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

Backgrounds: Reducing radiation exposure is the basic principle for performing percutaneous coronary intervention (PCI). Many studies have confirmed the effect of radiation protection for medical staff, but studies about the effectiveness of protection for patients and real measurement of radiation dose in patients’ specific organs are lacking. Aim: To measure the radiation doses absorbed by patients’ radiosensitive organs during PCI and the effectiveness of radiation protection. Methods: A total of 120 patients were included and allocated into three groups as the ratio of 1:1:2. A total of 30 patients received PCI at 15 frames rate per second (fps), 30 patients at 7.5 fps, and 60 patients wore radiation protective hat and glasses during PCI at 7.5 fps. The radiation doses were measured at right eyebrow (lens), neck (thyroid), back (skin), and inguinal area (genital organs) by using thermoluminescent dosimeters (TLDs). Results: Dose-area product (DAP) reduced by 58.8% (from 534,454 ± 344,660 to 220,352 ± 164,101 mGy·cm², p < 0.001) after reducing the frame rate, without affecting successful rate of PCI. Radiation doses measured on skin, lens, genital organs, and thyroid decreased by 73.3%, 40.0%, 40.0%, and 35.3%, respectively (from 192.58 ± 349.45 to 51.10 ± 59.21; 5.29 ± 4.27 to 3.16 ± 2.73; 0.25 ± 0.15 to 0.15 ± 0.15; and 17.42 ± 12.11 to 11.27 ± 8.52 μSv, p < 0.05). By providing radiation protective equipment, radiation doses at lens and thyroid decreased further by 71.8% and 65.9% (from 3.16 ± 2.73 to 0.89 ± 0.79; 11.27 ± 8.52 to 3.84 ± 3.49 μSv, p < 0.05). Conclusions: By lowering the frame rate and providing protective equipment, radiation exposure in radiosensitive organs can be effectively reduced in patients. Full article

Collagen fibers are essential structural components of mitral valve leaflets, their tension apparatus (chordae tendineae), and the associated papillary muscles. Excess or lack of collagen fibers in the extracellular matrix (ECM) in any of these structures can adversely affect mitral valve function. The organization of collagen fibers provides a sophisticated framework that allows for unidirectional blood flow during the precise opening and closing of this vital heart valve. Although numerous ECM molecules are essential for the differentiation, growth, and homeostasis of the mitral valve (e.g., elastic fibers, glycoproteins, and glycans), collagen fibers are key to mitral valve integrity. Besides the inert structural components of the tissues, collagen fibers are dynamic structures that drive outside-to-inside cell signaling, which informs valvular interstitial cells (VICs) present within the tissue environment. Diversity of collagen family members and the closely related collagen-like triple helix-containing proteins found in the mitral valve, will be discussed in addition to how defects in these proteins may lead to valve disease. Full article

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

Maintaining optimal low-density lipoprotein (LDL) cholesterol levels is necessary to prevent cardiovascular disease (CVD). Excessive fat mass and decreased muscle mass are both associated with increased risks of developing dyslipidemia. Thus, we investigated the longitudinal relationship between the fat-to-muscle ratio (FMR) and the non-achievement of LDL cholesterol targets. We analyzed a total of 4386 participants aged 40–69 years from the Korean Genome and Epidemiology Study. FMR was defined as the ratio of total fat mass to total muscle mass, measured by bioelectrical impedance. The non-achievement of an LDL cholesterol target was defined as an LDL cholesterol level higher than the established target level according to individual CVD risk. The adjusted hazard ratios and 95% confidence interval for the incidence of non-achievement of LDL cholesterol targets for the sex-specific middle and highest tertiles vs. the referent lowest tertile of FMR were 1.56 (1.29–1.90) and 1.86 (1.47–2.31) in men and 1.40 (1.18–1.66) and 1.31 (1.06–1.62) in women after adjusting confounders. Our findings suggest that FMR, a novel indicator of the combined effects of fat and muscle mass, is useful for predicting non-achievement of LDL cholesterol targets. Full article

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

This systematic review was conducted in accordance with the PRISMA guidelines to summarize the existing literature on the effects of different exercise interventions on cardiac autonomic control and secondary health factors. Resting heart rate variability (HRV) was used as indicator of cardiac autonomic control. Secondary factors were related to factors that contribute to cardiovascular health. Studies examining the effects of endurance, resistance, multimodal, or coordinative training interventions in healthy participants aged between 45 and 60 years old on average were considered. The methodological quality of the studies was examined using two assessment scales (TESTEX and STARD_HRV). PROSPERO registration number: CRD42020206606. The literature review retrieved eight studies fulfilling all inclusion criteria. Cardiac autonomic control and cardiovascular health improved after endurance and multimodal interventions. Resistance training had no significant impact on HRV or any secondary health factor. Coordinative exercise interventions showed inconclusive results regarding HRV but showed significant improvements in secondary health factors. The quality assessment tools revealed some methodological and reporting deficits. Despite the small number of studies, we suggest endurance and multimodal interventions including aerobic exercises for the enhancement of cardiac autonomic control and the reduction of cardiovascular risk in middle-aged adults. Further studies need to be conducted to examine the long-term effects of exercise in the midlife period. Full article

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

A bicuspid aortic valve (BAV) is the most common cardiac malformation, found in 0.5% to 2% of the population. BAVs are present in approximately 50% of patients with severe aortic stenosis and are an independent risk factor for aortic aneurysms. Currently, there are no therapeutics to treat BAV, and the human mutations identified to date represent a relatively small number of BAV patients. However, the discovery of BAV in an increasing number of genetically modified mice is advancing our understanding of molecular pathways that contribute to BAV formation. In this study, we utilized the comparison of BAV phenotypic characteristics between murine models as a tool to advance our understanding of BAV formation. The collation of murine BAV data indicated that excess versican within the provisional extracellular matrix (P-ECM) is a common factor in BAV development. While the percentage of BAVs is low in many of the murine BAV models, the remaining mutant mice exhibit larger and more amorphous tricuspid AoVs, also with excess P-ECM compared to littermates. The identification of common molecular characteristics among murine BAV models may lead to BAV therapeutic targets and biomarkers of disease progression for this highly prevalent and heterogeneous cardiovascular malformation. Full article

We report five cases of sudden intrauterine death due to premature closure of the ductus arteriosus. In four cases, this was caused by dissecting the hematoma of the ductus arteriosus with intimal flap and obliteration of the lumen. In one case, the ductus arteriosus was aneurysmatic, with lumen occlusion caused by thrombus stratification. No drug therapy or free medication consumption were reported during pregnancy. The time of stillbirth ranged between 26 and 33 gestational weeks. We performed TUNEL analysis for apoptosis quantification. The dissecting features were intimal tears with flap formation in four of the cases, just above the origin of the ductus arteriosus from the pulmonary artery. The dissecting hematoma of the ductus arteriosus extended downward to the descending aorta and backward to the aortic arch with involvement of the left carotid and left subclavian arteries. TUNEL analysis showed a high number of apoptotic smooth muscle cells in the media in two cases. Abnormal ductal remodeling with absence of subintimal cushions, lacunar spaces rich in glycosaminoglycans (cystic medial necrosis), and smooth muscle cell apoptosis were the pathological substrates accounting for failure of remodeling process and dissection. Full article

In congenital heart disease, the presence of structural defects affects blood flow in the heart and circulation. However, because the fetal circulation bypasses the lungs, fetuses with cyanotic heart defects can survive in utero but need prompt intervention to survive after birth. Tetralogy of Fallot and persistent truncus arteriosus are two of the most significant conotruncal heart defects. In both defects, blood access to the lungs is restricted or non-existent, and babies with these critical conditions need intervention right after birth. While there are known genetic mutations that lead to these critical heart defects, early perturbations in blood flow can independently lead to critical heart defects. In this paper, we start by comparing the fetal circulation with the neonatal and adult circulation, and reviewing how altered fetal blood flow can be used as a diagnostic tool to plan interventions. We then look at known factors that lead to tetralogy of Fallot and persistent truncus arteriosus: namely early perturbations in blood flow and mutations within VEGF-related pathways. The interplay between physical and genetic factors means that any one alteration can cause significant disruptions during development and underscore our need to better understand the effects of both blood flow and flow-responsive genes. Full article

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

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

Induction of cardiomyocyte proliferation is a promising option to regenerate the heart. Thus, it is important to elucidate mechanisms that contribute to the cell cycle arrest of mammalian cardiomyocytes. Here, we assessed the contribution of the pericentrin (Pcnt) S isoform to cell cycle arrest in postnatal cardiomyocytes. Immunofluorescence staining of Pcnt isoforms combined with SiRNA-mediated depletion indicates that Pcnt S preferentially localizes to the nuclear envelope, while the Pcnt B isoform is enriched at centrosomes. This is further supported by the localization of ectopically expressed FLAG-tagged Pcnt S and Pcnt B in postnatal cardiomyocytes. Analysis of centriole configuration upon Pcnt depletion revealed that Pcnt B but not Pcnt S is required for centriole cohesion. Importantly, ectopic expression of Pcnt S induced centriole splitting in a heterologous system, ARPE-19 cells, and was sufficient to impair DNA synthesis in C2C12 myoblasts. Moreover, Pcnt S depletion enhanced serum-induced cell cycle re-entry in postnatal cardiomyocytes. Analysis of mitosis, binucleation rate, and cell number suggests that Pcnt S depletion enhances serum-induced progression of postnatal cardiomyocytes through the cell cycle resulting in cell division. Collectively, our data indicate that alternative splicing of Pcnt contributes to the establishment of cardiomyocyte cell cycle arrest shortly after birth. Full article

Total arch replacement remains a very demanding surgical procedure. It can be associated with reasonable long-term outcomes but carries serious perioperative complications. Aortic arch surgery has progressed in recent years to a wider adoption of reproducible and reliable techniques. Conventional open, surgical aortic arch replacement is currently offered to the majority of patients, although hybrid and wholly endovascular techniques are gaining popularity. With regards to open arch replacement, the nuances of surgical technique, the mode of cannulation and the optimal cerebral protection protocols remain a matter of debate. We propose an alternative cannulation approach facilitated by the cooperation between cardiac and vascular surgeons. A three-way arterial cannulation including both carotid arteries and the femoral artery (or ascending aorta) is the key feature of this approach. A case series of complex patients is presented to show both the feasibility and relative safety of a standardised new approach with a 100% technical success rate and a 16% 30-day mortality. The three-way cannulation approach may have a role to play for complex and extensive procedures requiring prolonged cerebral protection. We believe that a shared skill set from cardiac and vascular specialists is essential for the safe management and successful outcomes using this adaptive technique. Full article

Background: Vitamin D supplementation may be associated with lower cardiovascular (CV) events, but the data are controversial. It remains speculative whether vitamin D supplementation has a direct effect on coronary atherosclerosis. We therefore set out to assess the influence of vitamin D supplementation on the coronary atherosclerosis profile quantified by coronary computed tomography angiography (CTA) in a retrospective case–control cohort study. Methods: 176 patients (age: 62.4 ± 10.4) referred to coronary CTA for clinical indications were included. A total of 88 patients receiving vitamin D supplementation (mean duration 65.3 ± 81 months) were 1:1 propensity score matched with 88 controls for age, gender, smoking, arterial hypertension, positive family history, dyslipidemia, and diabetes. Coronary stenosis severity (CAD-RADS^TM), mixed plaque burden (weighted for non-calcified), high-risk-plaque (HRP) features, and plaque density (HU) were quantified by CTA. Serum 25-hydroxyvitamin D (OH)-levels were measured in 138 patients and categorized into four groups (0: <20 ng/mL; 1: 20–40 ng/mL; 2: 40–60 ng/mL; and 3: >60 ng/mL) and compared with CTA. Results: The prevalence of atherosclerosis by CTA was similar in both groups (75.6% versus 74.3%, p = 0.999), >50% coronary stenosis was slightly higher in controls (p = 0.046), but stenosis severity score (CAD-RADS) was not different (p = 0.106). Mixed plaque burden (weighted for non-calcified) was lower in patients receiving vitamin D supplementation (p = 0.002) and high-risk-plaque prevalence was markedly lower (3.8% versus 32%, p < 0.001). CT plaque density (HU) was higher (p < 0.001) in the vitamin D group. Patients with serum vitamin D (OH) levels >60 ng/mL had higher plaque density (p = 0.04), indicating more calcified and less vulnerable plaque. Conclusions: In this retrospective case–control cohort study, vitamin D supplementation was associated with less high-risk plaque, less non-calcified plaque burden, and a higher calcified plaque independent of CV risk factors. Full article

Non-coding RNAs (ncRNAs) play a key role in the regulation of transcriptional and epigenetic activity in mammalian cells. Comprehensive analysis of these ncRNAs has revealed sophisticated gene regulatory mechanisms which finely tune the proper gene output required for cellular homeostasis, proliferation, and differentiation. However, this elaborate circuitry has also made it vulnerable to perturbations that often result in disease. Among the many types of ncRNAs, long non-coding RNAs (lncRNAs) appear to have the most diverse mechanisms of action including competitive binding to miRNA targets, direct binding to mRNA, interactions with transcription factors, and facilitation of epigenetic modifications. Moreover, many lncRNAs display tissue-specific expression patterns suggesting an important regulatory role in organogenesis, yet the molecular mechanisms through which these molecules regulate cardiac and skeletal muscle development remains surprisingly limited. Given the structural and metabolic similarities of cardiac and skeletal muscle, it is likely that several lncRNAs expressed in both of these tissues have conserved functions in establishing the striated muscle phenotype. As many aspects of regeneration recapitulate development, understanding the role lncRNAs play in these processes may provide novel insights to improve regenerative therapeutic interventions in cardiac and skeletal muscle diseases. This review highlights key lncRNAs that function as regulators of development, regeneration, and disease in cardiac and skeletal muscle. Finally, we highlight lncRNAs encoded by imprinted genes in striated muscle and the contributions of these loci on the regulation of gene expression. Full article

Background: Diabetic patients show higher adverse ischemic event rates and mortality when undergoing percutaneous coronary intervention (PCI) in acute myocardial infarctions. Therefore, diabetic patients might benefit even more from modern-generation drug-eluting stents (DES). The aim of the present study was to compare adverse ischemic events and mortality rates between bare-metal stents (BMS) and DES in diabetic patients admitted with ST-elevation-myocardial infarction (STEMI) with non-diabetic patients as the control group. Methods: All STEMI patients undergoing emergency PCI and stent implantation documented between 2006 and 2019 in the Bremen STEMI registry entered the analysis. Efficacy was defined as a combination of in-stent thrombosis, myocardial re-infarction or additional target lesion revascularization at one year. Results: Of 8356 patients which entered analysis, 1554 (19%) were diabetics, while 6802 (81%) were not. 879 (57%) of the diabetics received a DES. In a multivariate model, DES implantation in diabetics compared to BMS was associated with lower rates of in-stent thrombosis (OR 0.16, 95% CI 0.05–0.6), myocardial re-infarctions (OR 0.35, 95%CI, 0.2–0.7, p < 0.01) and of the combined endpoint at 1 year ((ST + MI + TLR): OR 0.31, 95% CI 0.2–0.6, p < 0.01), with a trend towards lower 5-year mortality (OR 0.56, 95% CI 0.3–1.0, p = 0.058). When comparing diabetic to non-diabetic patients, an elevation in event rates for diabetics was only detectable in BMS (OR 1.78, 95% CI 0.5–0.7, p < 0.01); however, this did not persist when treated with a DES (OR 1.03 95% CI 0.7–1.6, p = 0.9). Conclusions: In STEMI patients with diabetes, the use of DES significantly reduced ischemic event rates and, unlike with BMS, adverse ischemic event rates became similar to non-diabetic patients. Full article