J. Cardiovasc. Dev. Dis., Volume 7, Issue 1 (March 2020) – 11 articles

Carotid and/or femoral atherosclerotic plaques (AP) assessment through imaging studies is an interesting strategy for improving individual cardiovascular risk (CVR) stratification and cardiovascular disease (CVD) and/or events prediction. There is no consensus on who would benefit from image screening aimed at determining AP presence, burden, and characteristics. Aims: (1) to identify, in asymptomatic and non-treated subjects, demographic factors, anthropometric characteristics and cardiovascular risk factors (CRFs), individually or grouped (e.g., CVR equations, pro-atherogenic lipid ratios) associated with carotid and femoral AP presence, burden, geometry, and fibro-lipid content; (2) to identify cut-off values to be used when considering the variables as indicators of increased probability of AP presence, elevated atherosclerotic burden, and/or lipid content, in a selection scheme for subsequent image screening. Methods: CRFs exposure and clinical data were obtained (n = 581; n = 144 with AP; 47% females). Arterial (e.g., ultrasonography) and hemodynamic (central [cBP] and peripheral blood pressure; oscillometry/applanation tonometry) data were obtained. Carotid and femoral AP presence, burden (e.g., AP number, involved territories), geometric (area, width, height) and fibro-lipid content (semi-automatic, virtual histology analysis, grayscale analysis and color mapping) were assessed. Lipid profile was obtained. Lipid ratios (Total cholesterol/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol, LogTryglicerides(TG)/HDL-cholesterol) and eight 10-years [y.]/CVR scores were quantified (e.g., Framingham Risk Scores [FRS] for CVD). Results: Age, 10-y./CVR and cBP showed the highest levels of association with AP presence and burden. Individually, classical CRFs and lipid ratios showed almost no association with AP presence. 10-y./CVR levels, age and cBP enabled detecting AP with large surfaces (˃p75th). Lipid ratios showed the largest association with AP fibro-lipid content. Ultrasound evaluation could be considered in asymptomatic and non-treated subjects aiming at population screening of AP (e.g., ˃ 45 y.; 10-y./FRS-CVD ˃ 5–8%); identifying subjects with high atherosclerotic burden (e.g., ˃50 y., 10-y./FRS-CVD ˃ 13–15%) and/or with plaques with high lipid content (e.g., LogTG/HDL ˃ 0.135). Full article

Background: The timing for initiation of effective antithrombotic therapy relative to the onset of arterial thrombosis may influence outcomes. This report investigates the hypothesis that early administration of heparin anticoagulation relative to the onset of thrombotic occlusion will effect a reduction in occlusion. Methods: A standard rat model of experimental thrombosis induction was used, injuring the carotid artery exposure with FeCl₃-saturated filter paper, followed by flow monitoring for onset of occlusion and subsequent embolization events. Intravenous heparin administration (200 units/mL) was timed relative to the initiation of injury or onset of near occlusion, compared with controls (no heparin administration). Results: No occlusion was found for delivery of heparin 5 min prior to thrombus induction, whereas all vessels occluded without heparin. Unstable (embolic) thrombi were seen with heparin given at or shortly after initial occlusion. Only 9% (1/11) of the vessels had permanent occlusion when heparin was given at the time of thrombotic onset (p < 0.0001 vs. unheparinized), while 50% occluded when heparin was delayed by 5 min (p > 0.05). Conclusions: These findings provide evidence that antithrombotic therapy may need to be administered prior to the onset of anticipated loss of patency, with less effectiveness when given after occlusion has occurred. Full article

Cardiac hypertrophy in response to chronic pathological stress is a common feature occurring with many forms of heart disease. This pathological hypertrophic growth increases the risk for arrhythmias and subsequent heart failure. While several factors promoting cardiac hypertrophy are known, the molecular mechanisms governing the progression to heart failure are incompletely understood. Recent studies on altered translational regulation during pathological cardiac hypertrophy are contributing to our understanding of disease progression. In this brief review, we describe how the translational machinery is modulated for enhanced global and transcript selective protein synthesis, and how alternative modes of translation contribute to the disease state. Attempts at controlling translational output through targeting of mTOR and its regulatory components are detailed, as well as recently emerging targets for pre-clinical investigation. Full article

Avian embryos have been used for centuries to study development due to the ease of access. Because the embryos are sheltered inside the eggshell, a small window in the shell is ideal for visualizing the embryos and performing different interventions. The window can then be covered, and the embryo returned to the incubator for the desired amount of time, and observed during further development. Up to about 4 days of chicken development (out of 21 days of incubation), when the egg is opened the embryo is on top of the yolk, and its heart is on top of its body. This allows easy imaging of heart formation and heart development using non-invasive techniques, including regular optical microscopy. After day 4, the embryo starts sinking into the yolk, but still imaging technologies, such as ultrasound, can tomographically image the embryo and its heart in vivo. Importantly, because like the human heart the avian heart develops into a four-chambered heart with valves, heart malformations and pathologies that human babies suffer can be replicated in avian embryos, allowing a unique developmental window into human congenital heart disease. Here, we review avian heart formation and provide comparisons to the mammalian heart. Full article

Background: Recent European guidelines on diabetes, prediabetes, and cardiovascular disease developed for the European Society of Cardiology (ESC) in collaboration with the European Association for the Study of Diabetes (EASD) significantly changed some concepts on risk stratification, lipid goals, and recommendations for the use of lipid-lowering drugs. The objectives of this work were to describe the lipid-lowering treatment prescribed for patients with diabetes and to determine the percentage of patients that achieved the lipid goals recommended by the 2019 ESC/EASD Guidelines on Diabetes in real and simulated scenarios. Methods: A multicenter, cross-sectional study was performed. Subjects >18 years with type 2 diabetes were included. The recommendations of the 2019 ESC/EASD Guidelines were followed. The real and simulated (ideal setting using adequate doses of statins ± ezetimibe) scenarios were analyzed. Results: Overall, 528 patients were included. In total, 62.5% of patients received statins (17.1% high intensity). Most patients were stratified as “very high risk” (54.2%) or “high risk” (43.4%). Only 13.3% achieved the double lipid goal (LDL-C and non-HDL-C goals according to the risk categories). In the simulation analysis, the proportion of subjects that did not reach the therapeutic objective decreased in all risk strata, although a considerable proportion of subjects persisted outside the target. Conclusion: The difficulty of achieving lipid goals in diabetic patients was considerable when applying the new guidelines. The situation would improve if we optimized treatment, but the prescription of new lipid-lowering drugs could be limited by their high cost. Full article

Attrition is a major cause of failure in obesity treatment, which is still not fully understood. The identification of factors related to this outcome is of clinical relevance. We aimed to assess the relationship between sarcopenic obesity (SO) and early attrition. Early attrition was assessed at six months, and two groups of patients were selected from a large cohort of participants with overweight or obesity enrolled at the Outpatient Clinic of the Department of Nutrition and Dietetics at Beirut Arab University (Lebanon). Body composition was measured using a bioimpedance analyser (Tanita BC-418) and participants at baseline were categorized as having or not having SO. The “dropout group” included 72 participants (cases) compared to 31 participants (controls) in the “completer group”, with the former displaying a higher prevalence of SO than the latter (51.0% vs. 25.8%; p = 0.016). In the same direction, Poisson regression analysis showed that SO increased the relative risk of dropout by nearly 150% (RR = 1.45; 95% CI = 1.10–1.89; p = 0.007) after adjustment for age, gender, body mass index (BMI), age at first dieting, sedentary habits and weight-loss expectation. In conclusion, in a “real-world” outpatient clinical setting, the presence of SO at baseline increases the risk of dropout at six months. New directions of future research should be focused on identifying new strategies to reduce the attrition rate in this population. Full article

The identification of predictors of major cardiovascular events (MACES) represents a big challenge, especially in early and stable cardiovascular diseases. This prospective study comparatively evaluated the prognostic importance of left ventricular (LV) and right ventricular (RV) systolic and diastolic function, pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) in a stable patient’s cohort with cardiovascular risk factors. The LV ejection fraction, mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), functional mitral regurgitation (FMR), doppler tissue imaging of mitral and tricuspid annulus with systolic and diastolic peaks estimation, tricuspid regurgitation velocity (TRV), pulmonary velocity outflow time integral (PVTI), mean pulmonary artery pressure (MPAP) and PVR were estimated at enrollment. During the follow-up, MACES and all-cause mortality were recorded. 369 subjects with or without previous MACES were enrolled. Bivariate analysis revealed LVEF, TAPSE, MPAP, TRV, PVR, LV diastolic function, and FMR were associated with the endpoints. When computing the influence of covariates to the primary endpoint (all-cause mortality and MACES) through Cox analysis, only LV diastolic function and TAPSE entered the final model; for the secondary endpoint (MACES) only TAPSE entered. TAPSE was able to predict MACES and all-cause mortality in early and stable cardiovascular diseases. The use of TAPSE should be implemented. Full article

Septin genes were originally identified in budding yeast in 1971. Since their original discovery, at least 13 mammalian genes have now been found, which give rise to a vast array of alternatively spliced proteins that display unique spatial-temporal function across organs systems. Septin’s are now recognized as the 4th major component of the cytoskeleton. Their role in regulating ciliogenesis, actin and microtubule organization and their involvement in mechanotransduction clearly solidify their place as both a responder and driver of cellular activity. Although work on septin’s has escalated over the past decades, knowledge of septin function in the heart remains rudimentary. Whereas many cardiovascular diseases have been associated with genetic loci that include septin genes, new and additional concerted efforts will likely uncover previously unrecognized mechanisms by which the septin class of proteins contribute to clinical cardiac phenotypes. In this review, we place known function of septin proteins in the context of heart development and disease and provide perspectives on how increased knowledge of these proteins can mechanistically inform cardiac pathologies. Full article

Atrial septal defect (ASD) is a non-physiologic communication between the two atria, allowing the shunt between systemic and pulmonary circulation. Data about ASD prevalence among congenital heart disease patients (CHD) in Vietnam are still scarce. We aim to assess the trends in the prevalence of ASD patients and associated factors among CHD patients. This was a cross-sectional study, with data collected from medical records from 1220 CHD patients in Da Nang hospital from 1 January 2010 to 31 December 2015. Descriptive statistics were used to estimate the prevalence of ASD among CHD patients. Comparative statistical methods were used to compare groups and logistic regression to access associated factors with ASD. The overall prevalence of ASD among CHD patients was 18.5% between 2010 and 2015. The prevalence varied between periods, ranging between 15% and 31.9% during the period. The prevalence of ASD women among CHD (25.9%) was significantly higher than for men (16.0%). The prevalence of ASD increased gradually when the age group increased. The factors associated with increased ASD prevalence were being a female and being in an older age group. The findings suggest that targeted policy should provide more-specific health-care services of ASD for women and older patients. Full article

Studies in mice show a brief neonatal period of cardiac regeneration with minimal scar formation, but less is known about reparative mechanisms in large mammals. A transient cardiac injury approach (ischemia/reperfusion, IR) was used in weaned postnatal day (P)30 pigs to assess regenerative repair in young large mammals at a stage when cardiomyocyte (CM) mitotic activity is still detected. Female and male P30 pigs were subjected to cardiac ischemia (1 h) by occlusion of the left anterior descending artery followed by reperfusion, or to a sham operation. Following IR, myocardial damage occurred, with cardiac ejection fraction significantly decreased 2 h post-ischemia. No improvement or worsening of cardiac function to the 4 week study end-point was observed. Histology demonstrated CM cell cycling, detectable by phospho-histone H3 staining, at 2 months of age in multinucleated CMs in both sham-operated and IR pigs. Inflammation and regional scar formation in the epicardial region proximal to injury were observed 4 weeks post-IR. Thus, pigs subjected to cardiac IR at P30 show myocardial damage with a prolonged decrease in cardiac function, formation of a regional scar, and increased inflammation, but do not regenerate myocardium even in the presence of CM mitotic activity. Full article