Cardiac and Vascular Diseases: Pathogenesis, Pharmacological Treatments, Advances in Therapies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 61827

Special Issue Editors


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Guest Editor
Cardiology Department, Perinei Hospital, Bari, Italy
Interests: noninvasive assessment; heart failure; arrhythmias; preventive cardiology; cardiovascular pharmacology; cardio-oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular diseases are the leading cause of death worldwide. The relationship between cardiac and vascular structures is not always considered, and these diseases are often underdiagnosed.

The focus of this Special Issue is to develop new insights into the pathogenesis of vascular alterations in cardiac diseases by outlining the complex genetic, biochemical, and molecular aspects at the basis of these alterations.

Early identification of cardiac and vascular diseases as well as the correct evaluation of mechanisms and pathogenetic pathways will help to promote the development of targeted therapies.

The landscape of cardiovascular pharmacology is the further aim of this Special Issue: authors are invited to contribute their research in the field of pharmacological approaches to cardiac and vascular diseases by outlining the most recent advances in therapies and treatments.

The combination of research in pathogenesis and pharmacology will give a comprehensive overview of cardiovascular diseases and the attempts to improve the outcomes of patients suffering from them.

Dr. Francesco Massari
Dr. Pietro Scicchitano
Guest Editors

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Keywords

  • endothelial function
  • cardiomyopathies
  • cardiovascular pharmacology
  • cardiac therapeutics
  • noninvasive vascular treatments
  • molecular cardiac biomarkers
  • molecular vascular biomarkers

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Published Papers (24 papers)

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14 pages, 1224 KiB  
Article
Mechanistic Insights into Inorganic Nitrite-Mediated Vasodilation of Isolated Aortic Rings under Oxidative/Hypertensive Conditions and S-Nitros(yl)ation of Proteins in Germ-Free Mice
by Paul Stamm, Sanela Kalinovic, Matthias Oelze, Sebastian Steven, Alexander Czarnowski, Miroslava Kvandova, Franziska Bayer, Christoph Reinhardt, Thomas Münzel and Andreas Daiber
Biomedicines 2022, 10(3), 730; https://doi.org/10.3390/biomedicines10030730 - 21 Mar 2022
Cited by 1 | Viewed by 2346
Abstract
The prevalence and clinical importance of arterial hypertension are still growing. Inorganic nitrite (NO2) represents an attractive dietary antihypertensive agent, but its metabolism and mode of action, which we aimed to investigate with the present study, are not completely understood. [...] Read more.
The prevalence and clinical importance of arterial hypertension are still growing. Inorganic nitrite (NO2) represents an attractive dietary antihypertensive agent, but its metabolism and mode of action, which we aimed to investigate with the present study, are not completely understood. Isolated aortic rings from rats were treated ex vivo with oxidants, and rats were infused in vivo with angiotensin-II. Vascular responses to acetylcholine (ACh) and nitrite were assessed by isometric tension recording. The loss of vasodilatory potency in response to oxidants was much more pronounced for ACh as compared to nitrite ex vivo (but not in vivo with angiotensin-II). This effect may be caused by the redox regulation of conversion to xanthine oxidase (XO). Conventionally raised and germ-free mice were treated with nitrite by gavage, which did not improve ACh-mediated vasodilation, but did increase the plasma levels of S-nitros(yl)ated proteins in the conventionally-raised, but not in the germ-free mice. In conclusion, inorganic nitrite represents a dietary drug option to treat arterial hypertension in addition to already established pharmacological treatment. Short-term oxidative stress did not impair the vasodilatory properties of nitrite, which may be beneficial in cardiovascular disease patients. The gastrointestinal microbiome appears to play a key role in nitrite metabolism and bioactivation. Full article
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15 pages, 2494 KiB  
Article
Characterization of Systemic and Regional Hemodynamics and Vascular Dysfunction in Mice with Fecal Induced Peritonitis
by Forough Jahandideh, Sareh Panahi, Ronan M. N. Noble, Ferrante S. Gragasin, Rachel G. Khadaroo, Kimberly F. Macala and Stephane L. Bourque
Biomedicines 2022, 10(2), 470; https://doi.org/10.3390/biomedicines10020470 - 18 Feb 2022
Viewed by 1874
Abstract
Sepsis is associated with circulatory dysfunction contributing to disturbed blood flow and organ injury. Decreased organ perfusion in sepsis is attributed, in part, to the loss of vasoregulatory mechanisms. Identifying which vascular beds are most susceptible to dysfunction is important for monitoring the [...] Read more.
Sepsis is associated with circulatory dysfunction contributing to disturbed blood flow and organ injury. Decreased organ perfusion in sepsis is attributed, in part, to the loss of vasoregulatory mechanisms. Identifying which vascular beds are most susceptible to dysfunction is important for monitoring the recovery of organ function and guiding interventions. This study aimed to investigate the development of vascular dysfunction as sepsis progressed to septic shock. Anesthetized C57Bl/6 mice were instrumented with a fiberoptic pressure sensor in the carotid artery for blood pressure measurements. In subgroups of mice, regional blood flow measurements were taken by positioning a perivascular flow probe around either the left carotid, left renal, or superior mesenteric arteries. Hemodynamic parameters and their responsiveness to bolus doses of vasoactive drugs were recorded prior to and continuously after injection of fecal slurry (1.3 mg/g body weight) for 4 h. Fecal slurry-induced peritonitis reduced mean arterial pressure (62.7 ± 2.4 mmHg vs. 37.5 ± 3.2 mmHg in vehicle and septic mice, respectively), impaired cardiac function, and eventually reduced organ blood flow (71.9%, 66.8%, and 65.1% in the superior mesenteric, renal, and carotid arteries, respectively). The mesenteric vasculature exhibited dysregulation before the renal and carotid arteries, and this underlying dysfunction preceded the blood pressure decline and impaired organ blood flow. Full article
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18 pages, 882 KiB  
Article
Sex-Specific Impact of Different Obesity/Metabolic Phenotypes on Long-Term Cardiovascular Outcomes in Acute Coronary Syndrome Patients
by Egidio Imbalzano, Giuseppina T. Russo, Annalisa Giandalia, Angela Sciacqua, Luana Orlando, Vincenzo Russo, Maria Perticone, Arrigo F. G. Cicero, Antonio Giovanni Versace, Pierpaolo Di Micco, Vincenzo Antonio Ciconte, Giuseppe Dattilo, Giovanni Squadrito and Marco Vatrano
Biomedicines 2022, 10(2), 424; https://doi.org/10.3390/biomedicines10020424 - 10 Feb 2022
Cited by 6 | Viewed by 1800
Abstract
Obesity, a major risk factor for acute coronary syndrome (ACS), is a multifaceted disease with different metabolic phenotypes and sex-specific features. Here, we evaluated the long-term cardiovascular risk by different obesity/metabolic phenotypes and by sex in ACS patients. The occurrence of the composite [...] Read more.
Obesity, a major risk factor for acute coronary syndrome (ACS), is a multifaceted disease with different metabolic phenotypes and sex-specific features. Here, we evaluated the long-term cardiovascular risk by different obesity/metabolic phenotypes and by sex in ACS patients. The occurrence of the composite outcome of death, nonfatal reinfarction with or without PCI and/or stroke was evaluated in 674 patients (504 men; 170 women), consecutively hospitalized for ACS and followed-up for 7 years, who were stratified in metabolically healthy (MHNW) and unhealthy normal weight (MUNW), and in metabolically healthy (MHO) and unhealthy obese (MUO) groups. At baseline, 54.6% of patients were included in the MHNW group, 26.4% in the MUNW, 5.9% in the MHO and 13.1% in the MUO, with no sex-differences in the distribution of phenotypes. The overall rate of major outcome (100 person-years) in the reference group (MHNW) was higher in men than in women (RR: 1.19 vs. 0.6). The Kaplan–Meier curves for cumulative survival free from cardiovascular events according to obesity/metabolic status diverged significantly according to sex (log rank test, p = 0.006), this effect being more prominent in men (log 11.20; p = 0.011), than in women (log 7.98; p = 0.047). Compared to MHNW, the risk increased in obese men (RR: 2.2; 95% 1.11–1.54 in MUO group), whereas in women the risk was confined to metabolically unhealthy subjects (RR: 3.2; 95% CI 1.23–9.98, MUNW group). Our data show a sex-specific impact of obesity phenotypes on long-term cardiovascular risk in patients hospitalized for ACS. Full article
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14 pages, 967 KiB  
Article
E-Selectin Is Associated with Daytime and 24-Hour Diastolic Blood Pressure Variability in Type 2 Diabetes
by Dana Mihaela Ciobanu, Cornelia Bala, Adriana Rusu, Gabriel Cismaru and Gabriela Roman
Biomedicines 2022, 10(2), 279; https://doi.org/10.3390/biomedicines10020279 - 26 Jan 2022
Cited by 3 | Viewed by 2242
Abstract
E-selectin is an endothelial cell adhesion molecule involved in vascular inflammation. Elevated E-selectin has been reported in patients with high blood pressure and diabetes. Given the increasing clinical relevance of parameters derived from ambulatory blood pressure monitoring, further investigation of their relationships with [...] Read more.
E-selectin is an endothelial cell adhesion molecule involved in vascular inflammation. Elevated E-selectin has been reported in patients with high blood pressure and diabetes. Given the increasing clinical relevance of parameters derived from ambulatory blood pressure monitoring, further investigation of their relationships with E-selectin is of interest. In this study, we aimed to investigate the association between serum E-selectin, office blood pressure and 24 h ambulatory blood pressure parameters in patients with type 2 diabetes. Blood pressure variability was assessed by computing the standard deviation of mean systolic and diastolic blood pressure separately for daytime and nighttime during 24 h ambulatory blood pressure monitoring in a cohort of patients with type 2 diabetes (n = 132). Additionally, were assessed nighttime systolic dipping and pulse pressure separately for daytime, nighttime, and 24 h. Serum E-selectin was measured using the enzyme-linked immunosorbent assay technique. We found that E-selectin was consistently associated with 24 h diastolic blood pressure variability (r = 0.238; p = 0.019) and daytime diastolic blood pressure variability (r = 0.258; p = 0.012), after adjustment for confounding factors. No association of E-selectin with office blood pressure and other 24 h ambulatory blood pressure parameters was observed. In conclusion, endothelial activation indicated by elevated serum E-selectin is associated with increased ambulatory diastolic blood pressure variability in patients with type 2 diabetes. Full article
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12 pages, 1852 KiB  
Article
Dynamic Changes in Pentraxin-3 and Neprilysin in ST Segment Elevation Myocardial Infarction
by Rahel Befekadu, Magnus Grenegård, Anders Larsson, Kjeld Christensen and Sofia Ramström
Biomedicines 2022, 10(2), 275; https://doi.org/10.3390/biomedicines10020275 - 26 Jan 2022
Cited by 3 | Viewed by 1905
Abstract
Pentraxin-3 (PTX3) and neprilysin have been associated with increased morbidity and mortality in chronic inflammatory disease and heart failure, but these biomarkers have been studied less in patients with ST segment elevation myocardial infarction (STEMI). We investigated the dynamic changes in these biomarkers, [...] Read more.
Pentraxin-3 (PTX3) and neprilysin have been associated with increased morbidity and mortality in chronic inflammatory disease and heart failure, but these biomarkers have been studied less in patients with ST segment elevation myocardial infarction (STEMI). We investigated the dynamic changes in these biomarkers, as well as the well-known C-reactive protein (CRP), in STEMI patients. PTX3, neprilysin and CRP were measured in samples from 165 STEMI patients, collected at the acute stage, 1–3 days after and 3 months after percutaneous coronary intervention (PCI), and from 40 healthy donors. Patient survival was followed for approximately 8 years after the PCI. As compared with samples from healthy donors, plasma levels of CRP and PTX3 were significantly increased in the acute samples and 1–3 days after PCI, but not at 3 months. CRP levels peaked at 1–3 days, while PTX3 was similarly high in both acute and 1–3 days samples. For neprilysin, no significant differences were observed at the group level. We found no significant differences when comparing patients with patent versus occluded culprit vessels or between patients having a thrombus aspiration or not. However, we found a significant reduction in survival for individuals with PTX3 above the median, both for samples collected at the acute stage and 1–3 days after PCI (p = 0.0001 and p = 0.0008, respectively). For CRP, no significant differences were observed using this approach, but patients above the reference range for healthy donors in the acute samples showed significantly lower survival (p = 0.0476). Conclusions: Survival analysis suggests that PTX3 might be a promising marker to predict mortality in this patient population. Full article
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16 pages, 8009 KiB  
Article
Micro-RNA 92a as a Therapeutic Target for Cardiac Microvascular Dysfunction in Diabetes
by Mostafa Samak, Diana Kaltenborn, Andreas Kues, Ferdinand Le Noble, Rabea Hinkel and Giulia Germena
Biomedicines 2022, 10(1), 58; https://doi.org/10.3390/biomedicines10010058 - 28 Dec 2021
Cited by 5 | Viewed by 1570
Abstract
Microvascular dysfunction is a pathological hallmark of diabetes, and is central to the ethology of diabetes-associated cardiac events. Herein, previous studies have highlighted the role of the vasoactive micro-RNA 92a (miR-92a) in small, as well as large, animal models. In this study, we [...] Read more.
Microvascular dysfunction is a pathological hallmark of diabetes, and is central to the ethology of diabetes-associated cardiac events. Herein, previous studies have highlighted the role of the vasoactive micro-RNA 92a (miR-92a) in small, as well as large, animal models. In this study, we explore the effects of miR-92a on mouse and human cardiac microvascular endothelial cells (MCMEC, HCMEC), and its underlying molecular mechanisms. Diabetic HCMEC displayed impaired angiogenesis and a pronounced inflammatory phenotype. Quantitative PCR (qPCR) showed an upregulation of miR-92a in primary diabetic HCMEC. Downregulation of miR-92a by antagomir transfection in diabetic HCMEC rescued angiogenesis and ameliorated diabetic endothelial bed inflammation. Furthermore, additional analysis of potential in silico-identified miR-92a targets in diabetic HCMEC revealed the miR-92a dependent downregulation of an essential metalloprotease, ADAM10. Accordingly, downregulation of ADAM10 impaired angiogenesis and wound healing in MCMEC. In myocardial tissue slices from diabetic pigs, ADAM10 dysregulation in micro- and macro-vasculature could be shown. Altogether, our data demonstrate the role of miR-92a in cardiac microvascular dysfunction and inflammation in diabetes. Moreover, we describe for the first time the metalloprotease ADAM10 as a novel miR-92a target, mediating its anti-angiogenic effect. Full article
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33 pages, 5974 KiB  
Article
miR-210 Regulates Apoptotic Cell Death during Cellular Hypoxia and Reoxygenation in a Diametrically Opposite Manner
by Gurdeep Marwarha, Øystein Røsand, Nathan Scrimgeour, Katrine Hordnes Slagsvold and Morten Andre Høydal
Biomedicines 2022, 10(1), 42; https://doi.org/10.3390/biomedicines10010042 - 25 Dec 2021
Cited by 6 | Viewed by 3104
Abstract
Apoptotic cell death of cardiomyocytes is a characteristic hallmark of ischemia–reperfusion (I/R) injury. The master hypoxamiR, microRNA-210 (miR-210), is considered the primary driver of the cellular response to hypoxic stress. However, to date, no consensus has emerged with regards to the polarity [...] Read more.
Apoptotic cell death of cardiomyocytes is a characteristic hallmark of ischemia–reperfusion (I/R) injury. The master hypoxamiR, microRNA-210 (miR-210), is considered the primary driver of the cellular response to hypoxic stress. However, to date, no consensus has emerged with regards to the polarity of the miR-210-elicited cellular response, as miR-210 has been shown to exacerbate as well as attenuate hypoxia-driven apoptotic cell death. Herein, in AC-16 cardiomyocytes subjected to hypoxia-reoxygenation (H-R) stress, we unravel novel facets of miR-210 biology and resolve the biological response mediated by miR-210 into the hypoxia and reoxygenation temporal components. Using transient overexpression and decoy/inhibition vectors to modulate miR-210 expression, we elucidated a Janus role miR-210 in the cellular response to H-R stress, wherein miR-210 mitigated the hypoxia-induced apoptotic cell death but exacerbated apoptotic cell death during cellular reoxygenation. We further delineated the underlying cellular mechanisms that confer this diametrically opposite effect of miR-210 on apoptotic cell death. Our exhaustive biochemical assays cogently demonstrate that miR-210 attenuates the hypoxia-driven intrinsic apoptosis pathway, while significantly augmenting the reoxygenation-induced caspase-8-mediated extrinsic apoptosis pathway. Our study is the first to unveil this Janus role of miR-210 and to substantiate the cellular mechanisms that underlie this functional duality. Full article
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11 pages, 276 KiB  
Article
Adherence to Antiplatelet Medications among Persistent and Non-Persistent Older Patients with Peripheral Arterial Disease
by Martin Wawruch, Jan Murin, Tomas Tesar, Martina Paduchova, Miriam Petrova, Denisa Celovska, Petra Matalova, Beata Havelkova, Michal Trnka and Emma Aarnio
Biomedicines 2021, 9(12), 1800; https://doi.org/10.3390/biomedicines9121800 - 30 Nov 2021
Cited by 3 | Viewed by 1549
Abstract
Secondary prevention of peripheral arterial disease (PAD) includes administration of antiplatelet agents, and adherence to medication is a requirement for an effective treatment. The aim of this study was to analyse adherence measured using the proportion of days covered (PDC) index separately in [...] Read more.
Secondary prevention of peripheral arterial disease (PAD) includes administration of antiplatelet agents, and adherence to medication is a requirement for an effective treatment. The aim of this study was to analyse adherence measured using the proportion of days covered (PDC) index separately in persistent and non-persistent patients, and to identify patient- and medication-related characteristics associated with non-adherence in these patient groups. The study cohort of 9178 patients aged ≥ 65 years in whom PAD was diagnosed in 1/–12/2012 included 6146 persistent and 3032 non-persistent patients. Non-adherence was identified as PDC < 80%. Characteristics associated with non-adherence were determined using the binary logistic regression model. In the group of persistent patients, 15.3% of subjects were identified as non-adherent, while among non-persistent patients, 26.9% of subjects were non-adherent to antiplatelet medication. Administration of dual antiplatelet therapy (aspirin and clopidogrel) and a general practitioner as index prescriber were associated with adherence in both patient groups. Our study revealed a relatively high proportion of adherent patients not only in the group of persistent patients but also in the group of non-persistent patients before discontinuation. These results indicate that most non-persistent PAD patients discontinue antiplatelet treatment rapidly after a certain period of adherence. Full article
16 pages, 4780 KiB  
Article
B Lymphocyte-Deficiency in Mice Causes Vascular Dysfunction by Inducing Neutrophilia
by Ning Xia, Solveig Hasselwander, Gisela Reifenberg, Alice Habermeier, Ellen I. Closs, Maximilian Mimmler, Rebecca Jung, Susanne Karbach, Jérémy Lagrange, Philip Wenzel, Andreas Daiber, Thomas Münzel, Nadine Hövelmeyer, Ari Waisman and Huige Li
Biomedicines 2021, 9(11), 1686; https://doi.org/10.3390/biomedicines9111686 - 14 Nov 2021
Cited by 5 | Viewed by 2133
Abstract
B lymphocytes have been implicated in the development of insulin resistance, atherosclerosis and certain types of hypertension. In contrast to these studies, which were performed under pathological conditions, the present study provides evidence for the protective effect of B lymphocytes in maintaining vascular [...] Read more.
B lymphocytes have been implicated in the development of insulin resistance, atherosclerosis and certain types of hypertension. In contrast to these studies, which were performed under pathological conditions, the present study provides evidence for the protective effect of B lymphocytes in maintaining vascular homeostasis under physiological conditions. In young mice not exposed to any known risk factors, the lack of B cells led to massive endothelial dysfunction. The vascular dysfunction in B cell-deficient mice was associated with an increased number of neutrophils in the circulating blood. Neutrophil depletion in B cell-deficient mice resulted in the complete normalization of vascular function, indicating a causal role of neutrophilia. Moreover, vascular function in B cell-deficient mice could be restored by adoptive transfer of naive B-1 cells isolated from wild-type mice. Interestingly, B-1 cell transfer also reduced the number of neutrophils in the recipient mice, further supporting the involvement of neutrophils in the vascular pathology caused by B cell-deficiency. In conclusion, we report in the present study the hitherto undescribed role of B lymphocytes in regulating vascular function. B cell dysregulation may represent a crucial mechanism in vascular pathology. Full article
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11 pages, 35493 KiB  
Article
CCR6 Deficiency Increases Infarct Size after Murine Acute Myocardial Infarction
by David Schumacher, Elisa A. Liehn, Anjana Singh, Adelina Curaj, Erwin Wijnands, Sergio A. Lira, Frank Tacke, Joachim Jankowski, Erik A.L. Biessen and Emiel P.C. van der Vorst
Biomedicines 2021, 9(11), 1532; https://doi.org/10.3390/biomedicines9111532 - 25 Oct 2021
Cited by 1 | Viewed by 1743
Abstract
Ischemia-reperfusion injury after the reopening of an occluded coronary artery is a major cause of cardiac damage and inflammation after acute myocardial infarction. The chemokine axis CCL20-CCR6 is a key player in various inflammatory processes, including atherosclerosis; however, its role in ischemia-reperfusion injury [...] Read more.
Ischemia-reperfusion injury after the reopening of an occluded coronary artery is a major cause of cardiac damage and inflammation after acute myocardial infarction. The chemokine axis CCL20-CCR6 is a key player in various inflammatory processes, including atherosclerosis; however, its role in ischemia-reperfusion injury has remained elusive. Therefore, to gain more insight into the role of the CCR6 in acute myocardial infarction, we have studied cardiac injury after transient ligation of the left anterior descending coronary artery followed by reperfusion in Ccr6−/− mice and their respective C57Bl/6 wild-type controls. Surprisingly, Ccr6−/− mice demonstrated significantly reduced cardiac function and increased infarct sizes after ischemia/reperfusion. This coincided with a significant increase in cardiac inflammation, characterized by an accumulation of neutrophils and inflammatory macrophage accumulation. Chimeras with a bone marrow deficiency of CCR6 mirrored this adverse Ccr6−/− phenotype, while cardiac injury was unchanged in chimeras with stromal CCR6 deficiency. This study demonstrates that CCR6-dependent (bone marrow) cells exert a protective role in myocardial infarction and subsequent ischemia-reperfusion injury, supporting the notion that augmenting CCR6-dependent immune mechanisms represents an interesting therapeutic target. Full article
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8 pages, 3284 KiB  
Article
Artificial Intelligence Identifies an Urgent Need for Peripheral Vascular Intervention by Multiplexing Standard Clinical Parameters
by Kristina Sonnenschein, Stevan D. Stojanović, Nicholas Dickel, Jan Fiedler, Johann Bauersachs, Thomas Thum, Meik Kunz and Jörn Tongers
Biomedicines 2021, 9(10), 1456; https://doi.org/10.3390/biomedicines9101456 - 13 Oct 2021
Cited by 8 | Viewed by 1671
Abstract
Background: Peripheral artery disease (PAD) is a significant burden, particularly among patients with severe disease requiring invasive treatment. We applied a general Machine Learning (ML) workflow and investigated if a multi-dimensional marker set of standard clinical parameters can identify patients in need of [...] Read more.
Background: Peripheral artery disease (PAD) is a significant burden, particularly among patients with severe disease requiring invasive treatment. We applied a general Machine Learning (ML) workflow and investigated if a multi-dimensional marker set of standard clinical parameters can identify patients in need of vascular intervention without specialized intra–hospital diagnostics. Methods: This is a retrospective study involving patients with stable PAD (sPAD, Fontaine Class I and II, n = 38) and unstable PAD (unPAD, Fontaine Class III and IV, n = 18) in need of invasive therapeutic measures. ML algorithms such as Random Forest were utilized to evaluate a matrix consisting of multiple routinely clinically available parameters (age, complete blood count, inflammation, lipid, iron metabolism). Results: ML has enabled a generation of an Artificial Intelligence (AI) PAD score (AI-PAD) that successfully divided sPAD from unPAD patients (high AI-PAD in sPAD, low AI-PAD in unPAD, cutoff at 50 AI-PAD units). Furthermore, the probability score positively coincided with gold-standard intra-hospital mean ankle-brachial index (ABI). Conclusion: AI-based tools may be promising to enable the correct identification of patients with unstable PAD by using existing clinical information, thus supplementing clinical decision making. Additional studies in larger prospective cohorts are necessary to determine the usefulness of this approach in comparison to standard diagnostic measures. Full article
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11 pages, 572 KiB  
Article
The Prognostic Impact of Estimated Creatinine Clearance by Bioelectrical Impedance Analysis in Heart Failure: Comparison of Different eGFR Formulas
by Pietro Scicchitano, Massimo Iacoviello, Andrea Passantino, Piero Guida, Micaela De Palo, Assunta Piscopo, Michele Gesualdo, Pasquale Caldarola and Francesco Massari
Biomedicines 2021, 9(10), 1307; https://doi.org/10.3390/biomedicines9101307 - 24 Sep 2021
Cited by 7 | Viewed by 1902
Abstract
The estimation of glomerular filtration rate (eGFR) provides prognostic information in patients with heart failure (HF). Bioelectrical impedance analysis may calculate eGFR (Donadio formula). The aim of this study was to evaluate the impact of the Donadio formula in predicting all-cause mortality in [...] Read more.
The estimation of glomerular filtration rate (eGFR) provides prognostic information in patients with heart failure (HF). Bioelectrical impedance analysis may calculate eGFR (Donadio formula). The aim of this study was to evaluate the impact of the Donadio formula in predicting all-cause mortality in patients with HF as compared to Cockroft-Gault, MDRD-4 (Modification of Diet in renal Disease Study), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. Four-hundred thirty-six subjects with HF (52% men; mean age 75 ± 11 years; 42% acute HF) were enrolled. Ninety-two patients (21%) died during the follow-up (median 463 days, IQR 287–669). The area under the receiver operator characteristic curve for eGFR, as estimated by Cockroft-Gault formula (AUC = 0.75), was significantly higher than those derived from Donadio (AUC = 0.72), MDRD-4 (AUC = 0.68), and CKD-EPI (AUC = 0.71) formulas. At multivariate analysis, all eGFR formulas were independent predictors of death; 1 mL/min/1.73 m2 increase in eGFR—as measured by Cockroft-Gault, Donadio, MDRD-4, and CKD-EPI formulas—provided a 2.6%, 1.5%, 1.2%, and 1.6% increase, respectively, in mortality rate. Conclusions. eGFR, as calculated with the Donadio formula, was an independent predictor of mortality in patients with HF as well as the measurements derived from MDRD4 and CKD-EPI formulas, but less accurate than Cockroft-Gault. Full article
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12 pages, 1121 KiB  
Article
Reinitiation and Subsequent Discontinuation of Antiplatelet Treatment in Nonpersistent Older Patients with Peripheral Arterial Disease
by Martin Wawruch, Jan Murin, Tomas Tesar, Martina Paduchova, Miriam Petrova, Denisa Celovska, Beata Havelkova, Michal Trnka and Emma Aarnio
Biomedicines 2021, 9(9), 1280; https://doi.org/10.3390/biomedicines9091280 - 21 Sep 2021
Cited by 3 | Viewed by 2039
Abstract
The successful treatment of peripheral arterial disease (PAD) depends on adequate adherence to medications including antiplatelet agents. The aims of this study were (a) to identify the proportion of nonpersistent patients who reinitiated antiplatelet therapy and how many of them discontinued therapy after [...] Read more.
The successful treatment of peripheral arterial disease (PAD) depends on adequate adherence to medications including antiplatelet agents. The aims of this study were (a) to identify the proportion of nonpersistent patients who reinitiated antiplatelet therapy and how many of them discontinued therapy after reinitiation, and (b) to identify patient- and medication-related characteristics associated with the likelihood of reinitiation and discontinuation among reinitiators. The analysis of reinitiation was conducted on 3032 nonpersistent users of antiplatelet agents aged ≥65 years, with PAD newly diagnosed in 2012. Discontinuation (i.e., a treatment gap of ≥6 months without antiplatelet medication prescription) was analysed in 2006 reinitiating patients. To identify factors associated with the likelihood of reinitiation and discontinuation, Cox regression with time-dependent covariates was used. Reinitiation was recorded in 2006 (66.2%) of 3032 patients who had discontinued antiplatelet medication. Among these 2006 reinitiators, 1078 (53.7%) patients discontinued antiplatelet therapy again. Ischemic stroke and myocardial infarction during nonpersistence and bronchial asthma/chronic obstructive pulmonary disease were associated with an increased likelihood of reinitiation. University education was associated with discontinuation among reinitiators. Factors associated with the probability of reinitiation and discontinuation in reinitiators make it possible to identify older PAD patients in whom “stop-starting” behaviour may be expected. Full article
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19 pages, 2440 KiB  
Article
Overexpression of Neuron-Derived Orphan Receptor 1 (NOR-1) Rescues Cardiomyocytes from Cell Death and Improves Viability after Doxorubicin Induced Stress
by Per-Christian Berg, Åse Mari Larsen Hansson, Øystein Røsand, Gurdeep Marwarha and Morten Andre Høydal
Biomedicines 2021, 9(9), 1233; https://doi.org/10.3390/biomedicines9091233 - 16 Sep 2021
Cited by 3 | Viewed by 4427
Abstract
Following myocardial infarction, reperfusion injury (RI) is commonly observed due to the excessive formation of, e.g., reactive oxygen species (ROS). Doxorubicin (DOX), a widely used anti-cancer drug, is also known to cause cardiotoxicity due to excessive ROS production. Exercise training has been shown [...] Read more.
Following myocardial infarction, reperfusion injury (RI) is commonly observed due to the excessive formation of, e.g., reactive oxygen species (ROS). Doxorubicin (DOX), a widely used anti-cancer drug, is also known to cause cardiotoxicity due to excessive ROS production. Exercise training has been shown to protect the heart against both RI- and DOX-induced cardiotoxicity, but the exact mechanism is still unknown. Neuron-derived orphan receptor 1 (NOR-1) is an important exercise-responsive protein in the skeletal muscle which has also been reported to facilitate cellular survival during hypoxia. Therefore, we hypothesized that NOR-1 could protect cardiomyocytes (CMs) against cellular stress induced by DOX. We also hypothesized that NOR-1 is involved in preparing the CMs against a stress situation during nonstimulated conditions by increasing cell viability. To determine the protective effect of NOR-1 in CMs stressed with DOX challenge, we overexpressed NOR-1 in AC16 human CMs treated with 5 µM DOX for 12 h or the respective vehicle control, followed by performing Lactate dehydrogenase (LDH) activity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and caspase-3 activity assays to measure cell death, cell viability, and apoptosis, respectively. In addition, Western blotting analysis was performed to determine the expression of key proteins involved in cardioprotection. We demonstrated that NOR-1 overexpression decreased cell death (p < 0.105) and apoptosis (p < 0.01) while increasing cell viability (p < 0.05) in DOX-treated CMs. We also observed that NOR-1 overexpression increased phosphorylation of extracellular signal-regulated kinase (ERK) (p < 0.01) and protein expression levels of B cell lymphoma extra-large (Bcl-xL) (p < 0.01). We did not detect any significant changes in phosphorylation of protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β) and signal transducer and activator of transcription 3 (STAT3) or expression levels of superoxide dismutase 2 (SOD2) and cyclin D1. Furthermore, we demonstrated that NOR-1 overexpression increased the cell viability (p < 0.0001) of CMs during nonstimulated conditions without affecting cell death or apoptosis. Our findings indicate that NOR-1 could serve as a potential cardioprotective protein in response to Doxorubicin-induced cellular stress. Full article
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21 pages, 4947 KiB  
Article
The Cholinergic Anti-Inflammatory Pathway Attenuates the Development of Atherosclerosis in Apoe-/- Mice through Modulating Macrophage Functions
by Zhengjiang Qian, Haiyang Yang, Hongchao Li, Chunhua Liu, Liang Yang, Zehui Qu and Xiang Li
Biomedicines 2021, 9(9), 1150; https://doi.org/10.3390/biomedicines9091150 - 03 Sep 2021
Cited by 6 | Viewed by 2912
Abstract
(1) Background: The cholinergic anti-inflammatory pathway (CAP) has been implicated in the regulation of various diseases, including chronic inflammatory cardiovascular disorders such as atherosclerosis (AS). This study aims to explore the underlying regulatory mechanisms of CAP activity in the progression of AS. (2) [...] Read more.
(1) Background: The cholinergic anti-inflammatory pathway (CAP) has been implicated in the regulation of various diseases, including chronic inflammatory cardiovascular disorders such as atherosclerosis (AS). This study aims to explore the underlying regulatory mechanisms of CAP activity in the progression of AS. (2) Methods: The Apoe-/- mice were subjected to sham, bilateral cervical vagotomy surgery (VGX), and VGX supplemented with Gainesville Tokushima scientists (GTS)-21 (4 mg/kg/d) and then fed with a high-fat diet for 10 weeks. Atherosclerotic lesion size and inflammation levels were investigated by histology and inflammatory cytokines analysis. The blood M1/M2 macrophages were analyzed by flow cytometry. Primary mouse bone marrow-derived macrophages (BMDM), peritoneal macrophages, and RAW264.7 cells were treated with CAP agonists acetylcholine (Ach) and GTS-21 to study their effects on macrophage functions. (3) Results: Compared with the sham group, inhibition of CAP by the VGX resulted in growing aortic lipid plaque area, deteriorated inflammatory levels, and aberrant quantity of M1/M2 macrophages in Apoe-/- mice. However, these detrimental effects of VGX were significantly ameliorated by the reactivation of CAP through GTS-21 treatment. The in vitro study using macrophages revealed that stimulation with CAP agonists suppressed M1, but promoted M2 macrophage polarization through the upregulation of TNFAIP3 and phosphorylation STAT3 levels, respectively. Moreover, the activation of CAP inhibited the formation of macrophage foam cells in the peritoneal cavity by regulating genes related to cholesterol metabolism. (4) Conclusions: This study provides novel evidence and mechanisms that the CAP plays an important role in the regulation of AS development by controlling macrophage functions, implying a potential use of CAP activation as a therapeutic strategy for AS treatment. Full article
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24 pages, 1057 KiB  
Article
Postnatal Expression Profile of MicroRNAs Associated with Cardiovascular Diseases in 3- to 11-Year-Old Preterm-Born Children
by Ilona Hromadnikova, Katerina Kotlabova, Ladislav Krofta and Jan Sirc
Biomedicines 2021, 9(7), 727; https://doi.org/10.3390/biomedicines9070727 - 24 Jun 2021
Cited by 1 | Viewed by 1752
Abstract
(1) Background: Preterm-born children have an increased cardiovascular risk with the first clinical manifestation during childhood and/or adolescence. (2) Methods: The occurrence of overweight/obesity, prehypertension/hypertension, valve problems or heart defects, and postnatal microRNA expression profiles were examined in preterm-born children at the age [...] Read more.
(1) Background: Preterm-born children have an increased cardiovascular risk with the first clinical manifestation during childhood and/or adolescence. (2) Methods: The occurrence of overweight/obesity, prehypertension/hypertension, valve problems or heart defects, and postnatal microRNA expression profiles were examined in preterm-born children at the age of 3 to 11 years descending from preterm prelabor rupture of membranes (PPROM) and spontaneous preterm birth (PTB) pregnancies. The whole peripheral blood gene expression of 29 selected microRNAs associated with cardiovascular diseases was the subject of our interest. (3) Results: Nearly one-third of preterm-born children (32.43%) had valve problems and/or heart defects. The occurrence of systolic and diastolic prehypertension/hypertension was also inconsiderable in a group of preterm-born children (27.03% and 18.92%). The vast majority of children descending from either PPROM (85.45%) or PTB pregnancies (85.71%) had also significantly altered microRNA expression profiles at 90.0% specificity. (4) Conclusions: Postnatal microRNA expression profiles were significantly influenced by antenatal and early postnatal factors (gestational age at delivery, birth weight of newborns, and condition of newborns at the moment of birth). These findings may contribute to the explanation of increased cardiovascular risk in preterm-born children. These findings strongly support the belief that preterm-born children should be dispensarized for a long time to have access to specialized medical care. Full article
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Review

Jump to: Research, Other

16 pages, 1557 KiB  
Review
Strategies for Sudden Cardiac Death Prevention
by Mattia Corianò and Francesco Tona
Biomedicines 2022, 10(3), 639; https://doi.org/10.3390/biomedicines10030639 - 10 Mar 2022
Cited by 4 | Viewed by 2471
Abstract
Sudden cardiac death (SCD) represents a major challenge in modern medicine. The prevention of SCD orbits on two levels, the general population level and individual level. Much research has been done with the aim to improve risk stratification of SCD, although no radical [...] Read more.
Sudden cardiac death (SCD) represents a major challenge in modern medicine. The prevention of SCD orbits on two levels, the general population level and individual level. Much research has been done with the aim to improve risk stratification of SCD, although no radical changes in evidence and in therapeutic strategy have been achieved. Artificial intelligence (AI), and in particular machine learning (ML) models, represent novel technologic tools that promise to improve predictive ability of fatal arrhythmic events. In this review, firstly, we analyzed the electrophysiological basis and the major clues of SCD prevention at population and individual level; secondly, we reviewed the main research where ML models were used for risk stratification in other field of cardiology, suggesting its potentiality in the field of SCD prevention. Full article
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28 pages, 12140 KiB  
Review
Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population
by Estefanía Martínez-Barrios, Sergi Cesar, José Cruzalegui, Clara Hernandez, Elena Arbelo, Victoria Fiol, Josep Brugada, Ramon Brugada, Oscar Campuzano and Georgia Sarquella-Brugada
Biomedicines 2022, 10(1), 106; https://doi.org/10.3390/biomedicines10010106 - 05 Jan 2022
Cited by 9 | Viewed by 2753
Abstract
Sudden death is a rare event in the pediatric population but with a social shock due to its presentation as the first symptom in previously healthy children. Comprehensive autopsy in pediatric cases identify an inconclusive cause in 40–50% of cases. In such cases, [...] Read more.
Sudden death is a rare event in the pediatric population but with a social shock due to its presentation as the first symptom in previously healthy children. Comprehensive autopsy in pediatric cases identify an inconclusive cause in 40–50% of cases. In such cases, a diagnosis of sudden arrhythmic death syndrome is suggested as the main potential cause of death. Molecular autopsy identifies nearly 30% of cases under 16 years of age carrying a pathogenic/potentially pathogenic alteration in genes associated with any inherited arrhythmogenic disease. In the last few years, despite the increasing rate of post-mortem genetic diagnosis, many families still remain without a conclusive genetic cause of the unexpected death. Current challenges in genetic diagnosis are the establishment of a correct genotype–phenotype association between genes and inherited arrhythmogenic disease, as well as the classification of variants of uncertain significance. In this review, we provide an update on the state of the art in the genetic diagnosis of inherited arrhythmogenic disease in the pediatric population. We focus on emerging publications on gene curation for genotype–phenotype associations, cases of genetic overlap and advances in the classification of variants of uncertain significance. Our goal is to facilitate the translation of genetic diagnosis to the clinical area, helping risk stratification, treatment and the genetic counselling of families. Full article
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19 pages, 720 KiB  
Review
Vasomotor Dysfunction in Patients with Ischemia and Non-Obstructive Coronary Artery Disease: Current Diagnostic and Therapeutic Strategies
by Amr Abouelnour and Tommaso Gori
Biomedicines 2021, 9(12), 1774; https://doi.org/10.3390/biomedicines9121774 - 26 Nov 2021
Cited by 2 | Viewed by 2299
Abstract
Many patients who present with symptoms or objective evidence of ischemia have no or non-physiologically-significant disease on invasive coronary angiography. The diagnosis of ischemic heart disease is thus often dismissed, and patients receive false reassurance or other diagnoses are pursued. We now know [...] Read more.
Many patients who present with symptoms or objective evidence of ischemia have no or non-physiologically-significant disease on invasive coronary angiography. The diagnosis of ischemic heart disease is thus often dismissed, and patients receive false reassurance or other diagnoses are pursued. We now know that a significant proportion of these patients have coronary microvascular dysfunction and/or vasospastic disease as the underlying pathophysiology of their clinical presentation. Making the correct diagnosis of such abnormalities is important not only because they impact the quality of life, with recurring symptoms and unnecessary repeated testing, but also because they increase the risk for adverse cardiovascular events. The mainstay of diagnosis remains an invasive comprehensive physiologic assessment, which further allows stratifying these patients into appropriate “endotypes”. It has been shown that tailoring treatment to the patient’s assigned endotype improves symptoms and quality of life. In addition to the conventional drugs used in chronic stable angina, multiple newer agents are being investigated. Moreover, innovative non-pharmacologic and interventional therapies are emerging to provide a bail-out in refractory cases. Many of these novel therapies fail to show consistent benefits, but others show quite promising results. Full article
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29 pages, 1392 KiB  
Review
COVID-19: The Impact on Cardiovascular System
by Jozica Šikić, Zrinka Planinić, Vid Matišić, Tea Friščić, Vilim Molnar, Dorijan Jagačić, Lovro Vujičić, Neven Tudorić, Lana Postružin Gršić, Đivo Ljubičić and Dragan Primorac
Biomedicines 2021, 9(11), 1691; https://doi.org/10.3390/biomedicines9111691 - 15 Nov 2021
Cited by 5 | Viewed by 3891
Abstract
SARS-CoV-2 has been circulating in population worldwide for the past year and a half, and thus a vast amount of scientific literature has been produced in order to study the biology of the virus and the pathophysiology of COVID-19, as well as to [...] Read more.
SARS-CoV-2 has been circulating in population worldwide for the past year and a half, and thus a vast amount of scientific literature has been produced in order to study the biology of the virus and the pathophysiology of COVID-19, as well as to determine the best way to prevent infection, treat the patients and eliminate the virus. SARS-CoV-2 binding to the ACE2 receptor is the key initiator of COVID-19. The ability of SARS-CoV-2 to infect various types of cells requires special attention to be given to the cardiovascular system, as it is commonly affected. Thorough diagnostics and patient monitoring are beneficial in reducing the risk of cardiovascular morbidity and to ensure the most favorable outcomes for the infected patients, even after they are cured of the acute disease. The multidisciplinary nature of the fight against the COVID-19 pandemic requires careful consideration from the attending clinicians, in order to provide fast and reliable treatment to their patients in accordance with evidence-based medicine principles. In this narrative review, we reviewed the available literature on cardiovascular implications of COVID-19; both the acute and the chronic. Full article
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22 pages, 1755 KiB  
Review
The Evolution of Safe and Effective Coaguligands for Vascular Targeting and Precision Thrombosis of Solid Tumors and Vascular Malformations
by Fahimeh Faqihi, Marcus A. Stoodley and Lucinda S. McRobb
Biomedicines 2021, 9(7), 776; https://doi.org/10.3390/biomedicines9070776 - 04 Jul 2021
Cited by 2 | Viewed by 2535
Abstract
In cardiovascular and cerebrovascular biology, control of thrombosis and the coagulation cascade in ischemic stroke, myocardial infarction, and other coagulopathies is the focus of significant research around the world. Ischemic stroke remains one of the largest causes of death and disability in developed [...] Read more.
In cardiovascular and cerebrovascular biology, control of thrombosis and the coagulation cascade in ischemic stroke, myocardial infarction, and other coagulopathies is the focus of significant research around the world. Ischemic stroke remains one of the largest causes of death and disability in developed countries. Preventing thrombosis and protecting vessel patency is the primary goal. However, utilization of the body’s natural coagulation cascades as an approach for targeted destruction of abnormal, disease-associated vessels and tissues has been increasing over the last 30 years. This vascular targeting approach, often termed “vascular infarction”, describes the deliberate, targeted delivery of a thrombogenic effector to diseased blood vessels with the aim to induce localized activation of the coagulation cascade and stable thrombus formation, leading to vessel occlusion and ablation. As systemic delivery of pro-thrombotic agents may cause consternation amongst traditional stroke researchers, proponents of the approach must suitably establish both efficacy and safety to take this field forward. In this review, we describe the evolution of this field and, with a focus on thrombogenic effectors, summarize the current literature with respect to emerging trends in “coaguligand” development, in targeted tumor vessel destruction, and in expansion of the approach to the treatment of brain vascular malformations. Full article
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19 pages, 10393 KiB  
Review
Primary Soft Tissue Sarcoma of the Heart: An Emerging Chapter in Cardio-Oncology
by Pietro Scicchitano, Maria Chiara Sergi, Matteo Cameli, Marcelo H. Miglioranza, Marco Matteo Ciccone, Marica Gentile, Camillo Porta and Marco Tucci
Biomedicines 2021, 9(7), 774; https://doi.org/10.3390/biomedicines9070774 - 03 Jul 2021
Cited by 9 | Viewed by 2910
Abstract
Primary malignant cardiac tumors are rare, with a prevalence of about 0.01% among all cancer histotypes. At least 60% of them are primary soft tissue sarcomas of the heart (pSTS-h) that represent almost 1% of all STSs. The cardiac site of origin is [...] Read more.
Primary malignant cardiac tumors are rare, with a prevalence of about 0.01% among all cancer histotypes. At least 60% of them are primary soft tissue sarcomas of the heart (pSTS-h) that represent almost 1% of all STSs. The cardiac site of origin is the best way to classify pSTS-h as it is directly linked to the surgical approach for cancer removal. Indeed, histological differentiation should integrate the classification to provide insights into prognosis and survival expectancy of the patients. The prognosis of pSTS-h is severe and mostly influenced by the primary localization of the tumor, the difficulty in achieving complete surgical and pharmacological eradication, and the aggressive biological features of malignant cells. This review aims to provide a detailed literature overview of the most relevant issues on primary soft tissue sarcoma of the heart and highlight potential diagnostic and therapeutic future perspectives. Full article
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19 pages, 1020 KiB  
Review
Sugar Fructose Triggers Gut Dysbiosis and Metabolic Inflammation with Cardiac Arrhythmogenesis
by Wan-Li Cheng, Shao-Jung Li, Ting-I Lee, Ting-Wei Lee, Cheng-Chih Chung, Yu-Hsun Kao and Yi-Jen Chen
Biomedicines 2021, 9(7), 728; https://doi.org/10.3390/biomedicines9070728 - 25 Jun 2021
Cited by 19 | Viewed by 4367
Abstract
Fructose is a main dietary sugar involved in the excess sugar intake-mediated progression of cardiovascular diseases and cardiac arrhythmias. Chronic intake of fructose has been the focus on the possible contributor to the metabolic diseases and cardiac inflammation. Recently, the small intestine was [...] Read more.
Fructose is a main dietary sugar involved in the excess sugar intake-mediated progression of cardiovascular diseases and cardiac arrhythmias. Chronic intake of fructose has been the focus on the possible contributor to the metabolic diseases and cardiac inflammation. Recently, the small intestine was identified to be a major organ in fructose metabolism. The overconsumption of fructose induces dysbiosis of the gut microbiota, which, in turn, increases intestinal permeability and activates host inflammation. Endotoxins and metabolites of the gut microbiota, such as lipopolysaccharide, trimethylamine N-oxide, and short-chain fatty acids, also influence the host inflammation and cardiac biofunctions. Thus, high-fructose diets cause heart–gut axis disorders that promote cardiac arrhythmia. Understanding how gut microbiota dysbiosis-mediated inflammation influences the pathogenesis of cardiac arrhythmia may provide mechanisms for cardiac arrhythmogenesis. This narrative review updates our current understanding of the roles of excessive intake of fructose on the heart-gut axis and proposes potential strategies for inflammation-associated cardiac vascular diseases. Full article
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Other

Jump to: Research, Review

22 pages, 3316 KiB  
Systematic Review
Stereotactic Arrhythmia Radioablation as a Novel Treatment Approach for Cardiac Arrhythmias: Facts and Limitations
by Marina Chalkia, Vassilis Kouloulias, Dimitris Tousoulis, Spyridon Deftereos, Dimitris Tsiachris, Dimitrios Vrachatis and Kalliopi Platoni
Biomedicines 2021, 9(10), 1461; https://doi.org/10.3390/biomedicines9101461 - 13 Oct 2021
Cited by 2 | Viewed by 2685
Abstract
Stereotactic ablative radiotherapy (SABR) is highly focused radiation therapy that targets well-demarcated, limited-volume malignant or benign tumors with high accuracy and precision using image guidance. Stereotactic arrhythmia radioablation (STAR) applies SABR to treat cardiac arrhythmias, including ventricular tachycardia (VT) and atrial fibrillation (AF), [...] Read more.
Stereotactic ablative radiotherapy (SABR) is highly focused radiation therapy that targets well-demarcated, limited-volume malignant or benign tumors with high accuracy and precision using image guidance. Stereotactic arrhythmia radioablation (STAR) applies SABR to treat cardiac arrhythmias, including ventricular tachycardia (VT) and atrial fibrillation (AF), and has recently been a focus in research. Clinical studies have demonstrated electrophysiologic conduction blockade and histologic fibrosis after STAR, which provides a proof of principle for its potential for treating arrhythmias. This review will present the basic STAR principles, available clinical study outcomes, and how the technique has evolved since the first pre-clinical study. In addition to the clinical workflow, focus will be given on the process for stereotactic radiotherapy Quality Assurance (QA) tests, as well as the need for establishing a standardized QA protocol. Future implications and potential courses of research will also be discussed. Full article
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