 3D bioprinting, which are currently being used for modeling and studying Notch signaling in the cardiovascular system. At last, we provide insights into ancillary supports of bioengineering systems, varied types of cardiovascular cells, and advanced characterization approaches in further refining Notch signaling in cardiovascular development, disease, and regeneration. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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Article
Use of Echocardiography and Heart Failure In-Hospital Mortality from Registry Data in Japan
J. Cardiovasc. Dev. Dis. 2021, 8(10), 124; https://doi.org/10.3390/jcdd8100124 - 30 Sep 2021
Viewed by 452
Abstract
Background: Echocardiography requires a high degree of skill on the part of the examiner, and the skill may be more improved in larger volume centers. This study investigated trends and outcomes associated with the use and volume of echocardiographic exams from a real-world [...] Read more.
Background: Echocardiography requires a high degree of skill on the part of the examiner, and the skill may be more improved in larger volume centers. This study investigated trends and outcomes associated with the use and volume of echocardiographic exams from a real-world registry database of heart failure (HF) hospitalizations. Methods: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). A first analysis was performed to assess the trend of echocardiographic examinations between 2012 and 2016. A secondary analysis was performed to assess whether echocardiographic use was associated with in-hospital mortality in 2015. Results: During this period, the use of echocardiography grew at an average annual rate of 6%. Patients with echocardiography had declining rates of hospital mortality, and these trends were associated with high hospitalization costs. In the 2015 sample, a total of 52,832 echocardiograms were examined, corresponding to 65.6% of all HF hospital admissions for that year. We found that the use and volume of echocardiography exams were associated with significantly lower odds of all-cause hospital mortality in heart failure (adjusted odds ratio (OR): 0.48 for use of echocardiography and 0.78 for the third tertile; both p < 0.001). Conclusions: The use of echocardiography was associated with decreased odds of hospital mortality in HF. The volumes of echocardiographic examinations were also associated with hospital mortality. Full article
(This article belongs to the Special Issue Echocardiography in Cardiovascular Disease)
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Systematic Review
Coronary Heart Disease (CHD) in Elderly Patients: Which Drug to Choose, Ticagrelor and Clopidogrel? A Systematic Review and Meta-Analysis of Randomized Controlled Trials
J. Cardiovasc. Dev. Dis. 2021, 8(10), 123; https://doi.org/10.3390/jcdd8100123 - 30 Sep 2021
Viewed by 824
Abstract
Background: A new generation P2Y12 receptor inhibitor (ticagrelor) is recommended in current therapeutic guidelines to treat patients with coronary heart disease (CHD). However, it is unknown if ticagrelor is more effective than clopidogrel in elderly patients. Therefore, a systematic review was done to [...] Read more.
Background: A new generation P2Y12 receptor inhibitor (ticagrelor) is recommended in current therapeutic guidelines to treat patients with coronary heart disease (CHD). However, it is unknown if ticagrelor is more effective than clopidogrel in elderly patients. Therefore, a systematic review was done to assess the effectiveness and safety of ticagrelor and clopidogrel in older patients with CHD to determine the appropriate antiplatelet treatment plan. Methodology: We performed a systematic review of randomized controlled trials (RCTs) to compare the effectiveness and safety of ticagrelor vs. clopidogrel in elderly patients with CHD. We selected eligible RCTs based on specified study criteria following a systematic search of PubMed and Scopus databases from January 2007 to May 2021. Primary efficacy outcomes assessed were major adverse cardiovascular events (MACEs), myocardial infarction (MI), stent thrombosis (ST), and all-cause death. The secondary outcome assessed was major bleeding events. We used RevMan 5.3 software to conduct a random-effects meta-analysis and estimated the pooled incidence and risk ratios (RRs) with 95% confidence intervals (CIs) for ticagrelor and clopidogrel. Results: Data from 6 RCTs comprising 21,827 elderly patients were extracted according to the eligibility criteria. There was no significant difference in the MACE outcome (incidence: 9.23% vs. 10.57%; RR = 0.95, 95% CI = 0.70–1.28, p = 0.72), MI (incidence: 5.40% vs. 6.23%; RR = 0.94, 95% CI= 0.69–1.27, p = 0.67), ST (incidence: 2.33% vs. 3.17%; RR = 0.61, 95% CI= 0.32–1.17, p = 0.13), and all-cause death (4.29% vs. 5.33%; RR = 0.86, 95% CI = 0.65–1.12, p = 0.25) for ticagrelor vs. clopidogrel, respectively. In addition, ticagrelor was not associated with a significant increase in the rate of major bleeding (incidence: 9.98% vs. 9.33%: RR = 1.37, 95% CI = 0.97–1.94, p = 0.07) vs. clopidogrel. Conclusions: This study did not find evidence that ticagrelor is significantly more effective or safer than clopidogrel in elderly patients with CHD. Full article
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Review
Clinical Assessment of Ventricular Wall Stress in Understanding Compensatory Hypertrophic Response and Maladaptive Ventricular Remodeling
J. Cardiovasc. Dev. Dis. 2021, 8(10), 122; https://doi.org/10.3390/jcdd8100122 - 29 Sep 2021
Viewed by 301
Abstract
Ventricular wall stress (WS) is an important hemodynamic parameter to represent myocardial oxygen demand and ventricular workload. The normalization of WS is regarded as a physiological feedback signal that regulates the rate and extent of ventricular hypertrophy to maintain myocardial homeostasis. Although hypertrophy [...] Read more.
Ventricular wall stress (WS) is an important hemodynamic parameter to represent myocardial oxygen demand and ventricular workload. The normalization of WS is regarded as a physiological feedback signal that regulates the rate and extent of ventricular hypertrophy to maintain myocardial homeostasis. Although hypertrophy is an adaptive response to increased biomechanical stress, persistent hypertrophic stimulation forces the stressed myocardium into a progressive maladaptive process called ventricular remodeling, consisting of ventricular dilatation and dysfunction in conjunction with the development of myocyte hypertrophy, apoptosis, and fibrosis. The critical determinant of this pathological transition is not fully understood, but an energetic mismatch due to uncontrolled WS is thought to be a central mechanism. Despite extensive basic investigations conducted to understand the complex signaling pathways involved in this maladaptive process, clinical diagnostic studies that translate these molecular and cellular changes are relatively limited. Echocardiographic assessment with or without direct measurement of left ventricular pressure used to be a mainstay in estimating ventricular WS in clinical medicine, but in recent years more and more noninvasive applications with magnetic resonance imaging have been studied. In this review article, basic clinical applications of WS assessment are discussed to help understand the progression of ventricular remodeling. Full article
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Article
Deficient Myocardial Organization and Pathological Fibrosis in Fetal Aortic Stenosis—Association of Prenatal Ultrasound with Postmortem Histology
J. Cardiovasc. Dev. Dis. 2021, 8(10), 121; https://doi.org/10.3390/jcdd8100121 - 28 Sep 2021
Viewed by 432
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
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Article
Red Cell Distribution Width and Patient Outcome in Cardiovascular Disease: A ‘’Real-World’’ Analysis
J. Cardiovasc. Dev. Dis. 2021, 8(10), 120; https://doi.org/10.3390/jcdd8100120 - 26 Sep 2021
Viewed by 580
Abstract
Red cell distribution width (RDW) has been shown to predict adverse outcomes in specific scenarios. We aimed to assess the association between RDW and all-cause death and a clinically relevant composite endpoint in a population with various clinical manifestations of cardiovascular diseases. We [...] Read more.
Red cell distribution width (RDW) has been shown to predict adverse outcomes in specific scenarios. We aimed to assess the association between RDW and all-cause death and a clinically relevant composite endpoint in a population with various clinical manifestations of cardiovascular diseases. We retrospectively analyzed 700 patients (median age 72.7 years [interquartile range, IQR, 62.6–80]) admitted to the Cardiology ward between January and November 2016. Patients were divided into tertiles according to baseline RDW values. After a median follow-up of 3.78 years (IQR 3.38–4.03), 153 (21.9%) patients died and 247 (35.3%) developed a composite endpoint (all-cause death, acute coronary syndromes, transient ischemic attack/stroke, and/or thromboembolic events). With multivariate Cox regression analysis, the highest RDW tertile was independently associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 2.73, 95% confidence interval [CI] 1.63–4.56) and of the composite endpoint (adjusted HR 2.23, 95% CI 1.53–3.24). RDW showed a good predictive ability for all-cause death (C-statistics: 0.741, 95% CI 0.694–0.788). In a real-world cohort of patients, we found that higher RDW values were independently associated with an increased risk of all-cause death and clinical adverse cardiovascular events thus proposing RDW as a prognostic marker in cardiovascular patients. Full article
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Article
Radiation Dose and Image Quality of a High-Pitch Prospective Spiral First Approach in Coronary Computed Tomography Angiography (CCTA)
J. Cardiovasc. Dev. Dis. 2021, 8(10), 119; https://doi.org/10.3390/jcdd8100119 - 24 Sep 2021
Viewed by 545
Abstract
Objective: To investigate a high-pitch spiral first (HPSF) approach for coronary computed tomography angiography (CCTA) in an unselected patient cohort and compare diagnostic yield and radiation exposure to CCTAs acquired via conventional, non-high-pitch spiral first (NHPSF) scan regimes. Materials and Methods: All consecutive [...] Read more.
Objective: To investigate a high-pitch spiral first (HPSF) approach for coronary computed tomography angiography (CCTA) in an unselected patient cohort and compare diagnostic yield and radiation exposure to CCTAs acquired via conventional, non-high-pitch spiral first (NHPSF) scan regimes. Materials and Methods: All consecutive patients from 1 January 2015 to 31 December 2017 were included. Two investigation protocols (HPSF/NHPSF) were used with the aim to achieve diagnostic image quality of all coronary segments. Low-pitch secondary scans followed the initial examination if image quality was unsatisfactory. Dosage and image quality were compared between both regimes. Results: 1410 patients were subject to a HPSF and 236 patients to a NHPSF approach. While the HPSF approach led to a higher fraction of re-scans (35% vs. 11%, p < 0.001), the fraction of aggregate scans that remained non-diagnostic after considering the initial and secondary scan was comparably low for the HPSF and NHPSF approach (0.78 vs. 0%, p = 0.18). Aggregate radiation exposure in the HPSF protocol was significantly lower (1.12 mSv (IQR: 0.73, 2.10) vs. 3.96 mSv (IQR: 2.23, 8.33) p < 0.001). Conclusions: In spite of a higher number of re-scans, a HPSF approach leads to a reduction in overall radiation exposure with diagnostic yields similar to a NHPSF approach. Full article
(This article belongs to the Section Cardiac Imaging)
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Article
Left Cardiac Remodelling Assessed by Echocardiography Is Associated with Rho-Kinase Activation in Long-Distance Runners
J. Cardiovasc. Dev. Dis. 2021, 8(10), 118; https://doi.org/10.3390/jcdd8100118 - 24 Sep 2021
Viewed by 591
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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Article
Role of Transient Elastography to Stage Fontan-Associated Liver Disease (FALD) in Adults with Single Ventricle Congenital Heart Disease Correction
J. Cardiovasc. Dev. Dis. 2021, 8(10), 117; https://doi.org/10.3390/jcdd8100117 - 23 Sep 2021
Viewed by 483
Abstract
Fontan-associated liver disease (FALD) is an arising clinical entity that can occur long after a successful Fontan operation for correction of single ventricle (SV) congenital heart disease (CHD). Occurrence of FALD is characterized by liver cirrhosis and other hepatic complications, and determinates an [...] Read more.
Fontan-associated liver disease (FALD) is an arising clinical entity that can occur long after a successful Fontan operation for correction of single ventricle (SV) congenital heart disease (CHD). Occurrence of FALD is characterized by liver cirrhosis and other hepatic complications, and determinates an increased morbidity and mortality. Currently, there is no consensus on how to stage FALD. We report here our experience by an observational study in 52 patients with SV-CHD after Fontan operation that were recruited through a period of 36 ± 9.3 months. All cases underwent lab tests and liver and cardiac imaging evaluation, including liver stiffness (LS) measurement by transient elastography (TE) (FibroScan®). According to selective criteria for liver disease, we identified 23/43 (53.5%) cases with advanced FALD that showed: older age (p < 0.05), larger hepatic and cava veins diameter (p < 0.05), worsened NYHA class (p < 0.05), abnormal lymphocytes (p < 0.01), platelet count (p < 0.05), and GGT, prothrombin time (INR), albumin and cystatin C levels (p < 0.05), with respect to cases without advanced FALD. LS values were significantly increased in cases with advanced FALD, at cut-off values higher than 22 kPa (p < 0.001). LS, and its combined score with spleen diameter and platelet count (LSPS) successfully helped to detect 100% of cases with portal hypertension (p < 0.001). In conclusion, LS can be effective to stage FALD and to uncover cases with severe risk of complications, avoiding higher morbidity and mortality related to advanced FALD. Full article
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